Circulating megakaryocytes in patients with pulmonary inflammation and in patients subjected to cholecystectomy. 30 patients with pulmonary inflammation and 17 patients subjected to cholecystectomia à froid were investigated for circulating megakaryocytes in a cubital vein using the saponin-haemolysis leucoconcentration technique. The number of circulating megakaryocytes was significantly higher in patients with pulmonary inflammation than in healthy humans. In 15 patients with bronchitis, bronchopneumonia, and leucocytosis the arithmetic mean was 15.6 megakaryocytes per 1.5 ml blood (range 3 to 47). In 15 patients with bronchitis and a normal leucocyte count the arithmetic mean was similarly 14.1 megakaryocytes per 1.5 ml blood. After cholecystectomy a significant maximum increase in the number of circulating megakaryocytes to 3 times the preoperative value was found on the third postoperative day but not on the other postoperative days. Of the observed megakaryocytes 99% had only a narrow rim of cytoplasm or were naked nuclei.


Familial erythrocytosis.

Familial erythrocytosis. Erythrocytosis was found in 3 generations of an English family. The red cell mass was only moderately increased in some of the affected members but was accompanied by an unusually low plasma volume. Oxygen affinity of Hb was normal. Changes in serum and urinary erythropoietin showed an essentially normal pattern throughout a series of venesections. Venesection produced some transient clinical benefit in the older patient but there was no obvious change in the younger ones.


The diffusion chamber technique as an in vivo assay in mice for the effectiveness of antitumor agents. The diffusion chamber (DC) technique has been applied to the culture of L1210 cells in view of determining their sensitivity to chemotherapic agents. The surviving fraction of L1210 cells cultivated in DC's 4 d after i.v. injection of the host mice with 10 mg/kg of daunorubicin or daunorubicin-DNA was 40% and 9% respectively. The results suggest that the DC technique could be a useful in vivo predictive test for cancer chemotherapy.


High level of human growth hormone (HGH) in cerebrospinal fluid patients with pituitary tumors. Six patients with suprasellar extension of pituitary HGH-secreting tumors showed the cerebrospinal fluid (CSF) content in human growth hormone (HGH) to be very high, i.e. 164.3 +/- muU/ml (mean +/- SEM) (range 8.4--413.8 muU/ml) as compared to ten patients with uncomplicated acromegaly whose values were 50-fold lower, i.e. 3.4 +/- 0.5 muU/ml (range 0.6--7.0 muU/ml), and nine patients with suprasellar extension of other pituitary tumors, showing also low levels of HGH in the CSF, i.e. 2.9 +/- 0.8 muU/ml (range 0.6--7.2 muU/ml). A control group of 29 normal patients without pituitary or brain diseases showed extremely low values of HGH in the CSF (1.9 +/- 0.2 muU/ml), one third being below the sensitivity limit of the assay method. Another control group of 70 patients with hypothalamic diabetes insipidus (n = 18), brain traumatisms (n = 10), brain surgery (n = 20), as well as various brain diseases (n = 22), also showed low HGH levels in the CSF, like the normal control group. It is shown that a high level of HGH in the CSF has a potential usefulness in the diagnosis of suprasellar extension of the pituitary mass in acromegaly.


Evaluation of the activated whole blood clotting time (ACT) in vitro. The activated whole blood clotting time (ACT) was analyzed in vitro using blood samples from normal individuals and from patients with heart disease, scheduled for open heart surgery. The ACT was found to be normally distributed in a group of normal individuals with a mean of 135 sec. In patients with heart diseases, the average ACT was slightly shorter than in normal individuals. A linear relationship between ACT and heparin concentrations was established. Haemodilution and depletion of platelets did not significantly influence the ACT. When a clean venipuncture with disposable needles is used, ACT is a reliable, uncomplicated bedside technique by which heparinisation can be monitored.


[Heparin treatment. Comparison between intravenous and subcutaneous administration]. 48 patients with acute deep venous thrombosis of the lower limbs were treated with sodium heparin. In 23 patients heparin was injected subcutaneously (s.c.) twice a day and in 25 patients heparin was given by continuous intravenous perfusion (i.v.). Pain and edema disappeared after 8.7 days (s.c.) and 11.7 days (i.v.) respectively. One non fatal pulmonary embolism occurred in each group. A second venography was performed in 24 patients after 7 days of treatment and revealed no difference between the two groups. As judged by repeated thrombin time determination, anticoagulation was ineffective on at least one day in 39% of patients treated subcutaneously and in 60% of patients treated intravenously. The two pulmonary embolisms occurred in patients with ineffective anticoagulation. It is concluded that heparin  may be used either intravenously or subcutaneously in the treatment of acute deep venous thrombosis. Thromboembolic complications occurred with both methods of treatment when anticoagulation was ineffective.


Classification of opioids on the basis of change in seizure threshold in rats. Twenty opioids have been subdivided into four classes by using flurothyl-induced seizures in rats to measure dose-response relationships, stereospecificity, naloxone sensitivity, and tolerance-cross-tolerance. The data support current theories of multiple opiate receptor types. Since the receptors involved mediate effects that are antagonized, enhanced, or unaffected by naloxone, the model is uniquely suitable for detecting novel narcotic antagonists that can then be used to differentiate opiate receptors in other systems.


Reading without a fovea.

Reading without a fovea. A visual mask moving in synchrony with the eye obliterated foveal vision during reading under certain conditions. When foveal vision was masked, reading became difficult. In another condition, a window of readable text moved in synchrony with the eye, and parafoveal vision was masked on each fixation. The results point out the importance of foveal and parafoveal vision in reading.


Phenylethylamine in paranoid chronic schizophrenia. Phenylethylamine (PEA) is an endogenous amine that is structurally and pharmacologically related to amphetamine. Urinary PEA excretion is significantly higher in paranoid chronic schizophrenics than in nonparanoid chronic schizophrenics and normal controls. Diet, hospitalization, and medication do not account for differences in PEA concentrations. These findings offer some indication that PEA may be an endogenous amphetamine.


Cholecystokinin octapeptide: continuous picomole injections into the cerebral ventricles of sheep suppress feeding. Cholecystokinin octapeptide decreased food intake in a dose-related manner when injected continuously into the lateral cerebral ventricles of sheep that had been deprived of food for 2, 4, 8, or 24 hours. In sheep deprived of food for 2 hours, as little as 0.01 picomole per minute suppressed feeding 35 percent 1 hour after beginning injection. Pentagastrin also decreased feeding in the 2-hour group, but only at a much higher dose range. Secretin had no effect. These findings support the hypothesis that cholecystokinin octapeptide acts on central nervous system structures that are involved in control of food intake.


Stimulation of abducens nucleus supports classical conditioning of the nictitating membrane response. The acquisition and terminal performance of a classical conditioning group compared with a control group indicated that extension of the nictitating membrane elicited by direct electrical stimulation of the abducens nucleus was successfully conditioned to a previously neutral stimulus. The conditioning so obtained was associative and not due to such nonassociative factors as sensitization, pseudo-conditioning, or alteration in base-rate responding.


Gamma rays: further evidence for lack of a threshold dose for lethality to human cells. In experiments designed to measure human cell survival sith +/- 2 percent accuracy it was found that low doses (21 to 87 rad) of gamma-rays inactivated the colony-forming ability of cultured human cells with a probability of 0.00226 +/- 0.00012 per rad. There appears to be no threshold for the lethality of radiation to human cells in vitro.


Movement disorders of aged rats: reversal by dopamine receptor stimulation. When placed in a tank of water, aged rats (24 to 27 months old) showed marked impairments in swimming. Compared with young adult rats (3 to 4 months old), the older animals moved their limbs less vigorously and were less successful in keeping their heads above water. The young, but not old, rats maintained a position nearly horizontal to the water surface and planed across it. These movement dysfunctions of aged rats resemble those seen in young adult animals that have sustained injury to brain dopamine-containing neurons. The swimming impairments of the aged rats were reversed by the dopamine receptor stimulant apomorphine and by the biosynthetic precursor of dopamine, L-dopa. Thus, age-related alterations in brain dopaminergic systems may be responsible for some of the movement disturbances associated with senescence.


A correlation between platelet monoamine oxidase activity and plasma prolactin concentrations in man. Increases in plasma prolactin concentrations produced by alpha-methyl-p-tyrosine, a catecholamine synthesis inhibitor, varied inversely with baseline platelet monoamine oxidase activity in 12 patients with chronic schizophrenia. In normal volunteers with low monoamine oxidase activity and in unmedicated patients with chronic schizophrenia, plasma prolactin concentrations varied directly with platelet monoamine oxidase activity. No such relationship was found in normal subjects with high platelet monoamine oxidase activity. These data suggest that platelet monoamine oxidase activity reflects monoaminergic activity in the tubero-infundibular system, which in turn affects plasma prolactin concentrations. This relationship may be important in patients with low platelet monoamine oxidase activity, such as some chronic schizophrenics.


Can an ape create a sentence?

Can an ape create a sentence? More than 19,000 multisign utterances of an infant chimpanzee (Nim) were analyzed for syntactic and semantic regularities. Lexical regularities were observed in the case of two-sign combinations: particular signs (for example, more) tended to occur in a particular position. These regularities could not be attributed to memorization or to position habits, suggesting that they were structurally constrained. That conclusion, however, was invalidated by videotape analyses, which showed that most of Nim's utterances were prompted by his teacher's prior utterance, and that Nim interrupted his teachers to a much larger extent than a child interrupts an adult's speech. Signed utterances of other apes (as shown on films) revealed similar non-human patterns of discourse.


Dolphin lung collapse and intramuscular circulation during free diving: evidence from nitrogen washout. Intramuscular nitrogen tensions in Tursiops truncatus after a schedule of repetitive ocean dives suggest a lung collapse depth of about 70 meters and suggest that intramuscular circulation is maintained during unrestrained diving in the open ocean. Therefore, the bottle-nosed dolphin is not protected by lung collapse from the decompression hazards of dives to depths shallower than 70 meters.


Dopamine-related tetrahydroisoquinolines: significant urinary excretion by alcoholics after alcohol consumption. Concentrations of dopamine-related tetrahydroisoquinolines (salsolinol and O-methylated salsolinol) were significantly higher in the daily urine samples of alcoholic subjects admitted for alcohol detoxification than in the daily urine samples of nonalcoholic control subjects. Salsolinol concentrations in alcoholic subjects appeared to drop to trace (control) values 2 to 3 days after admission, following the disappearance of ethanol and its reactive metabolite acetaldehyde from the blood. These results indicate that physiologically active tetrahydroisoquinolines increase in humans during long-term alcohol consumption, presumably because of acetaldehyde's direct condensation with catecholamines. The presence of these or similar condensation products in the urine could be useful as clinical indicators of prior blood acetaldehyde concentrations in chronic alcoholics.


Temperature-dependent sex determination in turtles. The sex of hatchling map turtles is determined by incubation temperature of eggs in the laboratory as well as in nature. Temperature controls sex differentiation rather than causing a differential mortality of sexes. Temperature has no effect on sex determination in a soft-shelled turtle.


Target cells for 1,25-dihydroxyvitamin D3 in intestinal tract, stomach, kidney, skin, pituitary, and parathyroid. After mature rats that had been fed on a vitamin D3-deficient diet were injected with tritium-labeled 1,25-dihydroxyvitamin D3, radioactivity became concentrated in nuclei of luminal and cryptal epithelium of the duodenum, jejunum, ileum, and colon; in nuclei of the epithelium of kidney distal tubules including the macula densa, and in podocytes of glomeruli; in nuclei of the epidermis including outer hairshafts and sebaceous glands; and in nuclei of certain cells of the stomach, anterior and posterior pituitary, and parathyroid. These results reveal cell types that contain receptors for 1,25-dihydroxyvitamin D3 or metabolites of this compound both in known or hypothesized target tissues and in tissues that were previously unknown to participate in vitamin D3 metabolism.


A glucose-controlled insulin-delivery system: semisynthetic insulin bound to lectin. A stable, biologically active glycosylated insulin derivative that is complementary to the major combining site of concanavalin A has been synthesized. Hormone release is proportional to the quantity of glucose present. Glucose regulation of exogenous insulin delivery could have important applications in the therapy of diabetes mellitus.


Different nucleosome structures on transcribing and nontranscribing ribosomal gene sequences. Monomeric DNA lengths from Physarum nuclear chromatin occur in two subunit forms which differ from each other and from higher oligomers of nucleosomes in content of transcribed ribosomal DNA sequences. Labeled DNA restriction fragments from ribosomal RNA coding regions reanneal most rapidly with DNA from a monomeric subunit fraction. A particles, isolated from growing plasmodia and containing 144 base pairs of DNA in an extended conformation. Higher oligomers of nucleosomes are depleted in sequences from transcribing gene regions but are enriched in sequences from the nontranscribed central spacer of the ribosomal DNA palindrome. Nucleosome configuration on two 26S gene intervening sequences resembles that on adjacent coding regions.


Time-resolved europium(III) excitation spectroscopy: a luminescence probe of metal ion binding sites. A laser-induced luminescence technique is introduced for probing the structure and equilibria of lanthanide complexes and lanthanide ion binding to macromolecules. The method involves the excitation of the 7F0 leads to 5D0 transition between nondegenerate levels in the europium(III) ion by means of an intense pulsed dye laser source. Excitation profits obtained by scanning the laser through the transition region reveal distinct peaks characteristic of individual europium(III) ion environments. The technique may be used to characterize the species present in complex equilibria in solution or to study europium(III) binding to macromolecules. Distinct europium(III) binding sites in thermolysin with long and short excited state lifetimes are observed.


Microwaves: effect on thermoregulatory behavior in rats. Rats, with their fur clipped, pressed a lever to turn on an infrared lamp while in a cold chamber. When they were exposed to continuous-wave microwaves at 2450 megahertz for 15-minute periods, the rate at which they turned on the infrared lamp decreased as a function of the microwave power density, which ranged between 5 and 20 milliwatts per square centimeter. This result indicates that behaviorally significant levels of heating may occur at an exposure duration and intensities that do not produce measurable changes in many other behavioral measures or in colonic temperature. Further study of how microwaves affect thermoregulatory behavior may help us understand such phenomena as the reported "nonthermal" behavioral effects of microwaves.


Pyruvate dehydrogenase activation in adipocyte mitochondria by an insulin-generated mediator from muscle. Material in a chromatographic fraction from an extract of insulin-treated muscle stimulated pyruvate dehydrogenase activity in addipocyte mitochondria. This action was similar to insulin's activation of the enzyme in a plasma membrane-mitochondria mixture. Neither the chromatographic fraction nor insulin required adenosine triphosphate or magnesium ion (Mg2+), suggesting that both agents acted through a calcium-sensitive phosphatase. This fraction may contain a chemical mediator of insulin action.


Vascular smooth muscle: aerobic glycolysis linked to sodium and potassium transport processes. Under aerobic conditions, glucose is primarily catabolized by vascular smooth muscle to lactate, in spite of an adequate oxidative capacity. Although this is often considered to be indicative of some nonspecific metabolic insufficiency, there is evidence that aerobic glycolysis is specifically coupled to sodium and potassium transport processes, whereas oxidative metabolism is couple to contracticle energy requirements.


A direct role of dopamine in the rat subthalamic nucleus and an adjacent intrapeduncular area. The subthalamic nucleus, a clinically important component of the extrapyramidal motor system, and a lateral area extending into the peduncle contain catecholamine terminals and dopamine receptors coupled to adenylate cyclase. In addition, dopamine agonists administered in vivo enhance glucose utilization in the region. Thus, neuronal function in this region is directly affected by dopamine and dopaminergic drugs.


Perception of size of one object among many. Adaptation to a grating of properly chosen frequency may lead to two apparently conflicting observations: Another grating may then appear to be of increased frequency (compared with its "unadapted" frequency) while the individual bars of the grating appear to have widened. This perceived widening parallels previous results with single bars. By attending to only one grating bar, the subject effectively seems to change the grating frequency spectrum to that of a single bar.


Clonal characteristics of experimentally induced "atherosclerotic" lesions in the hybrid hare. The female hybrid hare (Lepus timidus x Lepus europaeus) is heterozygous for electrophoretically separable, X-linked isoenzymes of glucose-6-phosphate dehydrogenase. The isoenzymes of this animal have been used as cellular markers in the study of the clonal origins of experimentally induced atherosclerotic lesions. Aortic lesions produced in the hybrid hare by feeding cholesterol and injuring the aortic wall with a catheter have been shown to have polyclonal characteristics and in this way are fundamentally different from atherosclerotic fibrous plaques in man.


Legionnaires' disease: concentrations of selenium and other elements. Selenium concentrations in the serums of 17 acutely ill Legionnaires' disease patients were significantly lower than in their matching convalescent-phase serums. This trend was not observed in ten similarly paired samples of serum from control patients with pneumonia. There were no significant differences in the concentrations of nickel, copper, bromine, rubidium, lead, barium, or titanium in the serums of Legionnaires' disease and control patients.


Percutaneous needle biopsy for diagnosis of pancreatic cancer. Percutaneous fine needle aspiration biopsy of the pancreas is a safe procedure, which may be done inexpensively and rapidly accomplished with high diagnostic accuracy. The major drawback of this technique is the need for a competent cytopathologist for specimen interpretation. It is quite possible, as more trained personnel become available, that percutaneous fine needle aspiration biopsy may become the technique of choice for establishing the diagnosis of pancreatic malignancy.


Melorheostosis and the sclerotomes: a radiological correlation. Melorheostosis is characterised radiologically by hyperostotic linear densities in bone. These densities have a peculiarly segmental distribution which does not correspond with the anatomical course of blood vessels or mixed nerve roots of the limbs. So far this disbritubion has lacked any valid explanation, although it has been suggested to be a developmental error as a result of an embryonic metameric disturbance. Inman and Saunders in 1944 described a sensory nerve supply to skeletal structures with 'sclerotomes' representing the zones of the skeleton supplied by individual spinal sensory nerves. Radiographs of 30 cases from the Radiological Museum of the Institute of Orthopaedics, London, have been reviewed and an attempt has been made to correlate the sclerosing lesions with the sclerotomes. The investigation was handicapped by paucity of films and clinical information, but in 19 cases the skeletal abnormalities were considered to correspond with a single sclerotome or part thereof. These studies were convincing when films of an affected hand or foot were available. In the remaining 11 cases multiple sclerotomes appeared to be involved and the clinical manifestations were correspondingly more severe. It is proposed that melorheostosis may be the late result of a segmental sensory nerve lesion, to account for its sclerotomal distribution. The association with linear scleroderma is discussed, since it has been suggested that these cutaneous lesions are related to the same nerve segment. Eight cases showed paraarticular ossification of soft tissues which may be related to involvement of a corresponding myotome.


Computed tomography evaluation of fatty tumors of the somatic soft tissues: clinical utility and radiologic-pathologic correlation. The role of computed tomography (CT) in the evaluation of fatty tumors of the somatic soft tissues was investigated. Six surgically proven cases of fatty tumors were studied preoperatively by CT and standard radiographic means--conventional radiographs, xeroradiography, and angiography. Our case material included a simple lipoma, two infiltrative lipomas, an angiolipoma, and two liposarcomas. The radiologic-pathologic correlation was evaluated with respect to the various imaging modalities. The unique tissue characteristics of fatty tumors makes them particularly adaptable to CT scanning. In addition to its ability to define accurately tissue densities, the facility of CT in depicting depth, size, and extent of the lesion in the axial plane was found to be most useful in the preoperative evaluation of our case material.


Unilateral lateral mass compression fractures of the axis. Lateral mass compression fractures of the axis involve compression of the pedicle and displacement of the overlying facet, with or without an accompanying fracture of the odontoid. These unilateral fractures are not rare. Correlation is made between clinical cases and cadaver material with analysis of microradiographs. Criteria for recognition of the resultant healed fracture deformity include: (1) Tilting of the odontoid; (2) Loss of the odontoid shoulder on the affected side; (3) Increased downward slope of the affected facet; (4) Lateral compression, possibly with buckling; (5) Asymmetrical apophyseal joints between axis and atlas; and (6) Tilting downward of occiput on affected side, often with evidence of rotation between the occiput and the axis. Not all criteria need be present. Clinical sequelae often include persistent neck pain, limited rotation of the head, and occipital headaches radiating anteriorly.


[Phenobarbital determination using direct densitometry of thin-layer chromatography]. A report on the determination of phenobarbital in model specimens of plasma and blood using direct densitometry of thin-layer chromatograms, namely by measurements of fluorescence quenching using remission technique following previous conversion of phenobarbital to sodium salt. Phenobarbital is extracted by three fundamentally different techniques, the results of estimation are given statistical evaluation, and the yield of each of the techniques is compared. Since the processing of 1 ml serum still allows the estimation of quantities as low as 1 microgram per stain the proposed method can be recommended for the determination of toxic levels of phenobarbital in plasma or in blood.


Knee pain in runners.

Knee pain in runners. Of 149 runners seen with knee pain, 60 had common orthopedic problems as the cause. Eighty-nine had recurring pain but few or no classic findings. These runners were divided into four groups depending on localization of the pain. Gait mechanical problems were identified and treatment regimens developed. Questionnaires were returned by 40 runners who fit into these four pain groups. Treatment by injections, anti-inflammatory agents, and advice to rest or stop running had produced only temporary results. Correction of biomechanical problems related to running relieved or improved the pain in 37 of 40 patients.


Effects of epinephrine, benzalkonium chloride, and intraocular miotics on corneal endothelium. Drugs formulated for use both inside and outside of the eye were tested for their potential toxic effects on the corneal endothelium. Commercially available epinephrine 1:1000 was toxic to the corneal endothelium, but solutions diluted fivefold caused no endothelial damage. The toxic agent was the sodium bisulfite 0.1% preservative. Benzalkonium chloride is highly toxic to corneal endothelium in its commonly used concentration of 0.01% and had to be diluted one thousand times to prevent endothelial damage. Ophthalmic medications for extraocular use should never be used intracamerally. Miotics commonly used in surgery during intraocular lens implantation are generally nontoxic to the cornea, though caution is advised in the use of carbachol in patients with preexisting endothelial disease and in patients having procedures in which substantial mechanical trauma to the endothelium may occur.


Clinical and experimental correlations in temporal bone fracture: the facial nerve. In this review of 50 patients with fracture of the temporal bone, 11 patients had ipsilateral facial paralysis, three of immediate and eight of delayed onset. Eight patients with complete paralysis of the facial nerve had facial nerve decompression; six of these had incomplete return of function. Only one patient with a delayed complete facial paralysis had complete return of function. The poor functional results in patients with delayed complete facial paralysis due to temporal bone fracture encourage facial nerve decompression in all stable patients with the complete facial paralysis of temporal bone fracture.


Carbon dioxide laser in otolaryngology.

Carbon dioxide laser in otolaryngology. Laser therapy has been an addition to our therapeutic armamentarium. Although in certain conditions (ie, webs, granulomas, and to a lesser degree papillomas) it has been serviceable, conventional methods of treatment are used in the majority of our patients.


Acute sarcoidosis occurring during the course of systemic lupus erythematosus. A diagnosis of systemic lupus erythematosus (SLE) was established in a 54-year-old woman with a compatible history, as well as patchy alopecia, anemia, arthralgias, and a positive LE cell preparation. Sixteen months later bilateral hilar and mediastinal lymph nodes appeared on chest roentgenogram. Sarcoidosis was diagnosed when hypercalcemia and noninfectious, noncaseating epithelioid granulomas were found in the skin and liver. The sarcoidosis remitted with corticosteroid therapy, but slowly advancing renal failure ultimately resulted in the patient's death. We believe the concurrence of SLE and sarcoidosis had not been previously reported in the English literature. Immune mechanisms are discussed.


Obstruction of the inferior vena cava complicating hemodialysis in polycystic kidney disease. Two patients with polycystic kidney disease and renal failure developed profound hypotension within 30 minutes after starting hemodialysis. After ruling out all recognized causes of hypotension during early dialysis, we found that their vena cavas were obstructed by compression of the vessels against the spinal column by the greatly enlarged polycystic kidneys. Immediately after bilateral nephrectomy, the patients had dialysis, with removal of large amounts of fluid without causing hypotension. We speculate that compression of the vena cava by massively enlarged polycystic kidneys may significantly contribute to the renal insufficiency by greatly increasing renal venous pressure.


Nephrotic syndrome in anti-GBM antibody mediated glomerulonephritis. Glomerulonephritis induced by antibodies to the glomerular basement membrane is a well recognized cause of renal disease and is responsible for 5% to 15% of all glomerular disease. The patients usually present with an acute nephritic syndrome followed by rapidly progressive renal failure. We report two patients who presented with the nephrotic syndrome and anti-GBM glomerulonephritis, and who exhibited differing clinical courses not characteristic of "rapidly progressive glomerulonephritis" or Goodpasture's syndrome.


Radiologic appearance of pulmonary South American blastomycosis. South American blastomycosis is an uncommon type of systemic fungal disease endemic in the subtropical moist and wet areas of Latin America. Two illustrative cases are presented, with a review of the main pulmonary features of this infection.


Cardiac-pulmonary edema and low pulmonary capillary wedge pressure. We describe a patient who presented with acute massive pulmonary edema, clinically and on chest roentgenogram. Two hours later the patient became hypotensive and was found to have a low pulmonary capillary wedge pressure (PCWP). The blood pressure returned to normal after administration of fluids. Acute pulmonary edema develops if PCWP rises higher than 25 to 30 mm Hg. In our patient, the elevated PCWP fell to low normal within two hours, when chest roentgenogram and clinical examination still suggested severe pulmonary edema. A phase lag existed between lowering of the pulmonary capillary wedge pressure and clearing of fluid from the alveolar and interstitial spaces in the lungs. At least three different pathogenetic mechanisms in patients with coronary artery disease can produce this phase lag. Transient global ischemia of the left ventricle was thought to be the responsible mechanism in our patient.


Echocardiographically determined mitral valve prolapse in male patients. Mitral valve prolapse syndrome is a common clinical entity that may occur as an isolated condition or in association with other cardiovascular diseases. In this retrospective study, 41% (23/56) of the male patients with echocardiographically diagnosed mitral valve prolapse had an additional form of cardiovascular disease.


Recurrent atraumatic subungual splinter hemorrhages in healthy individuals. Four individuals with severe, chronic, recurrent splinter hemorrhages are reported. The duration of splinter hemorrhages ranged between six and 30 years. The fresh lesions were associated with burning sharp pain and tenderness which lasted for a few days. Although commonly located in the distal one third of nails, they were often found in the middle and the proximal third as well. In-depth review of these individuals' history, physical examination, and laboratory values failed to reveal recurrent trauma, drug use, or any underlying systemic disease. Based on these findings we conclude that chronic subungual splinter hemorrhages are nonspecific findings and may be seen in both health and disease states.


Fever in megaloblastic anemia.

Fever in megaloblastic anemia. Charts of 122 patients with megaloblastic anemia due to either B12 or folic acid deficiency were reviewed for the presence of fever. Fever, defined as a temperature of 100 F (37.8 C) or more, was present in approximately 40% of the patients with both. The elevation was usually minimal but was sometimes over 104 F (40 C), usually in those with more severe anemia and thrombocytopenia, and greater elevations of SGOT and bilirubin concentration. In uncomplicated cases, the temperature returned rapidly to normal after adequate vitamin therapy. Failure of the fever to disappear rapidly with treatment should suggest the probability of some cause other than megaloblastic anemia.


Doppler ultrasound in evaluating the localization and severity of peripheral vascular occlusive disease. We studied 150 arterial Doppler examinations on 150 patients by obtaining segmental pressures and the analogue wave tracings, and comparing the ankle/arm index to the arteriograms. Each limb was divided into iliofemoral, femoral, popliteal, and trifurcation segments. Of the 793 segments interpreted as normal by arterial Doppler, 758 were confirmed, with 96% true-negative and 4% false-negative results. Of 364 segments shown by arterial Doppler to be abnormal, 328 were confirmed by the arteriogram, ie, 90% true-positive and 10% false-positive results. Thus, a total of 1,157 segments were studied, with 94% correlation with the arteriogram in localizing the peripheral vascular occlusive disease. The ankle/arm index is helpful in determining the severity of the disease. The majority of patients with an ankle/arm index of 0.6 to 0.8 have significant disease. An index of less than 0.6 is indicative of severe disease.


Minoxidil therapy for refractory hypertension and chronic renal failure. Minoxidil, a potent vasodilator antihypertensive agent, was given to 14 patients with severe hypertension uncontrolled by conventional agents. Thirteen patients had elevated serum creatinine levels. Over a period of 20 months (mean duration of administration) minoxidil lowered blood pressure from 194/124 to 147/90 mm Hg (mean values), in combination with furosemide and a sympathetic inhibitor (usually propranolol). Progression of preexisting renal disease was halted in all but three patients. Fluid retention, cardiac failure, and angina were troublesome side effects. The occurrence of hypertrichosis also limited the usefulness of minoxidil, particularly in female patients.


Control of orthopedic nosocomial wound infections. The catastrophic effects of deep sepsis as a complication of total joint replacement, especially the hip and the knee, are well documented. This review identifies risk factors predisposing to surgical wound infection. Proven, investigational, and theoretic methods of reducing nosocomial wound infection rates, particularly pertaining to orthopedic procedures, are given.


Why is medical school difficult? Or, if it isn't difficult, why it should be. Given the intellect and motivation of the idealized contemporary medical student and the structure of contemporary medical education, one might not expect medical school to be difficult; experience dictates otherwise. Since medical school prepares one to become a physician, the inherent difficulty of medical school is expected to lie in the areas of the physician's attitudes, skills, and knowledge. This expectation is not supported; instead it is suggested that the difficulty may actually reside in the fact that the student must negotiate three different learning styles in the course of only two years.


Renal cell carcinoma diagnosed in three generations of a single family. Sixteen families have been reported in which hypernephromas have developed in several members of either one or two generations. This is the first reported instance in which three generations of one family were affected (the patient, the maternal aunt, and the maternal grandmother). For the first time, a complete review of the literature is included.


Partial trisomy 4q resulting from a familial 4/3 translocation. A case of trisomy 4q resulting from a balanced paternal translocation is described. Phenotypic similarity of cases with similar break points included hypoplastic nasal alae, short philtrum and pursed lips, and prominent ears. The birth of the proband was preceded by unexplained infertility, oligospermia in the father, and increased fetal wastage. Each of these features is an appropriate indication for cytogenetic analysis. If such an analysis had been done, the unbalanced translocation state in a liveborn, handicapped child could have been anticipated.


A teen-ager with 46,X,del(X)(q21).

A teen-ager with 46,X,del(X)(q21). A 19-year-old woman has a chromosome constitution of 46,X,del (X) (pter leads to q21:). X chromatin masses seen in buccal smears were fewer and smaller than normal. The deleted X has more darkly stained regions around the centromere, and the short arm is also shorter. She is 155.5 cm tall and the breasts are normally developed, as are the external genitalia; however, she had primary amenorrhea. There are no evocative somatic malformation of Turner's syndrome.


Christmas bow tragedies.

Christmas bow tragedies. Two cases of fatal accidents involving plastic buttons from Christmas bows are described. Although accidents are the commonest cause of death in children less than 3 years old, governmental mechanisms, properly enforced, can be instrumental in preventing such catastrophies.


Extensive gas in tissues of the forearm after horsebite. A 44-year-old man sustained lacerations of the forearm as a result of a horsebite. His arm became swollen after primary closure of the wounds, and a roentgenogram showed gas in the tissues of the forearm. Streptococcus anginosus and S mutans were isolated from the wounds.


Miliary tuberculosis and consumption of clotting factors by multifocal vasculopathic coagulation. We have reported a third case of miliary tuberculosis and associated consumption coagulopathy. It is proposed that clotting factors may be locally consumed, thus producing the syndrome of "multifocal vasculopathic coagulation."


Pheochromocytoma and fibromuscular hyperplasia. We have described a case which documents two possible surgical correctable causes for hypertension in a 55-year-old white man. Preoperative renal arteriograms and renal vein renin determinations suggested the possibility of renal artery stenosis due to fibromuscular hyperplasia. At operation, a pheochromocytoma was found in the left suprarenal area. The presence of two unusual causes for hypertension in a single patient suggests that more than one remediable cause of hypertension should at least be considered in a given hypertensive patient.


Endocarditis caused by Moraxella nonliquefaciens. We have described a case of endocarditis caused by Moraxella nonliquefaciens on a prosthetic Hancock valve, which was cured with a six-week course of ampicillin and gentamicin therapy. Cases of Moraxella septicemia or endocarditis are uncommon, and this apparently represents the first case of Moraxella nonliquefaciens endocarditis on a prosthetic valve. The fastidious growth characteristics of this and similar species may require prolonged incubation of blood cultures and development of different methods for testing the bactericidal activity of the patient's serum.


Opportunistic infections in chronic lymphocytic leukemia. Patients with chronic lymphocytic leukemia (CLL) are susceptible to infection from a variety of opportunistic pathogens. We have described an elderly man with CLL who had repeated, severe bacterial and fungal infections including recurrent cryptococcal meningitis, disseminated histoplasmosis, Vibrio fetus sepsis, Pasturella tularensis sepsis, and Aspergillus pneumonia. B cell and possible T cell defectiveness in CLL as well as chronic corticosteroid therapy contributed to the weakened host defenses.


Fatal pulmonary embolism in an adolescent with chickenpox. A fatal case of pulmonary emboli associated with varicella in an adolescent is reported. Review of the literature revealed confusion between pulmonary infarction and embolization, the latter having been documented with varicella only in adults before this report. Embolic phenomena should be considered in the differential diagnosis of pulmonary symptoms associated with varicella, since their recognition and treatment offers important supportive measures in the care of the frequently critically ill patients.


Plasmacytomas of the breast: an unusual manifestation of multiple myeloma. One of the presenting findings of the described patient with multiple myeloma was multiple plasmacytomas of the breast. Mammograms obtained before and after chemotherapy demonstrated the response to drugs. The finding of plasmacytomas of the breast is an unusual manifestation of multiple myeloma.


Pseudothyrotoxic myopathy: a complication of thionamide therapy in hyperthyroidism. A hyperthyroid patient treated with methimazole for three weeks developed proximal muscle weakness, myalgia, arthralgia, and fever, and thyrotoxic myopathy was diagnosed. The signs and symptoms spontaneously abated when antithyroid medication was discontinued. This case identified a complication of thionamide treatment mimicking thyrotoxic myopathy and points to the therapeutic necessity of making such a differentiation.


Soft tissue ameloblastoma.

Soft tissue ameloblastoma. A case of massive peripheral ameloblastoma is presented. The lesion had been present for many years and had apparently spread by direct extension. There has been no recurrence after two years of follow-up. Proper oropharyngeal continuity has been maintained by the placement of a maxillary prosthesis.


Simultaneous bilateral aspiration of foreign bodies. Aspiration of foreign bodies into the bronchial lumen continues to be a potential hazard especially in children. Bronchiectasis, lung abscesses, emphysema, or pleuropulmonary fistula may develop if untreated. The treatment of choice is extraction by bronchoscopy under general anesthesia. Our patient simultaneously aspirated two squirrel vertebrae, neither of which produced obstruction. The patient's symptoms were due mainly to the partial obstruction secondary to the formation of granulation tissue. One aspirated vertebra was extracted during the diagnostic fiberoptic bronchoscopy, but a rigid Jackson bronchoscope was necessary to remove the other foreign body. The patient has since been asymptomatic.


Vasodilator correction of hypotension in the postoperative period. This case is unusual in that hypotension, as opposed to hypertension, was a consequence of increased sympathetic tone in the postoperative period, but it illustrates the well known fact that patients in compensated congestive heart failure do poorly when faced with an elevated myocardial oxygen need from either increased rate or afterload. Vasodilator therapy was effective in immediately reducing afterload and systolic regurgitant fraction, thereby increasing oxygen supply and lowering myocardial oxygen consumption.


The value of radiography in the initial grading of the idiopathic respiratory distress syndrome. The initial chest radiograph obtained in infants with idiopathic respiratory distress syndrome was evaluated in relation to the clinical and biochemical status of the infant as well as to the prognosis. In 101 neonates a statistically significant correlation was demonstrated.


Fine-needle percutaneous cholangiography followed by drainage of the biliary system: An initial report. Fine-needle percutaneous transhepatic cholangiography has gained popularity for investigating patients with obstructive jaundice, after which percutaneous drainage of the biliary tree is frequently carried out. The technique is described and the results from 10 patients in whom the procedure was carried out are discussed.


Renal amyloidosis in blacks.

Renal amyloidosis in blacks. In a retrospective survey of renal amyloidosis in a large general hospital, only 7 cases were found. Patients generally presented with nephrotic syndrome and symptoms of fluid overload; hypertension on presentation was unusual. Renal failure was present in 5 out of 7 patients, and uraemia in 3. The disease was secondary in 5 patients and primary in 2, and the prognosis was uniformly bad.


Breast feeding in Cape Town.

Breast feeding in Cape Town. An interview survey of infant feeding practices was conducted among the mothers of 126 infants, aged 3-4 1/2 months, attending local authority clinics in two subeconomic residential areas of Cape Town. It was found that while at 1 month only 19% of the infants were wholly bottle-fed, at the age of 3-4 1/2 months this proportion was 60%, and only 14% were fully breast-fed. The factors found to be significantly associated with the cessation of breast feeding were young maternal age and maternal employment. A downward trend in the prevalence of breast feeding continues--despite the efforts of health services. Recommendations to promote breast feeding are made.


Attitude of middle-class mothers to breast feeding. A study in general practice. A survey of all mothers in a middle-income, suburban family practice who had been delivered of infants over a 2-year period was conducted. Their attitudes towards breast feeding and the role their doctors had played in influencing them was determined. The survey showed that there is much room for improvement in the promotion and encouragement of breast feeding in the community.


Early recognition of infantile autism.

Early recognition of infantile autism. This article is primarily concerned with the early recognition of infantile autism. Since this syndrome is always a manifestation of disturbed interpersonal relationships, the normal development of an early mother-infant interaction is described. It should thus be easy to observe distorted interaction and to investigate the cause. Autism is one of several manifestations of impaired interaction.


Tuberculous endocarditis: A report of 2 cases. Two patients with tuberculous endocarditis are described. In one patient the condition developed on a mitral valve prosthesis and in the other in thrombus adherent to a ventriculo-atrial shunt.


[Perforation of the heart during implantation of a transvenous pacemaker. A report on two cases]. Perforation of the right ventricular wall occurred in 2 patients during implantation of a transvenous temporary pacemaker. Although neither of the patients showed any signs of symptoms of pericardial tamponade, blood was found in the pericardial sac at thoracotomy, by means of which epicardial pacemakers were inserted. The possibility of tamponade should therefore be kept in mind when anaesthetizing patients who received a temporary transvenous pacemaker.


Coronary insufficiency in infancy and childhood. Thirteen cases of coronary insufficiency diagnosed in childhood are presented. The aetiology, signs and symptoms and course of the patients are described. Some of the causes of coronary insufficiency are amenable to treatment.


Hepatic infections. Part I. A serological evaluation of Fab antigens (Fab' and F (ab)2) and antibodies in patients and asymptomatic carriers of hepatitis B virus. Evidence for the association of Fab (antigen-binding) fragments of IgG and antibodies directed against receptors of these fragments (Fab' and F(ab)2) has been found in patients and asymptomatic carriers of hepatitis B antigen. Fab fragments of IgG are often detected in hepatitis B surface antigen (HBsAg)-positive sera where the intensity of antibody activity to these determinants is significantly reduced. The formation of strong antibodies to Fab fragments is often observed in association with the presence of hepatitis B surface antibodies (HBsAb). Comparative studies show that the appearance of Fab fragments in HBsAg-positive sera is not linked to the presence of hepatitis e antigen. This observation was supported by the finding of autologous Fab fragments of IgG in e antibody-positive sera. It was also established that the amount of Fab fragment in the serum is closely associated with the detection of high HBsAg titres. Preliminary investigations suggest that the Fab fragments of IgG detected in the serum of HBsAg-positive patients represent in vivo-digested HBsAb attached to the surface membrane of virus B particles. Further studies are in progress to determine the relationship of Fab fragments with a variety of other immunological events, especially the role of liver enzymes in the cleavage of intact antibodies.


Granulomatous ochronosis -- a cosmetic-induced skin disorder in Blacks. More skin eruptions than previously are appearing in Blacks after the application of a variety of topical cosmetics. Clinical and histological descriptions of these conditions are reviewed and classified. Four cases of sarcoid-like foreign-body granulomas are reported. The stricter control of cosmetics is recommended.


The effect of remedial teaching on children with learning disabilities. A study of questionnaires completed by the parents and class teachers of 70 children with learning diabilities revealed evidence of considerable parental satisfaction with scholastic progress and improved behaviour. These advances were attended by a significant reduction in domestic tension and concern about the children's future. However, teacher ratings indicate that despite prolonged remedial teaching more than half of the group remained at a scholastic level below the average class performance.


[Sex education for the general practitioner]. Patients with sexual problems commonly present in a family practice. The family physician, as the doctor of first contact, is in the best position to manage these problems, but his training in human sexuality is very often insufficient. A plea is made for the proper training of family physicians in family medicine, including human sexuality.


Management of the perineal wound with constant irrigation and suction after abdominoperineal excision for cancer of the rectum. A new suction/irrigation drain. The technique of primary closure of the perineal wound combined with continuous irrigation and suction of the operative site has been used in 21 patients who underwent abdominoperineal excision for cancer of the rectum or anal canal. Primary healing occurred in 19 patients within 18 days, and all patients healed within 2 months. These results are in marked contrast to those in 38 patients treated with constant suction alone, of whom only 17 healed primarily.


[Approaches to the analysis of radiographs of the lungs]. Different approaches to the analysis of radiographs of the lungs are briefly discussed. A systematic routine is proposed, outlined and briefly motivated. It is emphasized that radiological findings must be correlated with clinical findings if meaningful conclusions are to be drawn.


Interns' attitudes towards aspects of their medical education. During December 1977, the last month of the internship year, students who had obtained the M.B. B.Ch. degree at the University of the Witwatersrand at the end of 1976 completed questionnaires to reveal their attitudes towards aspects of their undergraduate education. Sixty-seven per cent of the class responded. The interns thought that their undergraduate education had prepared them ore adequately for manual tasks than for dealing with emotional aspects of patient care, especially a dying patient. More anxiety was aroused when managing a dying patient and his relatives than when performing diagnostic procedures. The health care function of allied professionals was not fully appreciated, and as a result their services were not fully used.


Observations and speculations.

Observations and speculations. During 25 years of private practice in East Griqualand I have made a number of observations, mostly on Black patients, which may be of interest to readers, and I would also like to put forward a few speculations about disease as seen in the Black.


Theophylline poisoning in an infant. A case report. A case of an infant poisoned with theophylline is described. Theophylline elimination was by first-order kinetics; the implications of this observation are discussed.


Sacral dermal sinus: A report of 3 cases. Three cases of sacral dermal sinus are reported. Although none of the patients developed meningitis, the danger of this serious complication and the need for early diagnosis and surgical excision are emphasized. Invasive radiological investigations may be dangerous and are seldom indicated. The relationship of sacral dermal sinus to other dermal lesions in this area is discussed.


The scope of primary hospital management for acute myocardial infarction and a suggested management regimen. The diagnostic problems in 1 775 patients with chest pain admitted to the Casualty Department of the H.F. Verwoerd Hospital during 1978 are discussed. A series of 102 patients with acute myocardial infarction admitted during a 3-month period in 1978 is described. Early diagnosis and treatment, as outlined, should reduce primary and possibly late mortality.


Comparison of 99mTc and 131I scans in thyroid function studies. Thyroid function was studied in 170 patients, using technetium-99m (99Tc) and oral radio-iodine (131I); 110 patients had normal thyroid function, and 60 had hyperthyroidism. The 20-minute 99mTc uptake gave an accurate assessment of thyroid function in 95% of patients, and the 24-hour 131I uptake was accurate in 92%. One hundred 99mTc and 131I scintiscans were compared by 3 observers. Scans obtained with each isotope were of comparable quality, and in only 1 patient were both scans of poor quality. 99mTc is as good as 131I for assessing thyroid function and morphology, but has several advantages over 131I.


Lumbar epidural anaesthesia.

Lumbar epidural anaesthesia. An outline of the anatomy, physiology, indications, contraindications, complications and technique of lumbar epidural anaesthesia is presented.


Bilateral pleural effusions associated with generalized primary lymphoedema and erysipelas. A case report and the probable pathogenesis. A case of bilateral pleural effusion in association with generalized primary lymphoedema and erysipelas, but without yellow dystrophic nails, is reported and the probable pathogenesis of the condition discussed. It is known that the primary defect lies in decreased lymphatic drainage. However, the consequent intravascular hypovolaemia and secondary hyperaldosteronism have not previously been demonstrated.


Countercyclical U.S. fertility and its implications. The following article is the verbatim text of a report based on research funded by the Social Security Administration and the National Institute of Child Health and Human Development to the Rand Corporation. The report looks at changing fertility rates in the United States and their implications for future population size and age distributions. An economic model of fertility rate is used to explain observed differences in fertility rates amond couples and to predict future rates. The focus is on trends since 1947 because post-World War II data are the most complete. Several explanations for changing fertility rates are examined, and their usefulness in predicting the future is evaluated.


Reversal of postoperative immunosuppression in man by vitamin A. The effects of therapy with vitamin A on immune responsiveness after extensive surgical treatment were studied in vitro. Postoperatively, in control patients, there was depression of the total lymphocyte count and the response in the mixed lymphocyte reaction to a pool of stimulating cells. Treatment with pharmacologic dosages of vitamin A prevented depression of these parameters in the postoperative period. The mitogenic response to phytohemagglutinin and monocyte mediated hemolysis was not consistently altered by operation in control patients, but there was a trend toward increased activity in those receiving vitamin A. Thus, vitamin A appears to be an immunostimulant in man.


Experience with hyperselective vagotomy in patients with duodenal ulcer. Hyperselective vagotomy is a relatively recent surgical procedure used for the treatment of duodenal ulcer. We report excellent results in 98 consecutive patients during the last four years. After a mean follow-up period of 2.2 years, the results, according to the classification of Visick, are excellent in a large number of patients. There was a significant gain in body weight in a majority of the patients. The recurrence rate for an ulcer is only 4.5 per cent. There is a significant reduction of basal acid output of 63 per cent, maximal acid output of 46.8 per cent and postinsulin acid output of 73.7 per cent.


Intraoperative assessment of intestinal viability with Doppler ultrasound. Following preliminary experimental animal studies showing Doppler ultrasound to be reliable in predicting intestinal viability and to correlate well with subserosal thermistor thermometry measurements, the Doppler technique has been used clinically for intraoperative intestinal viability assessment in colon-esophageal bypasses and colonic resections. Our clinical experience has shown Doppler ultrasound to be far superior to traditional predictive criteria. The presence of good Doppler sounds confirms adequate collateral pulsatile blood flow ensuring viability of the intestinal segment, whereas the absence of Doppler sounds indicates the need for appropriate revascularization. Based on the reliability of Doppler ultrasound, its simple technique and its relative inexpensiveness, we recommend the routine use of Doppler ultrasound for the evaluation of the quality and adequacy of intestinal blood flow in predicting the viability of a segment of the intestine.


Carcinoma in the supra-ampullary portion of the bile ducts. Thirty-four patients with carcinoma of the extrahepatic bile ducts were reviewed and the tumors grouped for surgical evaluation by anatomic locations. Diagnostic techniques of endoscopic retrograde cholangiography and percutaneous transhepatic cholangiography with the Chiba needle as well as angiography have made preoperative diagnosis and evaluation much more accurate. Of 27 patients who fell into the category of supra-ampullary bile duct carcinoma, 12 underwent surgical resection without an operative mortality. Long term results were discouraging, only five patients being described as having actual or potential cures. More aggressive surgical approaches to supra-ampullary carcinoma of the bile ducts offer some expectation of longer palliation and occasional cure.


Clinical presentation, natural history and prognostic factors in advanced malignant melanoma. A retrospective study of the clinical findings and natural history of 140 patients with disseminated malignant melanoma treated at Wayne State University over a ten year period was done. Multiple organ metastases were diagnosed clinically in 78 per cent of all patients and seen at all autopsies. Routine roentgenograms of the chest did not diagnose metastases to the lung in 27 per cent of the patients. The concimitant elevation of alkaline phosphatase, serum glutamic-oxalacetic transaminase and serum glutamic-pyruvic transaminase enzymes is suggestive of underlying metastases to the liver even with a negative liver scan or normal liver size. Electroencephalography was found to be sensitive in predicting and confirming metastases to the central nervous system prior to clinical manifestation with a 97 per cent accuracy rate in clinically confirmed instances as compared with a 60 per cent accuracy rate with brain scan. Age, sex and primary site of melanoma did not influence the survival once the disease became disseminated. Patients with a disease-free interval of more than six months statistically have a better chance of survival from the onset of systemic metastases, p = 0.001. Patients with a poor performance status of less than or equal to 40 per cent had a median survival period of one month as compared with six months with 90 per cent performance, p = 0.001. Patients who initially presented with metastases to the skin or lymph nodes without other visceral involvement had a 14 month median survival rate as compared with eight months in patients with metastases to the central nervous system only, four months with metastases to the liver and only one month in patients with multiple organ involvement, p = 0.0001.


Retrospective study of operations for peptic ulcer. Over a period of 20 years, 1,109 operations were performed for peptic ulcer. The site was duodenal in 873, gastric in 161 and marginal in 75. Eighty-three closures of perforations resulted in eight deaths and 28 second operations. Excluding closure of perforation and operation for marginal ulcer, the definitive operations and postoperative mortality were 446 gastric resections and 3.5 per cent; 181 truncal vagotomy with gastric resection and 1.6 per cent, and 326 truncal vagotomy with drainage and 3.2 per cent. Recurrence after operation for gastric ulcer was 5.3 per cent and for duodenal ulcer, 7.2 per cent. Based on the total number of operations for duodenal ulcer, a recurrence occurred after 348 gastric resections, 9.2 per cent; after 146 vagotomy with resection, 2.0 per cent, and after 309 vagotomy with drainage, 7.4 per cent.


Cysts and sinuses of the face resulting from dental abscesses. Cysts and sinuses of the face and neck should always bring to mind the possibility of causative underlying dental disease. This should be investigated by history, physical examination and appropriate roentgenograms of the teeth. Abscesses of the teeth are the most common dental causes for the suspicious facial mass or sinus tract. Appropriate management includes extraction or root canal therapy of the diseases tooth. Any residual facial scar can later be excised and reconstructed as appropriate.


Peripheral lymphocytes in carcinoma of the colon and rectum. Changes in peripheral lymphocyte counts have been reported in many different malignant conditions. We have studied 202 patients with carcinoma of the colon and rectum and have evaluated the relationship between peripheral lymphocytes and stage of disease as well as sex, location of tumor and carcinoembryonic antigen levels. We found a correlation between advancing stage of disease and lower levels of peripheral lymphocytes. An inverse relationship for carcinoembryonic antigen levels and lymphocyte values was also noted for the entire group as well as for individual Stages B anc C. It was suggested that the combination of both lymphocyte levels and carcinoembryonic antigen determinations might be useful as a prognostic indicator.


Pancreatic abscess.

Pancreatic abscess. Compared with the general hospital population of patients with pancreatitis, patients with biliary tract or peptic ulcer disease have de novo pancreatic abscesses develop more commonly than patients with alcoholic pancreatitis. The apparent greater predisposition of the patient with biliary tract or peptic ulcer disease to infection does not seem to be due so much to these patients having potential sources of infection, such as an infected biliary tract or leaking ulcer, as to the fact that many patients with alcoholism and hemorrhagic pancreatitis never survive the fluid loss phase of pancreatitis long enough to have a secondary infection and abscess. The mortality associated with the development of de novo pancreatic abscesses is higher in patients with biliary disease, peptic ulcer or idiopathic pancreatitis in comparison with those patients with alcoholic pancreatitis. Some complications of pancreatic abscesses, such as renal failure, may be avoided through appropriate management of fluid losses during the hemorrhagic phase of pancreatitis preceding absecess formation. Good medical management and aggressive use of newer diagnostic and therapeutic modalities may reduce the mortality and complications of pancreatic abscess. Prompt drainage of an abscess once identified is essential to survival. Proximal colostomy or ileostomy is indicated in the patient with a colonic fistula. Large particulate chunks of necrotic pancreas are not easily evacuated through Penrose, cigarette or sump drains. Marsupialization of the abscess may be considered in patients with this type of abscess.


The reproducibility of the treadmill walking test for claudication. Two standard treadmill walking tests were carried out one week apart upon 117 patients with stable claudication. Although total walking time achieved was reproducible, there was a highly significant delay in the onset of pain during the second test. Absolute limb pressures, determined by Doppler, were reproducible for the group as a whole, although individual variation could be significant. A single walking test is an inadequate assessment of claudication.


Operative techniques for the treatment of neonatal necrotizing enterocolitis. Operative management of infants with necrotizing enterocolitis and its complications requires a repertoire of surgical techniques, many of which are unique to pediatric surgery. Survival rates for infants with this once deadly illness are improving. Choice of the correct operative procedure and precise technical performance of the technique are mandatory for survival of the infant.


The role of stress hormones in the catabolic metabolism of shock. The role of catecholamines in shock metabolism in dogs was studied by comparing the metabolism of shock due to cardiac tamponade, shock with catecholamine depletion from prior reserpine adminstration and metabolism in the normal dog with continuous epinephrine infusion. It was concluded that the high serum concentrations of catecholamines in shock probably cause the increased blood lactate, initial hyperglycemia and, possibly, the poor free fatty acid oxidation seen in shock, but do not cause the increased protein catabolism of shock. With the simultaneous infusion of glucagon, cortisol and epinephrine in physiologic dosages, catabolic metabolism similar to that observed in shock was established in the normal dog. Lactacidemia, hyperglycemia, poor ability to oxidize free fatty acid and massive protein breakdown were observed. The decreased metabolic rate and diminished fatty acid mobilization of shock were not duplicated in those in the normal group and are probably a function of hypoperfusion. The importance of these observations is that impaired use of fat and increased protein breakdown, as seen in shock and trauma, are mediated by hormonal changes. It follows that there may be the opportunity to reverse or modify this catabolism by hormonal manipulation in the surgical patient.


Intraoperative hemodilution during elective vascular reconstruction. Intraoperative hemodilution and retransfusion were used for blood replacement in 30 patients who underwent elective reconstruction of the abdominal aorta, thoracic aorta or femoropopliteal segment. During each operation, 1,000 to 2,000 milliliters of autologous blood were collected through an arterial cannula during induction of anesthesia and the initial stages of operative exposure. Each volume of shed blood was replaced with 1.5 volumes of colloid and crystalloid solutions to maintain a stable intravascular volume despite transient low hematocrit values--mean, 25.8 +/- 2.1 per cent--during the period of maximum blood loss in the surgical field. Collected blood was stored in standard citrate-phosphate-dextrose disposable units and was reinfused at the conclusion of the vascular procedure. Swan-Ganz pulmonary artery catheters were inserted in an initial study group of 15 patients. Serial blood hematocrit and coagulation studies and hemodynamic parameters were measured or calculated before and after induction of anesthesia, during hemodilution, after reinfusion of autologous blood and 24 hours after operation. Improvement in cardiac output and reduction in peripheral vascular resistance maintained adequate systemic oxygen transport during hemodilution. Transient dilution of coagulation factors was documented by abnormal prothrombin and partial thromboplastin times, but serious bleeding tendencies did not occur. Twenty-one of the 30 patients received no homologous blood. Considering the entire series of 30 patients, each required only 0.46 +/- 0.87, S.D., unit of homologous blood during operation and the postoperative period.


Maximal cytoreduction, chemotherapy and contact nonspecific immunotherapy for stage III carcinoma of the ovary. A combination of therapeutic modalities was studied in 38 consecutive patients with intra-abdominally disseminated carcinoma of the ovary. Resection or destruction by electrocoagulation of all visible tumor was possible in 12 patients. Intra-abdominal chemotherapy and immunotherapy were given postoperatively and were continued systemically for one year. Serious postoperative complications and deaths did not occur. Five patients are well at 12, 22, 26, 34 and 49 months, and two are alive with disease at ten and 22 months. For 18 of the remaining 26 patients in group 2, elimination of all visible tumor was not possible technically, and in eight patients in group 3, an irresectable tumor was found. All of these patients received cyclic chemotherapy as those in group 1 but without immunotherapy. Patients in group 2 had a median survival time of about 16 months, no long term survivors and a mortality of 75 per cent at two years. The patients in group 3 had a median survival period of less than three months and were all dead before the end of the first year. Our results in this group are similar to those recently reported by others for patients with equally advanced disease treated by chemoimmunotherapy. Maximal tumor cytoreduction may be the most important of all the treatments we used, and a prerequisite to successful chemotherapy and immunotherapy. Contact nonspecific immunostimulation in this setting appears to be sound and safe and warrants further study to determine its ultimate contribution to patient survival.


Monitoring of heparin therapy with thromboelastography. The technique of thromboelastography was used to monitor the administration of heparin to patients with diagnosed deep vein thrombosis. The thromboelastograph uses a mechanical optical system to provide a continuous dynamic measure of the coagulation process. It has been found to be a highly sensitive device for the detection of response to heparin thus allowing a more precise administration of heparin frequently leading to a reduction in the dosage to maintain the coagulation process of the patient within therapeutic range. This allows a more individualized approach to the patient on anticoagulation therapy.


Penetrating wounds of the buttock.

Penetrating wounds of the buttock. Results of a study of 15 patients with penetrating wounds of the buttock managed during a recent five year period suggest that penetrating trauma to the buttock is a distinct injury syndrome accompanied by serious intestinal, bladder or vascular damage. Following a complete history, physical examination and appropriate roentgenograms, most injuries can be anticipated, but proctoscopy and cystography should be performed upon all patients at risk. Intravenous pyelography, a poor test of bladder integrity, may be misleading and should by supplemented by additional techniques. If a retroperitoneal or intraperitoneal injury is suspected, preoperative antibiotic therapy, followed promptly by aggressive intraoperative management of all injuries, is recommended.


Free intestinal autografts for reconstruction following pharyngolaryngoesophagectomy. After pharyngolaryngoesophagectomy in four patients, free intestinal autografts were used for reconstruction. A microvascular technique and a simultaneous two team approach allowed this to be done immediately following the resection. No graft failures have occurred. Good function was present in three of the four patients at the last follow-up examination or at death. Follow-up intervals vary from seven to 15 months postoperatively. Special problems, such as irradiation, tumor site and the relative merits of the large versus the small intestine, are discussed.


Renal vascular effects of stroma and stroma-free hemoglobin. To assess the renal effects of hemoglobulin infusion, intrarenal hemodynamics were studied in 14 dogs using radioactive microspheres following the infusion of hemoglobin and stroma. Fractional renal microsphere distribution in the outer cortex remained at control levels following the infusion of hemoglobin. When the infusion of stroma followed, there was a 4.3 per cent, p less than 0.01, increase in the outer cortex microsphere distribution at the expense of the inner cortex, p less than 0.05. When the order was reversed, the stroma suspension being infused first, again there was a significant increase in the outer cortex distribution--6.1 per cent; p less than 0.01. When the infusion of hemoglobin followed, the outer cortex microsphere trapping reverted to control levels. These data revealed no effect upon intrarenal blood flow following the infusion of hemoglobin. The previously reported renal toxicity of hemoglobin infusion is, therefore, probably secondary to contamination with stroma. Hemoglobin should be further investigated for use as an ideal resuscitation fluid.


Anorectal abscess.

Anorectal abscess. A five year retrospective review of anorectal abscesses included 181 admissions in which all but five were explained by the anal glandular hypothesis of causation. Delays in treatment occurred because of misdiagnosis, attempts at nonoperative management and inhospital procrastination. These abscesses are notorious for the recurrence rate after treatment. One-third of the patients in our series had a history of previous abscess and a postoperative recurrence rate of at least 6 per cent. Associated medical problems, such as diabetes mellitus, inflammatory intestinal disease or carcinoma, should be suspected in these patients. The fact that the majority of the patients in our series were afebrile and had minimal leukocytosis is a possible indication that our index of suspicion should be high in any patient with anorectal pain and that we must rely primarily on local findings. Treatment should be prompt incision and drainage under spinal or general anesthesia. Wide unroofing procedures and overzealous attempts at primary fistulotomy are discouraged as is the use of local anesthesia. Associated procedures, such as hemorrhoidectomy, can be safely performed and may prevent certain postoperative complications.


A technique for peritoneal lavage without risk or complication. A technique for peritoneal lavage with an extremely low risk of complications has been developed. This technique has been used on 110 patients by 45 different physicians without morbidity.


Structural alterations to the pulmonary circulation in fulminant hepatic failure. Like patients with chronic liver disease, those with coma due to fulminant hepatic failure may show arterial hypoxaemia even in the absence of pulmonary complications, and in both it is attributed to increased intrapulmonary arteriovenous admixture. This study is concerned with the structural alterations in the pulmonary circulation of patients who have died from fulminant hepatic failure. Precise quantitative morphometric techniques applied to the injected and inflated lung have shown the major abnormality to be a diffuse dilatation of the pulmonary vascular bed affecting arteries and veins of all structural types. At an intra-acinar level the diameter of arteries accompanying respiratory bronchioles was 232.97 micron (+/-SD 46.35) compared with 177.76 micron (+/-SD 30.43) in controls (P less than 0.01). In two-thirds of the patients pleural spider naevi were seen and, throughout the lung, similar significant dilatation of precapillary vessels; but in only one patient were precapillary anastomoses shown. While intrapulmonary venous admixture undoubtedly contributes to hypoxia in fulminant hepatic failure, its exact relation to the structural changes is not yet determined.


Pulmonary hypertension accompanying ventricular septal defect and patent ductus arteriosus. Management in infancy and early childhood. Forty-one infants and children with the combination of patent ductus arteriosus (PDA) and ventricular septal defect (VSD) were encountered over 20 years. Twenty-four presented in infancy with congestive cardiac failure. Pulmonary hypertension was present in 32, the cause in 19 being increased pulmonary blood flow. Increased pulmonary vascular resistance (PVR) was detected in 13 (indicated by a pulmonary to systemic resistance ratio (Rp : RS) greater than 0.24:1 and PVR greater than 4 units). Thus 22% had a pulmonary artery systolic pressure less than 30 mmHg and 68% had a pulmonary vascular resistance below four units, indicating an unusually mild form of the combined condition in these patients. Surgical management is discussed, and in particular the question of simultaneous closure of the defects during infancy. Cardiac failure, resistant to drug treatment, and increased PVR are indications of operation. The PDA should be closed and only if there is no substantial fall in pulmonary artery pressure is the VSD repaired.


Elective correction of intracardiac lesions resulting from penetrating wounds of the heart. Controversy exists regarding the timing and technique of total correction of traumatic intracardiac lesions. Five patients with penetrating wounds of the heart received emergency treatment aimed at securing normal haemodynamics. No attempt was made to identify intracardiac lesions at this stage. Cineangiography two months to seven years later showed aorto-right ventricular fistulae in all patients, associated in two with aortic cusp laceration and in one with an aorto-left atrial fistula. The surgical approach for aorto-right ventricular fistula was through the right ventricle or aorta. Valvar injuries were treated by plastic reconstruction. All patients showed good clinical results when seen four to 11 years later. Traumatic intracardiac lesions in patients with stable haemodynamics after initial treatment should be operated on electively. The aortic approach is preferable for aorto-right ventricular fistulae. Conservative plastic repair of valvar injuries achieves long-term competence thus avoiding prosthetic replacement.


Surgical treatment of bronchial obstruction in primary tuberculosis in children: report of seven cases. Seven children, aged 4 months to 10 years, with bronchial compression due to tuberculous hilar lymphadenitis have been treated surgically since 1974. The indications for surgical treatment were lack of response to chemotherapy and in particular the development of respiratory distress. Excision or curettage of the affected nodes was found to be a safe and sure method of relieving the acute symptoms and preventing permanent damage to the lung.


Surgical and haemodynamic considerations in middle aortic syndrome. Eleven patients with the middle aortic syndrome have been investigated during the past five years. Corrective surgery was possible in seven, five of whom survived. The maximum constriction in most cases was at the thoracoabdominal junction, an area normally surrounded by intestinal lymphatics. This may indicate that the aetiology is related to an immune response to parasitic infestation of the intestines. Comparison of the extent and severity of the disease as found at operation with the results of preoperative investigations such as angiography, radioisotope renography, and measurement of angiotensin in the renal veins showed that in some patients surgical exploration was more accurate in deciding the feasibility and the method of surgical correction.


Alterations to the bronchial and bronchiolar surfaces of adult mice after exposure to high concentrations of oxygen. We have studied the effects of inhalation of 95 to 100% oxygen on the surface morphology of the bronchi and bronchioles of adult mice, using scanning electron microscopy. Denudation of cilia and truncation of the remaining cilia were commonly observed during high oxygen exposure. Bleb formation, a "moth-eaten" appearance of the non-ciliated cell surface and desquamation of unidentified cells were present in the bronchus after 96 hours of oxygen exposure. Deformation of non-ciliated cells, denudation of cilia, and flattening of the luminal surface were also seen in the bronchiole. For studying the recovery process from acute oxygen damage, we returned mice to room air after four days of high oxygen inhalation and killed them four, seven and 15 days after. There were more variable and complex changes of surface morphology in individual mice during the recovery phase. We observed flattening of the epithelial surface in the bronchiole and bronchus, and noticed that deformation of non-ciliated cells were seen even after 15 days. High oxygen inhalation causes severe morphological changes in the bronchial and bronchiolar mucosa, and those morphological lesions remain for at least two weeks after cessation of oxygen inhalation.


Tantalum inhalation and airway responses. We studied the effects of tantalum inhalation bronchography on pulmonary function in 14 normal volunteers. Based on the radiographic type of deposition, the subjects were divided into three groups: (1) subjects who deposited tantalum mainly in the trachea, (2) subjects who deposited tantalum in segmental bronchi without radiographic evidence of bronchospasm, and (3) subjects who deposited tantalum in segmental bronchi with radiographic evidence of bronchospasm. Unlike the first two groups, the third group developed a significant but small decrease in the FEV. Airway reactivity as assessed by methacholine challenge did not explain the difference in response to tantalum in the third group. There were no consistent changes in total lung capacity, residual volume, or closing volume in any of the groups. Even though there were falls in FEV and specific conductance in individuals in groups 2 and 3, these changes did not pose any significant clinical risk.


Effect of body position on gas exchange after thoracotomy. To determine the effect of change in body position on gas exchange after thoracotomy, 12 patients with potentially resectable lung tumours were studied before and 24 hours after operation. Measurements of arterial blood gas tension (PaO2, PaCO2), alveolar-arterial oxygen difference (A--adO2), venous admixture effect (Qs/Qt percent), and physiological dead space to tidal volume ratio (Vd/Vt), were made in the supine, and left and right lateral decubitus positions. Preoperatively, altering position did not affect gas exchange significantly. After thoracotomy in the lateral position with the unoperated side dependent, PaO2 was significantly higher, and A--adO2 and Qs/Qt percent significantly lower than in the supine position. Postoperatively, the lateral position with the side of thoracotomy dependent was usually associated with the worst gas exchange. Only three patients achieved their best postoperative gas exchange in this position. In two this may have resulted from dependent small airway closure during tidal breathing, due to airways obstruction and old age, and in the third from postoperative atelectasis in this unoperated lung. No significant changes in mean PaCO2, Vd/Vt, or minute ventilation (VE) occurred with different positioning.


Tuberculin reactivity as a predictor of survival time in inoperable bronchial carcinoma. One hundred and two patients with inoperable bronchial carcinoma who had tuberculin tests at the time of diagnosis were followed up to see if there was any correlation between their degree of tuberculin reactivity and their subsequent survival time. There was a significant difference in survival between positive and negative tuberculin reactors (Log Rank Test P less than 0.05), the former having a median survival time almost twice that of the latter. This did not appear to be related to clinical differences between the groups at the time of testing, and other possible explanations are discussed. Tuberculin testing may be useful in helping to assess prognosis in patients with inoperable bronchial tumours.


Effect of posture on lung volume: airway closure and gas exchange in hemidiaphragmatic paralysis. The effects of posture on lung volume, airway closure, and gas exchange were studied in eight patients with hemidiaphragmatic paralysis. The mean vital capacity in the sitting position was 81% of predicted normal, and in the supine posture fell by a further 19% in right-sided but only 10% in left-sided paralysis. The mean arterial oxygen tension was less than predicted in the sitting posture and fell significantly on lying. Single breath gas transfer factor was normal in all cases whereas the diffusion coefficient was greater than predicted in the sitting posture and rose even further on lying. Closing volume showed no positional change but closing volume as a percentage of vital capacity was higher in the supine position. Regional airways closure was expressed as the relationship expiratory reserve volume minus closing volume. Negative values were found in only two of the subjects in the sitting position but seven had negative values supine, indicating significant airway closure during tidal breathing in this position.


A simple method for the representative sampling of lungs of diverse size. The proportion of non-parenchyma (non-gas exchanging tissue) varies with postnatal age and with the distance from the hilum of the lung. We have sampled 11 lungs varying in volume from 24.7 ml to 1308 ml and found that the mid-sagittal slice, or a combination of the two central slices in a lung producing four slices, adequately represents the amount of non-parenchyma and of air in bronchi and bronchioles in the entire lung.


Imaging sites of airway obstruction and measuring functional responses to bronchodilator treatment in asthma. The sites of airway obstruction and dilatation after terbutaline administration were studied by inhalation imaging and pulmonary function tests in 12 stable asthmatic patients. Inhaled terbutaline as a therapeutic aerosol decreased airway resistance (Raw) and improved radioaerosol (Ae) images in nine, delta V max50 in three, and xenon (Xe) images in five of 12 subjects, suggesting that its predominant site of action was on major airways. Subcutaneously injected terbutaline improved Raw, delta V max50, and Ae images in 11 and Xe images in eight subjects indicating that it released bronchospasm in the major and minor airways. These findings in asthma suggest that aerosol and Xe imaging procedures are sensitive indicators of large and small airway obstruction respectively.


Debanding and repair of ventricular septal defect: a new technique for older patients. Between October 1972 and April 1977 15 patients underwent definitive repair of a ventricular septal defect (VSD) and reconstruction of the pulmonary artery at the banding site. This report presents pre- and post-operative haemodynamic data in 12 patients, seven to 22 years after banding (mean 13.4). Banding of the pulmonary artery was performed before the age of 6 months (mean 4). The indications were increased pulmonary blood flow and intractable heart failure. As we had previously become dissatisfied with patch angioplasty of the main pulmonary artery, we introduced a new technique in this group of excising the site of the band and anastomosing the pulmonary artery end-to-end. The gradient between the right ventricle and pulmonary artery was abolished completely in nine cases and reduced to below 30 mmHg in the remaining three patients. This technique is used only in older patients in whom the banding has persisted for a long time. In children under 2 years of age we usually remove the band and dilate the pulmonary artery.


Parachute deformity of the tricuspid valve. A parachute deformity of the tricuspid valve occurred in a heart with atrioventricular concordance, double outlet right ventricle, and straddling mitral valve. Although to the best of our knowledge parachute deformity of the tricuspid valve has not previously been reported, in this case its presence was insignificant in relation to the other lesions.


Low frequency breathing at rest and during exercise in severe chronic obstructive bronchitis. The effect of low frequency breathing compared with spontaneous breathing was examined at rest and during exercise (40 watts) in 12 patients suffering from severe chronic obstructive bronchitis. At rest low frequency breathing improved significantly the alveolar ventilation and the tensions of oxygen and carbon dioxide in the arterial blood. There was no significant change in ventilation minute volume. During exercise low frequency breathing significantly decreased ventilation minute volume, and there was no significant improvement in gas exchange. The decrease in ventilation during low frequency breathing at 40 watts compared with spontaneous breathing at the same lung volume was due to expiratory flow limitation. The findings suggest that this technique may impair exercise tolerance in patients with severe chronic obstructive bronchitis.


Complete heart block in an adult with corrected transposition of the great arteries treated with permanent pacemaker. A 53-year-old patient with corrected transposition of the great arteries developed complete heart block with fainting episodes. After temporary pacing through the endocardium of the venous (anatomically left) ventricle, a permanent epicardial pacemaker was implanted. This case shows the progressive nature of the atrioventricular conduction disturbances, which are very common in association with this congenital cardiac anomaly.


Assay of Fletcher factor (plasma prekallikrein) using an artificial clotting reagent and a modified chromogenic assay. An artificial clotting reagent lacking in Fletcher factor (plasma prekallikrein, PPK) was made by mixing human plasma, activated by 5 mg/ml of celite, then kept 16 hours at 37 degrees to destroy most of the plasma kallikrein, plus rabbit plasma (which is devoid of XII and Fletcher activity). Chromogenic assay using a tripeptide substrate was also modified to exclude the interference of the endogenous contact factors. Celite eluate was used instead of kaolin or dextran sulphate for the activation. Using both these methods, it is possible to distinguish between Fletcher trait (PPK deficiency) and other contact factors such as factor XII and HMWK deficiencies, which do not activate with kaolin or dextran sulphate. These simple clotting and enzymatic assays give specific and well correlated results for PPK estimation.


The turnover in normal dogs of prothrombin and its fragments; effect of induced intravascular coagulation. When 125I-labeled canine prothrombin was given to normal adult dogs intravenously, it was calculated that 240% of the plasma prothrombin crossed the capillary barrier per day, 410% of the interstitial prothrombin returned to the blood stream daily, and 79% of the plasmatic prothrombin was catabolized per day. These data are in close agreement with those observed for bovine prothrombin in calves by Takeda (1970). When derived from normal dog prothrombin, prethrombin-1 is a mixture of 2 polypeptides, one larger than the other, and both present in about equal amounts. The longer peptide, "prethrombin-1-long," was catabolized twice as fast as prothrombin, and the shorter, "prethrombin-1-short," 4 times faster. Prothrombin fragment-1 was catabolized by the normal dog still more rapidly. The catabolism of prothrombin was not accelerated in 3 dogs receiving continuous infusions of a thromboplastic emulsion of dog brain. Nor was the level of prothrombin in their plasma remarkably altered.


Decreased heparin sensitivity of cyclohexanedione-modified factor Xa. Modification of 12 arginine residues of bovine Factor Xa with 1,2-cyclohexanedione has resulted in a decrease in heparin sensitivity of the reaction between enzyme and antithrombin-III, whereas the antithrombin-III sensitivity of modified Factor Xa was only slightly affected. It is suggested that heparin accelerates the Factor Xa-antithrombin-III reaction by interacting with Factor Xa.


Intravascular coagulation in autopsy cases with liver diseases. 184 autopsy cases with liver diseases were examined clinicopathologically with special reference to the incidence and distribution of microthrombi and classic thrombi in various organs. Microthrombi and/or classic thrombi were found in one or more organs in 50.0% to 59.4% of the patients with various liver diseases. But only 4 among 184 patients had many microthrombi in more than three organs and the incidence of disseminated intravascular coagulation seemed to be low in autopsy cases with liver diseases. Incidence of microthrombi showed no significant difference in the groups with and without portal vein thrombosis. Hemorrhage in the upper alimentary tracts of the patients with liver cirrhosis did not seem to develop by disseminated intravascular coagulation. Consumption of clotting factors in liver diseases seemed to occur by thrombus formation in portal vein and esophageal varices and by hemorrhage in various organs.


Effect of diuresis on urokinase excretion rate. UK excretion rate in the diuretic state was investigated in human and animal studies. Loading of water, beer or diuretics in man decreased the UK excretion rate as urine flow increased. A linear relation between UK excretion rate and urine specific gravity was observed. Simultaneous loading of water and exercise suppressed the decrease in UK excretion rate and the increase in urine flow. In animal studies, a null value for UK excretion rate was observed as a result of giving physiological saline and/or furosemide, and a remarkable increase in urine flow was induced. These results clearly suggest the existence of a relation between renal function and UK excretion rate.


The effect of agents which modify platelet behaviour and of magnesium ions on thrombus formation in vivo. The ability of potential anti-thrombotic agents to modify platelet-thrombus formation in injured cerebral arteries in the rabbit was tested. Low doses of heparin were without effect, while higher doses produced variable suppression of white body formation but at the expense of bleeding. Aspirin did not inhibit white body formation but another non-steroid anti-inflammatory agent, flurbiprofen was able to do so, as was the anti-gout agent, sulphinpyrazone. Magnesium salts both topically and parenterally, suppressed thrombus formation and increased the concentration of ADP which was required to initiate thrombus production at minor injury sites.


SEM observations on the mechanism of platelet release from megakaryocytes. Normal human bone marrow megakaryocytes were examined with the scanning electron microscope (SEM) to clarify the mechanism of platelet release. Several types of megakaryocytes were dtected according to their surface appearance, i.e. with wrinkles, ridges, villous formations, round blebs and cells with platelets still attached to the cell membrane. These observations are consistent with the concept that bleb formation is at least one of the mechanisms for platelet liberation.


Inhibition of spontaneous platelet aggregation by sulfinpyrazone. In a randomized double-blind crossover study in 16 patients with enhanced in vitro spontaneous platelet aggregation, sulfinpyrazone proved to be effective in normalizing platelet aggregability within 4 days after initiation of therapy.


Creatine phosphate in rat platelets decreased by ADP or thrombin. ADP or thrombin caused a transient change in creatine phosphate (CP) content of rat platelets. At 25 degrees C the CP content decreased most 30 sec after the addition of ADP or thrombin and recovered thereafter. ATP or AMP was without effect. The rat platelets aggregated at 25 degrees C by ADP or thrombin, but the changes in CP content by these inducers were also observed in the platelet preparations unable to aggregate by the lack of Ca2+. A persistent chilling made the platelets lose their ability to change CP content. It was suggested that in rat platelets CP is consumed in the early stage of the response to the aggregating agents, presumably donating the energy for shape change.


Relationship between mepacrine-labelled dense body number, platelet capacity to accumulate 14C-5-HT and platelet density in the Bernard-Soulier and Hermansky-Pudlak syndromes. We have used the mepacrine-labelling procedure to measure the dense body (serotonin storage organelle) content of the platelets of 2 hereditary disorders where abnormalities in dense body number were suspected. The platelets were incubated with mepacrine and examined by fluorescence microscopy. A mean number of 5.4 +/- 0.8 (SD) dense bodies per platelet was calculated from the data obtained using platelets isolated from 40 normal human subjects. In contrast the platelets of 2 patients with the Bernard-Soulier syndrome contained an average of 14 and 17 labelled granules. This increase was associated with a much greater capacity of the platelets to accumulate 14C-5-HT. The opposite result was obtained using the platelets from 2 patients with the Hermansky-Pudlak syndrome which contained few granules labelled by mepacrine and took up less 14C-5-HT than normal human platelets. Centrifugation of the patients' platelets on discontinuous sucrose gradients showed that the platelets of the 2 Bernard-Soulier patients were much denser than normal whereas a high proportion of low density platelets was observed in the Hermansky-Pudlak syndrome. These results further define the platelet abnormalities in the two syndromes and suggest that dense body number may be one of the factors governing platelet density.


Coagulation in the sand crab (Ovalipes bipustulatus). The coagulation mechanism of the sand crab (O. bipustulatus) has been investigated. From the coagulocytes (amoebocytes) present in the crab haemolymph (blood), fibrinogen (coagulogen) was isolated. It was shown to be homogeneous by electrophoresis on S.D.S. polyacrylamide gel and had a molecular weight similar to the A alpha-chain of human fibrinogen. Unlike human fibrinogen. Unlike human fibrinogen it cannot be dissociated by reduction. In fibrin polymerization, a crosslinking process takes place and this process was inhibited by glycine ethyl ester. A fibrin stabilizing factor is present in the crab haemolymph and this protein was able to cross-link human fibrin in the same manner as human factor XIII.