Limited survey of genital infection by guinea pig inclusion conjunctivitis agent. Cervical or urethral scrapings were collected from 245 guinea pigs that had clinical signs of guinea pig inclusion conjunctivitis (GPIC) or were parents of newborn young having clinical signs of GPIC. Giemsa-stained smears were examined for cytoplasmic inclusion bodies, and samples were passaged in 6-day-old embryonating eggs. Complement-fixation tests were performed on 44 samples passaged through eggs in an effort to detect the presence of GPIC antigen. Unequivocal evidence of chlamydial infection of the genital tract was not found.


Ultrastructural alterations in skeletal muscle of ducklings fed selenium-vitamin E-deficient diet. Newly-hatched ducklings were fed a selenium-vitamin E-deficient diet for 13 to 21 days. Ducklings were killed sequentially and the skeletal muscle alterations were studied by light and electron microscopy. An early alteration in skeletal muscle fibers was lysis of myofibrils, at first focal and later widespread. The sarcoplasm of damaged fibers appeared hyalinized by light microscopy. Degenerated skeletal muscle fibers with extensive lysis of myofibrils also had marked mitochondrial alterations, including swelling, formation of matrical densities, disruption of cristal membranes, and persistence of thick, dense, wavy, disrupted membranes. A sheath of external lamina persisted over degenerated segments of fibers which were invaded by macrophages that phagocytosed and removed the sarcoplasmic debris. Regeneration in damaged fibers was thought to proceed from thin subsarcolemmal satellite cells that survived the degenerative process. These satellite cells apparently developed into myoblasts, which fused to form myotubes that extended through the degenerated segments of fibers. Fibrillogenesis and sarcomerogenesis were apparent in myotubes. These structural alterations are discussed in terms of current knowledge of the combined biochemical role of selenium and vitamin E in maintaining cellular integrity.


Modification of Venezuelan equine encephalomyelitis virus infection in mice by X radiation. A highly virulent strain of Venezuelan equine encephalomyelitis (VEE) virus produced less severe histopathologic changes in brain tissues of mice previously exposed to sublethal total-body x-irradiation than it caused in nonirradiated mice. Prior exposure to 600 R of x-irradiation virtually eliminated the lesions of vasculitis and encephalitis that were found in the infected nonirradiated control mice. Mean peak brain lesion scores generally decreased as radiation exposure dose was increased. Irradiation of mice before inoculation often decreased median time to death, whereas the severity of pathologic changes in brain tissues from inoculated irradiated mice was often reduced, without significantly altering ultimate host survival. The inflammatory response did not appear to have a significant role in clearance of this virus from the brain. There was no evidence that participation of the immune response contributed to total mortality from VEE virus encephalitis, as indicated by the failure of radiation immunosuppression to reduce mortality. Death apparently was caused by the direct cytocidal effects of VEE virus replication.


Growth, virulence, and immunogenicity of Leptospira interrogans serotype szwajizak. Leptospira interrogans serotype szwajizak was characterized by (1) its growth in polysorbate 80-bovine albumin medium, (2) its virulence and course of infection in laboratory animals, and (3) its immunogenicity. Growth of this organism was continuous and vigorous at 29 C and 37 C in liquid medium for 10 serial subcultures. Some specific lots of agar were superior to other agars if tested for the ability to support the growth of small inoculums. Individual colonies resulted from growth of small inoculums on solid polysorbate medium. Virulence of the organisms did not appear to be altered by 10 serial subcultures in liquid medium incubated at 29 C. The estimated median lethal dose of szwajizak for hamsters by the intraperitoneal route was 2 cells. Virulence, infectivity, and pathogenicity of szwajizak were shown in the hamster and the guinea pig. Protection results indicate the heat-inactivated szwajizak bacterin was a substantially better immunizing agent than the chemically inactivated bacterin. Serotype hardjo bacterins provided hamsters some protection against death if challenge exposed with szwajizak, but afforded no protection against infection.


Anthelmintic activity of albendazole against gastrointestinal nematodes in calves. Anthelmintic activities of albendazole were evaluated in a controlled experiment. Forty calves experimentally infected with gastrointestinal nematodes were allotted to 4 groups. Calves in group 1 were used as nonmedicated controls; calves in groups 2, 3, and 4 were given (by oral route) a suspension containing albendazole at dose concentrations of 2.5, 5.0, and 7.5 mg/kg of body weight on the 35th day after administration of infective nematode larvae. In groups 2, 3, and 4 calves, average overall reductions (based on geometric means) were 77.1, 93.6, and 98.1%, respectively. These reductions were highly significant (P less than 0.01) in calves given doses of 5.0 and 7.5 mg/kg, and were significant  (P less than 0.05) in calves given the 2.5-mg/kg dose. Ostertagia ostertagi, Trichostrongylus axei, Cooperia onchophora, Cooperia punctata, and Oesophagostomum radiatum removals at the 5.0- and 7.5-mg/kg dose levels were all highly significant (P less than 0.01); whereas, removals of Haemonchus contortus were not significant, even at the 7.5-mg/kg dose level.


Canine bone scanning: its use as a diagnostic tool for canine hip dysplasia. The developing coxofemoral joint was evaluated in 7 dogs by means of pelvic scintigraphy (bone scanning) and pelvic radiography. Each procedure was performed monthly for 10 months to determine if early degenerative changes associated with canine hip dysplasia could be detected scintigraphically before they could be detected radiographically. At the end of the experiment, it was obvious that pelvic scintigraphy was a less sensitive tool for the diagnosis of canine hip dysplasia than pelvic radiography.


Serologic survey of leptospiral antibodies in horses in California. A serologic survey was made of the prevalence of common leptospiral infections in horses in California. A total of 465 serums were tested, using the microscopic agglutination method, against 5 leptospiral serotypes: Leptospira pomona, Leptospira icterohaemorrhagiae, Leptospira canicola, Leptospira grippotyphosa, and Leptospira hardjo. Of the serums tested, 127 (27.30%) were positive against 1 or more of the leptospires, with percentage distribution among the reactors as follows: L pomona, 12.47%; L icterohaemorrhagiae, 10.32%; L canicola, 3.22%; L grippotyphosa, 0.86%; and L hardjo, 0.43%. The prevalence of reactors to leptospiral antigens did not differ with the age or sex of the animals.


Pulmonary mechanics in fibrosing alveolitis: the effects of lung shrinkage. Pulmonary and airway mechanics were studied in 8 patients with severe fibrosing alveolitis. In this disease, the number of functioning alveoli is probably considerably decreased, but static compliance was low even when related to the decreased lung volume. Lung recoil pressures toward full inflation were high but were not increased at and below functional residual capacity. Airway function was broadly normal for lung recoil pressure but supernormal for absolute lung volume. Analysis of model pressure-volume and maximal flow-volume curves showed that (1) these features could be produced simply by replacement of some units by indistensible fibrous tissue and retention of normal function of the surviving alveoli, respiratory muscles, chest wall, and airways; (2) increased lung tissue volume may prevent an increase in lung recoil pressures in the lower part of the vital capacity; and (3) the decreased lung volume could result in a decrease in upstream conductance without structural change in the airways. Measurement of lung compliance, even when corrected for the decreased lung volumes, may not distinguish between loss of units (lung "shrinkage") and abnormal distensibility of the functioning alveoli, but the latter is likely if maximal expiratory flow is excessive in relation to the lung volume expressed as per cent vital capacity.


Bronchial lymphoepithelial nodules in the rat: morphologic features and uptake and transport of exogenous proteins. Using morphologic and ultrastructural criteria, the present study in the rat was undertaken to distinguish lymphoepithelial modules from lymphoid aggregates and lymph modes, and to demonstrate the uptake and transport of ferritin and latex particles, instilled in the trachea, by the lymphoepithelium. Unlike lymph nodes or lymphoid aggregates, lymphoepithelial nodules can be distinguished by the following characteristics of the lymphoepithelium: it is flattened and devoid of goblet cells; it contains intracellular and "intercellular" vacuoles; occasional macrophage-like cells infiltrates and surrounding lymphocytes clusters can be observed. At any time, no latex particle was found inside or under the lymphoepithelium, but until 1 hour after local instillation, ferritin particles were localized close to the cilia, at the luminal surface of the epithelium, within vesicles at the surface of some cells, and in the intercellular space. Moreover, ferritin particles were consistently present on both sides of the basement membrane after 1 hour. These results suggest that lymphoepithelial nodules may be considered as original structures capable of uptake and transport across the basement membrane of certain foreign materials.


Glycoprotein secretion by tracheal explants cultured from rats exposed to ozone. Tracheal explants from rats exposed to 0.8 ppm (1.9 mg per m3) of ozone 8 hours per day for 1 to 90 days were incubated in culture with glucosamine labeled with carbon-14 or hydrogen-3. Compared with tracheas from control rats exposed to filtered air, the explants demonstrated a decreased rate of glycoprotein secretion for exposure intervals of as long as one week, followed by a rebound to an increased rate of glycoprotein secretion for at least 12 weeks of continued exposure to ozone. Detailed study of the behavior of labeled glycoproteins from the culture medium on chromatography on columns of BioGel A-150m demonstrated that the ratio of the low to high molecular weight peaks increased when there was an increased rate of glycoprotein secretion. This is the first report of a direct biochemical effect induced by ozone on airway metabolism.


Apparent diminution of the blastomycin skin test; follow-up of an epidemic of blastomycosis. Eighteen persons involved in an epidemic of blastomycosis were followed for a period of 3 years. None of the symptomatic patients received antifungal therapy and all recovered spontaneously. During the period of follow-up observation all patients remained in excellent health, and none showed evidence of late exacerbation of the original illness. Two of the originally symptomatic patients continue to show stable pulmonary nodules on chest roentgenograms, whereas the previously abnormal chest roentgenograms in the other patients have become negative. Sixteen of these 18 patients showed a minimum of 5 mm of induration when tested with blastomycin skin test antigen. During the period of observation, the size of this induration tended to diminish.


Ventilatory muscle endurance training in normal subjects and patients with cystic fibrosis. Ventilatory muscles can become fatigued, and this can contribute to respiratory failure. Patients with chronic obstructive lung disease may benefit from improving their ventilatory muscle endurance to improve resistance to fatigue. Ventilatory muscle endurance was measured in 30 normal subjects and 55 patients with cystic fibrosis by finding the highest level of normocapnic hyperpnea that could be sustained for 15 min. Subjects with cystic fibrosis had 36 per cent higher ventilatory muscle endurance than normal subjects, reflecting the chronic training stress of breathing against increased respiratory loads. Four normal subjects and 4 subjects with cystic fibrosis participated in a specific ventilatory muscle endurance training program consisting of 25 min per day of maximal normocapnic hyperpnea 5 days per week for 4 weeks. The cystic fibrosis patients who trained improved their ventilatory muscle endurance by 51.6 per cent, whereas the normal subjects who trained showed a 22.1 per cent increase in ventilatory muscle endurance. Seven subjects with cystic fibrosis participated in a 4-week physical activity training program consisting of at least 1.5 hours per day of intensive swimming and canoeing at summer camp. They increased their ventilatory muscle endurance by 56.7 per cent. There were no other pulmonary function changes. Ventilatory muscle endurance can be readily improved in cystic fibrosis equally well by specific ventilatory muscle endurance exercise.


Bronchodilating effect and side effects of beta2- adrenoceptor stimulants by different modes of administration (tablets, metered aerosol, and combinations thereof). A study with salbutamol in asthmatics. Effects and side effects of an adrenergic beta2-stimulant (salbutamol) given by mouth and by inhalation from a metered aerosol were compared. Cumulative dose-response curves for both routes of administration concerning 1-sec forced expiratory volume, forced vital capacity, heart rate, blood pressure, and tremor were constructed. Tremor was found to be the dose-limiting side effect with both modes of administration. The metered aerosol in doses as large as 0.6 mg was shown to produce a greater increase in the 1-sec forced expiratory volume, with fewer side effects than could be achieved with tolerable doses of salbutamol by mouth. An oral dose of 6 mg is probably the maximal tolerable dose in most cases. Oral treatment seems to have a better effect than inhalation treatment on the forced vital capacity at the same effect on 1-sec forced expiratory volume, possibly due to a better effect on small peripheral airways. The effect of combining different oral doses of salbutamol with inhaled salbutamol was also studied. A very good additional effect of inhalations given after 4 and 6 mg by mouth was shown.


Pulmonary functional abnormalities after upper dorsal sympathectomy. Pulmonary function tests were performed in a group of 15 patients before and 1 to 3 months after upper dorsal sympathectomy. Significant decreases in all compartments of lung volume and maximal expiratory flows were found. Serial studies in 3 patients showed improvement after 6 to 8 months.


The effects of ethchlorvynol on pulmonary alveolar membrane permeability. Intravenous injection of ethchlorvynol (Placidyl) causes noncardiogenic pulmonary edema in humans and laboratory animals. We studied the effects of intravenous ethchlorvynol (15 to 25 mg per kg of body weight) on pulmonary alveolar membrane permeability to various endogenous and exogenous solutes in the in vivo saline-filled dog lung model. Baseline and postethchlorvynol times in minutes for 50 per cent equilibration between the blood and saline-filled alveoli were, respectively, for urea, 37.3 +/- 12.4 and 12 +/- 6.3; for albumin 8,160 +/- 4,400 and 267 +/- 93; for dextrans of molecular weight 10,400 daltons, 1,150 +/- 80 and 185 +/- 160; for dextrans of molecular weight 250,000 daltons, 24,000 +/- 800 and 1,120 +/- 900; for dextrans of molecular weight 500,000 daltons, 24,500 +/- 150 and 1,020 +/- 590. All of these pairs of values were significantly different (P less than 0.01). In addition, lung liquid histamine (but not blood histamine) concentrations increased significantly (P less than 0.001) after ethchlorvynol injection. Intravenous ethchlorvynol causes marked increases in alveolar membrane permeability.


Sarcoidosis: analysis of cells obtained by bronchial lavage. The cellular content of bronchial lavage was studied in 14 patients with sarcoidosis and 20 normal volunteers. There was no alteration in the total number of cells recovered, except for the expected increase in cellularity in smokers. Nonsmoking patients with sarcoidosis had 19.6 per cent lymphocytes, compared to 8.1 per cent lymphocytes in nonsmoking control subjects. The percentage of alveolar macrophages showing spontaneous adherence of one or more bronchial lymphocytes were, respectively, 10.8 and 8.4 in nonsmoking and smoking patients with sarcoidosis, compared to 1.8 and 2.1, respectively, in nonsmoking and smoking control subjects.


Experimental canine tracheal grafts with reversible squamous metaplasia. A technique for making bistomal tracheal pedicle grafts in dogs is described. The grafts were placed subcutaneously in the neck, and their mucosa was readily accessible to serial manipulations, endoscopic examinations, and biopsies, without requiring anesthesia. Squamous metaplasia developed in 5 of 8 grafts, or 63 per cent, within 1 week. Within 12 weeks, squamous metaplasia was seen in all grafts, and it was consistently accompanied by basal hyperplasia. After orthotopic reimplantation of the grafts, the squamous metaplasia proved to be reversible within 4 weeks. The preparation used for making these observations is a valuable research tool for sequential studies of the respiratory tract mucosa.


Carcinoma of the esophagus.

Carcinoma of the esophagus. We review 10 years' experience with cancer of the thoracic esophagus with an additional minimal six-year observation period of a few surviving patients. Differences must exist in this tumor because therapeutic response, especially irradiation varies in different localities. Very few intrathoracic cancers in our series were resectable. Operation or operation with irradiation produced the only longtime survivors. The number of candidates for resection can probably be increased by preoperative irradiation. Considering the lack of good methods of early detection, the technical problems of the fraility of the tissues involved and their locations, the survival time of the resected patients was surprisingly good. Until entirely new concepts of treatment are introduced, our efforts should be directed toward earlier detection if improved results are to be anticipated.


Surgical management of chylothorax.

Surgical management of chylothorax. We believe that proximal thoracic duct ligation is a relatively simple yet conclusive means of control of chylothorax. One should still attempt conservative management of the lesion with aspiration therapy, tube thorocostomy and the adminstration of medium length triglyceride fatty acid diets. However, if this is not successful within two to three weeks, one should not wait for disastrous nutritional degeneration before recommending this form of surgical intervention.


Successful revascularization of mesenteric infarction following aortography. Two cases of bowel infarction following abdominal aortography are presented. In both patients, two of the three major arteries supplying the bowel were occluded before the study. The superior mesenteric artery in one and the inferior mesenteric artery in the other were the only arteries supplying the bowel and their lumens were reduced. After the aortogram, the residual lumen clotted, leading to bowel necrosis. Survival was made possible in these two cases by revascularizing the superior mesenteric artery and resecting the necrotic bowel.


Carcinoma of the prostate diagnosed initially as carcinoma of the rectum. Carcinoma of the prostate appearing as a primary rectal tumor is more common than generally realized. Multiple biopsies with special stains and complete urologic investigation may be necessary before its prostatic origin can be established. The importance of making the proper diagnosis is underlined by the differences in treatment for the two lesions.


Surgical treatment of acute cholecystitis. A study of the results of surgical treatment of patients with acute cholecystitis showed that cholecystectomy is a safe procedure for the majority of patients during their initial hospitalization and avoids the risk of recurrent attacks and readmissions. Cholecystostomy has a limited place in the treatment of older patients with systemic disease and advanced local disease. Early aggressive management of acute cholecystitis will probably reduce complications of cholecystitis and reduce the need for cholecystostomy.


Sjögren's syndrome in progressive systemic sclerosis. Thirty-five consecutive patients with progressive systemic sclerosis were prospectively evaluated for evidence of Sjögren's syndrome. Six of the 35 (17%) were judged to have the disorder. This is a higher prevalence than in most reports, but much lower than that recently reportedly by Alarcón-Segovia and associates (7). An additional 17 of the 35 patients (48%) had significant fibrosis in the absence of sufficient mononuclear cell infiltrates to confirm the diagnosis of Sjögren's syndrome. This group had particularly aggressive scleroderma with serious visceral features, and five died after a short duration of illness. No significant abnormalities were found in biopsies from six patients with the mixed connective tissue disease syndrome, five with Raynaud's phenomenon alone, or in 29 autopsy control subjects who had no evidence of connective tissue disease. Fibrosis in the absence of mononuclear infiltration in minor salivary glands of patients with progressive systemic sclerosis indicates a poor prognosis.


Production of vitamin B 12 analogues in patients with small-bowel bacterial overgrowth. We investigated the presence of vitamin B 12 analogues (cobamides) and the bacterial conversion of 57Co-B12 (vitamin B12 cyanocobalamin, [57Co]-CN-Cbl) into cobamides in the intestinal contents of four patients with bacterial overgrowth. The (57Co)-CN-Cbl bound to intrinsic factor was given orally. Jejunal contents were aspirated for 24 h and cultured aerobically and anaerobically. The CN-Cbl and cobamides were separated by electrophoresis and chromatography and identified by bioautography. Radioactivity of cobamide zones from duplicate chromatograms showed bacterial conversion of (57Co)-cn-cbl into cobamides. Cobamides ([Ade]CNCBA, [2-Me Ade] CNCba, [CN]2Cbi and factor E) were found in the intestinal contents in three of the four patients, and in two of three patients cobamides represented more than 25% of the administered CN-Cbl. Thus bacterial production of cobamides, both de novo and from ingested CN-Cbl bound to intrinsic factor, occurs in humans with bacterial overgrowth states and results in a significant loss of vitamin B12 to the host.


Influenza immunization of adult patients with malignant diseases. To characterize the immunogenicity of influenza vaccine in patients with malignant disease, 21 patients with lymphoreticular neoplasms and 21 patients with solid tumors were immunized with inactivated influenza A/New Jersey/76 whole virus vaccine. The patients were randomized with respect to time of vaccine administration in relation to administration of chemotherapy. Fourfold or greater antibody titer increases occurred in 94% of controls and 71% of cancer patients (P less than 0.05), and the magnitude of antibody response was also significantly lower in cancer patients (P less than 0.01). There was no correlation of antibody responsiveness with sex, age, tumor type, absolute lymphocyte count, disease status, or type of chemotherapeutic agent used. Fifty percent of patients immunized at the time of chemotherapy administration showed seroconversion, which is significantly less than the 93% response rate observed in patients immunized between chemotherapy courses. It is thus recommended that individuals with malignant disease should receive influenza immunization between chemotherapy courses.


Disparate patterns of aldosterone response during diuretic treatment of hypertension. In 50 patients with essential hypertension treated with chlorthalidone, 100 mg daily for 6 weeks, treatment responders (fall in mean pressure, greater than or equal to 10%) and nonresponders experienced similar weight and electrolyte changes. Although induced increments and post-treatment values of plasma renin were higher in nonresponders than responders, there was a far more striking difference in aldosterone reactivity. Aldosterone excretion rose by less than 10% in the responders but almost doubled in the nonresponders. Again, within the normal renin subgroup alone (n = 28), nonresponders exhibited control renin values and treatment-induced changes in plasma renin closely similar to those in responders, but experienced a significantly greater increase in aldosterone excretion. Possibly this increase in aldosterone produced subtle volume retention or a direct pressor effect in nonresponding patients. Although changes in aldosterone and in renin correlated with each other in both responders and nonresponders, the slopes of the regression lines in the two groups differed significantly. Thus, cofactors governing sensitivity of the aldosterone response to renin stimulation ultimately may determine the antihypertensive effectiveness of diuretics.


Serum factors releasing serotonin from normal platelets: relation to the manifestations of systemic lupus erythematosus. In 13 patients with systemic lupus erythematosus, globulin fractions of sera from serial bleedings were assayed for the induction of serotonin release from normal platelets. Releasing activity appeared at some time in the sera of seven patients, five of whom had episodes of thrombocytopenia. Conversely, only one patient manifested thrombocytopenia without the occurrence of serotonin releasing activity at any time. In three patients with episodes of thrombocytopenia, increases in serotonin releasing activity temporally coincided with drops in platelet count. These data show that levels of circulating platelet serotonin releasing factor(s) vary in the course of systemic lupus erythematosus and these variations may be inversely related to the platelet count in particular patients.


Prolonged colchicine treatment in four patients with amyloidosis. The natural clinical course of four patients with systemic amyloidosis was favourably altered by continuous colchicine therapy. One patient had primary amyloidosis, and the other three suffered from amyloidosis of familial Mediterranean fever. All had a nephrotic syndrome, and one showed features of intestinal malabsorption. The institution of colchicine therapy was followed by a gradual remission of the nephrotic syndrome, a rise of serum albumin to normal values, a slight improvement of renal function, and regression of the intestinal malabsorption. This pattern has remained steady during an observation period of 30 months.


Hypokalemia with hypercalcemia. Prevalence and significance in treatment. Hypokalemia is a potentially life-threatening biochemical abnormality in patients with hypercalcemia. We studied a large group of patients with hypercalcemia to determine the prevalence of hypokalemia. One hundred three patients with normal renal function and no history of taking potassium-depleting drugs comprise the substance of this study. Thirty three of 103 patients (32%) were hypokalemic. A higher prevalence (52.3%) was found in patients with hypercalcemia associated with malignant disease than in those with primary hyperparathyroidism (16.9%). In addition, the degree and frequency of hypokalemia were greatest at the higher serum calcium levels. The presence of hypokalemia must be considered when treating severe hypercalcemia; otherwise, vigorous use of diuretics may result in profound hypokalemia and tachyrhythmias.


Tuberculosis after jejunoileal bypass for obesity. One hundred patients who underwent jejunoileal bypass for obesity were followed for a mean period of 2 1/2 years. Four patients developed a clinical illness that resembled a systemic form of tuberculosis during the first postoperative year. This incidence exceeds that found in the general population by sixtyfold. Any patient with jejunoileal bypass who develops an illness with accelerated weight loss, enlarged lymph nodes, and unexplained fever with chills should be suspected of having tuberculosis. Aggressive diagnostic measures are required. Treatment with isoniazid and ethambutol at usual doses can be successful, but blood levels should be measured to confirm adequacy until additional information becomes available.


Drug-related syndromes in clinical nephrology. The major clinical presentations of disease to a nephrologist can be grouped into six general areas: acute renal failure, chronic renal failure, nephrotic syndrome, fluid-electrolyte disorders, acid-base disturbances, and the uremic symptom-complex. Each of these major clinical syndromes can be caused by, or related to, drugs or environmental toxins. Prototype drugs can be used to highlight the features of each drug-related syndrome. Although it is preventable, drug-related disease may present opportunities to learn about general pathophysiologic mechanisms in clinical nephrology.


Phenformin-associated lactic acidosis: pathogenesis and treatment. Since phenformin's introduction into clinical medicine, a total of 552 cases of lactic acidosis have been reported in patients taking this hypoglycemic agent. In 306 cases, sufficient documentation was available to establish the diagnosis with reasonable certainty (blood lactate, 6 meq/litre or greater, and blood pH, 7.33 or less). The mortality rate among insulin-treated patients (15%) was considerably less than the mortality rate in the group as a whole (42%). Taken together with results from animal studies, these data suggest that insulin is the treatment of choice for phenformin-associated lactic acidosis. Sodium bicarbonate should be administered to patients with severe acidosis, but should be withheld from patients with mild acidosis. Overly aggressive administration of sodium bicarbonate can be deleterious and should be avoided. Although dialysis has been suggested by some authors for the treatment of phenformin-associated lactic acidosis, the mortality rate among dialyzed patients (48%) was roughly the same as for the group as a whole (42%).


Pleural mesothelioma: clinical features and therapeutic implications. A detailed review of the literature was done to define the epidemiology, pathology, clinical features, and treatment of pleural mesothelioma. It appears that pleural mesothelioma accounts for approximately 400 deaths each year in the United States. Asbestos has been definitely implicated in the etiology of this disease. The common clinical features include chest pain, pleural effusion, and radiologic findings of irregular pleural thickening or pleural densities. Therapeutic modalities used in the past have included surgery, radiation therapy, and, more recently, chemotherapy. A combined modality approach to treatment appears more promising.


Allowing or causing: another look.

Allowing or causing: another look. If "allowing to die" is really different from "causing to die," it is so on a much more subtle level than is generally thought. Efforts to compare the two by locating "cause" have been mistaken. What is really at issue is the location of moral responsibility. The physician has an obligation to save and is remiss if he does not try. The layman does not and is not. But as saving turns into pointless torture, the physician's obligation recedes, and he (ethically) becomes a layman. There is a range within which this turning point would take place for each of us, and the value of a "living will" can be seen as a means for each of us to specify that point for himself.


[Ludo Van Bogaert's cerebro-tendinous xanthomatosis. Apropos of 2 cases]. The authors report of two familial cases of Ludo Van Boggert cerebro-tendinous xanthomatosis. Biochemical studies carried out in one of the patients confirmed the work of Salen indicating that the disorder is due to an enzyme problem in the hepatic synthesis of primary bile acids from cholesterol (fault in the production and cholic and chenodesoxycholic acid an an increase in the synthesis of cholestanol).


[Trichinosis: review of the epidemic in the south suburbs of Paris in January, 1976 (apropos of 125 cases)]. The authors report the results of the trichinosis epidemic which occurred in the southern suburbs of Paris in January 1976. 125 patients from a total of 65 families were affected. The major signs: oedema of the face and eyelids, fever and myalgia, were commonly found. There were even laboratory abnormalities with eosinophilia, increase in muscle enzymes and positive specific serology. The course over a period of months was very favourable. There were no deaths. The most severe symptoms rapidly regressed. Only myalgia and headache, and above all fatugie, persisted for 3 to 4 months, in the adults. The biological course was marked by the disappearance in one month of the majority of the disturbances seen in the acute phase, apart from the eosinophilia and serological findings which remained pathological after one year in a number of cases. The particular aetiology, due to horsemeat, may be explained by modern industrial rearing techniques and the complexity of current commercial circuits.


[Trichinosis].

[Trichinosis]. The clinician is able to make the diagnosis of this rare disease only if he bears in mind that any patient with peri-orbital oedema of sudden onset may be suffering from trichinosis, even if the history is not convincing and even if the anademic context does not, or not yet, exist. The gravity of this parasitic infestation in the absence of treatment, and the remarkable effectiveness of the latter, underline the interest of this disease which may occur at any time, as shown by the minor anademic of three cases which we have reported.


[Spinal aneurysmal cyst with medullary compression. Apropos of a case with preoperative embolization]. The authors report the case of a vertebral aneurysmal bone cyst, at the thoracic level, with spinal cord compression. 16 months after operation, the initial neurological signs reappeared. Selective angiography pointed out a good picture, through not specific, of the lesion; the embolisation, then performed, provided considerable relief for the complete removal of the important vascular bone formation. The diagnostic, therapeutic and pathogenic problems of the vertebral aneurysmal bone cysts are discussed.


[Taxonomic characters of "Clostridium tyrobutyricum" (author's transl)]. The taxonomic characters of 77 strains of Clostridium tyrobutyricum have been studied and compared to those of known strains. This work shows the insufficiency of the Bergey's Manual (8th edition) nine characters distinguishing Clostridium groupe I to identify C. tyrobutyricum. To be more representative of the species, addition of one or two characters to this key of determination and some modifications to the complementary description of C. tyrobutyricum in this manual are proposed.


The counterimmunoelectrophoresis test for detection of antibodies to rabies virus. The screening for antibodies to rabies virus has been the subject of interst in ecologic studies and serologic surveys of this zoonosis. The methods most commonly used for these purpose have included the serum neutralization (SN) and indirect fluorescent antibody test [23, 22 6, 15]. The maintenance of laboratory animals or the requirement for special reagents are among the generally recognized limitations of these techniques. Furthermore, in the case of the SN test, a period of fifteen days is necessary before test results become available.


[Irradiated cell cultures applied to group A "chlamydiae" isolation (author's transl)]. The irradiated Mc Coy cell cultures method modified by Darougar et al. has been used to investigate the frequency of Chlamydiae in non-specific genital tract disease, in Reiter's disease and in patients suffering from conjonctivits associated with non-specific urethritis. Isolates were obtained from 104 men of the 660 suffering from acute urethritis, and from 18 men of the 67 suffering from conjonctivitis associated with urethritis. Fourteen female sexual contacts of these men were tested: Chlamydiae was isolated from 9. Seven patients suffering from acute Reiter's disease were tested: Chlamydiae was isolated from 4. These patients were tested by complement fixation and titers of 1/8 or more were only obtained in the 4 isolated positive cases, the three other cases remaining negative. Isolates of Chlamydiae were obtained from 10 women of the 67 women suffering from exocervicitis. No isolate was obtained, from 27 control patients.


Immune responses to influenza virus in rabbits after local immunization. II. Local and systemic cell mediated response. The development of local and systemic cell mediated immunity (CMI) was investigated in rabbits after intratracheal immunization with live or inactivated influenza A virus. Lymphocytes from bronchoalveolar washings and draining lymph nodes were used for the assay of local CMI response. Spleen cells were employed for determination of systemic responses. Since alveolar macrophages were found to be susceptible to the action of migration inhibiting factor, the development of CMI in lungs was assayed by macrophage migration inhibition test using bronchoalveolar was cells. Immunization with live virus induces beter local CMI response than inactivated virus. After primary immunization the peak responses were found between second and third week. The secondary response was detectable much earlier and peaked at one week after booster. Small amounts of inactivates virus, which was unsufficient to evoke a primary response, could elicit a strong secondary response. The development of rapid and accentuated secondary response in the local lymphoid tissues suggests the presence of memory in the local CMI response. The results also show a good correlation to exist between primary local CMI response and the skin reactivity to the immunizing antigen. However, lack of such correlation during the secondary response leaves the skin tests less reliable in the evaluation of CMI in viral infections. Some of the functions of alveolar macrophages in the local immune reponses are also discussed.


Clinical comparison of pilocarpine preparations in heavily pigmented eyes: an evaluation of the influence of polymer vehicles on corneal penetration, drug availability, and duration of hypotensive activity. Heavily pigmented eyes have been shown to be relatively resistant to pilocarpine, and present special problems in management of open-angle glaucoma. Studies have suggested that the hypotensive effect of pilocarpine may be influenced by the vehicle; therefore, 13 relatively resistant black patients (26 eyes) were selected for a clinical comparison of pilocarpine as delivered in two different polymer vehicles. One vehicle was composed of 1.67% polyvinylpyrrolidone and BP water-soluble polymers (Adsorbobase); the other of hydroxypropyl methylcellulose 0.5%. All patients had been under treatment with the pilocarpine/methylcellulose preparation; 20 of the 26 eyes were judged to be uncontrolled (IOP above 21 mm Hg). Control of intraocular pressure was promptly obtained with the pilocarpine/Adsorbobase solution, and maintained at lower pilocarpine concentrations than with the previous therapy. Often, frequency of instillation could be decreased. This clinical comparison suggests that the Adsorbobase vehicle appreciably enhances corneal penetration and availability of pilocarpine. Three cases are discussed demonstrating the need for titration when instituting a new therapy with as little as one fourth the concentration of the previous pilocarpine therapy.


Corneal thickness after vitrectomy and infusion with dextran solution. We studied with pachometry the degree of corneal endothelial decompensation in rabbits undergoing extracapsular lens extraction and vitrectomy. We used 3 different infusion solutions: (1) 0.9% sodium chloride; (2) 0.45% sodium chloride with 2.5% glucose; and (3) 0.45% sodium chloride, 2.5% glucose, and 2% dextran. Vitrectomy and vitreous replacement with the last solution demonstrated the least overall increase in corneal thickness. On the basis of these observations, dextran may be a useful colloid osmotic agent in intraocular irrigating fluids to control and decrease postoperative corneal edema.


Eosinophilic granuloma of orbit.

Eosinophilic granuloma of orbit. Three cases of orbital eosinophilic granuloma are reported. In all 3 the diagnosis was established histologically. In the follow-up period, ranging between 5 and 20 years, the disease has taken a benign course; incomplete surgical removal in 2 of the patients and radiation of the lesion in one have been equally effective in promoting healing. The first mode of therapy may be preferable in the region of orbit in order to avoid damage to the globe or optic nerve.


Scleritis and perceptive deafness: case report. There is some evidence in the past decade that a similar syndrome to Cogan's syndrome may exist in which a scleritis substitutes for the nonsyphilitic interstitial keratitis. A case is reported of a female patient, aged 39, with nonrheumatoid scleritis and associated bilateral perceptive deafness.


Shrinkage of conjunctiva, Terrien's marginal degeneration, and perforation of cornea in rheumatoid arthritis. The unusual occurrence of severe conjunctival shrinkage resembling ocular pemphigoid and bilateral Terrien's marginal degeneration of the cornea in rheumatoid arthritis is described. In less than two years the right eye was lost due to spontaneous corneal perforation and the left became totally blind because of scarring and shrinkage of the conjunctiva. A common unknown factor is speculated as an etiologic relationship between rheumatoid arthritis, ocular pemphigoid, and Terrien's marginal corneal degeneration.


Glaucoma in oculodermal melanocytosis.

Glaucoma in oculodermal melanocytosis. Case reports of oculodermal melanocytosis (nevus of Ota) and ipsilateral glaucoma often have other ocular disorders which could account for the glaucoma. It has not been clearly shown that the oculodermal melanocytosis alone can cause secondary glaucoma. In the present case report, optic nerve head and visual field changes, suggestive of a long-standing unilateral elevation of intraocular pressure, occurred in an eye with oculodermal melanocytosis and no other apparent ocular disorder to account for the chronic glaucoma.


Anterior chamber scroll and corneal edema. This case represents the successful removal of a transparent anterior chamber scroll and the subsequent resolution of corneal edema overlying the tissue. It emphasizes the clinical observation that a small area of endothelial touch can be associated with a disproportionately large area of overlying corneal edema, and may indeed be the cause of it.


[Generalized congenital fibromatosis (author's transl)]. About a spontaneously regressive case of osteo-cutaneous congenital fibromatosis, the authors describe the characteristics of the disease (32 observations). Although the majority of cases are sporadic, 3 familial observations are in favour of a dominant autosomal transmission of low penetrance. Study of the familial cases and analysis of the different localisations demonstrate the unicity of the so-called diffuse forms with visceral involvement and of the so-called generalized forms without visceral involvement congenital fibromatosis is characterized by several fibromas at birth: in two-thirds of the cases, it is a purely cutaneous or osteocutaneous form, which disappears spontaneously; in one third of the cases, it is a cutaneous or osteo-cutaneous form with lethal visceral involvement.


[Congenital nodular fibromatosis: report of six personal cases (author's transl)]. Six personal cases of nodular congenital fibromatosis are reported: one fibromatosis colli, two fibromas of the fingers one multiple fibromas of the toes and sole associated with osteoporosis and underlying bone lacunes, one recurrent plantar fibromatosis, one disseminated fibromatosis with multiple bone lesions. Such varieties of fibromatosis are very uncommon. Few are isolated such as fibromatosis colli or the fibroma of the fingers. The prognosis is generally good except for the generalized multinodular form which associates a very large visceral involvement. Aetiology is completely unknown. Only few arguments are in favour of an hereditary dominant autosomal transmission of the diffuse multinodular form.


[Reflections on the treatment of acropathia ulcerans et mutilans; interest of a removable appliance (author's transl)]. The authors report their experience in the treatment of acquired ulcerating and mutilating trophic lesions of the lower limbs. Ligature of the dorsalis pedis artery and of its collaterals did not give good results, according to the pathogenic concept of the authors, in which lesions of the nervous system predominate over vascular alterations. More important lesions (such as osteo-arthritis of the first and fifth metatarsals) require immobilization of the axis of the wounded toe, control of any superinfection and use of a plastic removable limb appliance.


[Immunological study and results of treatment by levamisole in 25 atopic patients (author's transl)]. The authors have studied humoral and cellular immunity in 25 atopic patients. Sequential treatment by levamisole has not allowed any significant improvement of these patients.


[Primary pharyngolaryngeal carcinoma, pulmonary metastases and carcinoma of the bronchus (author's transl)]. On the basis of 112 cases of pulmonary or mediastinal neoplasms observed during the treatment or follow-up of 952 carcinomas of the pharynx and larynx, the authors study in detail 45 cases of metastases. They draw the following conclusions:--metastases present clinically relatively early in the treated course of pharyngolaryngeal carcinomas: 85% before 18 months.--cannonball lesions are the commonest endo-thoracic clinical metastases: 6 out of 10.--carcinomas of the hypopharynx are at the origin of 2/3 of cannonball lesions (alpha less than or equal to 0.02) and 1/4 of mediastinal lymphadenopathies and pleural effusions.--endolaryngeal carcinomas are rarely at the origin of cannonball lesions and are associated almost exclusively with mediastinal lymphadenopathies and pleural effusions (alpha less than 0.001). The influence of the size of the primary tumour, of lymph node involvement, of capsular rupture and of failure to eliminate all malignant cells from the primary lesion are considered and discussed.


[Scleroderma en coup de sabre with homolateral chronic glaucoma (author's transl)]. A 37 years old woman presented with scleroderma en coup de sabre of the head with chronic homolateral ocular hypertony. Skin disorders appeared in the childhood and extended slowly until the age of 20. Glaucoma, found 5 years earlier, was unimproved by medical treatment; the opposite eye was normal. Two goniotomia in 1974 were uneffective. A trabeculectomy in 1975 was followed by scleral fistula with important ocular hypotonia. A scleral flap was followed by the disappearance of hypotonia with no return to previous hypertony. The connections between scleroderma and glaucoma are discussed; vascular and neurologic mechanisms are suggested. Up to now, glaucoma has been reported in patients with systemic soleroderma and Romberg disease.


[Personal results trial of classification and standardization in clinical impedancemetry (author's transl)]. The author analyses the results obtained in clinical impedancemetry for 2,799 ears: tympanometry and study of the acoustico-facial reflex. He proposes a trial of classification of the results. The author states the terminology to be used in impedancemetry according to the different probe tone frequencies of the clinical impedancemeters and the different acoustic stimulations systems in order to obtain the acoustico-facial reflex.


[The influence of oestroprogestational agents on cervico-facial cutaneous scars (author's transl)]. On the basis of a certain number of cases, it would appear that the ingestion of oestroprogestational agents has an untoward influence on cervico-facial cutaneous healing and may result in scars of poor quality and even cheloids.


[Costa's acrokerato-elastoidosis. Ultrastructural study (author's transl)]. Acrokerato-elastoidosis described by Costa is characterized by numerous little keratotic points and translucent horny wheals on the dorsal aspect of hands and (or) feet. The ultrastructural study shows lesions of the elastic tissue which is very rarefied with an abnormal structure, but also demonstrates alterations of the fibroblasts that contain dense granules at the periphery of their cytoplasm without elastic extracellular fibers, suggesting a trouble in the secretion or the excretion of the elastic material.


[IgG levels in the sera of melanoma patients (author's transl)]. 397 sera from 185 melanoma patients have been tested. We classified our subjects into three groups, according to the stage of disease. An alteration of the level of IgG4 subclass was found and related to the extension of the disease. The percentage of abnormalities was more frequent in stage II and III (55 p. 100 and 53 p. 100) than in stage I (19 p. 100). High titers of IgG 4 subclass were essentially detected in advanced disease. The biological significance is discussed.


[Physiopathology of acetylcholine delayed blanch in atopics. Thermographic study (author's transl)]. Controversy subsists about interpretations of "delayed cholinergic blanch" in atopic dermatitis. A physical approach of this vasomotor phenomenon using infrared and cholesteric thermography and direct recording of skin temperature shows that the delayed blanch is hyperthermic and cannot be the effect of a paradoxal cholinergic vasoconstriction. In the light of the beta-adrenergic blockade theory of Szentivanyi a new physiopathological interpretation is proposed.


[Epitheliomatous degeneration of chronic leg ulcers. Apropos of 9 cases]. The authors report nine cases of epithelioma occurring on chronic leg ulcers of venous origin (6), or on fistula from chronic osteitis (3). Compared with the other trophic leg ulcers observed during the same period, the risk of malignant change approximately is of 0,3 p. 100. It always concerns aged caucasian subjects (about 70 years old) and the evolution lats long (5/20 years), except in one of the cases. The first symptoms are hard, bleeding and exuberant granulations either on the edge of the ulcer, or on the ulcer itself. It is often necessary to repeat the biopsies to obtain histological corroboration of the diagnosis. Prognosis is severe (2 lung metastasis) and amputation seems to be the best treatment.


[Natural transmission of Schistosoma mansoni in Guadeloupe (French Antilles). Preliminary note (author's transl)]. Occasioning in Guadeloupe a high rate of morbidity, schistosomiasis is unequally spread in the field. The intermediate host, Biomphalaria glabrata, is wide-spread. But some biotopes only, most of them located on the coast belt of the montainous island, allow the parasite growth. Among them, the irrigation canals appear as the most dangerous source of contamination for human population.


[Principal factors involved in the settlement of Biomphalaria glabrata (Say, 1818), snail intermediate host of schistosomiasis in Guadalupe (author's transl)]. Six biotopes of Biomphalaria glabrata, the snail intermediate host of schistosomiasis in Guadalupe, were investigated during one annual cycle. These six biotopes included a pond, a freshwater mangrove, a stream, a mountain lake, a "microhabitat" and a canal. These six types of biotopes were characterized by various parameters whose fluctuations reveal the main factors regulating the B. glabrata populations. The climatic factors are essential in Grande Terre and resulted in an annual development cycle well determined of all the aquatic communities. The biotic factors (Predation, competition, parasitism) are important in every type of biotope, in Grande Terre as well as in Guadalupe proper. In every type of biotope, anthropic factors are also important, but mainly in canal nets which are the principal focus of human schistosomiasis. The chemical factors themselves are less important.


[Presence in Camargue of two sympatric, sexually isolated forms of Aedes (Ochlerotatus) detritus (Haliday, 1833) [Diptera-Culicidae] (author's transl)]. The study of allozymic variations at four enzymatic loci (Est-2, alpha-Gpd, Got-1 and Got-2) in populations of Aedes detritus (Hal.) from 27 localities in Southern France has shown that this species is composed of two kinds of sympatric populations which do not interbreed in nature. Single specimens of Aedes detritus can be attributed to one or other type of population (sibling species) by the genotype at the alpha-Gpd or Got-2 loci (type A populations are homozygous for Got-2R allele and the frequency of the alpha-GpdC allele is higher than 98%; type B populations are homozygous for Got-2L allele and the frequency of the alpha-GpdB allele is higher than 98%). Moreover, allelic frequencies at the Est-2 and Got-1 loci are different in both types of populations. The fact that both kinds of populations coexist in the same pond shows that the isolating mechanism is not an adaptation to the larval environment, but rather involves mechanisms pecular to adults (precopulatory mechanism or interpopulation sterility).


[Suburban biotopes of Rhipicephalus turanicus (Pomerancev, Matikasvili, Lototzki, 1940). (Acarina, Ixodoidea). Preliminary study (author's transl)]. Investigations carried out on the waste grounds of a certain number of large Mediterranean towns in Provence and Languedoc (France) show the prevalence of Rhipicephalus turanicus in such an environment. The authors analyse the conditions favourable to the installation of the species, and make a comparison between the suburban biotopes with Rhipicephalus turanicus and the homologous biotopes with Dermacentor reticulatus.


[Revision of Fuhrmaniella fausti Tseng Shen, 1932 (author's transl)]. The authors reexamined the original material of Fuhrmaniella fausti recolted by Faust and preserved within the collections of the University of Neuchâtel. They came to the following conclusions: 1. the description of F. fausti given by Tseng Shen, 1932 joins without any doubt the strobila of Microsomacanthus paramicrosoma Gasowska, 1931 and the scolex of the quite different species probably Microsomacanthus spiralibursata Czaplinski, 1956; 2. the specimens described by Spassky and Spasskaya 1961 as Microsomacanthus fausti belong to a different species, little known, which is proposed to be named Microsomacanthus beari sp. n.


[Cycle, ultrastructure of a Catenaria (Phycomycetes Blastocladiales) parasite of Crustacea Cyclopoida]. The ultrastructural modifications during the life cycle of a Phycomycetes parasite of Cyclops are studied. The cytoplasmic sporangium cleavage is brought about by the fusion of flagellar sheaths and cleavage vesicles. The uniflagellates zoospores are characterized by a nuclear-nuclear cap cluster, a large side-body (single mitochondrion, lipid bodies, granular material) and gamma particles. The fungus belongs to the genus Catenaria and probably to the species C. anguillulae. The ultrastructure of this Catenaria shows that this genus is closely related to Blastocladiales.


One year's experience with a regional hormone assay service. To provide a service in England and Wales for specialised assays, clinical chemists envisaged a multi-tier system with area, regional, and supraregional laboratories. The Department of Clinical Biochemistry at Addenbrooke's Hospital was established as a regional centre for hormone assays and formal operation started in June 1975. The assays which seemed most suitable for regional development in East Anglia were those for investigating the pituitary-gonad and pituitary-thyroid axes. Most of these were introduced in the first year of operation. A specialised laboratory was not set up: instead, endocrine assays were integrated into a large service laboratory and little expenditure was needed for specialised facilities or staff. The work load of endocrine assays increased markedly during the first year of operation, but the main source of requests was local rather than regional. This lack of use by a region has implications for all three tiers of the specialised service. It suggests that effective centralisation of specialised assays is impracticable unless a dictatorial approach to the problem of rationalisation is made at regional and area level.


Automated fluoride ion determination. Determination of urine fluoride ion levels. An automated method is described, using standard continuous flow techniques, for the determination of urine fluoride ion concentration using a fluoride ion selective electrode. It is shown that the kinetics of the electrode response to changes in fluoride ion can be used for the accurate measurement of fluoride ion concentration in urine, and that equilibration of the electrode response is not a prerequisite for the measurement of fluoride ion. Recovery experiments are in the range 83 to 90%; in-batch precision is between 0.9 and 1.6% and carryover 2.5% or less.


Automated fluoride ion determination. Determination of serum fluoride ion levels. A method is described, using standard continuous flow techniques, for the automated determination of serum fluoride ion concentration using a fluoride ion selective electrode. It is shown that the kinetics of the electrode response to changes in fluoride ion can be used for the accurate measurement of fluoride ion concentration in serum, and that equilibration of the electrode response is not a prerequisite for the measurement of fluoride ion. Recovery experiments are in the range 86.6-98.5%, in-batch precision is 1.0-6.1%, between-batch precision 5.5%, with carryover of -2.99%.


Blood sampling technique for lactate and pyruvate estimation in children. The effects of stress and muscular movements caused by direct venepuncture and of venestasis on the lactate and pyruvate levels in children have been examined. Direct venepuncture and venestasis significantly influence the obtained values. To measure reliable values for pyruvate and lactate in blood of children it seems advisable to insert an indwelling intravenous cannula. After 45 min of rest in bed the blood sample can be obtained.


Assessment of the Beckman System 1.

Assessment of the Beckman System 1. The System 1 produced results for glucose and urea which were precise and accurate. It proved suitable as a general laboratory instrument as it samples 28 mul of specimen, is able to calibrate itself, produces results in three minutes, and has the capacity to analyse 56 samples an hour.


Serum enzymes and isoenzymes after surgery. Serum creatine kinase, aspartate transaminase, and hydroxybutyrate dehydrogenase activities were abnormal in 76, 50, and 28% respectively of 50 patients studied within 26 hours of surgery. No patient showed clinical evidence of myocardial infarction. Creatine kinase MB isoenzyme elevation, and lactate dehydrogenase LD1 activity greater than LD2 (LD) greater than LD2) were infrequent (6 and 10% respectively). No patient showed the combination of transient MB isoenzyme elevation and LD1 greater than LD2, although their rare association without infarction after surgery is to be anticipated.


Diagnostic value of urine mercury measurements. A review of referrals to a regional heavy metals centre for possible mercury poisoning was made. Samples were received either from subjects who were well but were known to have some contact with mercury or from patients with an illness under investigation but undiagnosed. The problems associated with diagnosis of mercury toxicity in the absence of known exposure are illustrated by two case reports.


Human mitochondrial malic enzyme variants: properties of the different polymorphic forms. 1. The human mitochondrial malic enzyme polymorphism was found to exist in the Scottish population with similar allele frequencies to those reported previously for Caucasian populations. 2. The mitochondrial malic enzyme variants MEM1, MEM2-1 and MEM2 which form the polymorphism have been separated from the cytoplasmic malic enzyme and partially purified by DEAE Sephadex chromatography. 3. The properties of the three mitochondrial malic enzyme variants were examined. No differences were found between the variants in Km for NADP, Km for pyruvate, Mn2+ and Mg2+ activation, Ki for dicumarol, heat stability, pH or ionic strength optimum.


Inverting the information matrix in gene-frequency estimation in systems like ABO. It is shown that the matrix of second-order derivatives of the log likelihood function in the case of ABO-like systems can be subjected to explicit inversion in the general case of k antigens.


Estimation of the variance components for dermal ridge count. Refinements of the scoring algorithm to estimate variance components from pedigree data are developed. Subsequent to these modifications, heritability estimates were readily obtained from data for over 50 traits, including total finger ridge count reported here. A significant contribution to the total variance of ridge count could be attributed to the effects of dominance, a finding not previously reported for this dermatoglyphic trait.


Comments on the Penrose-Stanton model of assortative mating. A single-locus model of assortative mating proposed by Penrose and extended by Stanton is analysed. It is shown that the formulae giving values of correlations between males and relatives derived by Stanton apply to a general class of symmetric, non-selective mating schemes in equilibrium when genotypes have additive values. The canonical form of Stanton's system is derived, revealing that the assignment of additive values of genotypes does not apply also to the canonical vectors.


Testing the significance of risk estimates for the predisposition of heterozygotes to common diseases. A maximum-likelihood method has been used previously to estimate, from family studies, the relative risk of common disorders for heterozygous carriers of genes for certain autosomal recessive syndromes. In this paper statistical significance of relative risk estimates was evaluated using critical values from computer-generated sampling distributions of the test statistic. In several practical cases a significance test based on the computer-generated distribution was more conservative than a test which assumed normality for the sampling distribution.


The linkage relationships of the haemoglobin beta, delta and alpha loci with 34 genetic marker systems. An analysis of the linkage relationships of the Hbalpha and Hbbeta loci with 34 genetic marker systems is presented. No evidence of linkage of either haemoglobin locus with any of the marker loci was found. The Hbalpha locus may be excluded from approximately 7% and the Hbbeta locus from approximately one-third of the autosomal genome.


Tracing quantitative measurements on human chromosomes in family studies. Statistical methods are developed for tracing quantitative measurements on human chromosomes from parents to offspring. Tests for transmission are briefly considered.


Inbreeding effect on precocious mortality in Japanese communities of Brazil. Data on precocious mortality (from abortions up to the age of 20) are presented for three Japanese communities in Brazil. The inbreeding load (B approximately 1-5) is estimated on the basis of these data. B/A lies between 7 and 30. Three general working hypotheses are presented.


Hair patterns of the lower limb in Central Indian males. The distribution of hair of the right lower limb has been studied in a random sample of 220 healthy Central Indian males 17 to 45 years of age. The common hair patterns observed are the proximal phalangeal hair in all toes in 55.45%, the middle phalangeal hair in the third toe in 8.18%, the tibial on the dorsum of foot in 69.55%, and the pedo-cruro-femoral in the lower limb in 70.00% subjects. Comparison of these findings with those of the right upper limb shows that hairiness of the two limbs is correlated, that the dorsum of foot is less hairy than the dorsum of hand, and that the third and second toes are comparable with the fourth and third fingers, respectively, as regards their middle phalangeal hair. Comparison with the available literature shows that the Central Indian males resemble the Whites in having greater frequency of middle phalangeal hair than those of the Negroes, that the dorsum of feet of this population is less hairy than the White and more hairy than the Negroes, and that the general hairiness of the lower limb is more or less equal in the three groups of persons.


Hair patterns of the pinna among the Central Indians. The hair patterns of the pinna have been studied in a selected sample of 767 males and 5 females from Central India, all with hairy pinnae. The age of the males ranged from 21 to 85 years, and that of the females from 2.5 months to 32 years. All subjects were healthy and did not demonstrate any endocrine disturbance. The commonest hair pattern of the elevated areas of the pinna among the males was the helico-lobulo-antitragal, whereas in the females it was the helical. The hair pattern of the depressed areas of the pinna showing highest frequency was the conchal. The majority of the hairy pinnae are associated with bilateral tragal hair and the maximo-pilose distribution of the facial hair. The Central Indian males resemble the White males in their hair distribution of the pinna.


[Sex differences in hair color].

[Sex differences in hair color]. The hair-colours of an unselected Vienese sample (8399 male, 8176 female) of all ages and ascertained by the author himself have been analysed with regard to their sexual distribution. The comparisons of the age-groups necessary because of the individual age-changes of the hair-colour did not reveal any significant sexual dimorphism. Only during the periods of intensified growth the girls show a slight tendency to darker hair than the boys at the same age because of their faster development.


Association of finger ball dermatoglyphics with pulmonary tuberculosis. This paper includes the study of finger ball pattern dermatoglyphics of 200 normal individuals and 200 tubercular patients. The data on the former group were collected from local institutes and that on the latter one from Tuberculosis and Chest Diseases Dept., Govt. Medical College, Patiala. A comparison of two groups was made pertaining to the distribution of various subtypes, major types, indices, symmetry, monomorphic hands and pleiotropic hands to find out an association of finger ball dermatoglyphics with tuberculosis, if any. No statistical significant differences were observed in two groups in relation to these parameters except for the distribution of various subtypes in index fingers of both hands and little finger of right hand and the pleiotropic hands.


[Quantitative digital dermatoglyphic parameters--their distribution in families]. 112 mother-child-father tercettes have been examined for several quantitative dermatoglyphic parameters (total ridge count--TRC--, radial and ulnar differrences, index of pattern type [KEITER]). The distribution of pattern among children has been compared to those of their parents. In the majority of cases within the empirical distribution of the children extreme values outside of the variation range of the parents were observed. This is in contrast to the formal genetic model of additive polygeny (HOLT). These findings have been interpreted as manifestation of TRC-heterogeneity suggesting a modifying action of radial and ulnar ridge differences. The parent-child correlation for the radio-ulnar differences and the index of pattern type were lower than that for the TRC. The interpretation of unexpected differences in quantitative dermatoglyphic parameters of children in relation to the variation of their parents has to be discussed very carefully. Due to the small number of material a correlation between the isolated position of the children in TRC to mother-child-differences in serological markers could not be excluded in this study.


[Variability and formal genetics of labial grooves]. 320 adults and 100 family tercettes from the area of Hamburg were studied concerning the distribution and frequency of different lip patterns as well as special structures of lip ridges (whorls). Dividing the material in three phenotypic classes the phenotype corresponding to less wrinkle intensity was found to be most frequent. Simple branching ridges and complicated phenotypes were present in almost similar frequency. The complicated patterns as well as structural details were more frequent among males. In the family tercettes, the offsprings from parents with less branching patterns showed a wide range of variation. Dominant genetic factors could be suggested for the manifestation of paramedial double whorls on the lower lip. Embryological considerations as well as studies by Hirth et al. (1977) agree to these interpretations.


On the genetic control of human serum albumin levels. On 68 families with 134 children and on 115 mother-child pairs the serum albumin levels were examined by means of the single radial immundiffusion test after MANCINI et al. (1965). Neither age nor sex dependences were seen. Against that our materials indicate the existence of genetic factors controlling at least to some degree the concentration of this serum protein. Nevertheless, the serum albumin level is also influenced by non-genetic factors. At the present stage of research, however, it is not yet possible to separate exactly genetic and non-genetic variation from another.


[Dependence of shrinkage on the mineral content of experimentally burned bones]. Quantitative changes of the human femur compacta have been studied by dilatometer investigation. Furthermore it was found that increasing mineral content of cortical bone is significantly correlated with a decreasing value of thermally induced shrinkage. Therefore, cortical thickness should be a useful criterion for sexing cremated remains.


[Study of natural mutiple drug resistance in actinomycetes of the genus Streptomyes]. Natural strains of actinomycetes belonging to 3 systematic groups of the Streptomyces genera, i.e. blue, gray and globisporine were characterized for their resistance to antibiotics and sulfamids. The majority of the strains were shown to have stable inherited multiple resistence to a wide variety of antibiotics. Linkage analysis for resistance determinants in pairs showed random distribution of most of the determinants among the members of the blue and grey groups of the actinomycetes. Non-random distribution of the resistance determinants to Tc, Cm and Rm in TcCm, TcRm conbinations for the blue group actinomycetes and to Om, Rm, Fa, Lm, Em, Rm and Tc in OmRm, FaLm, EmPm, TcOm combinations among the members of the grey group of actinomycetes was found.


[Induced variability of Streptomyces galbus]. A-factor, a regulating substance is an obligatory participant of streptomycin biosynthesis by Str. griseus. Str. galbus also synthesizes streptomycin but without participation of A-factor. Mutant with various morphological properties were obtained under the effect of ethylenimine. No correlation between spore formation and streptomycin synthesis was found in the mutants of Str. galbus unlike Str. griseus. Correlation between a decrease in the capacity for production of a dark brown pigment and an increase in the level of streptomycin biosynthesis was shown: the mutants with the dark brown pigment did not synthesize streptomycin, while the mutants without the pigment synthesized streptomycin in the amounts 10-14 times higher than those in the initial strain. The same as the initial strain, the mutants of Str. galbus had no A-factor and did not respond to its addition into the medium by changing their properties and streptomycin synthesis.


[Study of the antibiotic sensitivity of Shigella newcastle isolated in Zaporozhe Province]. Sensitivity to antibacterial drugs of 510 strains of Shigella Newcastle isolated from both sporadic patients and cases during the disease outbreaks was studied. The studies revealed a rather high percentage of Shigella Newcastle resistant to the antibiotics widely used in clinical practice. Most of the strains, i.e. 90.5 per cent were resistant to tetracycline and a significant number of the isolates, i.e. 55.6--53.3 per cent were resistant to streptomycin and erythromycin. A statistically reliable predominance of the Shigella resistant to levomycetin and streptomycin in the disease foci was noted as compared to the Shigella isolated from the sporadic patients. Most of the isolates were simultaneously resistant to several antibiotics. Thus, resistance to 2,3--4 and 5--6 antibiotics was found in 28, 54.3 and I.I per cent of the cultures respectively. At the same time almost all Shigella Newcastle strains were sensitive to rifampicin, neomycin and monomycin (aminoglycoside antibiotics), enteroseptol (oxychinoline drug) and furazolidone (nitrofuran drug).


[Effect of euphylline and caffeine on the permeability of the hemato-encephalic barrier for benzylpenicillin in experimental and clinical meningococcal meningitis]. Higher benzylpenicillin levels in the cerebrospinal fluid and soft brain membranes were determined in experiments on a model of meningococcal meningitis of rabbits and in clinics in patients with meningococcal meningits subjected to combined treatment with massive doses of the antibiotic and the therapeutic doses of euphylline or caffeine. Benzylpenicillin excretion with urine and the antibiotic blood levels did not significantly change under the action of the diuretics. The phenomenon must be due to the vasolidative effect of the drugs of the purine group, improved blood supply of the soft brain membranes and increased permeability of the hemato-encephalic barrier for benzylpenicillin.


[Principles of antibacterial chemotherapy of wound infection in traumatology and orthopedics]. Staphylococci have been mainly isolated presently from the wounds of the traumatological and orthopedic patients. Sensitivity of the out-of hospital and hospital staphylococcal strains was studied. Higher sensitivity of the out-of-hospital strains was showed. Directed antibiotic therapy, control of the treatment courses, doses, drug levels in the blood serum and infection foci provided more effective results in patients with purulent complications.


In vitro inhibition of platelet function and coagulation by pentamidine isethionate. Pentamidine isethionate is a trypanocidal drug used for the treatment of Pneumocystis carinii pneumonitis. Hematological complications have occasionally been reported and include anemia, leukopenia, and thrombocytopenia. We report here several qualitative abnormalities of in vitro platelet function and coagulation that have not been described previously. Platelets were exposed in vitro to concentrations of pentamidine isethionate ranging from 0.5 to 100 mug/ml of platelet-rich plasma. Clot retraction, platelet adhesiveness to glass beads, and platelet aggregation (adenosine 5'-diphosphate [ADP], thrombin, epinephrine, collagen, and ristocetin) were inhibited in a dose-dependent fashion. The addition of pentamidine isethionate after aggregation had been initiated with ADP reversed both primary and, to a lesser degree, secondary aggregation. Platelet factor 3 availability and serotonin uptake and release (using collagen as the releasing agent) were not inhibited. Serotonin release with 10(-4) M ADP was slightly inhibited. Pentamidine isethionate prolonged the thrombin time of plasma at concentrations of 5 mug/ml and greater. The prothrombin time was prolonged at concentrations greater than 10 mug/ml of plasma. The inhibition of aggregation was reversed by washing and resuspension in plasma or by the addition of calcium or magnesium ions.


In vitro and in vivo antibacterial activity of T-1220, a new semisynthetic penicillin. T-1220, sodium 6-[d-(-)-alpha-(4-ethyl-2,3-dioxo-1-piperazinylcarbonyl-amino)- alpha-phenylacetamido] penicillanate, is a new semisynthetic penicillin derivative that possesses a broad spectrum of in vitro antibacterial activity against gram-positive and gram-negative bacteria. T-1220 is more effective than carbenicillin (CB-PC) against Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus species, and Serratia marcescens. Addition of human serum to culture media did not significantly alter the antibacterial activity of T-1220. Greater bactericidal activity toward various strains of gram-negative bacteria was demonstrated with T-1220 than with CB-PC. T-1220, like penicillin G, was hydrolyzed by penicillinase, but was sable to a type IV penicillinase produced by P. aeruginosa strains. In vivo antibacterial activities of T-1220, ampicillin (AB-PC), and CB-PC were compared, using systemic infections of mice with P. aeruginosa, K. pneumoniae, and Escherichia coli. The 50% effective doses (milligrams per kilogram) of T-1220 were consistently lower than those of AB-PC and CB-PC.


Effect of cefamandole nafate on the toxicity of tobramycin. Because of the potential for an interaction between cephalosporins and aminoglycosides leading to renal injury, an evaluation of the effect of a new cephalosporin, cefamandole nafate, on the toxicity of the aminoglycoside tobramycin was performed in laboratory animals. High doses of cefamandole nafate did not increase the acute toxicity (lethality) of tobramycin in rats or mice. In a subacute experiment in rats, dose-related tobramycin nephrotoxicity, as evidenced by blood urea nitrogen changes, increased kidney weights, and histologically determined tubular nephrosis and necrosis, was observed. Concomitant treatment with cefamandole nafate, 500 mg/kg, did not increase tobramycin nephrotoxicity, but protected against the aminoglycoside-induced renal injury. Determination of tissue radioactivity after administration of [(14)C]tobramycin indicated that cefamandole nafate treatment resulted in uniformly lower tobramycin tissue concentrations compared with the control, suggesting that the protective effect was produced by enhanced excretion of tobramycin after cefamandole nafate treatment.


Comparison of the nephrotoxicity of netilmicin and gentamicin in rats. The nephrotoxicity of netilmicin relative to that of gentamicin was examined in Sprague-Dawley rats. Balance studies were performed on rats injected with netilmicin or gentamicin (50 mg/kg per day for 14 days, 100 mg/kg per day for 8 days, and 150 mg/kg per day for 8 days). Control rats were injected with saline. Both drugs caused a dose-related decrease in urine osmolality and increases in urine volume, water intake, and serum creatinine; however, the magnitude of these changes was significantly less in netilmicin- than in gentamicin-injected rats. Light microscopy of renal tissue revealed less proximal tubular cell necrosis in netilmicin- than in gentamicin-injected rats. There was no significant difference between the renal cortical concentrations of the two drugs. Both drugs stimulated uptake of p-aminohippurate in rat renal cortical slices to the same degree. The data indicate that netilmicin is less nephrotoxic than gentamicin in rats, that the difference in nephrotoxicity cannot be explained by a difference in drug concentration in the renal cortex, and that the ability of aminoglycosides to stimulate the organic acid transport system of proximal tubular cells does not correlate with their nephrotoxic potential.


Antibiotic concentrations in serum, serum bactericidal activity, and results of therapy of streptococcal endocarditis in rabbits. The correlation between antibiotic concentrations in serum, serum bactericidal activity, and results of therapy was studied in rabbits with streptococcal endocarditis. Five days of procaine penicillin G reduced bacterial titers to <10 per g in 12 of 14 vegetations in rabbits receiving 75,000 U intramuscularly every 6 h and 10 of 20 in rabbits given 37,500 U. Ten days of 18,750 U every 6 h did not reduce the titers. To test for cure, rabbits were treated with 75,000 U every 6 h for 10 or 20 days and then received no therapy for 7 days. At the end of the 7-day period without therapy, vegetations were sterile in five of five and eight of eight animals, respectively. Rabbits received 37,500 U every 6 h for 5, 10, or 20 days and then no therapy for 7 days, after which vegetations were sterile in one of seven, four of nine, and seven of eight animals, respectively. The median maximal serum bactericidal dilutions at 1 h were 1/16 when 75,000 U of procaine penicillin G was administered, 1/8 to 1/16 with 37,500 U, and 1/4 to 1/8 with 18,750 U. Serum bactericidal activity could not be detected in 50% of the rabbits 6 h after administration of 37,500 U. Cure was related to a median maximal serum bactericidal dilution of at least 1/8 to 1/16 1 h after penicillin administration. A median maximal serum bactericidal dilution of 1/4 to 1/8 resulted in unsuccessful therapy.


Penicillinase-resistant penicillins plus gentamicin in experimental enterococcal endocarditis. Previous in vitro studies demonstrating that the penicillinase-resistant penicillins act synergistically in combination with gentamicin against some enterococci have suggested that these combinations might be effective therapy for enterococcal infections in vivo. To determine the in vivo effectiveness of such combinations, we treated rabbits with enterococcal endocarditis with gentamicin and either nafcillin, oxacillin, or methicillin. Despite doses of the penicillins equivalent to 12 or 24 g/day in a 70-kg patient, the percentage of animals in each treatment group with sterile valves at autopsy after spontaneous death or sacrifice after 21 days of therapy was low. High-dose therapy with the penicillins did not significantly increase survival over the low-dose treatment groups. Thus, it seems prudent to include penicillin with a penicillinase-resistant penicillin and gentamicin as the initial therapy of patients with endocarditis possibly caused by enterococci.


In vitro studies with cefaclor, a new oral cephalosporin. In vitro studies were performed to evaluate the activity of cefaclor in comparison with cephalexin against 180 clinical isolates. Broth dilution susceptibility tests showed cefaclor to be 4- to 16-fold more active than cephalexin against Streptococcus pneumoniae, Haemophilus influenzae, and cephalothin-susceptible Enterobacteriaceae. Neither drug was highly active against cephalothin-resistant Enterobacteriaceae or methicillin-resistant Staphylococcus aureus. Cefaclor zones with 30-mug disks were generally larger than cephalexin zones, 4 mm larger than cephalothin zones against Enterobacteriaceae, and 6 mm smaller than cephalothin zones against S. aureus. Quantitative kill curves indicated that killing by both cefaclor and cephalexin was slow and often incomplete over a 24-h period. Cefaclor-induced filamentation of gram-negative bacilli was not as extensive as that produced by cephalexin, and some spherule formation did occur. However, cefaclor was significantly more unstable in solution than cephalexin, with a half-life of less than 6 h at 37 degrees C. Thus, results obtained in tests after prolonged incubation may not provide an accurate measure of cefaclor's activity.


Double-blind evaluation of oral ribavirin (Virazole) in experimental influenza A virus infection in volunteers. The prophylactic effectiveness of oral administration of ribavirin (1-beta-d-ribofuranosyl-1,2,4-triazole-3-carboxamide) against experimentally induced influenza A infection was evaluated in a double-blind clinical trial in normal volunteers. Fourteen men received ribavirin capsules (1,000 mg/day in four divided doses) and 15 other men received identical-appearing placebo capsules beginning 6 h after the intranasal inoculation of 3.4 log(10) 50% tissue culture infectious doses of influenza virus A/Victoria/3/75 H3N2 and continuing for 5 days after challenge. The total number of moderate-to-severe symptom scores and the total number of temperatures >/=100 degrees F (37.8 degrees C) were significantly lower in the ribavirin group compared with the placebo group. The mean quantity of virus shed in nasal wash specimens and the total number of days that there were viral titers greater than 1.0 log(10) 50% tissue culture infectious doses per ml were significantly greater in the placebo group. There was no difference between the frequencies of virus isolated or the antibody responses in the two groups. Therefore, prophylactic ribavirin ameliorated symptoms and fever indicative of moderate-to-severe illness, but had no effect on the manifestations of mild illness in response to influenza A challenge. A transient rise in total serum bilirubin occurred in 29% of the ribavirin-treated volunteers and in none of the placebo-treated volunteers.


Plasmid-mediated resistance to gentamicin in Staphylococcus aureus. Two strains isolated from a recent outbreak of infections by gentamicin-resistant Staphylococcus aureus were examined to determine whether genetic control of this resistance is plasmid or chromosomally mediated. Curing techniques indicated a plasmid location in both strains. Physical isolation and characterization of the plasmid deoxyribonucleic acid from one strain revealed that the determinant for gentamicin resistance resides on a 50S plasmid.


Comparative study of 6-mercaptopurine metabolism in human leukemic leukocytes and L1210 cells. Leukocytes from patients with leukemia and L1210 cells from mice were examined for the rate of formation and cellular concentration of phosphoribosylpyrophosphate, the rate of thioinosinic acid formation, and a number of selected enzymes involved in purine nucleotide synthesis. The amount of thioinosinic acid formed in L1210 cells was much higher than that in human leukemic leukocytes. In cell extracts, the synthesis of thioinosinic acid was similar in both cell types, and the amount of purine phosphoribosyltransferase was not rate limiting in either case. Much higher concentrations and rates of formation of phosphoribosylpyrophosphate were found in L1210 cells than in human leukemic leukocytes. The difference in response to 6-mercaptopurine between L1210 cells and human leukemic leukocytes might be attributed to their difference in supply of phosphoribosylpyrophosphate. Phosphoribosylpyrophosphate-amidotransferase was found to be high in L1210 cells, but was not detected in human leukemic leukocytes.


Inactivation and inhibition of replication of the enveloped bacteriophage phi6 by fatty acids. The enveloped bacteriophage phi6 has been shown to be an interesting model system for the study of chemical agents that might have specific antiviral effects against lipid-containing mammalian viruses. In this report, we describe two types of antiviral activity exhibited by several fatty acids against bacteriophage phi6. Oleic acid (18:1) and palmitoleic acid (16:1) were potent inactivators of the virus. Treatment with either fatty acid at 50 mug/ml at 25 or 0 degrees C for 30 min reduced the virus titer to about 0.1% of the initial titer. Oleic acid at a concentration as low as 3 mug/ml ( approximately 10(-2) mM) reduced the virus titer to <1% of the initial titer within 30 min. Ultracentrifugation analyses of (14)C-amino acid- and (32)P-labeled virus treated with oleic acid indicated that the virion is largely disassembled by the treatment. Myristic acid (14:0) and palmitic acid (16:0) did not inactivate phi6 at 50 mug/ml, but nevertheless did prevent phi6 plaque production. Single-step virus growth experiments in which fatty acid was added at various times before or after infection indicated that it was an early stage of the phi6 replication cycle that was inhibited by the presence of myristic acid and that the inhibition occurred only if the myristic acid concentration in the extracellular growth medium was greater, similar10 mug/ml. phi6 could attach to its host cell in the presence of myristic acid at 50 mug/ml. We conclude that the fatty acids that prevent phi6 replication probably do so by interfering with the entry of the viral genome into the host cell.


Differentiation of catalases in Mycobacterium phlei on the basis of susceptibility to isoniazid: association with peroxidase and acquired resistance to isoniazid. Mycobacterium phlei contains two catalase activities and a single peroxidase activity. The latter is associated with one of the catalases. The single catalase-peroxidase enzyme accounted for 75% of the total catalase activity and was lost upon acquisition of resistance to the antitubercular drug isoniazid (INH). Heat-treated (68 degrees C) wild-type cells showed similar decreases in catalase activity as well as complete loss of peroxidase activity. Catalase activity in the INH-resistant strain of M. phlei (Inh(r)) was unaffected by heating. The heat-sensitive catalase of the wild-type M. phlei was completely inhibited by 0.1 M INH, and Cu(2+) enhanced this inhibitory effect by 100-fold. No inhibition of activity was found with the heat-stable enzyme. Equivalent inhibition of catalase was also observed with nicotinic acid hydrazide and benzoic acid hydrazide. Peroxidase activity was also completely inhibited by any one of the three hydrazides, either INH, benzoic acid hydrazide, or nicotinic acid hydrazide at 10(-3) M. The presence of two catalase activities and the loss of one (catalase-peroxidase) on acquiring INH resistance or heating wild-type cells was confirmed by acrylamide gel electrophoresis of the cell-free extracts.


Effect of aminoglycosides on the chemotactic response of human polymorphonuclear leukocytes. Leukocyte chemotaxis was inhibited 9.6% compared with control in the presence of 10 mug of gentamicin per ml and 10.5% when exposed to 20 mug of amikacin per ml. However, cells incubated with an injectable form of gentamicin, containing preservatives, were inhibited an additional 25.8% relative to cells incubated with pure gentamicin.


Antibiotic resistance patterns of metal-tolerant bacteria isolated from an estuary. Estuarine bacteria isolated on metal-containing media were also found to be antibiotic resistant; ampicillin and chloramphenicol were the antibiotics to which resistance was most common. Patterns of antibiotic resistance were found associated with a variety of taxa.


Gentamicin and tobramycin penetration into synovial fluid. The penetration of gentamicin and tobramycin into the synovial fluid of 12 patients with nontraumatic joint effusions was studied. Simultaneous serum and synovial fluid specimens taken after the intramuscular or intravenous administration of an antimicrobial agent were assayed. Synovial fluid levels of antibiotic were >50% of serum levels in all subjects studied. In five patients, synovial fluid levels were equal to or exceeded simultaneous serum values. These results suggest that intra-articular injection of aminoglycoside antibiotics is not necessary in the treatment of infectious arthritis.


Discrepant results of amphotericin B assays on fresh versus frozen serum samples. Amphotericin B assays on frozen serum samples (-20 degrees C) generally underestimate the serum levels obtained on promptly processed samples. The degree of the discrepancy is variable and independent of the length of time stored.


Anaerobic wound infections in cancer patients: comparative trial of clindamycin, tinidazole, and doxycycline. Clindamycin, tinidazole (a parent compound to metronidazole), and doxycycline were compared in vitro against 376 anaerobic bacteria isolated from clinical specimens. Bacteriostatic tests indicated that clindamycin was the most active drug, on a weight basis, against these strains except for Clostridium species. The three drugs were compared as therapies for anaerobic wound infections in cancer patients. In a randomized double-blind study, no statistically significant differences between clindamycin and tinidazole could be documented. Doxycycline was less active presumably because of the lack of clinical response in three out of four patients infected with doxycycline-resistant strains. No major untoward effects were observed. The bactericidal dilution of the serum was predictive of the clinical outcome.


Comparison of in vitro antibacterial activity of three oral cephalosporins: cefaclor, cephalexin, and cephradine. Cefaclor, a new oral cephalosporin, was compared in vitro with cephalexin and cephradine against 233 organisms. Evaluations were performed in Mueller-Hinton and nutrient broth and agar using two inoculum sizes. In agar, cefaclor had greater antibacterial activity than either cephalexin or cephradine against isolates of Escherichia coli, Proteus mirabilis, Staphylococcus aureus, Klebsiella pneumoniae, and Salmonella typhi. All three drugs were relatively inactive against isolates of enterococci, Enterobacter species, and indole-positive Proteus. Cefaclor, however, did exhibit the greatest activity of the three antibiotics against these organisms. Although there was wide variability with respect to test parameters, the broth results generally paralleled the agar results. In nutrient broth a clear separation of the results with these three cephalosporins was seen with K. pneumoniae, E. coli, and S. typhi. Cefaclor was the most active, cephalexin had intermediate activity, and cephradine was the least active. From the data obtained in this in vitro study, it can be concluded that cefaclor, which has a substituted chloro group attached to the molecule, had increased antibacterial activity over cephalexin and cephradine. Comparative clinical trials with cefaclor will determine whether the differences outlined above are of clinical significance.


Systemic metabolic alterations associated with repeated injections of a modified polyriboinosinic-polyribocytidylic acid complex. Polyriboinosinic acid-polyribocytidylic acid complexed with poly-1-lysine and injected intramuscularly into rats (0.3 or 3.0 mg/kg) produced fever, altered leukocyte count, slightly depressed plasma zinc, increased amino acid uptake into liver, and increased plasma acute-phase globulins two- to threefold. It is suggested that these systemic metabolic alterations are indicative of a mild inflammatory response to this drug. The metabolic alterations may have to be taken into consideration when polyriboinosinic acid-polyribocytidylic acid complexed with poly-1-lysine is used in therapy.


Gentamicin intravenous infusion rate: effect on interstitial fluid concentration. To assess the possible role of intravenous (i.v.) infusion rate as a determinant of degree and rate of interstitial fluid penetration, six rabbits, each with four intraperitoneal implanted capsules, were studied by crossover design after a single dose of 1.7 mg of gentamicin per kg by either slow 2.5-min i.v. bolus or 30 min i.v. infusion. The mean serum peak antibiotic level after slow bolus was 17.4 mug/ml. After 30 min of infusion, mean serum peak was 8.3 mug/ml (P < 0.025). Mean capsule fluid antibiotic levels at 30 min, 1, and 2 h were 0.9 mug/ml, 1.6 mug/ml, and 1.8 mug/ml, respectively, after slow bolus and 0.6 mug/ml, 0.9 mug/ml, and 1.3 mug/ml after 30-min infusion (P < 0.05 at 30 min, P < 0.001 at 1 h, and P < 0.05 at 2 h). Comparison of capsule levels beyond 2 h revealed no significant differences, and peak capsular concentrations achieved by the two methods were similar. Slow 2.5-min i.v. bolus administration of gentamicin established higher interstitial fluid levels during the first 2 h of therapy and may be the preferred mode of delivery when rapid extravascular penetration is desired.


In vitro activities of five oral cephalosporins against aerobic pathogenic bacteria. Cefaclor (Lilly 99638) and cefatrizine (BL-S640, SK&F 70771) are orally absorbed, broad-spectrum semisynthetic cephalosporins. They were compared in vitro with cephalexin, cephaloglycin, and cepharadine against a variety of aerobic pathogenic bacteria by an agar dilution procedure. Cefaclor and cefatrizine were found to be similar or superior to cephalexin, cephaloglycin, and cephradine in terms of activity against gram-positive cocci other than enterococci. Only cefatrizine demonstrated any potentially useful activity against some susceptible isolates of enterococci. Cefaclor and cefatrizine also were highly active, equally or more so than the other oral cephalosporins, against several gram-negative species including Escherichia coli, Enterobacter aerogenes, and Klebsiella pneumoniae. None of the cephalosporins were particularly active against Enterobacter cloacae. Both cefaclor and cefatrizine were active against Proteus mirabilis; cefatrizine was uniquely active against indolepositive Proteus species.


Lack of effect of methenamine in suppression of, or prophylaxis against, chronic urinary infection. Methenamine is frequently prescribed for patients who have chronic urinary infection to suppress bacterial growth during active infection or to prevent recurrence once an infection has been brought under control. We have examined the effect of methenamine mandelate and ascorbic acid on bacteriuria in para- and quadriplegics from a spinal cord unit. Patients with indwelling urinary catheters and those on a program of intermittent catheterization were included. No suppressive or prophylactic effect of this regimen was observed in any of our patients. Methenamine does not appear to be an effective antimicrobial agent in subjects who have an indwelling urinary catheter or in patients with spinal cord injury who are on intermittent catheterization. Since there appears to be reason to question the efficacy of methenamine in situations in which it is usually prescribed, evidence should be sought for a therapeutic effect in other cases. If no benefit is observed, the drug should not be used.


Bacterial flora of the sea urchin Echinus esculentus. A total of 85 isolates of mesophilic, aerobic, heterotrophic bacteria were isolated from the gut, peristomial membrane, and coelomic fluid from specimens of the sea urchin Echinus esculentus from the Clyde Sea area of Scotland. These isolates were compared with 26 isolates from sand and seawater in the same locality. Overall, strains of Pseudomonas and Vibrio predominated. Gut (with an average bacterial viable count of 2 X 10(7) per 3-cm section) and coelomic fluid (which was often sterile and rarely had more than 40 bacteria per ml) had similar distributions of genera, with Vibrio predominating and Pseudomonas and Aeromonas next in abundance. In contrast, the flora of the peristomial membrane (with an average count of detachable bacteria of 2.5 X 10(5) per membrane) resembled that of sand/seawater in having Pseudomonas predominating, gram-positive forms or Vibrio next in abundance, and smaller numbers of Aeromonas, Flavobacterium, Acinetobacter, and Moraxella.