Renosonogram in diagnosis of renal failure. Twenty patients (10 males, 10 females age 20-60 years) with normal renal function underwent standard IVP and renosonogram. Length of kidney in its longest axis on IVP and sonogram was 13.6 +/- 1.43 cm, and 11.76 +/- 1.61 cm respectively. The ratio of the length of kidneys on IVP and sonogram respectively. There was significant correlation between these two factors (r=.95, P less than .001). When these ratios were analyzed individually for right and left slides it was found that ratios on IVP for the right kidney were 4.05 +/- .29, and for the left kidney 4.21 +/- .37. The ratios on the sonogram were for the right kidney 3.45 +/- .33 and for the left kidney 3.67 +/- .42. Using these ratios expected length of renal shadows on sonogram were calculated in 15 patients with severe renal failure (mean creat. 13.79 mg/dl). In ten patients in whom the infusion IVP visualized the renal shadows, the sonographic findings were confirmed. In 5 patients where infusion IVP was not helpful renosonogram revealed hydronephrosis in three patients, a retroperitoneal mass in another and cross-ectopia in a third patient. The results of this study indicate renosonogram is a useful procedure in evaluation and management of patients with renal failure with no demonstrable toxicity and requiring little preparation.


NaHCO3 and NaCl tolerance in chronic renal failure II. In patients with chronic renal failure (CRF) (CCr less than 20 ml/min), we have previously demonstrated greater rates of Na excretion (ex) when Na intake was nearly all NaHCO3 as compared to NaCl (both 200 mEq Na daily). Chloride (Cl) wasting on NaHCO3 (with severe Cl restriction) occurred, however, and may in part explain the results. To avoid Cl restriction in 6 patients with CRF (CCr 10-15 ml/min) on an estimated 10 mEq Na and Cl diet, electrolyte ex was compared on NaCl supplements of 200 mEq/day versus a daily mixture of NaHCO3 (100mEq) and NaCl (100 mEq). Periods on NaCl and the mixture lasted 4 days (order randomized) separated by re-equilibration to baseline weight (wt). Mean +/- SEM ex of Na, Cl, HCO3 mEq/day and CCr and deltawt (lbs) are compared below for the 4th day of NaCl vs NaHCO3 intake. (see article). Also there were no significant differences in K excretion, blood pressure, or plasma renin activities. Mean serum HCO3 increased from 21.2 to 25.8 mEq/l (day 1 vs 5, P less than 0.01) reflecting the net positive HCO3 balance on the mixture indicated above. Thus increments of Na intake above a fixed NaCl intake were excreted similarly whether given as NaCl or NaHCO3. Greater Na ex on NaHCO3 may depend on severe Cl restriction and/or higher serum HCO3 levels. If dietary NaCl intakes are near maximum tolerance, NaHCO3 supplementation should be accompanied by reductions in NaCl intake to maintain Na balance,


Renovascular hypertension: the role of nonspecific factors in the antihypertensive effect of surgery. Effective surgical treatment was carried out in 67 patients who were selected from a population of 336 subjects with renovascular hypertension. Split renal function studies and estimation of plasma renin activity in both renal veins were made to demonstrate the functional significance of the stenosis. The degree of disturbance of these tests did not correlate with the preoperative blood pressure level. The percentage decrease in postoperative blood pressure was directly related to the preoperative blood pressure (P less than 0.01). In 23 postoperative patients followed yearly for 5 years, the blood pressure increased progressively and was positively correlated with the duration of follow up (P less than 0.02). Patients with renovascular hypertension had a lower frequency of blood group 0 and a higher frequency of blood group A than did normotensive controls. The results of the study suggest that, in renovascular hypertension, the antihypertensive effect of surgical treatment is not exclusively related to the physiological consequence of the stenosis and that nonspecific factors, possibly of genetic origin, may determine the blood pressure response after surgical treatment.


"Alice in Wonderland" syndrome as a presenting symptom of infectious mononucleosis in children: a description of three affected young people. Three cases of "Alice in Wonderland" syndrome (metamorphopsia) are presented and described as a presenting symptom of infectious mononucleosis in a preadolescent male and in two late teenage females. In each instance, the classical infectious mononucleosis symptoms and diagnosis followed the onset of visual aberration. Thorough physical and blood examination of patients who present with such a syndrome must be undertaken before these symptoms are ascribed to psychiatric abnormalities. It is emphasized that infectious mononucleosis is a diffuse disorder, often associated with encephalopathies, which may include visual imbalance symptoms.


Exploring the physically ill child's self-perceptions and the mother's perceptions of her child's needs: insights gained from the FIRO-BC--a behavior test for use with children. When dealing with the management of the dying patient and his family, systematic research has been very limited. Understanding the dying child's needs, as well as his family's, is important for approprirate therapy programs. The present study investigated the mother's awareness of her child's expressed and wanted needs in three areas of interpersonal relationships. It also studied the dying child's self-perceived needs and desires as compared with those of children with a non-life-threatening illness and with those of well children.


Plasma l-alpha-Acetylmethadol (LAAM) after acute and chronic administration. l-alpha-Acetylmethadol (LAAM) was administered orally to two groups of subjects; one group received methadone, 50 mg/day, for three months previously and the other group were heroin addicts who had no prior exposure to methadone or LAAM. Plasma elimination curves for methadone, LAAM, and its metabolites, noracetylmethadol (N-LAAM) and dinoracetylmethadol (DN-LAAM), were determined after acute and chronic administration. The plasma decay curve for LAAM was biexpoenential (t1/2alpha = 6 hr; t1/2beta greater than 50 hr) following acute or chronic administration. Following chronic administration, N-LAAM and DN-LAAM plasma levels increased 5- to 10-fold. At this time, N-LAAM had a t1/2 of 31 hr and DN-LAAM had a t1/2 of greater than 100 hr. There appear to be at least two factors which determine the long duration of action of LAAM: metabolic conversion to active metabolites and tissue or plasma binding. Both methadone and LAAM may compete for plasma protein or tissue binding sites. The clinical implications of this potential drug-drug interaction are discussed.


Effects of intravenous tetrahydrocannabinol on experimental and surgical pain. Psychological correlates of the analgesic response. Two intravenous doses of tetrahydrocannabinol (THC) (0.022 mg/kg and 0.044 mg/kg) were compared to intravenous diazepam (0.157 mg/kg) and to placebo (Ringer's lactate) as premedication for dental extraction in 10 healthy volunteers. Pain detection and tolerance thresholds were measured and psychiatric interviews were supplemented by Minnesota Multiphasic Personality Inventories (MMPI), the Zung Depression Scale (ZDS), Beck Depression Inventories (BDI), and the State-Trait Anxiety Inventory (STAI). Pain detection thresholds were altered unpredictably with high THC doses, but analgesia as indicated by pain tolerance was less than that after diazepam and placebo. In three subjects low-dose THC (0.022 mg/kg) was a better analgesic than placebo but not diazepam. Six subjects preferred placebo to low-dose THC as an analgesic; this group experienced increases in subjective surgical pain and were submissive, rigid, and less introspective with high State Anxiety and MMPI profiles that differed from subjects whose pain was not increased. STAI following THC presaged a poor analgesic response in this group.


Tricyclic antidepressant plasma levels and adverse effects after overdose. Forty patients ingesting tricyclic antidepressant (TAD) overdoses were studied as a pharmacologic model to determine whether total tricyclic antidepressant plasma levels correlated with major adverse effects and electrocardiographic findings. Maximum TAD plasma levels were higher in patients who died (p less than 0.025) or had cardiac arrest (p less than 0.02), needed respiratory support (p less than 0.005), were unconscious (p less than 0.02), had grand mal seizures (p less than 0.001), ventricular rate larger than or equal to 120/min (p less than 0.01), cardiac arrhythmia (p less than 0.05), QRS duration larger than or equal to 100 msec (p less than 0.001), or bundle branch block (p less than 0.05). TAD plasma levels correlated with the dose ingested by history (N = 29, r = 0.58, p less than 0.001). Measurement of total TAD (free and protein-bound) appears to correlate well with biologic response.


Plasma adriamycin and daunorubicin levels by fluorescence and radioimmunoassay. In 38 adriamycin experiments and 4 daunorubicin experiments, radioimmunoassay readily and reproducibly detects and estimates these drugs and immunologically similar metabolites in patients' plasma and urine to at least 120 hr after dosing without interference by concurrent medication. The plasma drug decay follows first-order kinetics in a triphasic pattern. Radioimmunoassay and fluorescence assay show similar decay up to 4 hr but diverge at that point with the fluorescence assay yielding higher values. Pharmocokinetic differences are amplified in patients with liver dysfunction and may be caused by fluorescent drug metabolites not sensitive to radioimmunoassay or nonspecific fluorescent materials. The radioimmunoassay offers the capability to measure adriamycin and daunorubicin in clinical settings in which fluorescence assay is not available.


Mechanisms of acquired resistance to Pasteurella multocida infection: a review. Pasteurella multocida is an animal parasite of considerable economic and veterinary importance. The organism produces both capsular polysaccharide and somatic (lipopolysaccharide) antigens used to serotype the organisms. Correlations exist between antigenic structure, host susceptibility and strain virulence. The host response seems to be predominantly polymorphonuclear in nature, with little evidence of a mononuclear component in the host response to infection. In the absence of specific opsonins, phagocytosis rates are very slow, the organisms multiplying freely in an essentially extracellular environment. Passive transfer studies indicate that acquired resistance is humorally modiated, presumably by promoting phagocytosis withing the peritoneal cavity. There is, however, no sign of early increased local bactericidal action within the peritoneal cavity; protection seems rather to be due to an inhibition of the rapid spread by the organisms to the bloodstream and other reticuloendothelial organs. Viable attenuated oral vaccines are effective for chicken and turkey poults, both experimentally and under field conditions. The nature of the protective immunoglobulins and their mode of action against an orally induced infection has not been widely examined as yet. Effective protection can be achieved in birds, cattle and experimental animals with a variety of killed vaccines (especially when presented in a suitable adjuvant). The lack of quantitative growth data in suitably vaccinated animals and the absence of definitive studies of the bactericidal mechanisms involved in the expression of this acquired resistance continue to limit our present understanding of defense against this important animal disease.


Mucormycotic hepatic lesions resembling bacillary hemoglobinuria infarcts in irradiated calves. To produce hematopoietic chimeras, 3 young, healthy calves were exposed to whole-body irradiation and, 6 days after irradiation, were injected with a bone-marrow suspension prepared from an unrelated, normal donor calf. Antibiotics were administered daily to control bacterial infection. One calf died 8 days postirradiation (PI), another died 10 days PI, and the third calf was killed in extremis 11 days PI. In addition to lesions of acute radiation injury, one to several spherical, firm, dry, reddish-black nodules were found in the liver of each calf. Hepatic changes and blood-stained urine were suggestive of bacillary hemoglobinuria. Fungi, identified by their morphologic features as members of the class Phycomycetes, were widely distributed in the tissues and lesions.


Diabetes mellitus in the bovine.

Diabetes mellitus in the bovine. Diabetes mellitus has not often been reported in the bovine. In the present report, the condition is described as it occurred in two cows and one calf. Diagnosis was made on the basis of clinical, laboratory and histopathological findings. All animals showed afebrile debilitation and polydipsia. Hyperglycemia was present with a quantitative reduction in the amount of pancreatic islet tissue.


Detection of antibody to the antiphagocytic factor produced by group E streptococci. Tests for opsonic activity, long chain formation, and precipitins were investigated for ability to detect antibodies to the antiphagocytic factor of group E streptococci. Rabbits, hyperimmunized to serum-grown group E streptococci developed antibodies to the antiphagocytic factor detectable after 2 weeks by the opsonic activity and long chain tests and at 4 to 6 weeks by a precipitin test in which a slide micro double diffusion method was used. Antiphagocytic factor antibodies were dected in swine serums 2 weeks after the swine were experimentally infected, and the antibodies persisted at the end of the experiment at 20 weeks. Demonstration of the antibodies in swine serum was made with the opsonic activity or long chains tests but not with the precipitin test.


Infection of weanling pigs with known numbers of Ascaris suum fourth stage larvae. Nineteen weanling pigs were each infected per os with 200 fourth stage Ascaris serum larvae and were fed either a low protein or a high protein diet for 8 weeks. Worms expelled during the 8 weeks were recovered and all worms remaining in the gastrointestinal tract at slaughter were collected. Fifty-four percent of all worms were recovered at slaughter. Ten of the 19 animals maintained an infection for 8 weeks; the other 9 showed no signs of A. suum infection. A total of 377 worms were recovered. Average worm burdens were 37.7 worms per pig, 50.8 worms per low protein pig, and 30.8 worms per high protein pig. Times of and possible causes for expulsion are discussed. Procedure for infection of pigs is discussed in detail and possible improvements in technique are suggested.


Mitral valve replacement: a comparison of two prostheses. Between November, 1965 and June, 1970, 175 patients underwent mitral valve replacement with the Smeloff-Cutter prosthesis (109 patients) or the toroidal valve (66 patients). The early mortality for patients with a toroidal mitral prosthesis was 18.2 percent (12 patients) and the late mortality 34.8 percent (23 patients). Among patients in whom Smeloff-Cutter mitral valves were inserted, the early mortality was 15.6 percent (17 patients) and the late mortality 23.9 percent (26 patients). During a follow-up period extending at least five years, thromboembolic complications occurred in 25.9 percent (14) of patients with toroidal valves and 7.6 percent (7) of patients with Smeloff-Cutter valves. Reoperation was necessary because of thrombosis of the prosthesis in seven patients with toroidal valves and two patients with Smeloff-Cutter valves. The incidence of endocarditis was the same in both groups. In this study, the Smeloff-Cutter mitral prosthesis proved to be superior to the toroidal valve because of a lower incidence of thromboembolism.


Airway response to short-term inhalation of tobacco smoke. Lack of racial differences. Airway response to short-term inhalation of cigarette smoke was studied in healthy black subjects. We have measured thoracic gas volume, airway resistance, maximum expiratory flow rates, and closing volume in 12 healthy black volunteers before and after smoking a cigarette. We found a significant reduction in airway conductance and midexpiratory flow rate after smoking the cigarette. The results are similar to those previously observed in white subjects. We conclude from our study that the response to short-term inhalation of cigarette smoke is identical in both white and black subjects.


Harbingers of paroxysmal ventricular tachycardia in acute myocardial infarction. We examined the harbingers of 68 episodes of paroxysmal ventricular tachycardia in 42 patients with documented acute myocardial infarction. Late ventricular premature contractions initiated 46 bouts of paroxysmal ventricular tachycardia, while 17 were engendered by early ventricular premature contractions and five by atrial premature contractions. Paroxysmal ventricular tachycardia related to early ventricular premature contractions tended to last longer and failed to respond to therapy with lidocaine more often than paroxysmal ventricular tachycardia begun by late ventricular or atrial premature contractions. Ventricular fibrillation occurred in six cases of paroxysmal ventricular tachycardia due to early ventricular premature contractions but was absent in paroxysmal ventricular tachycardia related to late ventricular or atrial premature contractions. The "malignant" potential of a given ventricular premature contraction cannot be assessed from its degree of prematurity alone.


Bacterial endocarditis due to Haemophilus parainfluenzae. We have evaluated three patients with Haemophilus parainfluenzae endocarditis. Two of the three had underlying heart disease. All presented with fever, chills and malaise of less  than two weeks' duration. Mitral valve involvement led to congestive heart failure in two of three cases. Treatment proved difficult, despite normally adequate dosages of antibiotics to which the pathogens were sensitive in vitro (ampicillin, 12-20 gm/dag; gentamicin, 3-5 mg/kg/day). Two patients were cured; one died. There was a suggestion of an inverse correlation between vegetation mass and favorable clinical response. Review of the English literature disclosed 22 documented cases of H parainfluenzae endocarditis, including 12 in the antibiotic era.


Selective mediastinoscopy.

Selective mediastinoscopy. Mediastinoscopy is often utilized for staging bronchogenic carcinoma. Whether it should be used routinely or selectively is controversial. Fifty-four patients with bronchogenic carcinoma were prospectively assigned to one of two groups based on the presence (group A) or absence (group B) of one or more of the following criteria: (1) central location; (2) mediastinal nodal enlargement; (3) involvement of laryngeal nerve; and (4) noncentral location plus linear stranding toward the hilum. Mediastinoscopy was performed on all patients in group A. Thoractomy for definitive staging was performed on those patients in group A with negative mediastinoscopic findings for neoplasm and on all patients in group B. Criteria 1, 2, and 3 were found to be valid; 22 of the 27 patients in group A who had any of these criteria had positive mediastinoscopic findings for neoplasm. Criterion 4 per se was found to be invalif; all seven of the patients in group A who had this isolated finding had negative mediastinoscopic findings for neoplasm and had resectable lesions. Twenty-three of the 27 patients in group B had no mediastinal involvement and had resectable lesions. These data indicate that selective mediastinoscopy using criteria 1 through 3 reduces the number of negative examinations and unnecessary thoracotomies to a minimum.


Measurement of mucociliary transport velocity in the intact mucosa. A new method for measuring the velocity of the tracheal mucous transport rate in anesthetized dogs is described. The length of the trachea is determined with the bronchoscope as the distance between the larynx and the lower end of the trachea at the level of the carina. A small volume (0.04 to 0.1 ml) of albumin microspheres 5 mgm to 7 mum in diameter labeled with radioactive 99m technetium or 113m indium is deposited on the mucosal surface at the lower end of the trachea via a catheter placed in the inner channel of a fiberoptic bronchoscope. The movement of the microspheres towards the larynx is visualized and recorded using a scintallation camera (Picker Dyna Camera) with a large field of view (30 cm in diameter) for 30 to 60 minutes, depending upon the time required for the spheres to reach the top of the trachea. Polaroid pictures are made immediately and every minute thereafter until the activity reaches the larynx. The data are also recorded and stored on magnetic tape for subsequent analyses by computer. The length in millimeters divided by the time in minutes gives the transport velocity rate. The mean velocity was found to be 19.2 +/- 1.6 mm/min (+/- SE).


The effects of transfemoral cardiac catheterization on limb blood flow in children. Blood flow was measured with a mercury-in-rubber strain-gauge plethysmograph in the utilized and intact extremity during and 24 hours after uncomplicated (with no clinical signs of vascular insufficiency) percutaneous right and left cardiac catheterization in 20 children. In this group, there was a significant decrease of the flow in the utilized extremity after entry into the artery, with the flow returning to normal within 24 hours after the procedure. Flow was markedly reduced in the utilized extremity of a child who developed thrombosis of the femoral artery after catheterization. Seven additional children were studied one to four years after retrograde catheterization. In this group the flows in utilized and intact extremities were equal at rest and with reactive hyperemia. It is concluded that uncomplicated transfemoral percutaneous cardiac catheterization in children does not impair the blood flow in the limbs.


Magnet noncontact apexcardiography. A new technique for registering chest motion. A new apexcardiographic recording system has been developed which is free of certain technical limitations. This noncontact magnetic transducer was tested alternately with a commonly used pneumatic piezoelectric transducer in a comparative study on ten normal subjects. The magnetic registration offered a more accurate timing and configuration of the ACG. Signal distortion, such as peaked waves and an early fall of the systolic wave, was eliminated. The magnetic transducer was capable of recording directional apex point tracings, as well as pulsations of a larger apical area. The new system proved to possess definite advantages and eliminated some of the inconveniences inherent in the pneumatically coupled system.


Thoracic metastasis in malignant melanoma. A radiographic survey of 65 patients. Sixty-five patients with malignant melanoma metastatic to the thorax were evaluated retrospectively. Chest x-ray films showed abnormalities in 63 patients and provided the first evidence of dissemination in 42 of the 62 with widespread metastasis. Frequent radiographic follow-up evaluations of patients with primary melanoma is necessary to detect metastasis at an early stage. Pulmonary metastasis was seen radiographically in almost 90 percent of the patients. Snowstorm metastasis denotes a poorer prognosis than other patterns of pulmonary involvement. Enlargement of mediastinal lymph nodes, bronchial obstruction with atelectasis, pleural effusion, bone metastasis with an extrapleural mass, and cardiomegally were also seen. Follow-up chest x-ray films are of limited value in evaluating patients once they are found to have thoracic metastasis. The rate of growth of metastatic lesions or the regression of the metastasis does not correlate with survival.


The management of pericardial effusion in cancer patients. The relatively little attention given in the literature to the problem of pericardial effusion in patients with cancer reflects the general attitude that if this complication is disclosed, the future of the patient is sealed, and therapy will not change his outcome. We challenge this pessimistic approach, and describe here our experience with seven patients with solid tumors, in whom pericardial effusion was diagnosed; one of them is described in detail. We advocate an active and sometimes even an aggressive therapy, which should always be related to the degree of the hemodynamic impairment. If instant relief is indicated, pericardiocentesis should be done; pericardiectomy is the treatment of choice if the fluid reaccumulates rapidly. After overcoming the urgent problem, the underlying disease and the local pericardial condition should be treated; and in our opinion, a combined approach, such as systemic or local chemotherapy, or both, with or without precordial irradiation, will lead to the optimal result.


Cardiac disease in the wheezing child.

Cardiac disease in the wheezing child. Cardiac and pulmonary disease are so closely interrelated that it is often difficult to determine in young infants which is the primary offender. As illustrated in these case reports, failure to recognize the true nature of the disease process may lead to unnecessary procedures and delays which can be life-threatening. Statistically, the wheezing infant very likely is suffering from primary pulmonary disease; however, congenital cardiac abnormalities can cause pulmonary symptoms which completely dominate the clinical picture and lead to erroneous diagnoses. Although rare, the basis of cough and wheezing may be a vascular ring which encircles and compresses the trachea. Lesions associated with large left-to-right shunts, such as ventricular septal defect and patent ductus arteriosus, also can cause cough and wheezing because of bronchial compression by a large tense pulmonary artery and a distended left atrium. These same lesions also produce isolated left ventricular failure with pulmonary venous congestion and episodes of cough and wheezing. Anomalous pulmonary venour return, cor triatriatum, supravalvular mitral ring, or mitral stenosis are other lesions which can cause cough and wheezing secondary to pulmonary venous obstruction.


Asymptomatic idiopathic syndrome of prolonged Q-T interval in a 45-year-old woman. Ventricular tachyarrhythmias precipitated by hypokalemia and therapy with amitriptyline and prephenazine. Recurrent ventricular tachyarrhythmias required multiple resuscitative efforts with electrical countershock in a 45-year-old woman with previously undiagnosed asymptomatic congenital prolongation of the Q-T interval. This patient represents the oldest person with symptoms relating to idiopathic prolongation of the Q-T interval found in the literature. Exacerbating factors, including diuretic-induced hypokalemia and the concomitant administration of perphenazine, were present. In such cases, initially refractory to therapy with antiarrhythmic agents, insertion of a transvenous pacemaker with overdrive suppression of the ventricular tachyarrhythmias may be lifesaving, allowing for the institution of therapy with agents that can selectively shorten the Q-T interval.


Transvenous pulmonary embolectomy for acute massive pulmonary embolism. Transvenous pulmonary embolectomy employing a vacuum-cupped directionally controlled catheter is a relatively new technique used in the management of major pulmonary embolism. We present the findings in a patient with acute massive pulmonary embolism who underwent transvenous pulmonary embolectomy, with immediate and marked improvement in hemodynamic function and survival. Insertion of a new intracaval filter at the same time provided protection against recurrent thromboembolism.


Pleuroscopy and cautery control of intrathoracic hemorrhage with a flexible fiberoptic bronchoscope. Intrathoracic hemorrhage from adhesions torn by a spontaneous pneumothorax is relatively uncommon. Continued hemorrhage from such adhesions after the evacuation of 1,500 ml of blood would usually require thoracotomy for control. Through a flexible fiberoptic bronchoscope, we confirmed the source of hemorrhage and cauterized the bleeding point. This case illustrates another application for pleuroscopic examination, further broadening the use of the flexible fiberoptic bronchoscope.


Forward angiography in the identification of vegetations in tricuspid endocarditis. A patient with staphylococcal endocarditis of unknown valvular location and resistant to antibiotic therapy was studied in order to localize the site of infection prior to cardiac surger. The injection of contrast material into the right atrium visualized tricuspid vegetations which were confirmed at surgery. In such situations, forward angiographic studies constitute a safe, simple, and potentially diagnostic procedure which avoids the hazards of advancing a catheter across an infected valve.


Paroxysmal supraventricular tachycardia with unusual induction. Concealed reentry or automaticity? In a patient with documented paroxysmal supraventricular tachycardia, earlier atrial extrastimuli consistently induced His-ventricle (H-V) block and "atrioventricular junctional" beats, which were always followed by an echo or paroxysmal supraventricular tachycardia. In "atrioventricular junctional" beats, a V wave was preceded by an H deflection with the same intervals as that of the sinus beat. As for the underlying mechanism of paroxysmal supraventricular tachycardia, two possibilities were considered: (1) concealed atrioventricular nodal reentry, and (2) "triggered automaticity."


Suicidal hanging. An association with the adult respiratory distress syndrome. This study of two victims of suicidal hanging describes a previously unknown association between near-fatal hanging and the adult respiratory distress syndrome. We report on the pathophysiologic results of this pulmonary complication and the implications of this finding regarding the treatment of these patients.


Mural endocarditis associated with recurrent false aneurysm of the left ventricle. Acute bacterial endocarditis developed in a 65-year-old man two years after surgical resection of a false aneurysm of the left ventricle. The patient had cerebral embolic manifestations, and coagulase-positive Staphylococcus aureus was cultured from each of six blood samples. A pericardial friction rub and a changing pansystolic murmur appeared during the third week of hospitalization. The presence of a false aneurysm was once again demonstrated on ventriculographic studies. This was successfully repaired, employing cardiopulmonary bypass. The sequence of events in this patient suggests that bacterial endocarditis at the site of a previous cardiomyotomy might have led to the development of the second pseudo-aneurysm.


Empyema due to Streptococcus mutans.

Empyema due to Streptococcus mutans. Empyema due to Streptococcus mutans occurred following dental manipulation in two patients with periodontal disease. Isolation of this dental pathogen from pleural fluid localized the site of origin of the empyemas to the oropharynx and precluded the need to search for a remote intra-abdominal source of these pleuropulmonary infections. Although there is controversy regarding the susceptibility of S mutans to penicillin, the isolates from our patients were markedly sensitive to the drug, and both patients were cured with penicillin therapy and surgical drainage.


Complete heart block following therapeutic irradiation of the left side of the chest. Two female patients had received therapeutic irradiation of the left side of the chest for adenocarcinoma of the left breast and 18 and 23 years later, respectively, developed atrioventricular block. Both patients had early and late cutaneous reactions, as well as fibrosis of the left lung, lymphedema of the left arm, and pathologic rib fractures but had no signs of recurrence of the carcinoma. One patient developed signs of congestive heart failure while the electrocardiogram revealed second and third degree atrioventricular block; subsequent pacemaker implantation relieved the congestive heart failure. In the second patient, fatigue was the only symptom leading to the diagnosis of transient second and third degree atrioventricular block; this symptom subsided after pacemaker implantation. Based on reports of radiation-induced cardiac damage, it is assumed that the heart block in these two patients might have been due to postirradiation fibrosis of the atrioventricular node, either direct or mediated by fibro-occlusive changes in the coronary vessels.


Bullet in the left ventricle from a remote gunshot wound to the heart. A bullet was found at necropsy in the left ventricle of a man who died of carcinoma of the urinary bladder. The bullet had entered the body at an unknown time in the remote past. The bullet probably gained entrance to the heart through the left atrial wall and lodged in the left ventricle.


Pharmacokinetic study of intravenous rifampicin. The time course of the serum and urine concentrations of rifampicin were evaluated during and after administration of an intravenous preparation of the antibiotic. 300, 450 and 600 mg dose levels of the antibiotic were evaluated, all being given as intravenous infusion after solution in 500 ml of glucose, the infusion lasting 3 h. The results have shown that the serum level curves and the kinetic parameters calculated on them do not differ to any major extent from those corresponding to the same doses given orally. No changes of relevance in the half-life values were observed between doses. Changes in serum bilirubin levels were observed with a pattern similar to that commonly seen with oral administration of rifampicin.


Evolution of sensitivity to fosfomycin in bacteria isolated in 1973, 1974 and 1975 in the Servicio de Microbiologia y Epidemiologia of the 'Clinica Puerta de Hierro', Madrid. The bacteriostatic activity of fosfomycin was studied in vitro against 1,243 clinical isolations of gram-positive cocci and 4,086 isolations of gram-negative bacilli that were obtained in 1973, 1974 and in the period from January to May of 1975. MIC was determined by the agar diffusion method, quantifying it by means of the standard curve that was worked out with the strain of E. coli NCTC 10,418. A slight increase in resistance was observed in the gram-positive cocci: 64 mug/ml were inhibitory for 63% of the 249 isolations obtained in 1973, 59.1% of the 716 isolations obtained in 1974, and 57.5% of the 278 isolations from 1975. A slight loss of sensitivity was also observed in the gram-negative bacilli: the aforementioned concentration of fosfomycin inhibited 36% of the 742 isolations from 1973, 33.6% of the 2,387 isolations from 1974 and 32.6% of the 957 isolations from 1975. 933 g of this antibiotic were consumed in our hospital in 1973, 4,203 g in 1974 and 957 g in 1975. The consumption rate per patient per year was 0.15, 0.72 and 0.20 g, respectively. In conclusion, although no change was observed in the sensitivity of some bacterial strains to fosfomycin, the overall study indicates a slight decrease in the sensitivity, although it does not apparently have any relationship to the consumption of fosfomycin in our hospital.


Pharmacokinetics of fosfomycin.

Pharmacokinetics of fosfomycin. Fosfomycin, an antibiotic discovered in Spain, has a unique chemical structure and pharmacologic features that are promising for clinical therapy. It is only partially absorbed orally, with relatively low blood levels. Intramuscularly, however, absorption is complete with peak blood levels 3-5 times as high as orally, and rapid intravenous injections give serum concentrations almost twice as high as intramuscularly. Some accumulation occurs with all three routes, and concentrations in excess of 1,000 mug/ml are consistently obtained in the urine with parenteral doses every 6 h. The serum half-life is 1.5-2 h, urinary excretion is by glomerular filtration, the antibiotic is not bound to serum proteins, and the volume of distribution is large. Diffusion into tissues and body fluids is good. Thus, the pharmacologic characteristics of fosfomycin along with its low toxicity make it comparable in these respects to other well-established antibiotics.


Pharmacokinetic study of fosfomycin and its bioavailability. The pharmacokinetics of fosfomycin in humans was studied in six young healthy volunteers after intravenous administration of 500 mg fosfomycin and after the same dose in oral administration in three different formulations. It was proven that fosfomycin follows a bicompartmental pattern, for which the disposition constants, the biological half-lives for the fast and slow phases, and the distribution constants were calculated. The renal excretion constant was evaluated making determinations of fosfomycin in the urine, and this constant together with the elimination constant allowed us to determine the extrarenal elimination. The concentration and quantity of the drug in the central and peripheral compartments were calculated and tabulated for different periods of time. An analogous behavior was obtained with the three formulations that were orally administered, with an average bioavailability of 37% in relation to the intravenous bioavailability, as evaluated by means of the accumulative renal excretion.


New studies on placental transfer of fosfomycin. Passage of fosfomycin across the placental barrier and the dynamics of maternal and fetal levels were determined in a group of ten mothers in active labor. To obtain a series of intrauterine fetal samples the Saling technique was used. There exists a clear relation between the levels reached in the mother and in the fetus and in function of time, as well as between the amount of antibiotic in the fetal blood 90 min after injection, and the weight of the placenta.


A study of the levels of fosfomycin in the cerebrospinal fluid in adult meningitis. In order to determine the liquor concentration of fosfomycin, we chose 27 patients who were suffering from meningitis with different etiology. According to route, type of administration and doses employed, we classified the patients into five groups. Blood samples were taken from the patients 1 h after concluding the administration of the antibiotic and 2 h after the CSF sample. The concentration of fosfomycin in the serum and the CSF were then determined in the laboratory. In order to evaluate the results we divided our cases into three groups according to the state of their meningeal inflammation. In the first group of patients with active meningitis, we obtained an average concentration of fosfomycin in the serum of 65.20 mug/ml and in the CSF of 10.88 mug/ml. In the second group of patients with meningitis in the remission stage, the concentration of fosfomycin in the serum was 83.58 mug/ml and in the CSF it was 9.63 mug/ml. In the third group of patients with their meningitis cured, the concentration of fosfomycin in the serum was 66.45 mug/ml and in the CSF it was 4.95 mug/ml. On the basis of the concentrations obtained and with regard to the sensitivity in vitro, we concluded that fosfomycin can be useful in the treatment of meningitis caused by Pneumococcus, Staphylococcus, E. coli and other gram-negative bacilli.


The passage of fosfomycin into the cerebrospinal fluid in children's meningitis. This report deals with the results of a study that was made on the passage of fosfomycin into the CSF in 22 children with meningitis (11 parotideal meningitis and 11 meningococcal meningitis). The plasma and liquor levels of fosfomycin were determined in the acute phase of the illness and after the normalization of the CSF, with the object of studying the passage of the antibiotic through the blood-brain barrier in the presence and absence of meningeal inflammation. A greater permeability of the meninges was found to exist when they were in an inflammatory state and there seems to be a certain accumulative effect in the CSF when the fosfomycin is administered by intravenous perfusion. The concentrations that were obtained in the CSF were not high enough to justify the exclusive use of fosfomycin in the treatment of meningitis. Nevertheless, considering its wide antibacterial spectrum, its MIC against different microbial species and its lack of toxicity, we believe that fosfomycin can be of use when associated with other antibiotics in the treatment of meningitis caused by S. aureus, D. pneumoniae, H. influenzae, E. coli, P. mirabilis and S. marcescens.


Blood and urinary concentrations of fosfomycin as a function of the renal function value. The following parameters were considered in studying 43 subjects under treatment for urinary infections with different degrees of renal insufficiency: the maximum blood concentrations, the plasmatic half-life, and the urinary concentrations of fosfomycin as a function of the plasma creatinine of the subject treated. The curve of the average maximum blood concentrations show a parabola-like increase, the plasmatic half-life followed the same tendency, while the curve of the average urinary concentrations presented an exponential decrease. The urinary concentrations were, nevertheless, always higher than 100 mug/ml regardless of the degree of renal insufficiency and even in the subjects who had a very high plasma creatinine. Given its absence of renal and systemic toxicity, the daily dosage of fosfomycin could remain unchanged regardless of the degree of insufficiency.


Renal insufficiency and fosfomycin.

Renal insufficiency and fosfomycin. After the parenteral injection of 1 g sodium salt of fosfomycin the serum levels of the antibiotic are detected in a series of eight adult patients with different degrees of chronic renal insufficiencies four of them submitted to periodical dialysis. The results obtained reveal that the levels as well as the time of elimination of fosfomycin maintain an obvious relation to the degree of renal insufficiency in the patients.


Fosfomycin in patients subjected to periodic hemodialysis. The sensitivity to fosfomycin which is found in organisms that are frequently found in urinary infections and the lack of toxicity of this antibiotic were the reasons for which we tested fosfomycin on patients who were subjected to periodic hemodialysis. We were interested in studying (1) if fosfomycin was dialyzable, and (2) its therapeutic pattern in these patients. We selected a group of 27 patients from our programme of periodic hemodialysis who spend 18 h each week in three sessions with an RSP Travenol artificial kidney, using Ultra Flo II as the dialytic unit. They were all free of infection and had not received any antibiotics for 40 days before the test was carried out. They were administered 1 or 2 g of fosfomycin by the intravenous route at the time of beginning the dialysis. Blood samples and samples from the dialytic bath were taken before administering the fosfomycin, and 1/2, 3 and 6 hours after administering it. Our results show that fosfomycin is 70-80% dialyzed by the membranes of the artificial kidney and that during the hemodialysis, given the clearance which the dialyzing membrane makes of the antibiotic, the usual doses of fosfomycin should not be altered. No side effects were observed in any of the patients.


Pharmacokinetics of fosfomycin during hemodialysis. A study was made of the elimination of fosfomycin by the membrane of the artificial kidney in 10 patients with hemodialysis and a creatinine clearance of less than 5 ml/min. To do so we determined the half-life, the dialysance, the percentage of total loss and the percentage of loss by the artificial kidney. We reached the conclusion that fosfomycin is heavily dialyzed (D = 64 ml/min), it is entirely eliminated by the kidneys and its half-life is therefore affected very little (an increase of only about 30 min is produced). All of this leads to a practical schema by which the entire initial dose should be replenished at the end of each dialysis.


Pharmacodynamic data on fosfomycin in underweight infants during the neonatal period. A study was made of the blood levels, half-life and elimination of fosfomycin in two groups of underweight infants during the 1st to 3rd days of life and after 3-4 weeks. The test dose was 50 mg/kg i.v., administered in a single dose. The times at which the blood was controlled were 5 min, 1, 3, 6, 9 and 24 h; and 0-24 h for the urine. All samples were evaluated by the microbiological method of diffusion in plate. The results obtained indicate that the elimination of fosfomycin after 24 h is slower and occurs in smaller quantities in the group of infants 1-3 days old than in the group of 3- to 4-week-old infants, the half-life of the antibiotic being 7 and 4.9 h, respectively.


Influence of fosfomycin on intestinal disaccharidases in rats. The influence of orally administered fosfomycin on intestinal disaccharidases in albino rats was studied. The enzymes were evaluated in a homogenate of the intestinal mucosa, using the method of SOLS and DE LA FUENTE which is based on the colored reaction of the glucose that is freed by the disaccharidases from disaccharides with a glucose-oxidase-peroxidase reagent and a chromogen (Glucostat). The results obtained in animals treated with a daily dose of 1 g/kg fosfomycin for 6 consecutive days are compared with the corresponding results of animals that received 1 ml/day of saline solution during the same period. Our conclusion was that fosfomycin has no effect on the intestinal disaccharidases in rats.


Effect of fosfomycin on the thrombocytal aggregation induced by ADP. The effect of fosfomycin on the thrombocytal aggregation induced by ADP was studied. Plasma rich in thrombocytes was used. It was obtained from blood donors. Fosfomycin was used in concentrations of 1.3 X 10(-3); 1.3 X 10(-2), and 1.3 X 10(-1)M and the ADP in concentrations of 1.17, 2.34 and 3.51 X 10(-6)M. Two experimental groups were used: the first group was made up of five experiments, with an incubation time for the fosfomycin with the thrombocytes of 2 min; the second experimental group was made up of five experiments whose incubation times were 5 and 10 min. Fosfomycin inhibits the thrombocytal aggregation which is induced by ADP. This inhibition (1) is larger, the smaller the concentration of ADP, (2) for a single concentration of ADP it is proportional to the concentration of fosfomycin that is used, and (3) there are no significant differences according to the time of incubation. This thrombocytal anti-aggregating activity is related to the presence of a phosphonic group in the molecule of fosfomycin.


Fosfomycin in the treatment of bacterial infections: summary of clinical trials in Japan. The Japan Research Committee of Fosfomycin was organized in the fall of 1972 to promote the basic and clinical studies on fosfomycin. First of all, a subcommittee of fosfomycin consisting of a limited number of members was organized to establish the methods of determination on its antibacterial activity and its concentration in the biological fluid, and the most applicable methods were devised. The clinical trials on its oral form in a small scale were commenced from spring in 1973, and then gradually expanded to almost all of Japan. The clinical trials on its parenteral intravenous form were also undertaken from the latter half of 1973. The basic and clinical results obtained from hospitals and institutes almost all over Japan, to which members of the above Committee belong, were presented by speakers under a hot discussion in two symposia which were held by the Japan Society of Chemotherapy; one on its oral form in June 1974, and another on its parenteral form in December 1974. I served as chairman in both of the symposia. The clinical results of fosfomycin in Japan which were mainly collected in both symposia are described below. Its antibacterial activity, and absorption and exretion will be presented elsewhere in this volume. Clinical results of its oral form: Dosage forms of fosfomycin-Ca salt, capsule and granules, were prepared for its clinical trials. It resulted effective in about 76% of 1,200 patients with infection due to gram-positive or gram-negative (Pseudomonas, Salmonella, Escherichia coli, etc.) bacteria in several fields. As far as rates of efficacy were concerned, it was more effective in surgical, urological, ophthalmic and some other fields than in internal and pediatric ones. Fosfomycin was given in a dose of 2-3 g/day for adults or 100-130 mg/kg for infants and children in most cases. Furthermore, it can be favorably mentioned that fosfomycin was proved to be effective in salmonellosis and resistant shigellosis by a certain research group specialized in the therapy of infectious enteritis. Clinical results of its parenteral form: Sterlized bulk material of fosfomycin-Na salt was prepared in a vial for clinical use. Similarly as in the case of oral form, it was applied to about 500 patients with several infections. It resulted effective in about 68% of them. This percentage was not as high because of the higher frequency of application to severe patients or patients with underlying disease. Fosfomycin was intravenously administered by one shot or drip infusion in a dose of 2-4 g/day for adults, or 100-250 mg/kg for infants and children in most cases. Adverse reactions: In oral form, the incidence of adverse reactions was about 10% but most of them were slight gastrointestinal disorders. In an extremely small number of patients a rise of SGOT and/or SGPT was observed. In parenteral form, the incidence of adverse reactions was a little higher, being about 17% including a rise of SGOT and/or SGPT, vascular pain, nausea, and vomiting, etc...


Bacteriological evaluation of fosfomycin in clinical studies. Since fosfomycin has behaved in vitro as a broad-spectrum antibiotic, an attempt has been made to evaluate this behaviour in controlled clinical study carried out at different Spanish hospitals. A total of 959 patients were treated for some of the following infectious clinical processes: gonococcal urethritis, typhoid fever, enterocolitis, acute and chronic urinary tract infections, osteomyelitis, chronic otorrhoea, septicaemia, meningitis, peritonitis, surgical and suppurative infections, bronchitis, pneumonia, pharyngoamygdalitis, burns, endometritis, ocular infection, whooping cough and nasal carriers of S. aureus. The results obtained as a function of the microorganism isolated in these clinical processes in percentage of clinical and bacteriological success have been 96% of the S. aureus infections, 95% of the Streptococcus sp. including S. pneumoniae, 90% of the N. gonorrhoeae infections, 94% of the E. coli infections including enteropathogenic E. coli, 90% of the S. marcescens infections, 76% of the Proteus sp. infections, 72% of the Klebsiella-Enterobacter infections, 66% of P. aeruginosa infections and 78% of the S. typhi infections.


Treatment of urinary infections with fosfomycin. This report deals with the study made of the treatment of 45 acute, subacute and chronic urinary infections in a department of general medicine. 43 of these were infections caused by a single species of bacteria and 3 were caused by more than one species. The sensitivity test of the isolated organisms (E. coli, Proteus, Serratia, Pseudomonas, Klebsiella and S. faecalis) showed 83.33% of the strains to be senstive and 16.8% of the strains to be resistant. Nevertheless, this last group of strains, with the exception of one Pseudomonas, proved to be sensitive to the association of fosfomycin with a beta-lactamin (carbenicillin, amoxycillin) or an aminoglycoside (gentamicin, tobramycin). Of a total of 45 cases, 34 were exclusively treated with fosfomycin (2 g by the intramuscular route and 2 g by the oral route) and 11 cases were treated with a double association of fosfomycin with a beta-lactamin (carbenicillin or amoxycillin) or an aminoglycoside (gentamicin), after having studied the bactericidal activity of the association in vitro. The clinical and bacteriological results were verified 4 weeks after the conclusion of the treatment and showed that there was an eradication of the urinary infection in 34 cases (75.55%), relapses in 6 cases (13.33%) and reinfections in 5 cases (11.22%). These results would seem to be favourable with regards to hospital infections and with respect to organisms that are considered to be very little sensitive or resistant.


Fosfomycin in the bacteriuria of paraplegic patients. A study was made of the activity of fosfomycin in vitro and in vivo against different bacterial strains localized in the urinary tract of paraplegic patients hospitalized for their rehabilitation in our Hospital. A total of 22 patients were studied and 24 treatments were carried out. A total of 33 organisms were isolated in the initial cultures. In all patients, the pattern of administration of the antibiotic was 4 g/day intramuscularly during 8 days. From the bacteriological standpoint, the results were excellent, although there was no question of clinical results due to the special circumstances of these patients. A sterilization of the urocultures was achieved in 20 of the 24 cases treated. No signs of intolerance or toxicity were observed in any of the patients upon administering the antibiotic.


Fosfomycin in puerperal infections and its elimination in lochia. 31 patients suffering from puerperal endometritis, 16 of whom with other concomitant infections (sepsis, infection of episiotomy, pyelonephritis) were treated with fosfomycin. 86% of the germs isolated were sensitive to fosfomycin. The results obtained have been excellent in 26 patients (84%) and null in 5 (16%). Fosfomycin showed to be an antibiotic of wide-spectrum, and it acted very rapidly, since apirexia of the patients was achieved after 2-3 days of treatment. The antibiotic had perfect tolerance. No disagreeable secondary effects nor changes in the haematological data were observed. We have also carried out a study on the elimination in lochia of fosfomycin in a group of 21 patients with normal birth and puerperium. The concentrations of the antibiotic in lochia, although variable, are sufficient to achieve the desired bactericide action.


Fosfomycin in the treatment of gynecological infections. Here we present the results obtained in the treatment with fosfomycin of 58 patients of diverse obstetric-gynecological infections manifested by clinical symptomology and by the initial isolation of 70 strains of different germs, all of them sensitive to this antibiotic. The types of infections were urinary, abdominal wall, perennial septicemias, and endometritis; 45 of them motivated by or resulting from pregnancy, and the remaining 13 from gynecological causes. The most frequent treatment was 1 g/6h during 10 days, using sodium salt intramuscularly in 33 cases, and calcium salt taken orally in 26. The clinical results were good in 50 cases (86.2%) with improvement in 3 (5.1%) and persistency of the infection in 5. The bacteriological evolution was good on 34 occasions (58.6%), partial in 4 (6.8%), and poor in 6 (10.3%). In 14 cases no control could be made since the wound healed. The tolerance to the antibiotic was good and no manifestations of toxicity were observed.


Treatment of acute and subacute gonococcal urethritis with fosfomycin. 70 patients, 69 male and 1 female, 23 suffering from subacute gonococcal urethritis and the other 47 suffering from acute gonococcal urethritis, have been treated with fosfomycin with the intramuscular method. The treatment was planned as follows: (1) in 12 patients a total dose of 4 g (2g/4h) was tried with 11 bacteriological and clinical cures (92%) and 1 failure; (2) in another 43 patients a single dose of 4 g was tried (2 g in each buttock), with 37 cures (86%) and 6 failures; (3) finally, in another group of 15 patients with subacute gonococcal urethritis, fosfomycin was administered at the rate of 2g/8h for 2 days, clinical and bacteriological cures being achieved in all patients (100%). The failures, a total of 7, are patients with subacute gonococcal urethritis who were given a single dose of 4 g.


Fosfomycin in infantile acute gastroenteritis. A clinical test was carried out on 83 children suffering from infectious diarrhoeal processes who were treated with fosfomycin with the oral and paranteral route. Coproculture was carried out in all the children before the beginning of treatment and in 51 of them it was repeated at the end of treatment. Antibiograms were made on the isolated germs and their MIC to fosfomycin studied. Tolerance and secondary effects of the medicament were also studied. The study was considered insufficient in 13 patients so that the evaluation was based on 70, making 4 failures and 60 clinical cures. Administration of fosfomycin causes the eradication of serotypeable E. coli and is followed by an increase in the number of Proteus sp. and Klebsiella/Enterobacter. The sensitivity of the faecal flora to fosfomycin has been very high, except for the strains of Proteus sp. and Klebsiella/Enterobacter. The accumulative percentage of the MIC to fosfomycin of all the strains isolated shows that more than 75% of them are inhibited at concentrations under 32 mug/ml. Tolerance was good and no secondary effects were observed except for the sporadic rise in the SGPT of the children.


Acute infantile pneumonopathies treated with fosfomycin. Reference is made to the results obtained in 24 children, from 11 months to 12 years, affected with acute pneumopathies and treated with fosfomycin with a dosage of 200 mg/kg/day. In all cases a clinical, radiological, biological and bacteriological study was carried out. At the same time, levels of fosfomycin in plasma and sputum were checked every 5 days during the course of treatment. In the 4 cases of pleurisy the level of antibiotic in the pleural liquid was also checked. The concentration of fosfomycin in the sputum gives very variable results with average values oscillating between 16.5 and 23.4% of the plasmatic level respectively at the beginning and end of treatment, a cumulative effect of the antibiotic being observed. Concentration in pleural liquid oscillates between 39 and 50%. The clinical, radiological and biological evolution has been favourable iin 21 cases, unfavourable in two cases and in one case treatment had to be suspended because of the apparition of a cutaneous necrosis. Apart from this case no notable toxic effects were observed. Children do not support intramuscular injections very well and intravenous injections often cause phlebitis.


Bactericidal synergistic effect due to chloramphenicol-induced inhibition of staphyloccal penicillinase. A synergistic bactericidal effect of chloramphenicol and penicillin-G was observed with 17 out of 20 beta-lactamase producing strains of Staphylococcus aureus. The synergism was due to chloramphenicol-induced inhibition of beta-lactamase production. With seven of the strains the synergistic effect was operative only with subinhibitory concentrations of chloramphenicol, while higher concentrations produced antagonism.


Clinical bacteriological evaluation of infantile bacteriuria treated with fosfomycin. The therapeutic action of fosfomycin has been studied in a group of 14 children, with simple and complicated infections of the urinary tract with congenital renal malformations. In the bacteriological study of the urine it was observed that the strains most frequently isolated were E. coli, Proteus sp. and Klebsiella sp. Of the 25 strains isolated 76% were sensitive to the disc of 50 mug fosfomycin and 24% moderately sensitive with a MIC of 64 and 128 mug/ml. The doses of fosfomycin used were 150 mg/kg/day in four administrations. In 13 cases it was administered orally alone and in one case orally and intramuscularly. The results have been good in 10 cases (71.4%) and bad in four cases. The antibiotic has shown good tolerance and no secondary effects have been noticed.


Fosfomycin in acute bronchopneumopathies. Fosfomycin has been tested in 25 adult patients with bronchial or bronchopulmonary acute processes, of which 13 were simple acute processes of a greater or lesser severity, and 12 acutenesses of chronic bronchial processes. The germs found most frequently in the sputum cultures were Streptococcus pneumoniae and Klebsiella. Fosfomycin was used intramuscularly with doses of 4 g/day, for an average of 10 days. The results obtained were 16 cures, 7 improvements and 2 failures, which represents 92% success with 8% failures.


Fosfomycin in treatment of respiratory bacterial infections. A study was made of 40 patients suffering from clinically and bacteriologically demonstrated bacterial respiratory infections which were all treated with fosfomycin as the only antibiotic. Studies were made of the sensitivity of the isolated organisms and control of the eradicated and selected organisms. Analytical controls were performed on all patients before, during and after treatment. The average dose employed was 60 mg/kg/day, divided into four doses and administered parenterally. The duration of the treatment fluctuated between 6 and 11 days in 87% of the cases. A clinical and bacteriological evaluation was made of the results. The clinical response was satisfactory in 75% of the cases, partial in 7.5% and poor in 17.5%. The bacteriological evolution was satisfactory in 62.5%, partial in 12.5% and poor in 20%. It was not possible to control the evolution in 15% of the patients. The concentrations of the antibiotic were determined in the sputum of 6 patients and fluctuated between 0.6 and 12.9 mug/ml. In no case could any significant disorders be attributed to the antibiotic.


Treatment of respiratory infections with fosfomycin. Results are presented for a series of 29 patients, 14 males and 15 females, with serious respiratory infections, in which fosfomycin proved effective. In all cases the study was completed by bacteriological, clinical, radiological and analytical controls. The average dose was 6 g/day (3 g orally and 3 g intramuscularly) for 1 or 2 weeks. The four isolated were P. aeruginosa, E. coli, Klebsiella-Enterobacter and D. pneumoniae. Overall sensitivity percentages were best for fosfomycin, gentamicin and colistin. Of the 29 germs isolated, only one strain of P. aeruginosa became resistant: this represents 3% resistance development. No side effects of intolerance or signs of hepatorenal insufficiency were observed during the treatment. Of the 29 patients treated, 22 were clinically cured, denoting 76% success.


Treatment of respiratory infections with fosfomycin. Evaluation was made of the clinical-bacteriological results of treatment with fosfomycin on a group of 27 patients with infectious respiratory pathology. The group is made up of patients with respiratory infections diagnosed as pneumonias, bronchopneumonias, acute bronchitis and chronic bronchopneumopathies. The doses of fosfomycin used varied between 4 and 12 g/day, administered during a period of 1 or 2 weeks. The results of the treatment expressed in clinical and bacteriological parameters have been successful in 15 and 21 cases for their bacteriological response and their clinical response respectively.


Activity of fosfomycin in the treatment of bacterial infections. 30 patients with different infections were treated with fosfomycin: 13 had urinary infections, 14 had pneumonial infections, 2 had staphylococcus osteomyelitis and 1 had staphylococcus septicemia. The antibiotic was administered in doses ranging from 100 to 230 mg/kg/day, with periods of treatment that lasted from 5 to 58 days. The doses were administered every 6 h by the oral or intramuscular route. A total of 35 organisms were isolated: 7 E. coli, 7beta-hemolitic Streptococcus, 6 Proteus sp., 6 S. aureus, 6 S. viridans, 2 Klebsiella sp. and 1 negative coagulase S. aureus. All were sensitive to fosfomycin in vitro, as was revealed by the diffusion in discs method. The therapeutic results were good in 29 of the 30 cases (96.7%). There were no important side effects. A patient complained of a local pain in the area of the injection. The transaminases increased temporarily in 2 patients. One patient had a moderate eosinophilia while under treatment.


Treatment of typhoid fever with fosfomycin alone and associated to chloramphenicol or ampicillin. Treatment with fosfomycin alone and associated to subtherapeutic doses of chloramphenicol or of ampicillin, has been tried on 50 patients with typhoid fever and on four carriers of S. typhi in the Hospital del Rey. 15 patients were treated with fosfomycin alone, 22 with fosfomycin plus chloramphenicol and 13 with fosfomycin plus ampicillin. The treatment lasted 15-20 days. The results have been evaluated clinically and bacteriologically, haemo- and coprocultures being carried out. The sensitivity of the isolated germs has been studied, including MIC and the synergism in vitro between fosfomycin-chloramphenicol and fosfomycin-ampicillin. Fosfomycin, chloramphenicol and ampicillin determinations have been carried out on the blood. The cures obtained were 67, 82 and 92% respectively with fosfomycin, fosfomycin-chloramphenicol and fosfomycin-ampicillin. We believe that this antibiotic can be useful in the treatment of typhoid fever, associating it to chloramphenicol or ampicillin, due to the synergism existing between them and given the results we have obtained.


Treatment of chronic suppurated otitis with fosfomycin. A group of 24 patients with suppurated chronic processes of the medial ear have been treated with fosfomycin. All the cases were studied bacteriologically, isolating in the pus or exudates pathogenic bacterial flora, in which P. aeruginosa (40%) of the isolations) and S. aureus (23%) predominated. The sensitiveness of the strains isolated to fosfomycin was 94%. The results obtained were 21 clinical cures accompanied by the sterility of the exudates and 3 failures, which represents 87.5% success and 12.5% failures. These results are considered very satisfactory in view of the complexity and chronicity of the processes treated. It is also pointed out that fosfomycin totally lacks ototoxicity, being, therefore, a suitable antibiotic for treating chronic infectious processes of the ear.


Surgical suppurating infections and surgical abdominal infections treated with fosfomycin. Two groups of patients suffering surgical infections were treated with fosfomycin. The first includes 21 suppurating dermic of soft underlying tissue lesions. The second group includes 29 surgical abdominal infections. The bacteriology of the first group was made up of gram-positive and gram-negative germs predominantly S. aureus and E. coli, all the isolated species appeared to be sensitive to fosfomycin. In the second group a gram-negative bacterial flora predominantly E. coli was obtained; with a sensitivity to this antibiotic of 90.5%. Surgical treatment accompanied the treatment with fosfomycin. In the first group, all the patients were cured with the oral administration of 2-6 g/day and in an average time less than that of the similar control group which did not receive the antibiotic. In the second group surgical treatment was necessary in 25 of the 29 patients and in all of them parenteral treatment was done with fosfomycin, preferably intramuscularly and in general the dosage was 4 g daily. All patients were cured except for one who was not operated on and who suffered from a fever of undetermined origin.


Fosfomycin in a traumatological department. Fosfomycin has been used in the treatment of 99 patients suffering from varying kinds of osseous processes and divided into 2 groups, one of 60 patients who were not operated on, and another of 39 who were operated. A treatment only with fosfomycin was tried initially by intravenous infusion (8-16 g/day during 2-4 days), then by the intramuscular route (2-8 g/day during 2-6 days) and finishing with treatment by the oral route (2-4 g/day during 2-6 days). The results have been excellent, all cases progressing with no septic complications. As for secondary effects, we have had only one case in which a rash appeared at the end of treatment. Intravenous infusion has been well tolerated with no sign of phlebitis in any patient.


Evaluation of fosfomycin in an intensive care unit. Sensitivity to fosfomycin has been studied and recorded throughout a period of 12 months in the bacteriological isolations originating from this Intensive Care Unit. The 548 samples were biological products obtained from patients admitted to this unit (bronchial exudates, urine, wounds, blood, cava catheters and cerebrospinal fluid). The highest percentage of sensitivity was given by S. aureus coagulase (+), S. fecalis and E. coli (91, 89 and 84% respectively), and the least by P. aeruginosa and Providencia (33 and 8% respectively). A summary is included of 8 seriously ill patients admitted with varied septic processes, produced by germs sensitive to fosfomycin and treated with this, in 5 cases alone and in 3 cases with gentamicin and carbenicillin. Of those who were treated with fosfomycin alone: three were cured, one died on the sixth day through circulatory, respiratory and renal deficiences and the other with respiratory deficiency. Those treated with the combined antibiotics: two were cured and the other died of sepsis on the fourth day.


Homocysteine compounds which influence the growth of a malignant neoplasm. Since homocysteine metabolism is important in the control of normal and abnormal growth, three homocysteine derivatives were synthesized and tested for effects on the growth of transplanted murine adenocarcinoma. Arachidonoyl homocysteine thiolactone (HCT) amide decreased growth, and oleoyl HCT amide increased growth of the neoplasm. Pyridoxal HCT enamine decreased the growth of the neoplasm when given for 2 weeks prior to transplantation, but the compound had no effect when given after transplantation. The two inhibitory substances were tolerated well by normal mice except in high doses. These findings suggest an approach to prevention and therapy of human malignancy which utilizes homocysteine derivatives of normal biochemical constituents.


Sensitivity of Bacteroidaceae to fosfomycin. The sensitivity of 116 strains of Bacteroides fragilis and 60 strains of Sphaerophorus to fosfomycin was studied. Of the 178 strains that were tested, 156 were isolated from pathological products in our department and the remainder came from the following collections: NCTC, ATCC and the Institut fur Mikrobiologie of the University of Bonn. Identification was made morphologically and biochemically in accordance with the scheme which we usually employ and which has previously been published. The sensitivities were determined by the progressive dilution method in a solid medium with a surface inoculation of the strain. The results obtained show that no matter what kind of B. fragilis was tested, none of them were sensitive to concentrations of 200 mug/ml fosfomycin. On the other hand, all strains of Sphaerophorus were sensitive to lesser concentrations than the aforementioned. The majority of these concentrations subsequently lie within therapeutic margins. The conclusion drawn from our results is that the sensitivity to fosfomycin constitutes a test for differentiating Bacteroides from Sphaerophorus and that fosfomycin is ineffective in injections caused by Bacteroides, although it is an active antibiotic against infections caused by Sphaerophorus.


Sensitivity of Vibrio spp. to fosfomycin. The behavior of 15 strains of Vibrio eltor, halophilic Vibrios and NAG vibrios with respect to 14 antibiotics was studied by means of the single disc method in Mueller-Hinton agar. In the case of fosfomycin, the MIC for all of them was determined as well by the technique of progressive dilutions in solid medium. No conclusions were made because of the small number of strains studied. Nevertheless, it can be asserted that there is a marked difference in the activity of fosfomycin, since it was minimal against V. eltor, moderate against the NAGs and maximal against the halophilic Vibrio.


Interactions of fosfomycin with other antibiotics. We selected 100 strains of organisms that were isolated in our hospital, which came from pathological products and which had an MIC of fosfomycin of 256 mug/ml or more and belonged to the genera Klebsiella, Pseudomonas, Escherichia coli, Serratia, Enterobacter, Proteus, Acinetobacter, Levinea and Staphylococcus. We have studied the effect of the association of fosfomycin with 15 antibiotics (beta-lactamins, cephalosporins, aminoglycosides, etc.) and 5 chemotherapeutics. The 11 selected strains were studied by the 'chess board' technique in agar. A study was also carried out on the action of fosfomycin on E. coli K12 E711 in the phase of logarithmic growth. The 11 selected strains were studied by the 'chess board' technique in agar. Synergic effect with fosfomycin associated to other antimicrobials was found in 9 strains.


The evolution of the sensitivity to fosfomycin over the past two years. The sensitivity of 1,823 bacteriological strains of differing types is shown (E. coli, Klebsiella-Enterobacter-Serratia, Proteus-Providence, Pseudomonas, Salmonella-Shigella-Citrobacter, Haemophilus, Staphylococcus and Streptococcus); all of clinical origin, isolated during March and April, 1975. The methods used were series of double dilutions in Mueller-Hinton agar and the disc-plate method (weight of 50 mug). A comparative study is made of the sensitivity between a part of the present strains (1,725) and another group of 1,664 germs, isolated and observed in January and February, 1973. Some variations are observed which, on general lines, do not seem to be significant, except for Klebsiella-Enterobacter and Serratia.


Cephazolin in severe purulent exacerbations of chronic bronchitis. Preliminary study. Cephazolin has certain advantages over other systemic cephalosporins. It was given in a dose of 2-3 g daily for 7 days in 40 patients with severe purulent exacerbations of chronic bronchitis, 11 with purulent bronchiectasis and 24 with secondarily infected bronchial carcinoma. Most had failed to respond to high doses of other antibiotics. Results were very good and toxicity minimal.


Trimethoprim-sulphamethoxazole in the treatment of cholera. Comparison with tetracycline and chloramphenicol. 67 of the bacteriologically proved adult acute cholera patients have been examined in order to evaluate the efficacy of TM-SMX in comparison with tetracycline and chloramphenicol in the eradication of Vibrio cholerae from stools. Our results demonstrated that all three drugs sterilized the stools of all patients within 3 days with the exception of one case of TM-SMX's group, which had negative culture stools after 4 days. On the basis of our experience it can be emphasized that TM-SMX can support chloramphenicol and tetracycline in the antibacterial treatment of cholera with the advantage that the drug is efficacious with daily administrations.


Comparative histologic study of adenomas of the large intestine in Japan and England, with special reference to malignant potential. The malignant potential of large-intestinal adenomas varies with size, histologic type, and grade of epithelial atypia in the same way in England and in Japan. Adenomas in England have greater malignant potential than those in Japan because they grow larger and more often show a villous growth pattern. Although the adenoma--carcinoma sequence operates in the same way in the two countries it is suggested that the higher incidence of colorectal cancer in England is due to the greater prevalence as well as the greater size of English adenomas. More studies of the epidemiology and geographic pathology of large-intestinal adenomas are needed to clarify their importance as a predisposing cause of colorectal cancer in low-risk as well as high-risk areas.


Combined horizontal and longitudinal colomyotomy for diverticular disease: preliminary report. The operation of horizontal and longitudinal colomyotomy for diverticular disease is described and satisfactory short-term results in six patients are presented. The indications and reasons for the use of this procedure are discussed. It is suggested that the operation is a satisfactory treatment, without the risks associated with division of all the circular muscle fibers, or with resection and anastomosis. The necessity for long-term high dietary fiber intake is stressed.


Closure of colostomy--a safe procedure?

Closure of colostomy--a safe procedure? A retrospective surgery of a series of 73 patients undergoing closure of colostomy has been carried out. Closure was complicated in 37.8 per cent of cases, and fecal fistulas occurred in 17.6 per cent. The overall mortality rate of the procedure was 2.7 per cent. The underlying disease (carcinoma or diverticulitis) did not influence the complication rate. Furthermore, intraperitoneal and ex-raperitoneal methods of closure appeared equally satisfactory. Closure of colostomy within a month of construction was associated with an unacceptably high incidence of fecal fistula of 33 per cent.


The cause and treatment of idiopathic pruritus ani. Six common foods can cause the clinical entity called "idiopathic" pruritus ani. They are coffee, tea, cola, beer, chocolate, and tomatoes. Pruritus ani occurs in 24 to 48 hours when a patient consumers more than a threshold amount of one or more of these foods and disappears spontaneously in a few days provided the threshold is not exceeded again.


The Ward Function Inventory (WFI): a scale for use with geriatric and demented inpatients. A behavioral rating scale for use with the geriatric and/or demented inpatient population is reported. It is called the Ward Function Inventory (WFI) and assesses 12 functions. Six independent reliability studies employing a total of 83 patients and 63 raters were done, yielding a mean reliability for the scale of .81 with a range of .73 to .93. The reliability stuides were done on a variety of patient types. The practical utility of the WFI is stressed.


Sigmoidal volvulus in childhood: report of two cases. Volvulus of the sigmoid colon is a very uncommon cause of acute obstruction in children. Although common in adults in India, it was found to account for only 0.8 per cent of all acute obstructions in infants and children in this institution. It causes a proximal torsional obstruction of the colon with an acute onset of symptoms. The onset of volvulus is characterized by colicky pain over the left lower quadrant, vomiting, tenderness, and rigidity in te left lower quadrant. A scout film of the abdomen may be inconclusive, but a barium-enema examination is diagnostic. The number of cases reported is too small to allow conclusions about the best treatment for children who have sigmoidal volvulus.


CPK: relationship of psychological and physical stress. In the past few years, the finding of elevated serum levels of creatine phosphokinase in some acutely psychotic patients has commanded a great deal of interest. Although structural abnormalities in nerve and muscle of some of these patients have been described, the cause remains obscure. Physical stress will raise CPK, but the role of psychological stress has been unclear. CPK levels of medical students were measured before and after an academic examination, but no relationship between examination stress and changes in CPK was found. A significantly higher number of CPK elevations were reported in association with vigorous exercise. These findings are consistent with a hypothesis that psychological stress plays an insignificant role in the CPK elevations seen in some acutely psychotic patients. The importance of physical activity in elevated CPK values was reconfirmed.


The Foster Kennedy sign: a case with papilledema contralateral to a sphenoid wing meningioma but without apparent optic atrophy. A 28 year old lady with a one year history of mental changes and headaches presented with right fundus normal but with marked papilledema on the left. Subsequent evaluation demonstrated a right sphenoid wing meningioma which was successfully removed as an emergency procedure. The case illustrates the well known clinical dictum that the side of unilateral papilledema offers little information concerning tumor localization.


[Desquamating intersitial pneumonia (author's transl)]. A rare case of desquamating interstitial pneumonia, in a 15-year-old boy, is reported. Symptoms consisted of dry cough, progressive dyspnoea and chest pain. The chest X-ray revealed bilateral basal opacities. There were hypoxaemia and restrictive ventilatory changes. Bacteriological, virological and serological tests were all negative. An open lung biopsy established the diagnosis and corticosteroids were given as the drug of first choice. Other drugs, such as cytostatic ones, should only be given if steroids are ineffective. Arterial blood gases proved to be the most sensitive indicator of improvement, while the chest X-ray remained abnormal for several months.


[An improved exercise test in coronary-heart disease: effect of molsidomin on erogometrically controlled exercise (author's transl)]. The protective effect of molsidomin (N-ethoxycarbonyl-3-morpholinosydnonimine) during ergometric exercise was tested on 40 patients with coronary insufficiency proven by preliminary exercise tests or coronary arteriography. Changes in arterial blood pressure, heart rate, pulmonary artery pressure, ischaemic S-T depression and maximal working capacity were used as criteria. The drug increased maximal working capacity and decreased S-T segment depression. In addition it caused a fall in systolic and diastolic blood pressure and pulmonary artery pressure, at rest and during exercise. Resting heart rate increased slightly but during exercise the heart rate was reduced at comparable load stages. The results suggest that molsidomon may be an effective drug in the treatment of angina pectoris.


[In-vitro sensitivity of Klebsiella-Enterobacter strains against cefazolin (author's transl)]. Investigation of the resistance of 290 strains of the Klebsiella-Enterobacter group (252 Klebsiella and 38 Enterobacter strains) against cefazolin showed that 63% of the Enterobacter strains were resistant and 50% of the Klebsiella strains were sensitive both in the serial dilution test and in the agar diffusion test. A total of 78% were inhibited by 32 mug cefazolin per millilitre. Isolates from the genitourinary tract were significantly more resistant than those from the respiratory tract.


[Pharmacokinetics of digitoxin in chronic renal failure (author's transl)]. Digitoxin concentration, measured by radio-immunoassay, was significantly lower in 51 patients in chronic renal failure (23.2 +/- 7.8 mug/l) than in 29 patients in heart failure (26.5 +/- 7.3 mug/l), although both groups were on the same maintenance dose of 0.1 mg daily. Despite a normal serum albumin concentration, digitoxin protein binding was less in uraemic patients than in those with normal renal function. Renal failure did not affect intestinal digitoxin absorption. In patients in chronic renal failure elimination half-time was significantly shorter (5.7 +/- 0.9 days) than in healthy controls (7.6 +/- 1.6 days). There was no significant difference in the excretion of water-soluble ("cardioinactive") digitoxin metabolites in urine between patients in chronic renal and those in heart failure. In patients with normal renal function, of dichloromethane-soluble (cardioactive) metabolites only digitoxin could be demonstrated by thin-layer chromatography. The results indicate that patients in chronic renal failure can safely be given the same dose as those with normal renal function, without danger of over- or underdosage.


[The importance of body weight in treatment with digoxin and digoxin derivatives (author's transl)]. A total of 1109 determinations of digoxin concentration in serum were performed in 317 patients with cardiac failure during oral maintenance therapy with digoxin, beta-acetyldigoxin and beta-methyldigoxin. It was shown that the optimal therapeutic serum concentration (1.21 to 1.70 ng/ml) can be obtained reliably if the dosage of digoxin and its derivatives is based on the body weight. The daily doses recommended for oral maintenance therapy are 4mug/kg for beta-methyldigoxin, 5 mug/kg for beta-acetyldigoxin, and 8 mug/kg for digoxin. For initiating cardiac therapy the double maintenance dose can be prescribed once. Digoxin derivatives should be preferred to digoxin when choosing the drug.


[New aspects on the treatment of pneumonia associated with acute mycoplasma infections (author's transl)]. Over a period of 16 months acute mycoplasma pneumonia was diagnosed in 20 patients. All were rapidly and completely cured by ampicillin and cephalosporins, which are ineffective against mycoplasma, indicating that acute mycoplasma infection in children does not require selective treatment, the pneumonia probably being caused by other micro-organisms. There is no prove that mycoplasma pneumonia heals spontaneously, without any therapy.


[Atypical pneumonia with positive cold agglutinins (author's transl)]. Raised cold agglutinin titres were observed in 16 patients with atypical pneumonia. In 7 cases serological demonstration of antibodies against Mycoplasma pneumoniae (complement binding reaction) was possible. In 4 cases the causative organism could not be demonstrated serologically and in 5 cases the demonstration of antibodies was not possible. There were 11 sporadic single cases and 5 patients from a mycoplasma family infection. The incubation time was between 7 and 16 days. History, clinical symptoms and the auscultatory findings in connection with the radiograph allow a preliminary diagnosis of primary atypical pneumonia which can be finally proved by the demonstration of cold agglutinins. The titres reach their highest levels within 2-3 weeks and fall again within 4-6 weeks. As the complement binding reaction with Mycoplasma pneumoniae is still positive after several weeks the diagnosis can also be proved retrospectively. Reconvalescence is markedly delayed and lasts several weeks. Clinically and therapeutically the cold agglutinin positive atypical pneumonias cannot be differentiated from mycoplasma pneumonias.


[Integrated chemotherapy and radiotherapy of inoperable bronchial carcinoma: preliminary results in 50 cases (author's transl)]. Fifty patients with inoperable bronchial carcinoma were treated with a combined schedule of adriamycin, cyclophosphamide and vincristine. In those cases with locally/regionally confined tumour spread this was followed - after three chemotherapy cycles - by radiotherapy to mediastinum, hilar region and tumour of 3000 rad focal dose. Remission was achieved in 25 of 27 patients with small-cell carcinoma: full clinical remission in 12, part remission in 13. Mean duration of the (in most instances still continuing) remission has so far been 4 + months. Mean survival time is, of course, not yet calculable. Only a few patients had to be admitted to hospital for short periods because of toxic reactions. Four full and 11 part remission (some still continuing) have so far been achieved in the group of larger-cell carcinoma (squamous cell, 4; large cells, 5; anaplastic, medium-large, undifferentiated or polymorph, 14).


[Treatment of patients with gallstones with chenodeoxycholic acid (author's transl)]. 24 patients with cholesterol gallstones were treated with chenodeoxycholic acid. In 7 out of 10 patients the follow-up showed complete dissolution of the gallstones after 7 to 18 months of treatment with 1 g of chenodeoxycholic acid daily. Two patients with biliary duct concrements had to be operated, in a third patient no change could be observed after treatment for 17 months. A transient increase of the transaminase GOT was seen in four patients. There were no changes of serum cholesterol and triglyceride levels. 14 patients had chologenic diarrhoea lasting only a few days. Toxic side effects indisputably due to chenodeoxycholic acid therapy have not been seen so far.


[Premature cutaneous porphyria caused by oral contraceptives (author's transl)]. Four women, aged 23 to 26 years, fell ill with cutaneous hepatic porphyria. All of them had taken oestrogen-contaning oral contraceptives three to eight years before the illness. In one instance there was a time relationship with a progestogen preparation. The clinical and biochemical signs were those of porphyria cutanea tarda, but contrary to this disease there was a shift towards heptacarboxyporphyrin in the uroporphyrin/heptacarboxyporphyrin ratio (thin-layer chromatography, classified according to Doss). This difference and the onset at an early age suggest that the described disease may be called a hormone-induced premature cutaneous porphyria.


[The glandular cyst, a polypoid lesion of the gastric mucosa (author's transl)]. Confusion in the nomenclature of gastric polyps and the resulting uncertainties regarding prognosis and treatment have made a new classification necessary, consisting of focal hyperplasia, polyp of manifold aetiology, adenoma, and benign hyperplasiogenic polyp, the latter the most common one, found only in the stomach. But 110 cases of polypoid mucosal changes could not be classified. These "polyps" grow to be at most 8 mm in diameter and are characterized histologically by non-inflammatory cysts of varying size located within the intact fundal glands. Possible causes are hamartoma or functional secretory disorders. These glandular cysts have not previously been described. They do not fit the pattern of cystic gastritis. The clinical significance lies in the differentiation from gastric polyposis.


[Intra-operative autotransfusion for massive bleeding (author's transl)]. Only intra-operative re-infusion with a special apparatus is suitable for autotransfusion in the management of massive and unexpected haemorrhage. Haemolysis and air embolism are the only problems directly related to it. Since haemolysis does not cause clinical complications it can be ignored, while air embolism can be prevented by continuous close supervision. Clotting disorders are the combined result of the underlying disease, circulatory shock, massive homologous blood transfusion and autotransfusion. No pulmonary problems have been encountered. The Bentley ATS system has proven to be the most effective means of replacing volume in life-threatening massive bleeding. It is a safe procedure which not only helps to save large volumes of homologous blood but also the life of many patients with extreme massive haemorrhages.


[Preliminary results of preoperative radiotherapy in carcinoma of the rectum (author's transl)]. Preliminary results were evaluated in patients with carcinoma of the rectum of whom 33 had preoperative radiotherapy and 23 were treated by operation only. The tumour stage was T2-4 NX MO in all patients. There was no significant difference between the groups as to postoperative mortality, would healing, and postoperative admission time. However, the recurrence rate was significantly lower in pre-irradiated patients than in those treated by operation only. The combination of radiotherapy and radical operation appears to be a possible means of significantly improving the survival rate of patients with carcinoma of the rectum.


Physicochemical properties of glucocorticoid receptors from mouse fibroblasts. Glucocorticoid-bound receptor macromolecules were prepared in three forms from mouse fibroblast cells: the cytosol receptor, the nuclear extractable receptor, and the nuclear residual form obtained by DNase digestion of chromatin samples. These receptor complexes were studied with respect to gel filtration properties, sedimentation velocities in various salt concentrations, partial specific volumes, isoelectric points, and thermal stability properties. The results indicate that the three forms of the receptor differ in their molecular properties, and nuclear translocation and binding ofthe receptor complex is associated with conformational and physical changes consistent with a reduction in apparent molecular weight.


Characterization of growth hormone and prolactin produced by human pituitary in culture. Fragments of a pituitary tumor from a patient with acromegaly were grown in tissue culture. The tumor secreted both growth hormone and prolactin,which were recovered in high concentrations. The nonpurified hormones were characterized and compared to their respective counterparts obtained by extraction from normal pituitaries obtained at autopsy. The tissue culture and pituitary extracted hormones were eluted from Sephadex G-100 with the same partition coefficients. Growth hormone from both sources showed parallel dose-response displacement curves, by logit-log transformation, in both specific immunoassay and in a specific lymphocyte binding assay. Prolactin from both sources was compared in specific immunoassay using three different antisera. Parallel logit-log displacement curves were seen with one antiserum, while the other two antisera yielded non-parallel curves, indicating structural differences between prolactin from the two sources. Quantitative polyacrylamide gel electrophoresis was performed using multiphasic buffer systems previously developed for characterization of each hormone. By the criteria of joint 95% confidence envelopes of retardation co-efficient and relative free mobility, tissue culture growth hormone and prolactin were indistinguishable from their pituitary-extracted counterparts. This study demonstrates that, prior to purification, tissue culture derived hormone can be characterized by multiple criteria and compared to a standard preparation. Structural differences can be detected, as in the case of prolactin. When the hormones are indistinguishable, as in the case of growth hormone, it becomes worthwhile to increase the scale of tissue cultured production, with the prospect that tissue culture may serve as a source of hormone for both experimental and therapeutic use.


Acute and chronic responses to iodine deficiency in rats. Various indices of thyroid function were measured in rats at early (2 to 26 days) and at late (up to 55 weeks) intervals after the onset of an iodine deficient diet (LID). Control groups received the same diet with iodine-supplemented drinking water. The measurements included: thyroid total 127I concentration, thyroid weight, [131i] mit/[131i]dit and [131i]t3/[131i]t4 after a labeling period of 18--24 h, serum T4, serum T3, and serum TSH. In the acute experiments serum T4 was significantly decreased at 6--7 days. Thereafter, the decrease was rapid and progressive, and by 26 days serum T4 was reduced to undetectable levels (less than .05 mug per 100 ml). Thyroid T4 decreased more rapidly than serum T4, suggesting that the turnover rate of thyroid T4 increased soon after the onset of LID. Serum T3, in contrast to serum T4 showed no significant change during the 26 day period. Thyroid T3 decreased less rapidly than thyroid T4, but was greatly reduced by 26 days. Presumably the turnover rate of thyroih was slightly but significantly elevated at 4 days, before there was any detectable decrease in serum T4. Thereafter, the results were somewhat variable, but there appeared to be no significant further rise in serum TSH up to about day 15, despite the observation that serum T4 fell rapidly during this period. Only after 15 days did serum TSH display a sharp increase. It is apparent from these results that there is no simple inverse relationship between plasma T4 and plasma TSH. In the chronic experiments serum T4 remained undetectable. Serum T3 was decreased to about 50% of the normal level at 7 weeks but there appeared to be no further decrease even at 55 weeks. Serum TSH rose to very high levels at 12 weeks but showed no further increase thereafter. Thyroid 127I concentration reached its lowest value at 15 weeks and showed no further decrease. Thyroid weight, on the other hand, appeared to increase progressively. To evaluate the effect of severe iodine deficiency on thyroid status, rats that had been on LID for 3-4 months were exposed to a cold environment (4--5 C). Body temperature and survival rates were compared with those of matched controls receiving LID + KI drinking water. The body temperatures of the latter group increased significantly on exposure to cold, and all animals survived. On the other hand, the body temperature of rats on LID alone began to decrease about 5 days after the onset of cold exposure, and when the diet was sufficiently low in iodine the majority of the rats died within 15 days. These results suggest that thyroid function in severely iodine deficient rats is not adequate to meet the challenge of acute cold stress. In this sense, therefore, these animals may be daid to display signs of hypothyroidism.


Xylitol, a partial homologue ot alpha-D-glucopyranose: potent stimulator of insulin release in dogs. A direct comparison was made in healthy female dogs of the potency of xylitol and mutarotated glucose as stimulators of insulin release (both first and second phases), and also of their urinary excretion and arterio-venous difference across a hind-limb. Xylitol or glucose was given by constant infusion into a systemic vein for 50 minutes in paired experiments. Three dose levels were used in 12 dogs. Plasma insulin levels during xylitol infusion were as high as or higher than those during glucose infusion, with increases in arterial xylitol levels equal to or less than those in glucose. More xylitol was lost in the urine, but the overall uptake of xylitol was at least 70% also the arteriovenous difference for xylitol across the hind-limb was greater than for glucose, when each was divided by the arterial sugar concentration. It is suggested that both the striking potency of xylitol in stimulating both phases of insulin release, and its rapid uptake by tissues, may result from its homology with alpha-D-glucopyranose, the alpha-anomer of glucose. The concept of a glucoreceptor on the surface of the pancreatic beta-cell, with stereospecificity for alpha-D-glucopyranose or closely similar molecules, is supported by our results.


Thyrotropin stimulation of 32P incorporation into the phospholipids of canine thyroid adenocarcinoma. Six carcinomas of the canine thyroid were studied. Five of the six tumors were functional on 131I scan and caused hyperthyroidism in two cases. The tumors were all of predominantly compact cellular histology with rare to moderate numbers of microfollicles. After surgical removal tumor slices were incubated with 32P in Krebs-Ringer-tris buffer with or without 0.1 U/ml of bovine TSH, and the specific activity of the extracted phospholipids was measured. TSH stimulated phosphatide turnover clearly in 5 cases and probably also in the 6th. Analysis of fractionated phospholipids in 2 cases showed that the response to TSH was mainly in the phosphatidic acid and phosphatidylinositol. These studies show that a malignant tumor may still retain at least one complete control system extending from TSH receptors to the final metabolic response.