Life-threatening hyperkalemia induced by arginine.

Marked hyperkalemia was observed during and immediately after an infusion of arginine monohydrochloride in two patients with severe hepatic disease and moderate renal insufficiency. Both patients had received brief courses of spironolactone before arginine treatment. In one of the patients, the hyperkalemia was associated with a fatal cardiac arrhythmia. Arginine has been shown to shift potassium from cells to the extracellular compartment, an effect directly related to its serum concentration. The profound hyperkalemia that occurred in these two patients is thought to be the result of an inability to metabolize the administered arginine and excrete the excess extracellular potassium. Caution is advised in administering arginine to patients with renal or hepatic insufficiency, or both.


Goodpasture's syndrome: diagnosis by transbronchial lung biopsy.

A 28-year-old man developed recurrent hemoptyses, breathlessness, anemia, and bilateral pulmonary infiltrates after mild smoke inhalation. He had no laboratory evidence of kidney involvement. Transbronchial lung biopsy showed erythrocytes, iron-containing macrophages within alveolar spaces, normal basement membranes, and strongly positive linear staining of alveolar septa for immunoglobulin G (IgG). Serum antiglomerular basement-membrane antibody was strongly positive by radioimmunoassay. Kidney biopsy showed normal findings by light and electron microscopy but strongly positive linear staining of glomerular capillaries for IgG. Follow-up 9 months later while the patient was taking prednisone revealed no clinical evidence of pulmonary or renal disease. This case shows that immunopathologic study of transbronchial lung biopsies is helpful in differentiating between Goodpasture's syndrome and idiopathic pulmonary hemosiderosis, while the absence of clinical and microscopic evidence of kidney disease does not exclude Goodpasture's syndrome.


Primary amyloidosis associated with Gaucher's disease.

Elevations in serum immunoglobulins, frequently monoclonal in nature, are known to occur in patients with the adult form of Gaucher's disease. We describe amyloidosis in a 46-year-old woman of Italian ancestry with Gaucher's disease, who also had 3100 mg/dl of monoclonal IgA. She died of restrictive cardiac disease. A 50-year-old sister, also with Gaucher's disease, had 1300 mg/dl of polyclonal IgM but no evidence of amyloidosis. A glucosyl sphingosine-Sepharose affinity column provided no evidence that the large amount of immunoglobulin present has specific affinity for glucosyl ceramide. This, to our knowledge, is the first report of amyloidosis complicating Gaucher's disease.


Influenza vaccine: recommendation of the Public Health Service Advisory Committee on Immunization Practices.

Influenza vaccine for 1978--79 will consist of inactivated trivalent preparations of antigens of influenza viruses expected to be prevalent. Alternative vaccine formulations will be available for different age groups. Annual vaccination is recommended for persons at greatest risk: chronically ill adults and children, and those over 65. Current influenza virus vaccine has been associated with few side effects, but three types of systemic reactions have been described. Pregnant women do not appear to have any special risk from influenza vaccination; physicians evaluating them should use the same criteria applied to other persons.


Hairy cell leukemia: a clinical review based on 71 cases.

We studied the clinical and laboratory characteristics of 71 patients with hairy cell leukemia to ascertain whether prognostic factors important for the therapy of the disease existed. Granulocytopenia of less than 500/mu 1 was associated with the occurrence of a serious infection in 46% of the patients, compared to 19% of patients whose absolute granulocyte count was greater than 500/mu 1 (P less than 0.05). In most patients with symptoms of thrombocytopenia or leukopenia, splenectomy led to improved blood counts. Patients treated with splenectomy only had a significantly longer survival than those treated with steroids only (P less than 0.05). A group of patients who were slightly older and had minimal splenomegaly and few hairy cells in the peripheral blood did well without therapeutic intervention. Twenty-four patients have died, 16 of an infectious process. The actuarial survival for the group is 51% at 4 years, and there has been no change subsequently.


Intravenous antibiotic therapy at home.

During a 12-month period, 23 patients aged 12 to 78 years were treated for 8 to 40 days (mean, 23 days) at home with intravenous (i.v.) antibiotics. Diseases treated included bone and joint infection (14 patients), blastomycosis (two), actinomycosis (two), staphylococcal bacteremia (two), endocarditis (two), and candidal pyelonephritis (one). After initial in-hospital training, patients self-administered their drugs through a heparin-lock i.v. cannula, which was changed regularly by a visiting home care nurse. Antibiotics administered included cloxacillin, penicillin G, cephalosporins, gentamicin, carbenicillin, and amphotericin B. Patient and family acceptance of the program was good, the program was therapeutically effective, and, apart from a decreased prevalence of phlebitis with the heparin lock at home, side effects were no different from those of in-hospital-treated patients. The cost of home therapy was $ 40 per patient-day compared with an estimated $ 137 had the patients remained in hospital. Most patients were able to resume normal activities while receiving home i.v. therapy.


National study of internal medicine manpower: II. A typology of residency training programs in internal medicine.

This second paper of the National Study of Internal Medicine Manpower describes the differing environments of residency training programs. Using previous studies as prototypes, the authors apply factor analysis to data from questionnaires returned by residency training directors and residents to illustrate the myriad interrelations within training programs. The most important result of this study is the demonstration that the largest residency programs have the most subspecialty programs, and their residents are more likely to pursue subspecialty fellowships after completing their third residency year. However, preliminary findings show no associations between the typology (typologic categories of residencies and their trainees) used and desired practice locations in states having few physicians relative to the population or in states with fewer urban inhabitants. The typology also does not predict the future practice aspirations of residents who are more likely to care for the poor or minority populations. A separate set of factors, possibly unrelated to training environments, will help to predict such career outcomes. Further specification of these factors will be the subject of a later paper in this series.


Common infections in ambulatory patients.

Most illnesses in ambulatory patients are infections; most of these are upper, middle, or pararespiratory infections. Although these diseases are rarely serious, they result in immense amounts of time lost from work and incalculable expense for over-the-counter medications. Guidelines for antibiotic and other drug therapy for these diseases need a better scientific foundation.


Effect of infections on hospital care.

To determine research priorities in infectious diseases, the impact of infections on hospital care in the United States is estimated from the number of infectious diseases observed in hospitals that cooperate with the Center for Disease Control in surveillance of community-acquired and nosocomial infections. Each year, over 3 million community-acquired infections require persons to be hospitalized, and over 2 million nosocomial infections are acquired. Approximately 90% of the infections treated in hospitals are bacterial. These infections account for an estimated 29 million days of acute hospital care, which is approximately 10% of the patient days in United States acute-care hospitals. The direct hospitalization costs for treating infectious diseases are estimated to be over $4.8 billion. Treatment of infectious diseases accounts for a major portion of hospital care in the United States.


Septicemia and nosocomial infections in a community hospital.

Data on the incidence of community-acquired and nosocomial septicemia, on the incidence and distribution of nosocomial infections, and on the additional hospital costs due to nosocomial infections are shown to be different in a community teaching hospital from data in university, federal, or country hospitals. Incidence of septicemia and nosocomial infection varies in direct relation to the underlying disease categories "nonfatal," "ultimately fatal," and "rapidly fatal." Patient population mixes of these underlying disease categories are different between community and noncommunity hospitals. These differences can account for the reported difference in incidence of septicemia and nosocomial infections between such hospitals. National extrapolation of incidence data must take these differences into account.


Infectious diseases in small hospitals. Prevalence of infections and adequacy of microbiology services.

In a 1-day prevalence survey nosocomial infections were found in 7.2% and community acquired infections in 20.4% of 525 patients hospitalized in 18 small hospitals. Pneumonia was the reason for admission in 11% of patients in small hospitals. The patterns of nosocomial infections and antibiotic usage in small hospitals are similar to those found in large hospitals. The adequacy of bacteriologic services was assessed using a process audit technique. The routine approach to common bacteriologic specimens and antibiotic disk susceptibility tests was frequently inadequate. Approaches used in large hospitals for the control of nosocomial infection and the performance of bacteriology tests were not practical for most small hospitals. Specific research into methods for doing clinically adequate bacteriology and approaches for the control of nosocomial infection in the small hospital setting are needed.


Infections related to medical devices.

Medical devices have become an integral part of hospital-based care but also predispose patients to more than 850 000 device-related infections annually. Devices predispose to infection by damaging or invading epithelial and mucosal barriers to infection, by supporting growth of microorganisms and thus serving as reservoirs, by impeding host defense mechanisms, and, when contaminated, by directly infecting patients. Epidemics of device-related infections appear to have increased in frequency since 1965, have been due mainly to gram-negative bacilli, usually have resulted from in-hospital contamination of devices, and most often have been linked to urinary catheters, intravenous infusion devices, hemodialysis, and respiratory therapy equipment. Endemic device-related infections include those traced to these same commonly used medical devices as well as infections that follow use of specialized devices such as prostheses. Urinary catheters and intravenous infusion devices represent major sources of nosocomial septicemia. In most instances, measures currently recommended to control device-related infections have not be assessed with respect to either efficacy or practicality, and further study of the pathogenesis and prevention of these infections is needed.


Prevention of surgical wound infection.

Operative wound infection is examined through classifications based on estimation of frequency, severity, and sources of infection. These classifications help in identifying preventive and corrective measures. All surgeons are concerned with postoperative infection because it can convert a superior technical result into a disaster. The analysis of postoperative infection is complicated by the complex and constantly changing relations among host, challenging microbe, and the existing antimicrobial measures. The effect of physical, pharmacologic, and biological variables is estimated with emphasis on measures that promise further control of infection in the surgical patient. Proposals are offered for further efforts in controlling this hazard.


Hospital infections: gynecologic, obstetric, and perinatal infections.

Increased perinatal use of invasive monitoring techniques and a higher rate of cesarean section have led to an increase in the rate of maternal infection and to new types of infections in newborns. Control measures for maternal infections include antibiotic prophylaxis, direct administration of antibiotics to the amniotic fluid, extraperitoneal cesarean section, and cesarean hysterectomy. New types of infections in newborns include abscess resulting from use of electrodes to monitor fetal heart rate and the development of group B beta hemolytic streptococci infection, particularly in association with prolonged rupture of maternal membranes. Prospective studies are needed of preventive measures and proper management of maternal and perinatal infections. Obstetric and gynecologic problems that need further investigation include pelvic infection after vaginal hysterectomy, salpingooophoritis, and antibiotic dosages for pregnant women.


What should the clinician expect from the microbiology laboratory?

Many physicians do not know what they should expect from the microbiology laboratoy. What physicians need from the microbiology laboratory varies according to type of patient and type of physician. The laboratory should provide information that will affect clinical management guidelines for obtaining specimens, microbial identification, antimicrobial susceptibilities, rapid collection of material, and reporting of data and educational updating. Data are needed to establish how the physician responds to microbiologic reports.


Constraints under which the microbiology laboratory functions.

The relevance, usefulness, quality, and cost of performance of many clinical microbiology laboratories have been questioned. Major, common constraints under which most microbiology laboratories operate in the United States include lack of trained manpower, wide variation in the level and sophistication of clinical microbiology service, lack of physician-laboratory communication and interaction, inadequacies in medical education, and often inadequate laboratory space. Governmental regulations, requirements, and standards have improved the quality of many laboratories' work, but also result in greatly increased costs, excesses of often trivial procedures, and diversion of trained manpower from clinical service to regulatory procedures, with a resulting increase in manpower needs. The usefulness, relevance, and cost of regulatory requirements and procedures are unknown. Lack of reliable, standardized reagents impedes utilization of rapid and low cost procedures, and proliferation of complex tests results in costly additional demands on existing manpower.


The laboratory microbiologist in clinical medicine.

Laboratory microbiology provides to clinicians caring for patients with infectious diseases objective data regarding etiologic agent identification and antimicrobial susceptibility. Mutual communication is essential to ensure appropriate selection of materials for culture, prompt collection and transport, and efficacious handling in the laboratory. Training programs for physicians and clinical scientists are too few in number and are in need of expansion. Program in pathology and postdoctoral programs must emphasize clinical and laboratory experience so that communication can be improved.


Magnitude of antibiotic use.

Trends in antibiotic prescribing can be examined by a review of data from dispensed prescriptions and from antibiotic certification records of the Food and Drug Administration (FDA). Prescription data on selected oral antibiotics and anti-infectives were obtained from IMS America's National Prescription Audit. Data compiled between 1965 and 1977 show increasing use until 1973--with a plateau thereafter--for antibiotics judged by physicians to be relatively "safe," namely, the erythromycins, ampicillin and other penicillins, and the cephalosporins. Tetracycline use, although rising until 1973, declined somewhat thereafter, perhaps because of increasing concern with dental staining in children. Sulfonamide use has declined steadily since 1965, presumably for safety reasons. Used of clindamycin was nearing a level similar to that of cephalosporin use until 1975, when its risk of precipitating severe colitis, including pseudomembranous colitis, became well-known. The FDA's antibiotic certification records show that the volume of injectable cephalosporins and gentamicin administered has increased steadily and as of 1977 was still rising.


Hospital use of antimicrobial drugs. Survey at 19 hospitals and results of antimicrobial control program.

Costs and use of antimicrobial agents in 1976 at 19 hospitals were surveyed by review of pharmacy records. Total costs of antimicrobial drugs at individual hospitals ranged from $0.65 to $1.75 per patient day and accounted for 16% to 41% of total pharmacy drug costs. There was marked variation among hospitals in use of specific antimicrobial agents, especially cephalosporins and clindamycin. The cephalosporin and aminoglycoside antibiotics accounted for 66% of the total cost of antimicrobial agents. An 18-month antimicrobial drug control program at one hospital decreased antimicrobial drug costs by 31%. The major effect was in reducing cephalosporin use. The results of the control program document that a significant portion of hospital antimicrobial use is inappropriate and can be eliminated without apparent detriment to patient care.


Surveillance of antibiotic prescribing in office practice.

Using fiscal and administrative data routinely collected by the Tennessee Medicaid program, we conducted epidemiologic analyses of physicians' prescribing of selected antibiotics in office practice. This research has defined several subgroups of physicians who regularly malprescribed chloramphenicol or tetracyclines (to children less than 8 years old). After special educational mailings to all physicians, prescribing of these antimicrobial drugs diminished. Similar analyses could enable the profession to design specific remedial educational interventions, target them at physicians needing contemporary information, and assess their impact by monitoring subsequent prescribing. Such a program might diminish inappropriate drug use, reduce adverse drug reactions, help contain medical care costs, and produce better educated physicians.


Problem of antibiotic usage. Definitions, causes, and proposed solutions.

Standardized surveillance methods are needed in order to obtain valid comparison among institutions concerning use of antimicrobial agents. These include use of data from the hospital pharmacy and review of routine orders for propolyaxis in surgery and for specific infectious diseases. Audits of individual agents should be based on standardized guidelines for use. Attempts to improve the quality of use of antimicrobial agents require understanding of the constraints of medical practice that effect use of drugs to solve problems. These include the practice setting, cost and availability of laboratory support, and patient expectation. Promotion by the pharmaceutical industry capitalizes on the motivation of the physician to help his patient, often in setting in which diagnosis and management are uncertain. Promotion is a continuous process beginning early in medical school and extending to the media and university teaching staffs. The overall solution to inappropriate antibiotic use requires more than educational programs. There should also be a well-structured hospital program regulating pharmaceutical representatives, the formulary, antimicrobial susceptibility tests, justification for  high-cost agents, and development of mutually agreed on guidelines for use.


Manpower resources for research.

Several trends in medical education affect our supply of future physicians. The number of new physicians has increased so that each year there is an excess of about 6000 over the number of physicians produced per year a decade ago. Increasing numbers of women and members of minority groups are entering the profession as well. These new students are being subjected to increased social pressures to elect primary-care careers, and although there is ample evidence that a significant portion will continue to choose subspecialty careers, fewer of them may be interested in traditional academic and research careers. We must make academic and research careers sufficiently attractive so that an adequate manpower resource of physicians is maintained for the future. This can be done by improving the structure of training programs and by fostering research opportunities for young investigators.


Physician manpower needs and research training in infectious diseases.

As a result of recent and continuing studies of internal medicine manpower, data are now becoming available on training and manpower, data are now becoming available on training and manpower in infectious diseases. In 1976-1977, there were 121 training programs graduating a total of about 180 infectious disease specialists each year. Most funding for these fellowship programs comes from the federal government and hospital revenues. It is conservatively estimated that 2300 medical subspecialists in infectious diseases will be practicing in 1986-1987. About 55% of graduates of infectious diseases training programs plan careers in academic medicine. Information from manpower studies should be of value in the development of a national policy on the training of infectious disease specialists.


Training and certification of clinical microbiologists.

Microbiologists are being effectively absorbed into the labor market. As a group they have a considerably lower unemployment rate (1.2%) than the national average. This is also applicable to medical and clinical microbiologists. Certification of microbiologists by nationally recognized certifying organizations is standardized for those with bachelor's or master's degrees. For those with doctorate degrees there are inconsistencies of postdoctoral training requirements and of reciprocal recognition of the two major certifying organizations. Bilateral reciprocal recognition of board-certified doctoral-level microbiologists is vital for meeting manpower needs. Improved and equitable certification could be achieved by maintaining an adequate number of funded, approved training programs in medical and clinical microbiology and augmenting them with uniform continuing medical education programs designed to meet the requirements for periodic recertification.


Training needs of the infection control nurse.

To provide adequate numbers of infection control nurses the following areas need attention: an established curriculum for formal education, policies that will assure implementation of infection control practices, and surveillance and research to establish that current infection control practices work.


How is the medical student being trained in microbiology and infections?

Reduction in curriculum time and shifts in interests of microbiology and epidemiology departments have altered the nature of the exposure of medical students to clinical problems of microbiology and infectious diseases. Major objectives of training in microbiology and infectious diseases are poorly met because of the large mass of material the student needs to assimilate. Students graduate from medical school using antimicrobial agents as a substitute for diagnostic acumen, without an understanding of how microbiologic laboratories should be used. Methods to improve this situation should be studied.


An overview of public policy and infectious diseases.

Major problems face this nation's health care system; infectious disease and their management are a major and growing part of these problems. It is clear from available information that 40 years after the introduction of the sulfonamides, infection and its management remain an enormously important cause of morbidity and mortality. We are far from being in the "post-infectious-disease era." Unless society and the medical profession understand this and take vigorous remedial steps, our problems may intensify, despite the availability of a remarkable effective group of therapeutic agents.


Clinical investigators and the pharmaceutical industry.

Virtually all new drugs are introduced, evaluated, and marketed under the control of the pharmaceutical industry and general supervision of the Food and Drug Administration (FDA). The clinical investigator must look to the pharmaceutical industry for support of studies of drugs, and the industry, in turn, needs the investigator to evaluate agents before FDA approval and to present findings in the medical media. A survey of members of the infectious Disease Society of America has shown heavy dependence on the pharmaceutical industry for support of applied studies of antibacterial and other chemotherapeutic agents. More than half the respondents believed that industry support was essential, about one third felt it was useful, and about one quarter would prefer other sources of support. Several proposals are presented to clarify the relations between investigators and the pharmaceutical industry and to provide for a broad-based clinical infectious disease consortium to provide research funds and plan educational programs in the field of infectious disease.


Issues in human experimentation.

The current status of two difficult and controversial issues--confidentiality of preliminary results of clinical studies and compensation for research-related injuries--is outlined. The principle of not publicizing results of clinical research until enough data have been accumulated to give statistically valid support for conclusions is in conflict with the principle of ready availability to the public of results of government-conducted and government-sponsored research. New legislation may be required to resolve the problem. The lack of a mechanism to compensate research subjects for unanticipated injuries that are not the result of negligence is a barrier to obtaining truly informed consent. A plan for overcoming this problem through Department of Health, Education, and Welfare regulations has been proposed and awaits implementation.


Infectious disease problems in pediatrics that need investigation.

The opinions of 28 investigators representing all areas of pediatric infectious diseases were sought regarding priorities for research. Seven general areas were most commonly emphasized: new diagnostic methods (especially for viral infections), vaccines (bacterial, respiratory viruses, herpesviruses, and varicella-zoster), diarrhea (pathogenesis), National Institutes of Health (NIH)-sponsored studies of antimicrobial agents, NIH-sponsored cooperative studies of uncommon infections, host factors related to susceptibility and resistance and host responses to infection, and studies of bacterial-viral interaction and mechanisms of antimicrobial resistance. Where pediatric and adult medicine interests overlap, collaborative studies would be desirable.


Problems that merit investigation in clinical microbiology laboratories.

Research is needed in the following areas in clinical microbiology: specimen collection, microbial identification, automation and instrumentation, rapid microbial diagnoses, microbial metabolism, computerization, relevance and laboratory utilization, physician influence, training in clinical microbiology, media and reagents, quality control, and antimicrobial susceptibility and assay determinations. For optimal progress in many of these categories, federal funding should be made available.


The kidney in progressive systemic sclerosis: a prospective study.

Nine normotensive progressive systemic sclerosis patients with normal renal function underwent renal biopsy. Four specimens had prominent vascular abnormalities, two mild vascular abnormalities, and three were normal. Vascular deposits of C3 were present in all specimens. Plasma renin activity was elevated in three of four patients with prominent vascular abnormalities, one of two patients with mild vascular lesions, and none of two patients with normal biopsies. Plasma renin activity elevation in response to cold pressor testing in the four patients with prominent vascular lesions was 5.6 ng/ml.h compared to 0.55 ng/ml.h in those with mild or no lesions and 0.26 ng/ml.h in six control subjects. These data indicate that renal vascular lesions may be present in normotensive patients. Elevation or a substantial rise in plasma renin activity (1.8 ng/ml.h or greater) in response to cold pressor testing suggests preclinical renal involvement.


Sequential carcinoembryonic antigen levels in the therapy of metastatic breast cancer: a predictor and monitor of response and relapse.

Serial measurements of plasma carcinoembryonic antigen (CEA) levels were analyzed in 42 patients with advanced breast cancer undergoing systemic chemotherapy. Pretreatment CEA levels exceeded 5 ng/ml in 22 patients, and 19 of 22 serial assays uniformly heralded tumor regression as well as subsequent tumor relapse. A significant quantitative alteration in CEA levels was established as a minimum change of 20% within 8 weeks of therapy. In 13 of 15 patients responding to chemotherapy and in all patients with CEA levels higher than 35 ng/ml, this criterion was not abrogated, and there were no discordant observations. Rising CEA levels were correlated with subsequent progression of disease in all patients with elevated baseline levels at a minimum of 8 weeks before the progression was clinically evident. In advanced breast cancer the effectiveness of therapy and the development of tumor resistance may be monitored by serial plasma CEA levels, and specific quantitative criteria should be applied.


The syndrome of basal encephalocele and hypothalamic-pituitary dysfunction.

We documented hypothalamic-pituitary dysfunction in three patients with congenital herniation of the brain through the base of the skull (basal encephalocele). All had growth hormone deficiency, although one has attained normal height. One had diabetes insipidus. Two had hypogonadotropic hypogonadism. Prolactin secretion was elevated in one, normal in another, and borderline low in the third. Two patients were euthyroid, but in response to thyrotropin-releasing hormone (TRH) injection, one patient's thyrotropin (TSH) level increased to levels exceeding normal while the other's did not attain normal levels. In the third patient, TSH response to TRH went from subnormal to normal after treatment with growth hormone and thyroxine. No patient had evidence of ACTH deficiency. These heterogeneous findings do not permit assignment of an unequivocal anatomic or functional site to the endocrine defect(s). Pituitary function should be evaluated in all patients with basal encephalocele, and this entity should be considered in the differential diagnosis of central endocrine malfunction.


Articular manifestations of rheumatic fever in adults.

Six adult patients had a syndrome indistinguishable from childhood rheumatic fever, with few cardiac findings and an arthrutis that had a characteristic pattern. The joint disease was abrupt in onset, rapidly additive, and eventually symmetrical, with a lower-extremity, large-joint predominance and a profoundly symptomatic tenosynovitis. Emphasizing the benign prognosis associated with a lack of heart disease and a "typical" pattern of articular involvement, we have reassessed the sensitivity of the traditional diagnostic Jones' criteria and suggest that this syndrome in adults may be more properly termed "poststreptococcal arthritis."


Resolution of muscle calcification in rhabdomyolysis and acute renal failure.

We studied four patients with acute renal failure associated with nontraumatic rhabdomyolysis to evaluate the presence and progression of calcium deposits in damaged muscle tissue. Conventional and electron radiography and technetium-99m diphosphonate (TcDP) scans were done during the oliguric phase of acute renal failure and repeated after renal function returned to normal. Three patients showed deposits of calcium by conventional radiography and all by electron radiography and TcDP during the oliguric period. When the patients recovered renal function and muscle injuries healed, calcium deposits disappeared. The results show that calcium deposits in damaged muscle occur during the oliguric phase of acute renal failure due to rhabdomyolysis and the calcification disappears with recovery of renal failure; and TcDP scans are the most sensitive method of detecting calcium deposits in these patients.


[The infraclinical diagnosis of lead poisoning (author's transl)].

Laboratory study of 16 workers handling lead made it possible to define a state of infraclinical lead poisoning. Estimation of alpha-dehydrase and of free erythrocytic protoporphyrins is the most sensitive test for diagnostic purposes. The estimation of erythrocytic pyrimidine 5' Nucleotidase would seem to be of value in the diagnosis of mild lead poisoning. The urinary lead tolerance test confirms the diagnosis and indicates the degree of intoxication. Its repetition make it possible to treat the intoxication.


[Epidemiologic investigation about 23 cases of lead poisoning due to industrial cider (author's transl)].

We reported 23 cases of lead poisoning due to industrial cider being contaminated during its fabrication, this being caused by the detergents used to clean the piping. Microscopic examination of the stippled erythrocyte is not effective. On the other hand the elevation of protoporphyrines erythrocyte remains constant, and this is the most honest, long standing sign of lead poisoning. There is certainly the cumulative effect of toxication but it is the acute increase by ingestion above a certain limit (between 3 and 10 mg of lead daily according to the individual) wich provokes clinical signs and symptoms.


[Difficulty in manual prehension under visual control (author's transl)].

Visuomotor ataxia causes difficulty in the prehension of objects under visual control which can occur without paralysis of ocular fixation and spatial agnosia. This can involve the total visual field or the right or left half-fields, and can affect both hands or one only. 1) Unilateral visuomotor ataxia is localized to the two right or left homonymous half-fields and can affect both hands or one only. It is direct when the ataxic hand is on the same side as the affected visual half-field, and crossed when the ataxic hand is contralateral to the affected visual half-field. 2) Bilateral visuomotor ataxia involves the total visual field. Each hand may be ataxic only for the contralateral visual field with a crossed bilateral visuomotor ataxia, or in the homolateral field with a direct bilateral visuomotor ataxia. The anatomical and clinical observations reported imply the existence of visuomotor connections, both direct and crossed, the latter crossing the median line through the corpus callosum.


[Aspect of the prisoner's psychological universe].

This paper deals with an aspect of inmate's psychology. One of us is consultant psychiatrist in a jail. According to his experience, the behaviour of the prisoners appears to be very regressive. Inmates chiefly complain of digestive pains. They put a great emphasis on food, nourishment and drinking. That regression to the oral phase explains an unconscious will of staying in jail: It is rather frequent, for example, to see prisoners, who are about to recover their freedom, attempting a ridiculous and futile escape, with, as only result, one more year in jail. Obviously they want, through this absurd acting out, to keep living their childish and regressive way of life.


[Immersion: From mental anorexia to behavioral therapeutics].

The flooding is an extinction process of an emotion or a pulsion through a mechanism of Pavlov of conditioned inhibition. The author does here an experimental study of this process. This study allows to explain the exact flooding mechanism. So we can better understand and better introduce the practical flooding applications in therapeutic as well as in psychopathology.


[Experimental infection in mice with Yersinia enterocolitica (strain biotype 4, serogroup O:3, phage type VIII): growth of the inoculum in athymic or cyclophosphamide treated mice (author's transl)].

Intravenous infection of Swiss mice with a strain of Yersinia enterocolitica unable to colonize normal mice by the oral route, induced a systemic infection. Viable bacteria were isolated from homogenates of liver, spleen and lungs, as early as one hour after the challenge and have been detected during two weeks. On the other hand, the number of viable bacteria isolated from the blood has always been very low. Faecal samples permitted the isolation of Y. enterocolitica even after two weeks, while at this time no more bacteria were isolated from the tissues. The duration of the infection remained unchanged with an inoculum of 10(3), 10(4) or 10(5) viable bacteria. Depending on the size of the inoculum, liver macroscopic abscesses occurred more or less rapidly after the challenge. These abscesses disappeared spontaneously. A single intravenous injection of cyclophosphamide (200 mg/kg) six days after the challenge was followed by an important rise of the number of bacteria in all the tissues. Comparative studies of intravenously infected athymic (Nude) mice and controls showed a higher number of bacteria in the liver and spleen of the athymic animals.


[Phage-typing modifications induced by "in vitro" transfer of R plasmids. I.--Phage typing of Salmonella typhi (author's transl)].

The phage-typing modifications induced by transfer of antibiotic-resistance plasmids wre studied in two S. typhi Vi+ strains: n 2411 (phage-type A) and Ty2 (phage-type E1a). Forty-one R plasmids belonging to twenty-two incompatibility groups were investigated. Twenty-two plasmids were unable to produce any phage typing modifications. Among the groups of plasmids with phage-typing restriction capacity,four (I1, 10.B.O., N and W) groups were found heterogeneous with regard to this property and one (F1 group) caused significant modifications of the phage-types defined by the Vi phage-typing international system.


[Homogeneous suspensions of mycobacteria: application to the evaluation of bactericidal activity (author's transl)].

This work describes a technique of emulsification of mycobacterial cells (including tubercle bacilli) in order to obtain homogeneous suspensions containing up to 10(8) cells/ml. The suspensions are used in a modified AFNOR method for the evaluation of bacterial activity: within five min virulent strains are more resistant than are avirulent ones but, within 30 min and in the presence of proteins, the behaviour of all strains is quite similar.


[Production of a photo-sensitive lipid antibiotic by the marine diatom Chaetoceros lauderi (Ralfs) (author's transl)].

A lipid antibiotic was extracted from whole cells of the marine diatom Chaetoceros lauderi (Ralfs) and roughly identified as an unsaturated fatty acid by thin layer chromatography. A number of Gram-positive terrestrial bacteria and several Gram-negative marine bacilli were sensitive to this antibiotic, whereas Gram-negative enteric bacteria were resistant. Solar irradiation led to its partial disappearance and to the production of more polar antibiotics with a stronger antibacterial activity. This observation is compared to similar data culled from literature, and its significance in a natural environment is discussed.


Large scale purification of hepatitis B surface antigen (HBsAg).

In October 1975, a specific immunization by means of a formalin inactivated hepatitis B vaccine has been introduced to protect patients and staff members of three haemodialysis units of the Loire Valley (Tours, Blois, Orléans). After two years follow-up the innocuity and efficacy of this preparation have been shown to be very satisfactory in the conditions under which it was used. A method of vaccine preparation has been instituted in the development of industrial batches of vaccine to be used for broad clinical trials in France. The HBsAg purification was carried out by four different steps including, successively, selective adsorption-desorption on colloidal silicate (Aerosil), precipitations by polyethylene glycol, gel filtration and finally zonal ultracentrifugation. Step-by-step results of the purification are presented. Up to 65 % of the starting antigen was recovered at the end of the purification process. One dose of vaccine (1 ml) has a titre in HBsAg of 1/4 in countercurrent electrophoresis and a protein amount of 2-10 micron/ml. It contains traces of homologous serum proteins only detectable after high concentration. Purity, antigenic quality and safety of the vaccine are analysed in regards to its use for immunization against hepatitis B in man.


[Arabinose, melibiose and xylose oxidation and fermentation in "Serratia" (author's transl)].

The oxidative and fermentative metabolisms of D(+)raffinose, D(-)arabinose, L(+)arabinose, D(+)melibiose and D(+)xylose were compared in 181 strains belonging to the genus Serratia, including collection strains and clinical isolates from various sources. At 30 degrees C, raffinose was neither fermented nor oxidized by S. marcescens, but was fermented by S. liquefaciens and S. rubidaea. D(-)arabinose was oxidized by all strains. L(+)arabinose, melibiose and xylose were fermented by all S. liquefaciens and S. rubidaea, while they were oxidized by most S. marcescens. Two strains of the latter species, however, were able to ferment xylose. The use of Hugh and Leifson's oxidation-fermentation medium containing melibiose or L(+)arabinose can help to differentiate S. rubidaea from pigmented strains of S. marcescens and to differentiate S. liquefaciens from unpigmented strains of S. marcescens.


Amino acids produced by bifidobacteria and some Clostridia.

A lot of 121 strains of bifidobacteria and 9 strains of clostridia were examined for their ability to release free amino acids in the culture broth. The bifidobacteria studied belong to 18 species or "homology group" and the clostridia to 8 species. The growth in a synthetic medium with ammonium salts as sole nitrogen source was also studied. All the clostridia and the majority of the bifidobacteria produce various amino acids. The possible ecological significance of these findings is suggested.


[Alcohol fermentation: effect of temperature on ethanol accumulation within yeast cells (author's transl)].

During fermentation, yeast growth is rapidly stopped when the concentration of alcohol in the medium increases but fermentive activity is not entirely inhibited until high alcohol concentrations are reached. The rate of alcohol accumulation within the cells and certain kinetic parameters were simultaneously determined in such fermentative processes using Saccharomyces carlsbergensis cells. The growth inhibitory effect of alcohol was related to its retention inside within the cells; i.e. yeast multiplication is stopped when intracellular alcohol concentration reaches a maximum value. Moreover, the higher the temperature, the deeper the inhibitory effect of ethanol and the higher the maximal intracellular alcohol concentration. Activation energy determinations showed that ethanol accumulation within the cells was a consequence of the resistance to its diffusion through the cell wall from within to outside the cell.


[Amoebae in swimming-pools: microbiological and epidemiological aspects (author's transl)].

An inquiry was held to determine the occurrence and quantitative importance of "Limax" amoebae in 8 swimming-pools of the North of France. The influence of water flow system, filters and water disinfectants was studied. The connections with the bacterial flora growing at 37 degrees C and the presence of strains able to grow at 41 degrees were analyzed. The significance of their presence in the swimming-pools is discussed from the obtained results.


Bandage lenses and the use of topical solutions containing preservatives.

Eight patients with severe keratoconjunctivitis sicca and filamentary keratitis requiring treatment with continuous wear bandage lenses and frequent instillation of artificial tears were studied. The lenses were removed after wear from 3 to 8 weeks and subjected to ultraviolet spectrophotometric evaluation for the presence of the preservative, benzalkonium chloride. No evidence of benzalkonium chloride in the lenses was seen and no clinical evidence of corneal damage was noted. The use of topical medication containing benzalkonium chloride as a preservative in conjunction with hydrophilic lens appears to be clinically acceptable.


Ptosis with contralateral lid retraction due to excessive innervation of the levator palpebrae superiorus.

Two patients are presented with unilateral ptosis and contralateral lid retraction. The lid retraction disappears upon manual elevation of the ptotic lid. Each patient with this phenomenon would be expected to have a frank tropia, or monofixation syndrome and prefer to fix with the ptotic eye. Extraordinary innervation is transmitted to the levator of the ptotic eye and, since we believe the levators follow Hering's law, this excessive innervation is also transmitted to the contralateral levator. This results in lid retraction in the second eye. If the ptotic lid is manually elevated, levator innervation decreases and the contralateral lid retraction disappears. This previously unreported maneuver of manually elevating the ptotic lid is superior to patching the ptotic eye for a period of days, the previous method for demonstrating this phenomenon. These considerations are important in the evaluation of lid retraction, and in determining the nature and extent of corrective surgery.


Lathe-cut hydrophilic contact lenses: report of 100 clinical cases.

In a review of the literature, it became apparent that there were very few articles describing the advantages, as well as the fitting techniques, of lathe-cut hydrophilic contact lenses. Few practitioners, including those who fit other types of hydrophilic lenses and hard lenses, have had any experience with this lens, and considerable interest has been generated by fragmentary reports of good results. This paper describes in detail the geometry of the first lathe-cut hydrophilic lens approved by the Federal Drug Administration, the fitting methods utilizing trial lenses, and the results of 100 patients successfully fitted.


Foreign body granuloma of the conjunctiva.

Foreign body granulomas of the conjunctiva of children and deer were studied. The granulomas can develop rapidly and may not be readily diagnosed.


Racial influences in open-angle glaucoma.

Blindness due to glaucoma is much greater in blacks than in whites. Using a computerized diagnostic index we identified more than 1,300 patients being treated for glaucoma in our outpatient clinics. Analysis of this clinic population indicated that open-angle glaucoma is more prevalent among blacks than in whites. They also indicate that open-angle glaucoma occurs at a younger age in the black population. We have very limited data that tend to indicate that open-angle glaucoma is a more severe disease in blacks than in whites; however, this evidence is far from conclusive. Finally, our findings indicate that in our institution we are seeing the full range of the glaucomatous process in the black population and not merely the end-stage disease.


The ultrasound guided 32P test.

The accurate and early diagnosis of intraocular malignant melanoma in eyes with opaque media remains a diagnostic problem. Ultrasonography and the radioactive phosphorus (32P) uptake test have been used separately as modalities for diagnosis of choroidal melanoma. However, their combined use has received limited attention. This report presents our experience in 5 cases with the combined use of a contact B-scan ultrasound unit and a posterior eye probe. In all cases we were able to accurately perform the 32P uptake test with simultaneously ultrasound visualization of the tumor and the probe.


Results of immunosuppressive treatment in Bechçet's disease: report of 55 cases.

The favorable effects of immunosuppressive agents in the treatment of Behçet's disease seems outstanding. Fifty-five cases showed great imporvement in both ocular and extraocular symptoms. Emphasis has been placed on the strengthening effect of the steroids, given in very low dosage. Only a few and unimportant side effects have been observed.


Pars plana vitrectomy in the management of blood-induced glaucoma with vitreous hemorrhage.

Four consecutive cases are reported in which pars plana vitrectomy was used to treat eyes with blood-induced glaucoma complicating vitreous hemorrhage after cataract surgery. Vitrectomy resulted in removal of the posterior reservior of cells and cellular debris and cured the elevated intraocular pressure in 3 eyes. One eye required a second glaucoma procedure and long-term acetazolamide therapy. The excised vitreous was examined microscopically with several techniques, including use of a millipore filter to concentrate the cellular elements combined with a modified Papanicolaou staining technique, routine staining of sections of millipore filters, and routine staining of vitreous processed in a celloidin bag. These techniques showed variable proportions of erythrocytes, erythrocytic debris, free hemoglobin, ghost erythrocytes and macrophages containing erythrocytic debris and hemosiderin.


Early vitrectomy for retained intraocular foreign body.

A retained intraocular foreign body can cause progressive damage to an eye if not removed. Such removal, whether done with a magnet or with a vitrectomy instrument, is often more successful if surgery is not delayed excessively. A two-instrument intraocular approach for resistant foreign bodies can sometimes be avoided in favor of a simpler one-instrument technique if surgery can be performed in the first few weeks.


[Chronic otitis in the one remaining functional ear: therapeutic problems and sequelae (author's transl)].

What should one do when a patient presents with a potentially dangerous chronic otitis, and the other ear is absent? An analysis of such dangerous cases with a cholesteatoma, more especially those with a labyrinthine fistula. Responsibility has to be taken. Medico-legal problems are evoked.


[Some enigmas concerning the pathogenic etiology of certain cases of sudden deafness (author's transl)].

Some facts relating to the numerous uncertainties concerning sudden deafness, which is often attributed to vascular or viral causes without convincing proof. The possible role of a cochlear hydrops, electrolyte disturbances, or rupture of the fenestra. This critical study includes many observations but the list is not exhaustive.


[A case of laryngeal histoplasmosis (author's transl)].

Report on a case of histoplasmosis with laryngeal symptoms only, affecting no other organ, especially the lungs, which is rare. Diagnosis was made by histological identification of the intracellular mycosis without culture. Immunological reactions were positive against American forms whereas the patient had lived in Africa. Healing occurred after intravenous amphotericin.


[Rhinological surgical approach to the nasal ducts (author's transl)].

An obstruction along the nasal duct can be approached and removed by an operation through the nose: Rouge's technique for access to the orifice below the inferior turbinate, incision of the mucosal diaphragms over a sound passed into the nasal duct, insertion of a drainage tube; all under microscopic observation.


[Facial nerve neurinoma masked by otosclerosis (author's transl)].

A case of operation for presumed otosclerosis. Discovery of a neurinoma between the branches of the stapes probably originating from the geniculate. Facial paralysis was not present either before or after the operation which, in fact, was only partial (a more extensive operation was refused later on). A curious F.P. "to cold", 30 years beforehand, recovered without sequelae.


[Recent modifications of Rethi's operation (author's transl)].

Rethi's operation for laryngotracheal stenosis is discussed, together with P. Aboulker's modifications (hollow teflon intralaryngeal tube surrounding a fenestrated tracheal canula, which can be moved rapidly). The tube has been modified and its length can be more easily adjusted. Its extremities are rounded and polished (less risk of trauma), and it has an upper diaphragm which has a temporary action but is very useful for avoiding wrong directions in the first days of use.


[Study of the effectiveness and tolerance of Pevaryl 1 % milk in the treatment of mycoses of the external auditory meatus (author's transl)].

Otomycoses account for approximately 20 % of cases of otitis externa. Often unrecognised, they may be induced by various factors, in particular local antibiotic and corticosteroid therapy. The authors studied the effectiveness and tolerance of Econazole (1 % milk) in the treatment of otomycoses. In each of 30 cases, a bacteriological examination was made before and one week after treatment, the latter consisting of the insertion into the E.A.M. of a wick soaked in Econazole (1 % milk) every night. From a mycological standpoint, the fungus disappeared in all cases. Clinically, in relation to the criteria of assessment, a successful result was recorded in 28 cases out of 30. In 87 % of cases, cure was obtained in less than 2 weeks, and apart from a transient and brief subjective sensation of an increase in certain symptoms (17 %), tolerance was perfect. Econazole (1 % milk) would appear to be the drug of choice in the treatment of otomycoses of the E.A.M., being effective against the fungi usually responsible (Aspergillus niger, fumigatus, flavus, Candida albicans, krusei etc.), as well as having a bactericidal action against Gram + bacteria.


Diagnosis and treatment of carotid body tumors.

The diagnosis and management of carotid body tumors are discussed, including the importance of good arteriography which allows visualization of all major feeding vessels. These include the carotid bulb, internal and external carotid arteries and the often neglected but important vertebral and ascending cervical arteries. Emphasis is placed on the importance of establishing tourniquet control of the common, internal and external carotid arteries. Surgeons removing carotid body tumors should be experienced in arterial wall repair by means of vascular shunts, end-to-end arterial anastomosis, and vein graft replacement of a segment of arterial wall.


Fourth Daniel C. Baker, Jr. memorial lecture. Energy and the larynx.

Review of the logistics of energy supply in animals indicates that the advent of the larynx was part of a response to an earlier energy crisis. It permitted a major increase in the flow of energy available to the organism and became the mechanical control point and rate-limiting factor of the increased inflow. Phylogenetically, a succession of structural innovations steadily enhanced the flow capacity of the larynx and rendered the mechanism more versatile, most recently with the accrual of phonation (in mammals), pressurized closure (in primates and odontocetes), and vocal formants and efficiency (in man). The larynx is thus a marker of the animal's capabilities for energy intake, energy utilization and information emmission and, apparently, of the size and complexity of the brain. Today's energy crises appear to continue those of the past.


Hemangiomas of the head and neck.

Hemangiomas are an interesting group of lesions which affect many anatomical structures of the human body. Interest today is confined to head and neck lesions which can occur in the infant, child or adult. Benign lesions affect the great majority of patients as contrasted to malignant ones. Diagnosis of the superficial lesions is usually made by inspection and palpation while additional diagnostic procedures (radiological studies and surgical exploration) may be indicated in patients with deep lesions.


Clinical correlation of anomalies of the supraglottic larynx with the staged sequence of normal human laryngeal development.

The clinical correlation of the authors' observations on human laryngeal development with existing literature supports the suggestion that earlier concepts, specifically by Frazer, may not be valid. It is further proposed that development of the human larynx may similarly correspond in man to that of the rat. Congenital laryngeal malformations are fundamentally associated with a disturbance of epithelial mesenchymal interactions, particularly related to a premature arrest of the normally vigorous epithelial activity.


Subglottic stenosis of the larynx in the infant and child. Methods of management.

This presentation is a ten-year retrospective study on all patients with proven subglottic stenosis admitted to the Department of Otolaryngology, Hospital for Sick Children, Toronto. Some of these patients have required no treatment, others one or two dilatations of the stenosis only; others tracheotomy only; some tracheotomy plus dilatations; some the Fearon-Cotton operation, and a few who had very extensive stenosis of the larynx and trachea, extensive reparative surgery. In this presentation, the authors describe the different types of management, and the results of treatment are assessed and compared.


Management of subglottic stenosis in infancy and childhood. Review of a consecutive series of cases managed by surgical reconstruction.

The management of mature subglottic stenosis secondary to endotracheal intubation in infancy and childhood remains a controversial issue. If treated similarly to congenital subglottic stenosis by tracheotomy and a "wait-and-see" period then there is a considerably higher mortality and morbidity for the acquired disease compared with the congenital. Eighteen children with severe acquired subglottic stenosis managed by surgical reconstruction are presented; 17 have been successfully extubated. The longest follow-up is 5 1/2 years. No evidence of interference with laryngeal growth is evident.


Management of choanal atresia with the carbon dioxide laser.

Congenital choanal atresia frequently demands immediate recognition in the newborn, and provision of a nasal airway as soon as possible. A variety of techniques are available to correct this problem, but none is entirely satisfactory. Transpalatal procedures are associated with significant morbidity in the newborn, and transnasal microsurgical procedures are less predictable when a thick bony plate is present in the choanal obstruction. Transnasal resection with the CO2 laser has been carried out in seven patients (ten sides), whose ages ranged from 16 hours to 14 years. From this early experience, it appears that the procedure is entirely feasible and convenient. It seems to have significant advantages over conventional microsurgical techniques. Eight out of ten choanae have remained patent for four months or more. A lumen keeper is needed during the immediate postoperative period for at least two to three weeks. The procedure is associated with minimal morbidity.


Hypersensitivity problems in otorhinolaryngology.

The average otolaryngologist is confronted with allergic problems in well over 50% of his patients. It would seem imperative that he either recognize the problem and be able to instigate appropriate therapy himself or refer the patient to someone who can. In the latter case, he should have a basic knowledge which would allow him to evaluate adequately the therapy provided.


Control of road trauma epidemic in Australia.

This lecture discusses initiatives taken by the Road Trauma Committee of the Royal Australasian College of Surgeons to reduce fatality and injury on Australian roads. In 1970 the Road Trauma Committee and the communications media initiated a national campaign in support of legislation for the compulsory wearing of seat belts. Public ignorance and Parliamentary inertia were countered. Victoria became the first State in the Western world to introduce this legislation. All other Australian States followed. Significant and marked reductions in fatality and injury were achieved and have been maintained. Recognising alcohol as the single most important cause of serious road crashes and injuries in Australia, the committee advocated legislation for compulsory blood alcohol tests on all adult road crash casualties. In 1973-74 legislation was enacted in South Australia and Victoria and in 1976 in Queensland. Results show that more than one-quarter of driver casualties have alcohol concentrations above the legal limit of 0.05 g%. Half of these exceed 0.15 g%. On the other hand less than 3% of the general driving population exceed the legal limit. Further advocacy led in 1976 to the enactment of random roadside breath-test legislation in Victoria. The majority of Australian convicted drinking drivers have alcohol-related social problems. A quarter incur reconvictions. The conventional penal approach has failed. At present the Road Trauma Committee is campaigning for compulsory medical assessment of convicted drinking drivers. Reissue of a driving licence would be dependent upon evidence of re-education and/or rehabilitation. Pilot re-education programmes have been shown to lessen recidivism markedly. Prevention of drink-driving behaviour is the major strategy. The tactics entail deterence, improved secondary-school and driver education, and the implementation of a national policy for control of alcohol abuse.


The evaluation of emergency care. Development of a quantitative criterion.

A method based on comparing proportions of immediate and later deaths has been used in a retrospective study of fatal road traffic accidents occurring in North Yorkshire from January 1974 to July 1976. The method enables comparative data to be expressed in terms of a care index based on morbidity distribution as indicated by the ratio of immediate to later deaths. Using this method the general practitioner scheme in operation in North Yorkshire appears to give a higher standard of emergency care than elsewhere in the county.


Evaluation of randomized preoperative and postoperative radiation therapy for supraglottic carcinoma. Preliminary report.

One hundred and ten patients with supraglottic squamous cell carcinoma have been randomized for preoperative radiation therapy and surgery versus surgery and postoperative radiation therapy. Data have been analyzed on 94 patients in this preliminary report. The differences between the two groups with respect to local control and survival are not statistically significant at this time. Additional accrual and continued follow-up are necessary in order to make a more definite treatment comparison.


A comparative study of road traffic accidents in West Malaysia.

The problem of road traffic accidents in developing countries is now becoming a cause for concern. This is more so as preventive measures have not kept pace with economic progress and development. This paper reviews the present situation in West Malaysia, one of the better developed countries of the East, during the period 1970 to 1975. A comparative study has been made between the United States and Malaysia. To enable the urgency of the problem in developing countries to be appreciated the increases in the country's population and in the number of vehicles in use and their relation to the lesser increase in road mileage over the period of study have been discussed. The study has considered every aspect of the causative factors leading to traffic accidents, such as the effects of weather, seasonal variation, and road and lighting conditions. The common human errors leading to accidents have been discussed. Other factors, such as the ethnic distribution in Malaysia, and their relation to road accidents have shown the effect of the social structure on the problems. The data evaluated in this study make it clear that preventive measures are very necessary in underdeveloped as well as in developed countries.


Thorotrast induced pharyngeal necrosis.

Thorotrast, a radioactive contrast material used between 1930 and 1950, is often permanently retained within the patient. Individuals who have had diagnostic studies with Thorotrast may develop serious complications many years later. These complications fall into two major categories, desmoplastic and neoplastic. The inadvertent infiltration of Thorotrast into soft tissue, usually the neck during carotid arteriography, may later result in severe fibrosis with constriction of the surrounding vessels and nerves. Malignancies, the second major problem, have occurred at the site of previous Thorotrast instillations throughout the body. The following report describes the clinical course of an 82-year-old woman who presented with a Thorotrast induced desmoplastic reaction of her neck, complicated by pharyngeal necrosis and the development of a pharyngeal cutaneous fistula. The latter problem is quite rare, having been previously reported only once. Despite extensive tissue destruction conservative management prevailed. Repetitive debridement, controlling the intermittent infections, maintaining her nutritional status, and relieving her pain allowed spontaneous healing to occur.


Diverticular disease in an indigenous African community.

Sixteen cases of diverticular disease of the colon occurring in an urban hospital in Ghana are described. Ten of the patients had diffuse diverticulosis affecting the greater part of the colon. Apart from a high incidence of presentation with rectal bleeding the disease shows no particular differences in manifestation from what is encountered in the advanced countries. Sixty per cent of the patients belonged to the higher social classes, but all had lived on traditional African high-residue food. Other factors as yet unknown may contribute to the pathogenesis of this disorder.


Treatment of radiation-induced tissue injury by hyperbaric oxygen.

Hyperbaric oxygen therapy appears to be a beneficial adjunctive treatment modality in the management of radionecrosis of bone and soft tissue in the head and neck. The mechanism of such wound healing enhancement appears to be related to oxygen stimulation of fibroblastic activity and neovasculation. In this pilot study, involving 13 cases of refractory mandibular radionecrosis treated with hyperbaric oxygen, complete healing of soft tissue disease with covering of exposed bone has been noted in seven cases 11 to 27 months posttreatment; transient healing was seen in three cases; moderate to marked improvement in soft tissue disease has been noted in three cases. Pain relief was marked in six cases, moderate in four cases, and slight in one case of the 11 patients with significant pretreatment pain. Radiographic improvement was slight to moderate in ten cases. Four of the five patients with pathologic fractures developed a firm fibrous union of the mandibular segments during or shortly after treatment. Three additional cases of head and neck radionecrosis of other sites have noted significant improvement in their lesions during treatment. Three other patients with radionecrosis of the foot, hip, and vagina have also been treated with good results only in the vaginal case. None of the 19 patients treated with hyperbaric oxygen developed persistent or significant complications.


Voice spectrography in the evaluation of myasthenia gravis of the larynx.

Myasthenia gravis is a neuromuscular disorder that affects striated muscles especially those innervated by the cranial nerves. The standard diagnostic regimen is to find a reversal of symptoms by acetylcholine esterase administration. The permanent and objective recording of this effect is the key to an accurate assessment of this test. The voice spectrograph is a noninvasive means of evaluating the voice. It has been used successfully to make a clear and specific diagnosis of myasthenia gravis as it affects the larynx. The test can be used to distinguish myasthenia gravis from other functional, anatomical and neuromuscular laryngeal disorders.


Acute gallbladder disease.

The pathology, clinical features, diagnosis, and management of acute cholecystitis are outlined with reference to 311 cases out of a total of 631 patients treated for gallstones over a 15-year period. Operative procedures and the choice of antibiotics are discussed.


Prostatic cysts.

The classification, clinical features, and treatment of prostatic cysts are discussed with reference to 2 personal cases which differed in origin, in mode of presentation, and in the management required.


The role of local treatment for primary carcinoma of the breast.

The rationale of the conventional treatment of carcinoma of the breast by radical mastectomy is examined and is shown, in the light of modern concepts of the biology of the disease, to be faulty. It is proposed that the primary management of breast cancer should have three aims--preoperative diagnosis so that mastectomy may be avoided in patients with overtly disseminated disease, adequate local control of the disease with the maintenance of good life quality, and staging by minimal examination of the axillary contents or pectoral node biopsy as a guide to such adjuvant systemic therapy as may prove necessary.


Concentrations of organic acids in the urine of healthy newborn children.

Urine concentrations of organic acids were determined by a gas chromatographic technique in healthy, full-term neonates at the ages of 2 and 5 days. Significant reductions in the interindividual variation were obtained by relating the levels of organic acids to urine creatinine concentration or osmolality. Citrate was the predominant organic anion found. Urine concentrations of fumarate, 3-hydroxy-3-methylglutarate, adipate, and suberate decreased during the first week of life, and their concentrations were significantly intercorrelated. It is suggested that these findings reflect the predominantly fat-utilising, hyperketonaemic state during the first days of life. The urine concentrations of the aromatic end-products, p-hydroxyphenylacetate and hippurate, increased during the first week of life, probably as an effect of dietary factors. It is concluded that analysis of intermediary organic acids in urine could be of value in the assessment of the metabolic state in neonates.


Measurement of plasma renin activity as a valid estimation of plasma angiotensin status.

Measurement of plasma renin activity is widely used as an indirect assessment of plasma angiotensin II concentration. There has been some controversy over the validity of this assay as an estimate of circulating angiotensin II levels because, during the in vitro generation of angiotensin I by renin, over a period of time, substrate concentration may diminish to such an extent that it becomes rate-limiting, giving an artificially low reflection of angiotensin II levels. In this paper the initial angiotensin I concentration, that is the concentration before in vitro angiotensin I generation, has been compared with the corresponding plasma renin activity for 2752 individual plasma samples. A linear relationship was found between the initial angiotensin I concentration and the plasma renin activity below 60 ng ml-1 h-1. This indicates that, under the conditions of this assay, substrate does not appear to become rate-limiting except at exceedingly high levels of plasma renin activity. These results appear to provide further validation for the use of plasma renin activity measurement as a reflection of the concentration of circulating angiotensin II levels.


Evaluation of a kit for the colorimetric determination of inorganic phosphate.

An evaluation of a colorimetric kit method for the determination of inorganic phosphate (Pierce Phosphorus Auto/Stat Kit) is described. The within-batch and between-batch precisions were shown to fulfil current criteria, and recovery experiments, linearity studies, analyses of quality control materials, and studies of possible interfering substances evidenced good accuracy. Comparison of the results obtained on samples from patients with those obtained by the vanadate/molybdate continuous-flow method showed that the test method had a comparative positive bias. The use of a calibration reference serum as standard is recommended. The kit method is technically simple, requiring no protein precipitation, and analyses can be performed rapidly.


Comparison of three kits for the enzymatic determination of urea.

A comparative evaluation of Beckman (A), Boehringer (B), and Calbiochem (C) kits for the enzymatic end-point determination of urea has been carried out. Acceptable within-day and day-to-day precision was obtained with all kits. The recoveries obtained fulfilled the criteria of Logan (CRC Critical Reviews in Clinical Laboratory Sciences, 1972, 3, 271-289). Correlation between the results obtained by all kit methods and the diacetyl monoxime continuous-flow method, the reference method in this study, was excellent, but all methods evidenced a net negative bias at urea levels up to at least 20 mmol/1. We recommend kit A as the most satisfactory for routine use, consider kit B to be in the main acceptable, and suggest that kit C has disadvantages regarding both the accuracy attainable with quality control materials and the lack of information on blank correction for interfering compounds.


Dealing with specimen problems in a computerised clinical chemistry laboratory.

The use of a laboratory computer system to deal with specimen problems is described. Problems such as 'insufficient material' or 'haemolysis' are entered by reception staff or by bench workers so that resolution of the problem will not be overlooked; problems are then listed and dealt with by the duty biochemist. Specimens on printed worksheets are annotated 'urgent' where appropriate. Results obtained on-line, which are above top standard, automatically cause the specimen to reappear on the next worksheet marked 'dilution required'. Data relating to its use over a three-month period are presented together with some comments on the causation of specimen problems and their prevention.


Drift correction--a comparative evaluation of some alternatives.

Three drift correction methods are described. The results obtained from computer simulation of these methods and their application to raw data obtained from a survey of multichannel continuous-flow analysers are discussed, with particular reference to the effects of each method on analytical precision and accuracy, and on between-analyser variation. A geometrically derived method of drift correction was found to be the most satisfactory.


Prolactin secretion in patients with chromophobe adenomas of the pituitary: incidence and presentation of hyperprolactinaemia: results of surgical treatment.

In order to assess the frequency of hyperprolactinaemia in patients with "functionless" pituitary tumours, serum prolactin concentrations have been measured (by radioimmunoassay) in 111 patients with enlargement of the sella turcica who do not have acromegaly, Cushing's syndrome or Nelson's syndrome. The diagnosis of a chromophobe adenoma was confirmed in 76 patients who underwent surgery and was presumptive in the remaining 35. 45 of 64 (70%) patients studied before treatment and 15 of 47 assessed only after pituitary surgery had hyperprolactinaemia. Patients with raised prolactin levels usually presented with amenorrhoea or impotence, whereas reproductive disorders were rare in normoprolactinaemic patients. In many cases the presence of an underlying pituitary tumour was not initially suspected. The results of pituitary surgery were assessed in 25 patients with a chromophobe adenoma; of the 21 hyperprolactinaemic patients, surgery was most successful in those who had a small tumour treated by transsphenoidal adenomectomy. In conclusion, chromophobe adenomas formerly described as "functionless" are commonly associated with hypersecretion of prolactin and the hyperprolactinaemic patients frequently present with amenorrhoea or impotence. Prolactin levels should be measured in all patients with AMENORRHOEA or impotence and in patients with known (or suspected) pituitary tumours, before or after pituitary surgery.


[Phaeochromocytoma with hypokalaemia (two cases) (author's transl)].

Two cases of phaeochromocytoma with hypokalaemia are reported. In the first, a carcinoma, hypokalaemia was potentially secondary to hyperreninaemia and hyperaldosteronism in association with probably paraneoplastic hypercorticism. The other was benign and the origin of isotopically demonstrated potassium deficiency was less clear, because hyperreninaemia, hyperaldosteronism and hypercortisolism were moderate.


Progressive dialysis encephalopathy.

The clinical features of 42 patients with the only recently recognized and generally fatal neurological syndrome of progressive dialysis encephalopathy are reviewed and the electroencephalographic and neuropathological findings are summarized. Despite apparently successful hemodialysis, these patients develop a wide spectrum of neurological abnormalities. Of these, sudden onset of hesitant, nonfluent speech is the most characteristic and usually the earliest sign. Both dysphasic and dysarthritic elements are found, though the former predominate. Myoclonus, dementia, seizures, and gait difficulty are also seen in the majority of these patients. EEGs are more abnormal than would be expected for the clinical severity, with some type of high-voltage spike-wave pattern intermixed with abundant slow activity. The combination of clinical and EEG features in the appropriate setting is virtually diagnostic. Transient episodes with variable periods of complete or partial remission have been recognized. Neuropathological changes are surprisingly mild and nonspecific. The cause is uncertain; current speculation focuses on aluminum as the offending neurotoxin. Treatment remains unsatisfactory.


Relationship of lymphocyte invasion and survival of brain tumor patients.

The length of survival of 149 patients harboring primary brain tumors was retrospectively correlated with the presence and location of lymphocytic infiltration. Mononuclear invasion of malignant gliomas confined to the perivascular spaces was the only histolgical finding that correlated significantly with survival. Patients with malignant gliomas containing perivascular infiltration live up to four months longer than those with no lymphocyte infiltration. The survival of patients with brain tumors who had lymphocyte invasion associated with areas of hemorrhage and necrosis beyond and separate from perivascular spaces was the same as far as for those with no lymphocyte involvement.


Psychiatric disturbances in neurological patients: detection, recognition, and hospital course.

The Mini-Mental State and General Health Questionnaire were used to detect cognitive defects and emotional disturbances, respectively, in 126 consecutively admitted neurological patients. The Mini-Mental State was revalidated in this sample as a measure related to cerebral disorder. Sixty-seven percent of the patients tested had cognitive defect, emotional disturbance, or both. Thirty percent of the patients with psychiatric disturbance were not recognized by their physician. The majority of psychiatric disturbances persisted at the time of discharge. Since psychiatric disturbances are common among neurological inpatients and are frequently unrecognized, further evaluation of the psychiatric training of neurologists is needed. Simple screening tests may help to increase the recognition of psychiatric disturbance. It is concluded that the Board requirement for neurologists to know psychiatry accurately reflects "the nature of their case material."


Sparing of the Onufrowicz nucleus in sacral anterior horn lesions.

Sacral anterior horns were examined with special reference to the Onufrowicz nucleus in 3 patients with Werdnig-Hoffman disease, 2 with healed anterior poliomyelitis, and 1 who had undergone amputation of both legs above the knee. None of these patients showed symptoms of either urethral or anal sphincter disturbances. The Onufrowicz nucleus of the second sacral anterior horn appeared normal in all the patients examined, though the lateral portion of that horn and the medial nuclear group of the third sacral segment were frequently involved. These findings support the view that the Onufrowicz nucleus may be innervating the external sphincter muscle of the urethra and the anus.


Acetylcholine receptor in myasthenia gravis: increased affinity for alpha-bungarotoxin.

Studies of the binding of 125 I-labeled alpha-bungarotoxin to myasthenic motor end-plates have been interpreted as showing a decrease in the number of acetylcholine (ACh) receptors at these end-plates. Equilibrium binding studies of 125 I-tagged alpha-bungarotoxin rather than to a decreased number of receoptors. Our results show increased rather than decreased affinity of myasthenic receptors for alpha-bungarotoxin and also suggest that the number of ACh receptors is indeed reduced. The presence of a change in binding affinity, in addition to the reduced number of ACh receptors, suggests the presence of membrane changes that may contribute to the pathogenesis of myasthenia gravis.


Alteration in erythrocyte membrane structure in Duchenne muscular dystrophy.

Freeze-fracture studies of erythrocytes from patients with Duchenne muscular dystrophy revealed depletion of particles on both fracture faces of the plasma membrane. This study indicates that the structure of the erythrocyte plasma membrane is abnormal in Duchenne dystrophy and supports the concept that a generalized membrane abnormality is present in this disease.


Cerebral hypoperfusion in the sudden infant death syndrome? Brainstem gliosis and vasculature.

Gliosis is increased in the respiratory control area of the brainstem in victims of sudden infant death syndrome (SIDS), as it is in infants who have died of congenital heart disease. In the latter, the lesions appear to result from hypoxia or ischemia, and studies of the brainstem microvasculature of SIDS victims indicated a close relationship between the gliosis and adjacent vasculature. It is postulated that cerebral hypoperfusion may play a role in SIDS.


Brain dopamine receptor stimulation and the relief of Parkinsonism: relationship between bromocriptine and levodopa.

The relationship between dopamine receptor stimulation by bromocriptine or levodopa and the relief of parkinsonism was studied in 24 patients with Parkinson disease. Bromocriptine, 30 mg daily for 20 weeks, elicited an improvement in the parkinsonian clinical features, but this was less than the subsequent improvement with levodopa and benserazide, 800 mg and 200 mg daily, respectively. There was a negative correlation between the pretreatment severity of the disease or changes in cerebrospinal fluid homovanillic acid (HVA) and improvement in parkinsonian disability during bromocriptine treatment. Futhermore, it was found that clinical improvement and HVA responses in the cerebrospinal fluid after dopamine receptor stimulation by bromocriptine may predict the clinical response to levodopa.


Weakness in malignancy: evidence for a remote effect of tumor on distal axons.

Malignant tumors are known to have a "remote" or nonmetastatic effect on the central and peripheral nervous systems. Eight patients were seen with proximal muscle weakness in association with bronchogenic carcinoma (5), carcinoma of breast (2), and leukemia (1). Electromyography demonstrated small polyphasic motor unit potentials. Muscle biopsy, however, showed evidence of denervation. Electron microscopy revealed morphological abnormalities in the intramuscular segments of axons. This combination of EMG and biopsy findings is presented as evidence for a remote effect of tumor on the intramuscular distal axons.


Treatment of elevated intracranial pressure in Reye syndrome.

Continuous intraventricular monitoring of intracranial pressure appears to be a useful aid in the management of patients with Reye syndrome, especially those in stage 3 or 4 coma, in which the mortality rate remains high. Elevations in intracranial pressure can be treated promptly and before the patient shows clinical signs of deterioration. Careful attention to adequate airway care is essential. The use of paralytic agents to reduce pressure secondary to muscle movement is useful. The minimum dose of mannitol required can be carefully titrated, and sudden pressure changes can be combated by release of small amounts of cerebrospinal fluid.


HLA antigens in the Landry-Guillain-Barré syndrome and chronic relapsing polyneuritis.

Forty-four patients with inflammatory demyelinating polyneuritis (22 with Landry-Guillain-Barré syndrome, 6 with subacute polyneuritis, and 16 with chronic relapsing polyneuritis) were typed for genetic markers in and around the HLA region of chromosome 6. Patients with chronic relapsing polyneuritis showed a definite association with HLA-AW30 and AW31 and probable associations with HLA-B8, HLA-DW3, and glyoxalase I. No significant associations were demonstrated with the Landry-Guillain-Barré syndrome although an increase in glyoxalase I was significant if combined with the results of typing in chronic relapsing polyneuritis. The total patient group showed significant increases in HLA-AW30, HLA-AW31, and HLA-DW3. The results support the view that HLA-linked genetic factors influence susceptibility to chronic relapsing polyneuritis and may contribute to the differences in clinical patterns observed in inflammatory demyelination of the peripheral nervous system.


[Aspects of the therapeutic action of proteolytic enzymes and antibiotics in experimental staphylococcal infection. The effect of lincomycin, chymotrypsin and their combinations on leukocyte phagocytic activity].

The effect of leucomycin, chimotrypsin and their combination on the leucocyte phagocytic activity was studied on mice with experimental staphylococcal infection. Lincomycin and chimotrypsin were administered in doses of 150 and 2 mg/kg respectively. In the study of the leucocyte phagocytic activity it was found on the 3rd, 7th, 14th and 21st days after the beginning of the animal infection and treatment that the experimental staphylococcal infection stimulated the non-specific phagocytosis. Lincomycin inhibited the leucocyte phagocytic activity. The use of chimotrypsin in the process of the staphylococcal infection treatment resulted in increased phagocytosis activity. The combined use of chimotrypsin and leucomycin decreased the inhibitory effect of the latter on phagocytosis.


[Sensitivity study of dog kidney membrane-bound ribosomes to the action of amphotericin B in vitro].

The effect of amphotericin B on the number of the ribosomes bound with the endoplasmic membranes in the dog kidney cells was studied in vitro. The binding of the ribosomes was evident from the RNA/protein ratio. It was found that the RNA/protein ratio in the rough membranes treated with amphotericin B in a concentration of Igamma/ml remained at the normal level. An increase in the antibiotic concentration up to 100 gamma/ml did not either change the number of the ribosomes bound to the membranes. On the basis of the results of the study it was possible to conclude that the toxic effect of amphotericin B on the kidneys was not associated with damaging of the ribosomal-membrane complexes in the kidney cells.


[Growth kinetics model of the oxytetracycline producer taking into account the concentrations of 2 substrates].

The effect of starch and ammonium sulphate on the growth of the oxytetracycline-producing organism was studied using the procedure of acute experiments. It was proposed to use a mathematical model for description of the dependences taking into account the possibility of limiting or suppressing the growth of the culture by any of the above substrates as dependent on their ratio in the medium. Satisfactory confirmity of the model to the experimental data was shown. It was noted that similar models may be successfully used for description of such dependences as curves with flat plateau in the region of the maximum which are often met in microbiological processes.


[Effect of the cultivation temperature on the dynamics of the ATP and ADP levels and on the growth of P. nigricans Thom. Strains in the presence of various carbon sources].

The effect of the medium high temperature (28--28.6 degrees C) on the yield of the dry mycelium and the levels of ATP and ADP in the cells of the highly and low productive strains of P. nigricans Thom, 117 and B at different developmental periods (2, 5, 9 and 13 days) on the mineral medium using glucose, succinate or acetate as the carbon sources was studied. It was shown that the effect of the high temperature depended on the strain and the carbon source. The growth stimulating effect of this factor observed in strain 117 grown on the media with the above carbon sources and strain B grown on the media with glucose and acetate as the carbon sources was evident at different periods and later replaced by suppression. The growth of strain 177 in the presence of succinate was not inhibited, while that of strain B was suppressed during the whole developmental cycle. Such an effect of high temperature on the culture growth was the result of different supply of energy in the form of ATP to the strains which was confirmed by the study of the dynamics of the levels of ATP and ADP and their ratio in the strains during the developmental process.


[Stability of drug resistance in staphylococci under various conditions and the effect on it of prolonged culture storage on artificial nutrient media].

The literature and experimental data on stability of resistance ot benzylpenicillin, streptomycin, tetracycline, chloramphenicol, erythromycin, kanamycin and methicillin in staphylococci stored for prolonged periods of time on artificial nutrient media were systematized. When the staphylococcal cultures were not in contact iwth the antibiotics for 5 to 18 months, sensitive cells to separate drugs were detected in 51.0--67.4 per cent of the strains. The number of such cells in the populations of some strains ranged from 1 to 100.0 per cent. The effect of the resistance multiplicity on the stability of resistance to benzylpenicillin, tetracycline, chloramphenicol and erythromycin was not observed.


[Dynamics of the changes in the level of antibiotic sensitivity of staphylococci isolated in 1959-1977].

The study of antibiotic sensitivity in staphylococci isolated from the patients in the clinic of the N. N. Burdenko Research Institute of Neurosurgery of the USSR Academy of Medical Sciences in 1977 showed that in this stationary in 1977 predominated cultures resistant to benzylpenicillin. The number of the isolates resistant to streptomycin, levomycetin and erythromycin was high. The percentage of the strains resistant to tetracycline was the least. Still up to 1973 the resistance level to tetracycline among staphylococci was high. Possibly such a dynamics of the changes in the staphylococcal sensitivity to tetracycline was relative and mainly defined by the changes in the system of the results estimation using the paper disc procedure.


[Distribution, concentration and the interrelationship of free and bound tetracycline in the body of animals with multiple administrations].

When tetracycline was used for a long period of time, constant changes in the distribution regularities of free and bound fractions of the drug were observed. The changes were accompanied by a successive increase in the concentrations of both the fractions in the animal organs, tissues and fluids, as well as by a change in their levels, accumulation rate and percentage content.


Prediction of cefazolin penetration in high- and low-protein-containing extravascular fluid: new method for performing simultaneous studies.

The effect of extravascular fluid protein concentration and drug-protein binding was studied in rabbits with subcutaneously implanted Visking chambers. Chambers containing serum or saline were simultaneously studied in three animals by injecting cefazolin (30 mg/kg) intramuscularly every 4 h for four doses. Five additional animals were then studied for an 8-h period while receiving two doses of cefazolin. Peak and trough serum and chamber fluid were assayed for cefazolin concentration. The three-animal experiment demonstrated that equilibrium in the subcutaneous chambers was reached after two intramuscular injections and that the extravascular fluid levels were stable in comparison to the wide fluctuation of the serum levels. The five-animal experiment demonstrated that after two doses the serum-filled chambers contained 12.9 mug of cefazolin per ml, whereas saline-filled chambers contained 1.8 mug of cefazolin per ml. Ratios of chamber to peak serum for the second study were 12.4% for serum chambers and 1.7% for saline chambers. The cefazolin concentration in high-and low-protein extravascular fluid in both studies could be predicted from the logarithmic mean of the peak and trough serum cefazolin concentration and the antibiotic binding to rabbit serum and extravascular fluid proteins. These observations explain the previously published apparent discrepancies seen in studies of extravascular penetration of highly protein-bound antibiotics such as cefazolin.


Susceptibility of Campylobacter fetus subsp. jejuni to twenty-nine antimicrobial agents.

The activity of 29 antimicrobial agents was tested against 95 strains of Campylobacter fetus subsp. jejuni isolated from human stools. Furazolidone and gentamycin were the most active agents. The tetracyclines, erythromycin, and chloramphenicol were very active against most of the strains, but with each antibiotic a few resistant strains were found. The penicillins were relatively inactive, and the cephalosporins tested were only active against occasional strains.


SCE-963, a new broad-spectrum cephalosporin: in vitro and in vivo antibacterial activities.

SCE-963 {7beta-[2-(2-aminothiazol-4-yl)acetamido]-3-[({1-(2-dimethylaminoethyl)- 1H-tetrazol-5-yl}thio)methyl]-ceph-3-em-4-carboxylic acid}, a new semisynthetic cephalosporin, showed excellent antibacterial activity against gram-positive and gram-negative bacteria, including Haemophilus influenzae, indole-positive Proteus, Enterobacter species, and Citrobacter freundii. The minimum inhibitory concentrations of SCE-963 against most strains of clinically isolated Escherichia coli, Klebsiella pneumoniae, H. influenzae, and Proteus mirabilis were within the range of 0.2 to 0.78 mug/ml. These activities were about 10 times more potent than those of cefazolin, cephaloridine, and cephalothin. Variations in pH, addition of horse serum, and type of growth medium had no significant effect on the activity of the cephalosporin, but the inoculum size elicited a considerable effect on the activity of beta-lactamase-producing strains of bacteria. SCE-963 exerted bactericidal and bacteriolytic effects on Staphylococcus aureus and E. coli. The pronounced in vitro activity was reflected in the remarkable protection in mice infected with a wide range of gram-negative bacteria, such as E. coli, K. pneumoniae, P. mirabilis, Proteus vulgaris, Proteus morganii, and Proteus rettgeri. The protective effects of SCE-963 in mice infected with E. coli, K. pneumoniae, and P. vulgaris varied according to the challenge dose. The activity of SCE-963 was far more potent when the drug was administered parenterally rather than orally.


Effect on antibiotics on protease production by a viridans streptococcus.

A viridans streptococcus (Streptococcus MG intermedius 974) isolated from a confirmed case of subacute bacterial endocarditis was studied for the production of extracellular proteases during exponential growth and after penicillin (0.10 mug/ml) and/or streptomycin (20 mug/ml) treatment. Exponentially growing cultures produced a variety of extracellular proteases, as determined by the elution profiles of active proteins from Sephadex G-100 and Sepharose 4B columns. Examination of supernatant fluids from cultures of S. MG intermedius treated with penicillin or streptomycin for 12 h indicated a reduction of at least 50% in the number of different proteolytic species produced. However, some of the proteases produced by the cultures during penicillin or streptomycin treatment had significantly higher specific activities when compared with proteases produced by exponentially growing cells. The combination of penicillin and streptomycin further reduced both the number and the specific activities of the extracellular proteases on a cell dry weight basis.


Comparative susceptibilities of anaerobic bacteria to metronidazole, ornidazole, and SC-28538.

The susceptibilities of 284 anaerobic bacteria, including 55 strains of the Bacteroides fragilis group, were determined by an agar dilution technique to metronidazole and two newer nitroimidazoles, ornidazole and SC-28538. All three agents showed marked in vitro activity against virtually all anaerobic bacteria tested. At concentrations </=1 mug/ml, SC-28538 was significantly more active than either metronidazole or ornidazole. At concentrations of >1 mug/ml, the activities of all three agents were comparable. Propionibacterium and Actinomyces showed significant resistance to all three agents. Anaerobic and microaerophilic members of the genus Streptococcus were also often resistant, in contrast to Peptococcus and Peptostreptococcus strains. In addition, the bactericidal activities of ornidazole and SC-28538 were determined against 27 strains of the B. fragilis group by a broth dilution technique. The minimal inhibitory and minimal bactericidal concentrations of each agent were very close. At concentrations of </=0.5 mug/ml, SC-28538 showed greater bactericidal activity; at concentrations of >/=2 mug/ml, the activies of both agents were similar.


Concentration relationships of cefaclor in serum, interstitial fluid, bile, and urine of dogs.

The concentrations of cefaclor in the serum, urine, bile, and tissue fluids of the abdominal wall, kidney, and liver of dogs were compared over a 4-h period after oral administration of a single dose of this drug. The concentration of cefaclor in the soft-tissue interstitial fluid peaked 2 h after administration, thereby demonstrating a diffusion rate similar to those of other cephalosporins. Both urine and bile concentrations greatly exceeded the serum levels, whereas none of the tissue fluid concentrations were greater than the serum concentrations at the times of measurement.