Disposition of sulfonamides in food-producing animals: concentrations of sulfamethazine and its metabolites in plasma, urine, and tissues of lambs following intravenous administration.

A sensitive, precise, and efficient analytical method for sulfamethazine in the liver, kidney, heart, skeletal muscle, and fat of lambs is reported. The method involves freezing cubed tissue in liquid nitrogen, powdering the frozen tissue in a liquid nitrogen-cooled blender, and extracting the tissue on a sodium sulfate column with chloroform:acetone. A thin-layer chromatographic procedure capable of separating and quantitating sulfamethazine and 3 metabolites (acetyl, hydroxylated, and polar conjugate(s) in lamb urine is also reported. Sulfamethazine was administered intravenously (107.25 mg/kg body weight) to 14 cross-bred ewe lambs. The concentration of sulfamethazine in plasma and tissues and sulfamethazine and its metabolites in urine were determined in samples collected at specific postdosing times. The concentration of sulfamethazine in plasma exceeded 5 mg/100 ml for 18 to 24 hours after drug administration. The excretion of diazotizable materials in the urine was essentially complete at the 60th hour after dosing. The drug was excreted in the urine as sulfamethazine, a hydroxylated metabolite, acetylsulfamethazine, and polar conjugate(s). Tissue concentrations of the drug were greatest in the kidney and less (in decreasing quantities) in liver, heart, skeletal muscle, body fat, and omental fat.


Disposition of sulfonamides in food-producing animals: pharmacokinetics of sulfathiazole in sheep.

Plasma and urine data on sheep following administration of sulfathiazole as single intravenous and oral doses were examined. A one-compartment open model was developed to describe the pharmacokinetics of sulfathiazole in sheep. The drug was rapidly eliminated, primarily by renal excretion of unchanged sulfathiazole and metabolism to acetyl sulfathiazole, with a biological half-life of 1.3 hours. Sulfathiazole was absorbed slowly (half-life, 18 hours) and relatively completely (73%) after oral administration in solution.


[Clinical, biological and genetic study of 500 cases of mixed hyperlipemia].

Based on 500 case histories, the writers discuss the main clinical signs, cardiovascular complications, lipide, glucide, and puride anomalies, and the genetic transmission observed in mixed hyperlipidemia. They stress a certain number of criteria which enable them to make mixed hyperlipidemia a specific clinical, highly frequent, and extremely formidable form of essential hyperlipidemia, falling between hyprecholesterolemia of type IIIa and endogenous hypertriglyceridemia of type IV. The variability of the electrophoretic phenotype from one patient to another, and in the same patient from one day to another, leads them to recommend a classification based on the values of plasma lipide fractions. A predominately late appearing genetic transmission of the autosome type supports this view.


[Study of hemostasis factors in nephrotic syndrome. Pathogenic interpretation and therapeutic deductions].

Thrombo-embolic accidents are extremely common during nephrotic syndrome (8 p. 100). They share the garvity of thrombo-embolic accidents occurring under other circumstances (20 p. 100 mortality). They are accompanied by numerous disturbances in clotting factors the mechanisms of which are discussed. Nevertheless the study of these disturbances does not make it possible to predict the onset of a thrombo-embolic problem. By contrast, the degree of hypoalbuminaemia is significantly correlated with the thrombotic risk (p. 0.001) and serves as an indication for the necessity of preventive heparin therapy, in the form of calcium heparinate. In this way the authors have been successful in eliminating the thrombo-embolic risk in association with nephrotic syndrome.


[Curable ECHO 5 virus encephalitis. Clinical, electroencephalographic, virologic and ultrastructural study].

A 10 1/2 years old boy fell brutally ill with a fit followed by confusion, and then by deep coma, with 40 degrees C fever and morbilliform rash. Consciousnesse came back within ten days, with transient Parkinson-like tremor. Myoclonus persisted for about six months. Complete recovery was followed up for six years. A diagnosis of encephalitis was considered on early EEG evidence (stereotyped repetitive sharp wave bursts) and was confirmed by isolation of ECHO 5 virus from brain specimen, and ultrastructural observation of characteristic cytopathic effect (disappearance of organelles, proliferation of smooth membranes) and of probable viral particules in astrocytes, without any inflammatory process.


[Pleural and intraspinal tumor with hypercalcitoninemia].

The authors report a case of probably ectopic secretion of calcitonin in a 35 year old woman suffering from a malignant tumour in a double intra- and extra-spinal form. Hormone levels returned to normal after complete excision of the tumour, in which it was impossible to demonstrate the presence of calcitonin despite a very marked secretory appearance by electron microscopy. Study of the literature concerning the secretion of calcitonin by malignant tumours indicates the high degree of contradiction concerning the origin and the significance of increased radio-immunological levels of this hormone, which it is not possible to use without criticism as a "marker" of carcinomas.


[Status of vampirism and autovampirism].

Any interpretation of the perversion called vampirism ought to take into consideration the myths in which the relations between living and dead people (vampires, incubi, succubi, etc...) are represented, myths through which the persons alive project onto the dead ones to ambivalent, sexual and agressive, wishes they had toward the dead when they were still alive. Clinically the word vampirism should be used to name all sexual or agressive acts, whether blood-sucking happens or not, committed on a dead or dying person. In one third of the cases the act has both a sexual and an agressive components (mutilation of the dead body); in the other two thirds the act seems to have only a sexual component (sexual pleasure in the presence of or in contact with the dead body). The origin and the meaning of this exceptional perversion are discussed. Auto-vampirism, even more exceptional than vampirism, differs from the latter by the fact that blood succion is the essential symptom and by the fact that it is not on the side of sadism but on the side of masochism. In the light of two case-histories, one of which never published before, and on the basis of the Freudian theory of masochism, an interpretation of the data is propounded.


[Prevention and control of child and juvenile delinquency and criminality. The home of the child and its parents].

The author: 1. Summarizes the finding to date governing the behaviour children's problems of delinquency and serious efforts that will be made to prevent and combat juvenile delinquency, to help the individual child who runs into difficulty by offending essential rule of the legal code. This can be done in institutions as it has been shown brillantly by Anglo-American psychiatric and psychoanalytic teachers. It is built up through the establishment of a good relationship which accepts and treats instead of resenting the child and his inevitable initial rebuffs. The greatest gain will come from psychiatric treatment of the casual breakdown. Nobody in the present culture is better prepared to give the better solution than an experienced psychiatrist. 2. Propose insight simplified organisation to prevent early brain injuries and early psychological trauma: the home of parents and child.


[Present-day prevention. Mental hygiene aspects of child and juvenile delinquency and criminality].

To make useless attempts to stop adult truancy there is only one effective way: The prevention by mental hygiene of parent's psychological and ethic education which govern parental behavior to give early their offspring's warmth which is in them. The time has come when it is possible to single out the chiefs principles which have to do with the concept of prevention itself: maintaining health converging on the same issue genuine parental fondness devoid of overprotection, coercition, etc. T'is is the cornerstone of prevention mental hygiene. Brief report of the organization of the "Home of parents and children" to assist the growing plague of juvenile delinquency and behavioural deviances.


[Psychopharmacology and psychotherapy: a dynamic therapeutic parallelism to be integrated].

In a brief expose, the author wants to integrate the psychoanalytic data towards a better clinical use of psychopharmacology. Starting from a triadic situation "patient-physician-medication", he proposes a dynamic rather than a static attitude in the patient's approach, aiming at an eventual diadic relation "patient-physician" and, if at all possible, a relative or total independance of the patient. After alluding at the role of the physician, of the patient and of the medication, in such a process, the author refers to intra and extra psychic influence in disease. The concepts of "team approach" and "milieu therapy" are related to the key-role of the psychiatrist and to the availability of competent and well-motivated paramedical professionals in sufficient numbers. The notions of transference, countertransference and control as well as the symbolic of the symptoms are briefly outlined. The author concludes that the complementary elements of psychoanalysis and psychopharmacology will benefit the patient if the clinician knows how to integrate them along with the changing and dynamic process of the illness.


Oral, pharyngeal and laryngeal manifestations in Urbach-Wiethe disease.

Twenty-eight patients suffering from Urbach-Wiethe disease (UWD) and originating in northern Sweden are presented. The disease is characterized by amorphous deposits in the mucous membranes of the mouth, pharynx and larynx. Hoarseness since early childhood is the most common and striking symptom. Most of the patients also had severe changes in the true vocal cords. Characteristic deposits are also seen in the lower lip, tongue, palate and the posterior pharyngeal wall. These changes could be defined as pathognomonic of UWD. To confirm the diagnosis of UWD, biopsies should be taken from the skin or mucous membranes of the mouth. Biopsies from the vocal cords are not necessary and should be avoided.


Causes of death among female patients with cancer of the breast and intestines.

The cause-specific mortality of women with cancer of the breast or of the intestines (= small intestine and colon) diagnosed in 1953-70 in Finland was analyzed with respect to the extent of the disease, the age of the patient at the time of diagnosis, and the follow-up time. The total mortality in breast-cancer patients was higher than had been expected during the entire follow-up period (maximum of 18 years), whereas in patients with intestinal cancer no more than slight excess mortality existed after 5 years of follow-up. The mortality from cardiovascular diseases was less than had been expected among patients with intestinal cancer. Patients with non-localized cancer of the breast had a risk of dying from accidents and other violent causes of death during the first 5 years of follow-up which was slightly higher than expected. From information compiled from various sources, the Finnish Cancer Registry records not only the official cause of death mentioned on the death certificate, but also a "corrected" cause of death. With this correction, the mortality from forms of malignancy other than the primary cancer was lower than had been expected during the first 5 years of follow-up, and subsequently reached the level expected. In regard to specific sites, mortality lower than that expected was observed for cancer of the stomach (both breast- and intestinal-cancer patients), and cancer of the cervix uteri (breast-cancer patients). In patients with localized breast cancer, the mortality from leukaemia was higher than that expected after 5 years of follow-up. No mutual excess risk was demonstrable with breast and intestinal cancers.


Echocardiography after mitral valve replacement and criteria of paraprosthetic regurgitation.

19 patients with Björk-Shiley mitral tilting disc valve prostheses were studied by echocardiography before the valve replacement operation and postoperatively every three months up to one year. In 14 patients with normal prosthetic function the left atrial diameter decreased markedly after operation (p less than 0.001), but echocardiographic dimensional indices of left ventricular performance remained unchanged. Paradoxical or markedly hypokinetic motion of the interventricular septum was observed within 3 months of operation in 46% of the patients, but in only 28% in studies performed 9 - 12 months after the replacement. The ampliture of the disc was on average 11 +/- 2 mm. In 5 patients with paraprosthetic regurgitation the left atrial diameter increased with the development of regurgitation and decreased again after successful reoperation. In these patients the left ventricular end diastolic and stroke volumes were great (p less than o.01) than in patients with normal prostheses. The septal motion was in the normal direction in all these 5 patients and the septal amplitudes were greater (p less than 0.01) than in the patients with normal prostheses. The amplitudes of the disc were normal, but abnormal anterior movement of the disc at the beginning of the diastole was observed. These data demonstrate that echocardiography is useful in the diagnosis of paraprosthetic mitral valve regurgitation.


The reliability of 99mmTc-pyrophosphate scintigraphy in the diagnosis of bony metastases.

A series of 183 patients suffering from cancer examined with 99mTc-yrophosphate scintigraphy is presented. Of the 74 cases with radiologically confirmed metastases or primary tumour in the skeleton 67 (91%) had an isotope accumulation. Four cases with false positive accumulations were detected. In three cases the uptake disappeared subsequently, in the fourth the uptake persisted, all patients being at least on year without any osseal symptoms. Even when the 99mmTc-pyrophosphate scintigraphy is recommended as the first diagnostic measure in skeletal lesions, the scintigraphy alone is not sufficient for deciding the treatment of a cancer patient.


Serum immunoglobulin A changes in alcoholic patients.

1. Serum concentrations of immunoglobins IgA and IgG were determined in: Alcoholic men without liver damage (normal laboratory tests and only slight abnormalities in liver biopsy). 2. Patients at different stages of alcoholic liver disease. 3. Non alcoholic patients with liver disease. The serum IgA concentration was increased in all groups of alcoholics and this increase was related to the severity of liver damage. It was also raised in non alcoholic patients but both the degree of increase and the IgA/IgG ratio could be used to differentiate them. The increase in the serum IgA concentration in alcoholics without liver damage has not previously been proved and the reasons put forward for it in alcoholics are not valid for this group.


Haemoptysis. A bronchological evaluation.

A series of 342 patients with haemoptysis, who underwent bronchological examination at Päivärinne Chest Hospital during the period 1967-73, is presented. The most frequent cause of haemoptysis was bronchial carcinoma (86 cases, 25%), with chronic bronchitis in 73 cases (21.5%, inactive pulmonary tuberculosis in 33 (9.5%), bronchiectasis in 22 (t.5%), active pulmonary tuberculosis in 21 (6%) and pneumonia in 17 (5%). The cause of bleeding remained unkown in 73 cases (21.5%). Bronchoscopic findings were normal in 86 patients (25%) and only inflammatory mucosal changes were found by bronchoscopy in 181 patients (53%). A bleeding bronchial carcinoma was identified in 42 patients. The exact bleeding point was observed in the mucosa in 10 patients, and bleeding could be traced to the segmental bronchus in 18 patients, to the lobar bronchus in 2 and to the main bronchus in 3. One attack of haemoptysis, in a case of tuberculosis ended fatally. In all cases in which bleeding was still present at the time of bronchoscopy the bleeding point could be traced at least to the segmental bronchus.


The clinical assessment of cancer tests: a statistical approach to the prediction of "false positive" rates from controls.

As the sensitivity of the new in vitro cancer detection techniques increases, a larger number of "false positive" results can be expected from control populations apparently free from malignant disease at the time of the test. An attempt is made to predict the number of unexplained positives, together with the expected age and sex distribution, using published cancer registration statistics. The predicted numbers are compared with the observed numbers of unexplained positives in two clinical trials of the MEM test.


Acquired tracheobronchomalacia.

In a series of 2150 patients subjected to bronchoscopy 94 (4.5%) were found to have tracheobronchomalacia. Tracheomalacia alone was diagnosed in 21 patients (22%), tracheobronchomalacia in 59 (63%) and bronchomalacia alone in 14 (15%). Mild malacic changes were noted in 44 patients (47%), moderate in 38 (40.5%) and severe in 12 (12.5%). The main symptoms were dyspnoea (63%), chronic cough with expectoration (49%) and haemoptysis (33%), and the most frequent concurrent diseases chronic bronchitis (53%), bronchial cancer (27.5%) and pulmonary tuberculosis (19%). Bronchoscopy performed under local anaesthesia enabled the dynamics of the tracea and bronchi to be observed during spontaneous breathing and during coughing, and it is the best available diagnostic procedure. Histologically the number of longitudinal elastic fibres in the pars membranacea was clearly reduced throughout the whole tracheal area in one patient with tracheomalacia but no differences were found in the amount of collagen, mucopolysaccharides and elastin in the cartilages of trachea and bronchi. This disease seems to be associated with chronic obstructive pulmonary diseases such as chronic bronchitis, and it apparently shares the same aetiological factors.


Plasma renin activity in pregnant women with oedema treated with hydrochlorothiazide.

Fourteen pregnant women with oedema and inappropriate weight gain were treated with hydrochlorothiazide, 50 mg daily. Plasma renin activity (PRA) increased form 2.89 +/- 0.44 (mean +/- SEM) to 10.46 +/- 1.61 ng/ml/h after one week and remained high (10.07 +/- 1.36 ng/ml/h) after three weeks of drug therapy. Eight women were considered to be "responsers" because of a marked increase of PRA) (greater than 9.5 ng/ml/h) and six subjects ranked as "weak responders", with PRA increases of less than 6.0 ng/ml/h. These subgroups had different patterns of sodium excretion, weight loss and systolic blood pressure. The different reactivity of the renin-angiotensin system suggests that there may be at least two, basically different, types of pathophysiology in pregnancy associated edema.


Electrocardiographic low-frequency QRS notching and ventilatory impairment in patients with pulmonary tuberculosis.

The occurrence of notching in the initial and terminal parts of the QRS complex of the ECG was studied in a series of 1072 patients with active or healed pulmonary tuberculosis. Terminal notchings were associated with ventilatory impairment: in the male group the percentage of patients with terminal notching increased from 5 to 20% as the FEV1.0% decreased from larger than or equal to 80 to below 40. Initial notchings were not associated with ventilatory impairment. The relationships were similar when studied separately in groups with and without left heart disease.


Urinary chromium excretion and atherosclerotic manifestations in two Finnish male populations.

The urinary exretion of chromium was studied for relationships to atherosclerotic diseases in two rural Finnish male populations, aged 55 to 74; one from eastern Finland, the other from the southwestern part of the country. A 10-year follow-up had shown a particularly high mortality from coronary heart disease in the eastern area where the concentrations of chromium in the drinking water were lower than in the western area. The 24-hr urinary excretions of chromium of the two populations were markedly low (east, mean +/- SEM, 3.60 +/- 0.15 microgram; west, 3.74 +/- 0.13 microgram), suggesting a suboptimal chromium intake in both populations. No consistent differences were found in urinary chromium excretions between groups with atherosclerotic diseases and reference groups. The role of low chromium intake in the pathogenesis of atherosclerosis deserves further study.


Missed sacral fractures.

During 1974 156 patients with pelvic fractures were admitted to our hospital. Of them 63 (40.4%) had double vertical lesions, which broke the pelvic ring in two sites. In 12 patients the diagnosis of a sacral hairline fracture was not made initially. The difficulties in making a radiological diagnosis are mainly due to the curved form of the sacrum in plain radiographs. The use of sophisticated radiological methods does not remove the difficulties. Double lesions were missed most often in elderly female patients with low-energy hairline fractures in osteoporotic sacra. The typical indirect signs observed in combination with sacral fractures were no help in the search for these missed hairline fractures, and the contribution of these fractures to the prediction of dangerous complications can be regarded as minimal.


Effect of cardioselective beta-blockade by metoprolol on the phasic myocardial blood content and epi/endocardial ratio.

Using I131-albumin labelling of plasma and a special biopsy cutting device, the blood content of the subendocardium and subepicardium was determined in guinea pig hearts. Measurements were done both in untreated animals and after intravenous administration of metoprolol, a new cardioselective beta-blocking compound. The data were compared with results obtained with propranolol and practolol. Metoprolol decreased the blood content less than propranolol. Practolol in a small dose even increased the blood content in the subendocardium in end-systole. The heart rate decreased by about the same magnitude after all the compounds tested, suggesting that the cardioselectivity of metoprolol was the likely explanation for its differing response from propranolol.


[Use of flour from sunflower oil cake in the biosynthesis of antigungal antibiotics].

The possibility of replacing soybean meal and corn-steep liquor by food wastes of the oilpress industry and the meal of the sunflower oil cake in particular is discussed as applied to the fermentation media for production of antifungal antibiotics, such as levorin, mycoheptin, amphotericin. The studies showed that replacement of soybean meal by sunflower oil cake meal with simultaneous increasing of the amount of carbohydrates in the medium increased the levorin levels by 60--70 per cent as compared to the media used at present. When soybean meal and corn-steep liquor were simultaneously replaced by sunflower oil cake meal in amounts of 3--4 per cent the levels of mycoheptin in the fermentation broth increased by 30--65 per cent respectively. Replacement of soybean meal and corn-steep liquor by 3 per cent of sunflow oil cake meal in the medium used presently increased the amphotericin levels by 27 percent as compared to the control. Therefore, sunflower oil cake meal is a substitute of full value for soybean meal and corn-steep liquor in the fermentation media for production of antifungal antibiotics.


[Sensitivity to antibiotics of bacteria of the genus Citrobacter isolated from patients with acute intestinal infections of unclear etiology].

Sensitivity of Citrobacter isolated from the patients with acute gastro-intestinal infections of unknown etiology in Volgograd was studied. The antibiotic sensitivity to antibiotics was determined by the method of dilution in nutrient agar. Most of the isolates were sensitive to kanamycin, tetracycline and polymyxin. All strains were resistant to ristomycin. The sensitivity of the local strains differed from that described in the literature. Among sero groups 05, 08 and 023 all strains were resistant to oleandomycin, lincomycin and ristomycin. Polyresistant strains of Citrobacter were registered in Volgograd. The greater part (79 per cent) of the strains were simultaneously resistant to 4-6 antibiotics.


[Microflora of the nasal cavity and its sensitivity to antibiotics in patients with chronic rhinitis treated by cryotherapy].

Cryotherapy is used in treatment of chronic rhinitis and pharyngitis. The effect of cryotherapy on the qualitative and quantitative composition of the microflora was studied. Staphylococci prevailed in the rhinitis patients, streptococci, Clebsiella and Neisseria being registered more rarely. The staphlococcal isolates were  highly sensitive to monomycin, neomycin, erythromycin and levomycetin. The results of the dynamic study showed that the flora composition did not significantly change during cryotherapy and the sensitivity level of the staphylococcal isolates to the antibodies remained unchanged.


[Effect of synthetic poly-electrolytes of the cationic type on staphylococcal sensitivity to benzylpenicillin].

The study of the effect of synthetic polyelectrolites of the cationic type on benzylpenicillin resistant staphylococci showed that the cation polyelectrolites induced changes in the cell membrane permeability and increased penicillin absorption by the cells thus increasing sensitivity of the penicillin-resistant staphylococci to the antibiotic. Low inhibitory effect of the polyelectrolites with respect to penicillinase and hyaluronidase was shown. Changes in the membrane apparatus of staphylococcus cells due to the effect of polyelectrolites were found.


[Results of a study of the pharmacokinetics of actinomycete RNAase in the bodies of white rats].

The pharmacokinetics of RNA-ase from Act. rimosus was studied on albino rats. The enzyme activity in the biological tests was determined spectrophotometrically by the increase of the acid-soluble products formed as a result of RNA-ase effect on RNA. The preparation was rapidly absorbed into the blood and organs, the maximum levels in the blood and organs being observed 30 minutes and 1 hour after the preparation administration. The preparation levels in the organs with the exception of the liver and kidneys were rather low. The highest levels observed in the kidneys and liver were 19.6 and 3.37 per cent respectively on the RNA-ase amount administered. Within the first 3 hours of the enzyme administration insignificant amounts of the substance were registered in the urine. Penetration of RNA-ase through the hemato-encephalic barrier was low.


[Optimal regime of intravenous administration of lincomycin in osteomyelitis].

The pharmacokinetics of lincomycin in the blood of 8 patients with osteomyelitis was studied on the drug single and uninterrupted intravenous administration in therapeutic doses. It was found that when the antibiotic was administered continuously according to the routine scheme, its therapeutic blood levels were attained only 1.5 hours after the drug infusion. The optimal regimen of lincomycin uninterrupted infusion providing its constant rate in combination with the single intravenous administration was estimated with the help of the constants of the two-compartment model of lincomycin pharmacokinetics. According to the calculations the rate of the antibiotic  administration necessary for providing therapeutic levels should be 2.2 mg/kg in complex with the loading dose equal to 5.4 mg/kg. Practical trials showed that intravenous administration of lincomycin with the above regimen remained within therapeutic range already 10 to 20 minutes after the beginning of the drug infusion. Therefore, from the pharmacokinetic point of view the recommended regimen for lincomycin infusion should be considered preferable to that used presently.


[Effect of successive cyclic administration of oleandomycin and tetracycline on the immunogenic reactivity and indices of non-specific bodily resistance in experimental staphylococcal sepsis].

The effect of subsequent cyclic administration of oleandomycin and tetracycline on the titer of the complement, the content of lysozyme, the bactericidal properties of the serum and the presence of the antibiotic specific antibodies in the blood serum found in the Hoigne reaction were studied on rabbits. It was found that the subsequent cyclic administration of the antibiotics to both the intact animals and the animals with experimental staphylococcal sepsis was accompanied by an increase in the titer of the complement only on the 7th day of administration of oleandomycin, the first antibiotic. The subsequent administration of tetracycline and especially discontinuation of the antibiotics use resulted in a significant, stable and prolonged decrease in the complement titer. The cyclic subsequent administration of oleandomycin and tetracycline for 7 days was accompanied by an increase in the lysozyme content and serum bactericidal properties. Changes in the factors of non-specific resistance under the effect of the subsequent cyclic administration of oleandomycin and tetracycline on both the intact animals and the animals with experimental staphylococcal sepsis were accompanied by an appearance, progressive increase and prolonged preservation in the serum of the antibiotic specific antibodies found in the Hoigne reaction. A possibility of producing specific antibodies simultaneously to the 2 antibiotics, i. e. oleandomycin and tetracycline in their administration in subsequent 7-day cycles was shown.


[Effect of semi-synthetic penicillins and cephaloridine on indices of immunologic reactivity and protein metabolism during treatment of puerperal infection].

The effect of semisynthetic penicillins, such as methicillin and oxacillin and cephalosporins, such as cephaloridin of immunity and protein metabolism was studied on 63 patients with postnatal mastitis and endomyometritis. It was shown that the above antibiotics had no significant effect on the immunological reactivity and protein metabolism. However, lower titers of alpha-antitoxin, lysine levels and C-reactive protein content were registered in the mastitis patients treated with cephaloridin. Therefore, while recomending antibacterial drugs their effect on the immunity and protein metabolism should be taken into account and from this point of view semisynthetic penicillins are preferable in treatment of mastitis patients and semisynthetic penicillins and cephaloridin are preferable in treatment of endomyometritis patients.


[Effect of several antibiotics and their combination with prodigiozan on Y. pestis EV, engulfed by macrophages].

The effect of various antibiotics, such as streptomycin, gentamicin, ampicillin, benzylpenicillin, tetracycline, chlortetracycline and levomycetin on the plague bacteria (strain Y. pestis EV) located inside the cells was studied. Peritoneal macrophages of albino mice with aceptic inflammation of the abdominal cavity caused by intraperitoneal administration of 2 ml of sterile meat-peptone broth were used in the experiments. The ratio of the macrophages and microbes was 1 : 50. A part of the mice were treated with prodigiozan 24 hours before taking the exudate. The preparations of the macrophages of albino mice with the microbes absorbed by them served as the control. The effect of the antibiotics and their combinations with prodigiozan was stimated by the coefficient of multiplication suppression against the control. The observations were made in dynamics. The studies showed that the macrophage activity of the mice treated with prodigiozan after exposure to the antibiotics was reliably higher than that in the control and digestion of the microbes located inside the cells started earlier, providing more complete phagocytosis.


[Cytotoxic and antitumor effect of antibiotic PSX-1 in vitro and in vivo].

The inhibitory effect of antibiotic PSX-1 on tumour cells was studied in vitro and in vivo. The antibiotic inhibited above all the utilization of the added 14C-labelled uridine and adenine in EAC cells. After a short exposure to PSX-1 (180 min) the synthesis of nucleic acids and proteins in EAC proliferating in vitro was suppressed. Antibiotic PSX-1 in concentrations of about 2.5 mg/ml showed relatively low toxicity on normal human fibroblasts but caused a marked cytotoxic and cytopathic effect on tumour cells. A potential antitumor effect of PSX-1 was evaluated in vivo by using gradually EAC and L 1210 tumours. All the animals treated with the antibiotic in doses of 2.5--5.0 mg/kg/day with the use of EAC and 5.0 mg/kg/day with the use of L 1210 survived for 90 and 40 days respectively and no tumours developed in the treated mice during this period.


[Penetration of oleandomycin into the subarachnoid space of neurosurgical patients].

Penetration of oleandomycin into the subarachnoid space in neurosurgical patients treated with the drug administered orally and intramuscularly in doses of 375 and 500 mg respectively was studied. The oleandomycin levels in the blood and cerobrospinal fluid were determined after a single administration of the antibiotic at an interval of 30 minutes to 7 hours. A total of 52 observations were recorded. Relation between oleandomycin penetration into the cerebrospinal fluid from the blood and the administration route was shown. The index of penetration through the blood-liquor barrier for the antibiotic intramuscular or oral administration was 9--70 and 3--40 per cent respectively. The maximum concentrations of the drug in the liquor were found in the patients with the clinical picture of meningitis.


[Formation of a new antibiotic, nocamycin, by a culture of Nocardiopsis syringae sp. nov].

A culture of a new actinomycetous species, Nocardiopsis syrinage was isolated from a soil sample. The antibiotic produced by it was named nocamycin. It accumulated in the culture fluid on cultivation of the organism in a nutrient medium containing soybean meal, glycerin, sodium chloride and calcium carbonate. Crystalline nocamycin had an antitumor effect. In inhibited by 72--73 per cent the development of an intraperitoneally implanted lymphadenosis of strain NK/LI in mice.


[Study of the dynamics of hepataene and pentaene formation by a culture of Streptoverticillium mucoheptinicum strain 44B/1 in the process of biosynthesis].

In the process of growth Streptoverticillium mycoheptinicum, strain 44B/I produced simultaneously a two-component pentaenic antibiotic (mycopenten) and a heptaenic antibiotic (mycoheptin) by the 1st day of cultivation. The ratio of the components remained constant during the whole fermentation process. When grown on the medium with sodium thiosulfate (under conditions of the changed medium potential) the culture produced the heptaen and a mixture of the components with the background absorption of the UV spectrum at 290--360 nm. The ratio of the heptaen and the mixture was also constant during the whole fermentation process.


[Intensification of the action of antibiotics with cationic surface-active substances].

The antimicrobial effect of cationic surface-active substances, such as cetylpyridinyi chloride, alkylmethylbenzylammonium chloride ("roccal" and "catamine AB") and chlorhexidine was studied in vitro. The above compounds had a high bactericidal activity against poly-resistant staphylococcal strains. In non-bactericidal concentrations they significantly increased the efficacy of antibiotcs with different modes of action, i.e. penicillins, tetracyclines, amino-glycosides, macrolides. The effect of the cationic surface-active substances increasing the antibiotic activity against staphylococci did not depend on the resistance type, i.e. chromosomal or extrachromosomal. This was mainly associated with impairement of the function of the bacterial cytoplasmic membrane by these compounds. The cationic surface-active compounds were poor inhibitors of the specific enzyme of Bac. licheninformis 749/C, i.e. penicillinase. A marked inhibition of the enzyme was observed only at concentrations above the bactericidal ones and those damaging the cell membrane of staphylococci.


[Antibiotic sensitivity of Staph. aureus strains isolated from the upper respiratory tracts of healthy carriers].

Sensitivity of 1004 cultures of Staph. aureus isolated from the upper respiratory tracts of the staff of a maternity hospital was studied by the method of serial dilutions in agar with respect to 11 antibiotics. It was found that 61.9, 39.5 and 16.5 per cent of the isolates were resistant to benzylpenicillin, tetracycline and levomycetin respectively. Most of the cultures were sensitive to streptomycin and oleandomycin. The cultures of Staph. aureus isolated from the staff were sensitive to low doses of kanamycin, oxacillin and lincomycin. Most of the isolates were inhibited only by high doses of methicillin, ampicillin, ristomycin and cephaloridin.


[Drug resistance of hospital strains of Staphylococcus epidermidis belonging to different biological types].

A total of 567 strains of Staph. epidermidis isolated from the bacteria carriers in several surgical units were studied. The cultures were typed according to the method developed by the authors. Their resistance to 12 antibiotics, mercuric chloride and cadmium sulphate was determined. Comparison of the strain biotypes and their drug resistance showed in some cases statistically significant correlation. It should be especially noted that staphylococci with pronounced polyresistance (simultaneous resistance to 7--12 antibiotics) prevailed among the strains belonging to biotypes 1 and 3.


[Drug resistance of staphylococci to chemotherapeutic preparations].

A total of 640 strains of pathogenic staphylococci isolated from patients in Kiev in 1971--1975 were studied. High percentage of strains resistant to benzylpenicillin, tetracycline, streptomycin, chloramphenicol and ampicillin was registered. Strains resistant to erythromycin and oleandomycin amounted to 34.4 and 21.5 per cent respectively. Most of the strains proved to be sensitive to neomycin, monomycin, kanamycin, methicillin, oxacillin, lincomycin,rifampicin, ceporin and novobiocin. Strains resistant to ristomycin or oxychinolinic and nitrofuranic drugs were not found among pathogenic staphylococci.


[Pharmacology of rifampicin].

The data on pharmacological study of rifampicin prepared at the All-Union Research Institute of Antibiotics are presented. It was found that by its acute toxicity the drug conformed to rifampicin manufactured by "Lepetit (Italy). When it was administered for a prolonged period of time to rats in doses equivalent to the therapeutic ones for humans, the drug had no effect on the cardiovascular system, the function of the liver and kidneys, growth and debelopment of the rats, the pictures of the peripheral blood. When rifampicin was used in doses 4--8 times higher than the therapeutic ones, it sometimes induced a decrease in the erythrocyte count and hemoglobin level, changes in the liver function, a reliable arrest of the rat growth, some changes in the liver and gastric mucosa revealed on histological examination. No allergic properties of rifampicin were observed in guinea pigs of light colour. No differences in the effect of rifampicin of the Soviet, Italian and Polish production were found.


[Cytomorphological study of lincomycin toxicity].

It was concluded on the basis of the analysis pf the experimental data that lincomycin had a low cytotoxic effect in cell culture and exerted no embryotoxic effect on chick embryoes. Histological examinations showed that on intravenous administration lincomycin had a low irritating effect on the vessel walls and on intramuscular administration it had an insignificant irritating effect without any signs of total toxic effect.


[Effect of the anthracycline antineoplastic antibiotics, rubomycin and carminomycin, on the glycogen and nucleic acid content in the myocardium of white mice].

The effect of 2 anthracycline antibiotics, i.e. rubomycin and karminomycin on the content of glycogen, RNA and DNA in the cardiac muscle of albino mice was studied on their five-fold intravenous administration once every 5 days in equieffect doses by the lethal outcome. It was found that under the effect of the above antibiotics accumulation of glycogen in the cardiac muscle of mice took place, this was most pronounced in the animals treated with karminomycin in doses of 2.15 mg/kg. A decrease in the absolute content of RNA and DNA in the mouse heart after the first 4 administrations and in the ratio of RNA to DNA was observed as compared to the analogous values in the control animals at the account of a more intensive decrease in the content of RNA than that of DNA.


[Study of the equilibrium conditions for the extractive purification of oleandomycin].

Dependence of the oleandomycin distribution coefficient on the antibiotic concentration, duration of the filtrate storage, extraction temperature and salting-out agents was studied. The distribution coefficient of oleandomycin in the system of fermentation broth filtrate--butylacetate was much lower (about 3 times) than that in the system of oleandomycin phosphate aqueous solution--butylacetate. Addition of sodium sulfate to the aqueous phase provided a significant increase in the oleandomycin distribution coefficient.


[Quantitative determination of the gentamicin and dimethyl sulfoxide in the "Gentaplast" film-forming aerosol preparation].

A method for quantitative determination of gentamicin and dimethylsulfoxide (DMSO) in "Gentaplast", a film-forming aerozol preparation was developed. Gentamicin was determined microbiologically after extraction. DMSO was determined by titration with the use of the Redox method. The results of determination of gentamicin and DMSO in "Gentaplast" were statistically treated.


[Study of the possibility of stabilizing a levorin microbiological standard].

The effect of a number of factors, providing increased stability of the levorin microbiological standard was studied. It was shown that air-tight packing and inert gas atmosphere (antibiotic storage in ampoules sealed under nitrogen) significantly increased the antibiotic stability. It was also shown that hydrochinone had the highest positive effect on levorin stability.


[Study of the drug resistance of bacteria of the genus Erwinia].

Sensitivity of 788 strains of Erwinia isolated from natural substrates and received from other laboratories was studied with respect to penicillin, streptomycin, tetracycline, chloramphenicol and kanamycin. It was found that 346 (43.9 per cent) strains were drug resistant. However, the levels of the resistance to most of the drugs tested were not high and amounted to 5-10 gamma/ml. Penicillin resistance was the most frequent characteristics of the strains studied (341 strains). The resistance levels to this drug were higher than those to the other drugs and ranged from 25 to 100 gamma/ml. In some cases they were higher. Analysis of the drug resistance spectra showed that Erwinia strains resistant to 1 (172 strains) or 2 (149 strains) antibiotics were most frequent. 25 strains were multiresistant (to 3-5 drugs). All the resistant strains had 18 types of drug resistance. The genetic control of the drug resistance feature was carried out in the experiments on crossing of the drug resistant strains of Erwinia with the sensitive bacteria of the same genera, i.e. Erwinia chrysanthemi EP-3 and E. coli K-12. The results of the experiments were negative, which should be considered as an evidence of chromosomal localization of the antibiotic resistant genes in the Erwinia bacteria studied.


[Combined action of benzylpenicillin and bile acids on staphylococci].

The antimicrobial effect of benzylpenicillin in combination with bile acids on staphylococci was studied. It was shown that bile acids increased the bacteriostatic and bactericidal effects of the antibiotic. The highest potentiating effect was found with combination of benzylpenicillin and desoxycholic and choleic acids. When resistant strains of staphylococci were exposed to the combination of the bile acids and benzylpenicillin they became highly sensitive to antibiotic.


[Pharmacokinetics of lincomycins in experimental staphylococcal sepsis].

Pharmacokinetics of lincomycin hydrochloride and 7-chlor-7-desoxylincomycin hydrochloride (chlolincocin) was studied on albino mice and rabbits with experimental staphylococcal sepsis caused by intravenous introduction of highly pathogenic cultures. The septic process was accompanied by impairement of the kidney function, the pathological changes in the kidneys being most pronounced. The antibiotic levels in the blood and tissues of the internal organs, i.e. liver, kidneys, lungs and spleen increased in the infected animals, while the content of the antibiotic in the urine decreased. Determination of the plasmatic, kidney and extrakidney clearance revealed the increasing role of the extrakidney clearance. The shudy of the concentrations of 7-desoxylincomycin in the bile of the animals subjected to cholecystostomy showed that the role of the liver in elimination of lincomycin increased in the animals with experimental staphylococcal infection. As the state of the animals improved the changes in the pharmacokinetics of lincomycin decreased.


[Action of carminomycin on the kinetics of cell proliferation and some problems of its combined use with other cytostatic agents].

It was found autoradiographically that karminomycin in the therapeutic dose (0.7 mg/kg) significantly hindered cell proliferation of ascitic tumour L-1210, if the cells were at the stage of DNA proliferation during the drug administration. It was shown that karminomycin in a dose of 0.35 mg/kg administered intraperitoneally decreased the number of the leukemic cell of ascitic tumour P-388 by more than 2 times. Then the number of the leukemic cells increased and it doubled during 47 hours. Karminomycin in a dose of 0.7 mg/kg hindered leukemic cell proliferation during 120 hours. The effectiveness of karminomycin therapy in combination with phopurin or cyclophosphan depended on the treatment regimen. Potentiation of the antileukemic effect was noted in the simultaneus use of the drug or in the primary use of cerminomycin 2 hours before administration of phopurin or cyclophosphan. When phopurin or cyclophosphan was used 2 hours before administration of karminomycin, therapeutic effectiveness was lower.


Inducible high resistance to colistin in Proteus strains.

Wild-type Proteus strains are usually resistant to colistin. We have observed an increase in the level of colistin resistance in four clinical isolates of P. vulgaris, P. morganii, and P. rettgeri by prior treatment with subinhibitory concentrations of the drug. The enhanced resistance in these strains was lost after cultivating them in colistin-free medium, indicating that the enhanced resistance in the Proteus group is inducible.


Pharmacokinetics and tolerance of a single twelve-tablet dose of trimethoprim (960 mg)-sulfamethoxazole (4,800 mg).

To evaluate the potential usefulness of a single large oral dose of trimethoprim-sulfamethoxazole (TMP-SMZ) for the treatment of uncomplicated genitourinary gonorrhea, the pharmacokinetics of a 12-tablet dose containing 960 mg of TMP and 4,800 mg of SMZ were studied in 15 male volunteers, and the tolerance of this regimen was compared to that of a placebo in a double-blind crossover study. Both TMP and SMZ were rapidly absorbed. Peak mean serum concentrations (+/- standard deviation) of TMP, total SMZ, and free SMZ were 9.2 +/- 2.2, 259.4 +/- 40.9, and 233.7 +/- 33.6 mug/ml, respectively. Elimination half-lives were 16.7, 14.6, and 12.9 h, respectively. When results were compared to data from similar studies after smaller doses, peak mean serum concentrations were proportional to dose, but elimination half-lives were longer after larger doses. Urinary concentrations of TMP, total SMZ, and free SMZ were many-fold higher than serum concentrations. Percents recovery (+/- standard deviation) in urine were 60.6 +/- 10.6, 80.2 +/- 7.8, and 37.4 +/- 6.5%, respectively, during the 48 h after administration. The incidence of severe headache and of objective transient oliguria was significantly higher after TMP-SMZ than after placebo. Although the observed serum concentrations of TMP and SMZ surpassed concentrations necessary to inhibit clinical isolates of Neisseria gonorrhoeae in vitro for longer than 24 h, the adverse reactions associated with a 12-tablet dose of TMP-SMZ would preclude the clinical usefulness of such a therapeutic regimen.


In vitro evaluation of three iodine-containing compounds as antiplaque agents.

The antibacterial activity of three iodine-containing compounds was determined for strains of four dental plaque-forming microorganisms, using an in vitro preclinical plaque model system. Solutions of inorganic iodine, povidone-iodine, and Wescodyne were tested for antiplaque activity against preformed plaques of a number of strains of Streptococcus mutans, Streptococcus sanguis, Actinomyces viscosus, and Actinomyces naeslundii. Solutions of inorganic iodine were more effective as antiplaque agents, with respect to minimal bactericidal concentration and time and frequency of treatments, than solutions of Wescodyne and povidone-iodine. Inorganic iodine appeared to be particularly effective against the most cariogenic (S. mutans) and periodontopathic (A. viscosus) organisms while allowing survival of the least orally pathogenic plaque-forming microorganism (S. sanguis). It is suggested that topical application of solutions of inorganic iodine may be useful in controlling dental caries and actinomyces-associated periodontal disease.


Human interferon: mass production in a newly established cell line, MG-63.

MG-63 cells, a line derived from an osteosarcoma, produced high yields of interferon after superinduction with polyinosinic acid.polycytidylic acid, cycloheximide, and actinomycin D. Advantages of MG-63 cells over diploid fibroblasts as a substrate are: no requirement for aging between confluency and induction, no requirement for priming, and 3.7-fold higher yields per square centimeter of culture surface. Physicochemically and biologically, MG-63 cell interferon resembles fibroblast rather than leukocyte interferon.


Failure of type 1 herpesvirus to develop resistance to ribavirin.

Exposure (10 passages) of type 1 herpesvirus to ribavirin or idoxuridine in Vero cells results in resistance to idoxuridine, but not to ribavirin.


Pharmacokinetic study of netilmicin.

Netilmicin at a dose of 2 mg/kg was infused intravenously into 10 healthy volunteers. A peak serum concentration of 16.56 mug/ml was obtained at the end of the infusion. Thirty-nine percent of the infused dose was excreted in the urine during the first 8 h after infusion. The pharmacokinetic parameters of netilmicin were derived by analyzing the elimination data according to a two-compartment model.


Lytic effect of mycobacillin and its derivatives on erythrocytes.

Mycobacillin as well as its O-acetyl (tyrosyl and seryl) and ester derivatives is known to have antifungal activity. The antibiotic also possesses hemolytic activity. This latter property is not appreciably altered by partial or complete esterification of its free carboxyl groups. On the other hand, acetylation of the molecule at the two tyrosyl hydroxyl groups nullifies selectively the hemolytic activity.


2"-O-phosphorylation of gentamicin components by a Staphylococcus aureus strain carrying a plasmid.

A wild-type strain of Staphylococcus aureus that inactivates the 4,6-glycosidically linked deoxystreptamine aminoglycoside antibiotics by a plasmid-mediated process was found to harbor two enzymes: an acetyltransferase of the AAC(6') type and a new phosphotranferase specific to the gentamicin components. The target of this last enzyme is the 2''-hydroxyl function of these antibiotics, since one inactivated compound is 2''-(O)-phosphorylsisomicin.


Cefuroxime, a new parenteral cephalosporin: collaborative in vitro susceptibility comparison with cephalothin against 5,887 clinical bacterial isolates.

Cefuroxime, a new parenteral cephalosporin was compared with cephalothin by broth microdilution susceptibility testing against 5,887 routine clinical bacterial isolates in four large clinical laboratories. The minimal inhibitory concentrations (MICs) of cefuroxime against the Enterobacteriaceae were consistently lower than those of cephalothin. This was most striking among the Enterobacter species, which were generally susceptible to cefuroxime (MIC </= 8 mug/ml), but resistant to cephalothin. Similar results occurred with Haemophilus species, Acinetobacter anitratus, meningococci, and Aeromonas hydrophilia, but Pseudomonas species and enterococci were resistant to high concentrations of both drugs. Streptococci showed slightly greater susceptibility to cefuroxime than to cephalothin. By contrast, staphylococci were more susceptible to cephalothin. Bacteroides fragilis was resistant to cefuroxime, but other anaerobes were generally susceptible.


Electrical impedance measurements in the reading and monitoring of broth dilution susceptibility tests.

Electrical impedance changes in the medium were studied during traditional broth dilution tests. Tests involved clinical isolates of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Enterobacter sp., Klebsiella, and enterococcus and ten antibiotics. Minimal inhibitory concentration (MIC) values from overnight visual readings were compared with MIC values determined from electrical impedance end points, using inocula of 10(6) organisms per ml. Ninety-three percent of the results were within one twofold dilution of each other. When the impedance end point was determined at 6 h, this correlation was lowered to 34%. By increasing the initial electrical impedance inoculum 10-fold, the correlation between the 6-h impedance MIC and the overnight visual MIC was improved to 74%. Ampicillin, tetracycline, and polymyxin E results accounted for most discrepancies. Continuous monitoring of impedance changes suggested that better correspondence could be obtained by adjusting the end point criteria for the 6-h impedance MIC with different antibiotics. Electrical impedance methods for reading bacterial end points in automated clinical laboratory instruments appear promising.


Metabolic fate of [14C]cefamandole, a parenteral cephalosporin antibiotic, in rats and dogs.

The biotransformation of the parenterally effective cephalosporin antibiotic cefamandole nafate (I) has been studied in rats and dogs. After rapid in vivo hydrolysis of the nafate pharmaceutical form to cefamandole (II), the antibiotic was found to be very resistant to metabolic degradation in both species. In dogs, cefamandole escaped metabolism and was eliminated as unaltered antibiotic almost exclusively by renal excretion. In rats, cefamandole was somewhat labile to metabolism; however, a major portion of the administered antibiotic was eliminated unchanged principally by renal excretion.


Antimicrobial activity of several antibiotics and a sulfonamide against Chlamydia trachomatis organisms in cell culture.

Minimum inhibitory concentrations of several antibiotics and a sulfonamide for growth of the 15 known immunotypes of Chlamydia trachomatis were determined in HeLa 229 cell cultures. The concentrations for complete inhibition of infectious-organism production were (per milliliter): tetracycline, 0.02 to 0.5 mug; rosamicin, 0.05 to 0.25 mug; erythromycin, 0.1 to 0.5 mug; chloramphenicol, 10 mug; penicillin, 0.02 to 50 U; ampicillin, 0.1 to 50 mug; and sulfisoxazole, 2 to 200 mug. The same concentrations of tetracycline, rosamicin, erythromycin, and chloramphenicol were sufficient to inhibit C. trachomatis inclusion formation. An increased concentration of sulfisoxazole was often needed to inhibit inclusion formation. Penicillin at 100 U/ml and ampicillin at 100 mug/ml failed to completely inhibit inclusion formation.


Comparison of pharmacological and antimicrobial properties of cefadroxil and cephalexin.

Pharmacological and antimicrobial properties of cefadroxil, a new cephalosporin antibiotic, were compared with cephalexin. Absorption and excretion were studied in 20 healthy men. Peak concentrations of the drugs in serum were similar after ingestion of single 500-mg tablets. The concentration of cefadroxil in serum was more sustained than that of cephalexin. Levels of cefadroxil in serum after a dose of 1,000 mg were approximately twice those after a 500-mg dose through 6 h. Each drug administered in a dose of 500 mg every 6 h for 24 h resulted in concentrations in serum that were similar to a single dose without accumulation. Ninety-three percent of the cefadroxil and 85% of the cephalexin were excreted in urine after ingestions of single 500-mg tablets. The urine concentration of cefadroxil was more sustained than cephalexin. Minimal inhibitory and minimal bactericidal concentrations for clinical isolates were comparable with each drug. Cefadroxil compares favorably with cephalexin in this study. Sustained levels of cefadroxil in serum and urine suggest that this drug may be given at less frequent intervals than cephalexin.


Pharmacokinetics of nafcillin in patients with renal failure.

Nafcillin, a pencillinase-resistant penicillin, is frequently used for treatment of staphylococcal infections in hemodialysis patients. Despite its widespread use, there is a paucity of available data regarding the pharmacokinetics of nafcillin in hemodialysis patients. Therefore, sodium nafcillin, 25 mg/kg, was given intravenously over a 5- to 15-min period to 12 hemodialysis patients. Eleven patients were studied during dialysis, and eight of these were studied again during the interdialysis period. The initial serum half-life for nafcillin was 0.208 h during dialyses and 0.278 h between dialyses. The terminal half-life was 1.48 h during dialyses and 1.89 h between dialyses. There was no statistically significant difference between these values. These data indicate that renal failure does not appreciably affect the serum half-life of nafcillin, and hemodialysis does not accelerate the rate of clearance of nafcillin from the blood. Therefore, no modification of the usual nafcillin dosage is necessary when using this drug in hemodialysis patients.


Penetration, permeation, and absorption of triamcinolone acetonide in normal and psoriatic skin.

Penetration studies of radiolabelled Triamcinolone acetonide from ointment or cream preparations revealed that in cases of normal as well as psoriatic skin 70-90% of the applied substance remains on the surface. Normal horny layer stores up to 30% of the steroid. Nevertheless, a rapid penetration into the living layers of the skin is observed, whereby the epidermal concentrations reach levels between 5-10(-6) and 3-10(-5) M (mol per liter of tissue). The excretion in the urine took more than 72 h after removal of the excess of substance from the skin. In psoriatic skin, the epidermal and dermal concentrations were 3-10 times higher than in normal skin. This increase lies in the same range as the one resulting from removal of the horny layer by stripping prior to the application, as reported earlier.


SDS-polyacrylamide gel electrophoretic determination of type I and type III collagen in small skin samples.

A sodium dodecylsulfate-polyacrylamide electrophoretic method, which in contrast to other biochemical procedures, e.g. differential salt precipitation or ion exchange chromatography and molecular sieve chromatography, is applicable to smallest amounts of protein, is shown to be suitable for the determination of the collagen types from small skin samples, such as routine skin biopsies. After urea extraction, the tissue samples are cleaved with cyanogen bromide. The resulting CNBr peptides derived from the different alpha-chains are resolved in 12% SDS-polyacrylamide gels. Densitometric profiles of the gel electrophoretic patterns correspond to the collagen type content of the tissue specimens. Comparing fetal to adult skin, the higher content of type III collagen in the case of fetal skin can be demonstrated.


The significance of fluorescein angiography in the early diagnosis of lesions on ocular fundus at pseudoxanthoma elasticum patients.

The role of fluorescein angiography in early diagnosis of lesions on fundus of the eye at pseudoxanthoma elasticum patients has been shown. The authors show angiographic changes on the basis of three cases of pseudoxanthoma elasticum patients.


Histological features of "pagetoid reticulosis" (Woringer-Kolopp) in pre-mycosis fungoides.

The case of a 66-year-old female with chronic skin lesions is described, which clinically resembled parakeratosis variegata but histologically showed the pattern of "pagetoid reticulosis" (Woringer-Kolopp). The intraepidermal pagetoid cells were lymphoid cells which, by electron microscopy, could be identified as small Sézary cells. The intraepidermal presence of numerous  atypical reticulum cells does not support the theory of "pagetoid reticulosis" as a separate nosological entity, but rather stresses the epidermotropic character of (pre-)mycosis fungoides just known from intraepidermal Pautrier microabscesses.


Factors responsible for dermally induced epidermal hyperplasia.

The secondary epidermal hyperplasia seen over some dermal lesions can be experimentally induced in the guinea pig by the intracutaneous injection of carrageenan. This paper documents experiments directed to determining the factors that cause this epidermal reaction. Indomethacin, aspirin and polyphloretin phosphate were found to block the epidermal thickening. "Non inflammatory" stretching of the skin induced by a silastic implant caused an increase in the germinative population but no sustained epidermal hyperplasia. Rubbing into the skin a rubefacient cream produced more epidermal hyperplasia than did the base cream alone. It is suggested that the secondary epidermal hyperplasia from dermal abnormalities is multifactorial in its causation but that prostaglandin release might be involved and that increased blood flow may also play a role.


Local skin necroses after intramuscular injection -Experimental animal studies-.

The pathogenesis of local skin necroses after intramuscular injection of various drugs such as phenylbutazone (Embolia cutis medicamentosa, Nicolau's syndrome) is not clear. In an attempt to simulate this clinical feature experiments were performed on the rabbit ear lobe. A 20% phenylbutazone solution was injected paraarterial, intraarterial and paraarterial after perforation of the vessel. The drug produced a violent inflammation with all kinds of application. The local inflammation induced by paraarterial injection resulted in a fine scarring. Both other kinds of application produced necroses or even perforations. The histological examinations in these cases revealed massive destructions of the inner arterial wall. In control-experiments necroses or perforations were nerve observed. From these data the following conclusions on the etiology of Nicolau's syndrome can be drawn: Phenylbutazone injected into the vascular or perivascular tissue causes an obligatory inflammation. After lesion of an artery complete destruction of the vessel followed by necrosis of the skin may occur. It seems obvious that this secondary effect can not completely be avoided.


Testosterone levels and gonadotrophins in Klinefelter's patients treated with injections of mesterolone cipionate.

Hormone levels were measured in patients with Klinefelter's syndrome after treatment with 100 mg mesterolone cipionate (twice monthly). There was no difference in plasma testosterone and FSH levels in treated and untreated patients. The basal and maximum LH levels were lower, but remained raised. The urinary excretion of testosterone as measured by liquid gaschromatography was higher in treated patients after treatment was discontinued.-From these results it is concluded that in spite of reported decreases of plasma testosterone during therapy with mesterolone cipionate this drug does not lead to severe impairment of the endogenous hormone production after discontinuing treatment.


Influence of some inflammatory or antiinflammatory substances on skin biopsies investigated with microcalorimetry and respiratory techniques.

Thermal effects were achieved from skin biopsies (epidermis, corium, subcutis) measured by batch-microcalorimetry, after exposure to potent inflammatory or antiinflammatory substances (compound 48/80, histamine, serotonine and hydrocortisone phosphate). Exothermic effects were achieved from 48-80, histamine and hydrocortisone phosphate, when exposed to the skin and lasting for varying time. From serotonine initial endothermic signals were achieved but after about 50 min there was stabilizing of the thermal reaction at the baseline. To analyze the nature of these non-specific thermal effects, determinations of O2 consumption and CO2 production were performed, using Warburg technique on exactly matched tissue pieces exposed to the same substances and run parallely with the microcalorimetrical determinations. An increased respiration, probably as an indicator of increased metabolism was registrated for all test substances acting on the skin. It felt, that the thermal effects reflect an increased metabolism of the tissue exposed to the test substances.


Effect of morestan and other substituted quinoxalines on the activities of various rat hepatic mixed-function oxidases.

Morestan (6-methyl-2,3-quinoxalinedithiol cyclic-S,S carbonate) and two of its metabolites: methyl-2,3-quinoxalinedithiol and 6-methyl-2,3-quinoxalinedihydroxy were administered to male and female rats by intraperitoneal route for 4 consecutive days (50 mg/kg/daily). Morestan was also administered by esophageal intubation for 4 days at the dose of 75 mg/kg/daily. After evaluating the pentobarbital sleeping time in the animals on the 5th day, aminopyrine N-demethylase, p-nitroanisole O-demethylase and aromatic aniline hyroxylase activities and levels of cytochrome P450, proteins and RNA were measured in the microsomal hepatic fraction. Protein and nucleic acid levels were also measured in whole liver. The 3 substances studied caused considerable decreases in activity of certain microsomal enzymes: morestan inhibits some hepatic mixed-function oxidase systems; in females it is more active by peroral administration, and in males by intraperitoneal route. However, 6-methyl-2,3-quinoxalinedithiol is an even more powerful inhibitor of monooxygenase activities both in males and females. 6-methyl-2,3-quinoxalinedihydroxy also decreases activity by microsomal enzymes, but its action is inferior to that of the other two products investigated.


Identification and determination of ionic surface active agents.

A general colorimetric method has been developed to analyze either anionic or cationic surfactants in fresh water. An appropriate dye will react with ionic surfactant to form a chloroform-soluble, colored complex in the presence of chloroform. The color intensity of the vigorously rocked and subsequently settled chloroform layer is proportional to the concentration of the "dye-ionic surfactant complex", and can then be measured by making spectrophotometric readings of the chloroform solution at the optimum wavelength of the instrument used. When cationic surfactants are to be analyzed, methyl orange shall be used as a dye; when anionic surfactants are to be analyzed, azure A or methylene blue shall be used as a dye; Other chemical reagents, apparatus and spectrophotometers, however, can be nearly identical for either cationic surfactant or anionic surfactant measurement. The new analytical method is stoichiometric, and can be easily performed by a laboratory technician within a very short period of time.


Physiological response to organophosphate residues in field workers.

The physiologic response of 21 male agricultural field workers exposed to foliage-borne Guthion residues was monitored during routine peach-thinning operations in a northern California orchard. Surveillance included daily venipuncture and urine collection to determine whole blood cholinesterase (CHE) activity and level of dialkylphosphate excretion for 3 baseline (nonexposed) and 5 normal work days. Foliage samples were obtained to measure dislodgeable and total Guthion residues. A decrease in group-mean CHE activity by 15% over the surveillance period was found. Apart from one worker who showed a consistent decrease in CHE activity, reaching a maximum of 30% below baseline at the end of the work week, daily changes in individual CHE activity were erratic. Group-mean dialkylphosphate excretion levels provided a semiquantitative indication of exposure to Guthion. Medical examination before and after the exposure period revealed an absence of clinical signs of organophosphate intoxication.


[Prinzmetal's angina. Response to the treatment with reserpine. Review of its physiopathological mechanisms].

A case of Prinzmetal angina refractory to classic medical treatment, in which the angina attacks were suppressed with the administration qf reserpine is presented. The possible physiopathologic mecanisms of this entity are reviewed. The possibility of coronary spasm due to an alteration in the regulation of the coronary arterial tone from an autonomic.nervous system illness is established, an abnormal coronary vascular reactivity is also reviewed. It is emphasized that the Prinzmetal angina is an original entity, idfferent from the coronary arteriosclerotic heart disease, which may coexist with it but which cannot be treated in the same way, because its physiopathologic mecanisms are different.


[An explanation of ventilation problems in congenital heart disease with left to right shunt].

The problems associated with the ventilation of children who have congenital heart disease with left to righ shunts and pulmonary hypertension are more likely to be acquired than due to the congenital malformation. Haemodynamic, angiographic, bronchoscopic and bronchographic studies demonstrated that ventilation problems arose because of compression of the bronchus by the pulmonary artery. The bronchial compression should be treated by surgery to the heart defect without removing the lung. The intervention should be early to obtain maximum benefit and to avoid irreversible damage to the bronchus.


[Epilepsy, anticonvulsants and pregnancy].

A statistical study, using a computer, of 343 epileptic women with 775 pregnancies led to the following conclusions: 1. The influence of pregnancy on epilepsy is very variable: null once out of 2 times, pregnancy is more often favourable than unfavourable in the remaining 50% of the cases. 2. The influence of epilepsy on pregnancy seems to be null with regard to the course of pregnancy, its termination and the post-delivery period. The perinatal mortality rate is, however, higher. 3. Concerning the very present question of the teratogenic risk due to anticonvulsants, it appears that an epileptic woman has a slightly higher risk to bear a child with a congenital defect than does a non-epileptic mother; 4.04% of malformations in treated epileptic women, 2.32% in non-treated; 2.2% and 1.8% in two control groups.


[Measurement of colloidosmostic pressure].

In the patient in a critical state there are numerous conditions which alter the COP (Coloidosmotic pressure), which is important for the exchange of liquids at the capillary level of the entire organism. As a consequence for these changes, problems occur with the accumulation of water in the intersticia and a malfunction of organs. A device to measure the COP in a reliable, rapid, and economical form is described. Its simple operation is of great use in the intensive care units for the rapid diagnosis and adequate management of the alterations in the water balance of the critical patient.


[Doppler findings in intracranial vascular disorders. Differential diagnosis of extracranial and intracranial vascular occlusions (author's transl)].

Directional Doppler sonography of the carotid arteries in the neck (selective for the common carotid artery, external and internal carotid arteries) and of the supratrochlear artery permits reliable diagnoses and localizations of extracranial stenoses and occlusions of these arteries. In addition, severe intracranial vascular disorders may also be detected by these methods. Characteristic combinations of Doppler results are described in occlusions of the trunk of the middle cerebral artery, cerebral circulatory breakdown, large arteriovenous angiomas of one hemisphere and carotidcavernous fistulas, and are compared with angiographic findings. The knowledge of these Doppler findings is indispensable for the differential critical evaluation of such disorders found at the level of the neck arteries and at the fronto-orbital terminal branches of the ophthalmic artery.


Regional cerebral blood flow in a case of bromide psychosis.

A case of bromide psychosis is described. A course of repeated measurements of the regional cerebral blood flow (rCBF) was followed, using the 133Xe inhalation method. At the first examination, when the serum bromide level was 45 mmol/1, the cerebral blood flow was reduced to about one-third of the normal. The regional flow pattern was also abnormal with low flows in frontal and parieto-occipital regions. Hemodialysis was performed with an overall improvement of the condition and a successive normalization of rCBF. The pronounced decrease of the cerebral blood flow, together with the positive effects of hemodialysis, seems to indicate that bromide psychosis is of a toxic origin and not an abstinence phenomenon.


Autonomic activation and endogenous depression.

Psychophysiologic parameters were investigated in 10 patients with endogenous depression during the course of electroconvulsive therapy. Changes in the depressive mood were assessed by the patients at regular intervals using a general mood scale. EEG and heart rate response and habituation were recorded before, during, and after E.C.T. Prior to treatment a low variance and responsiveness and striking intra-individual stability were found in the physiologic parameters. At the start of E.C.T. there was a significant increase in the deviation values of heart rate and a significant increase in the occurrence of typical biphasic heart rate responses. The EEG showed increased amplitudes and a slowing of background activity. Treatment-dependent differences were also seen in the habituation of the EEG amplitude response. Regarding improvement in the depressive mood, differences were found between the retarded and the agitated patients. Agitated patients demonstrated a continous gradual decline of their depressive condition, while in retarded patients the general trend toward improvement passed through a period of increased mood lability. The results are interpreted with reference to the activation dependency of heart rate responses.


Memory impairment after convulsive therapy. Influence of age and number of treatments.

The influence of age and number of treatments on memory impairment was studied in depressed patients after a series of convulsive treatments: bilateral ECT, unilateral ECT on the nondominant hemisphere, and fluorothyl convulsive therapy. Before and after the completed convulsive therapy course the patients were tested with a memory test battery and the symptoms rated with a depression scale. Before treatment older age-groups had decreased ability to learn, but their post-treatment forgetting score was not significantly higher than in other age-groups. An increase in the number of ECTs did not seem to correlate with the degree of memory impairment. The conclusion of the present study is that age (up to 65) and the number of ECTs (up to 10) have no apparent influence on memory impairment after electroconvulsive therapy.


[AMP system: longitudinal studies of psychopathologic and somatic symptoms. An empiric investigation of the problem of side effects (author's transl)].

The psychopathologic and somatic state of 681 psychiatric patients were investigated in longitudinal studies within the scope of different psychopharmacologic trials. Most psychologic symptoms occur less frequently, whereas somatic symptoms are found to increase, which suggests side effects from psychotropic drugs. The analyses show that the AMP-system can be reduced by 49 (possibly 45) symptoms, as initial findings and developments show that these symptoms are rare, and do not allow of differentiation between diagnostic groups.


[Neuropsychological investigations of thought processes in aphasics (author's transl)].

Fifteen aphasics and 10 patients with cortical lesions of the right (nondominant) hemisphere were examined using 10 nonverbal psychological tests with 23 variants. The number of correct solutions and the duration of fulfillment of each variant were recorded with statistical significance and standard deviations. Aphasics as well as patients with right-sided cortical damage have lower scores than normal individuals for both correctness and duration of performance. The two groups of patients differed in that the number of correct solutions was higher in aphasics than it was in right-sided cortical injury cases. Aphasics required a longer time to perform the tests used by the authors than normals did, and those with right-sided cortical lesions required an even longer time. The results were also dependent on the kind of test applied. For example, the differences shown by tests 4, 5, 6, and 10 were comparatively less among the three groups (normals, aphasics, and right-sided damage of the cortex) and nonsignificant. The results are discussed in relation to thought processes, language, and aphasia.


Multifrequency tympanometry.

The tympanogram shape has been investigated in 290 patients as a function of probe tone frequency (from 200 to 2000 Hz). As the frequency of the probe tone rises, the tympanogram undergoes characteristic modifications which have been grouped, according to their morphologic similarities, in three classes: V, W and inverted-V shape. These three tympanometric configurations are consistently observed both in normals and in some patients with middle ear disorders. Exceptions to this regular behaviour are the pathological pictures of the middle ear in which the structure or the dynamics of the tympano-ossicular system are significantly altered (massive tympanosclerosis, glue ear and cholesteatoma). The frequency interval at which the characteristic tympanometric configurations appear is the most important factor for differentiating pathophysiologic conditions of the middle ear.


Middle-ear impedance measurements in screening.

Middle-ear disorders are the major cause of hearing loss in the young school child, the majority of sensorineural disorders already having been detected. Mild conductive deafness may lead to educational retardation, psychological and social problems as well as to more severe middle-ear problems. It is consequently important to detect persistent middle-ear conditions as early as possible. Pure-tone audiometry has been shown to be a poor method of identifying middle-ear effusions. Impedance measurement is considerably more efficient, and different approaches are reviewed in the light of long-term studies of middle-ear effusion.


The intra-aural muscle reflex in retrocochlear pathology: a model study in the rabbit.

An animal model for the evaluation of the acoustic stapedius reflex is described. The intra-aural muscle reflex in the rabbit can be recorded with a technique identical to that used in man. The validity and reproducibility of the measurements are good. Lesions in the reflex pathway were shown to be followed by changes in reflex properties. The type of alteration depended on the location of the damage. Lesions in the dorsal cochlear nucleus were not followed by reflex changes. Lesions in the ventral cochlear nucleus and/or the eighth nerve were followed by a rise of reflex threshold and often, but not always, by reflex decay. Lesions in the midline of the trapezoid body were followed by specific changes in the crossed reflex, whereas the ipsilateral reflex was unaffected. The advantage of making simultaneous ipsilateral and contraleral reflex recordings was pointed out.


A further examination of the use of the stapedius reflex in the diagnosis of acoustic neuroma.

Criteria proposed by ANDERSON et al. for the diagnosis of early acoustic neuromas using the acoustic stapedius reflex were examined. Populations of normal hearers and subjects with sensorineural hearing losses were studied and yielded high false-positive detection rates by the threshold criteria. It is suggested that the threshold asymmetry of the reflex may be more useful than the absolute threshold.


Multifrequency impedance testing in relation to otospongiotic stapedial fixation and other factors.

After reviewing COLLETTI'S research, the authors describe their own experimental work on multifrequency impedance testing in relation to stapedial fixation in otospongiosis, and other factors. Their findings, based on 266 tested ears, lead the authors to the conclusion that : (1) the most useful frequencies, from the clinical point of view, are the low ones (220, 660 and 800 Hz); (2) the research frequencies, range beyond (900 to 2 000 Hz), for a finer diagnosis, but are confused by numerous artefacts and are not always reliable; (3) COLLETTI'S conclusions on the inversion of the peak and on the shifting of M and W, are valuable, but not always reliable in some cases.


Diagnostic application and interpretation of tympanometry and the acoustic reflex.

Tympanometry and the acoustic reflex constitute a powerful middle ear measurement battery. Together, these measurements provide us with direct objective information about the integrity and mobility of the middle ear system and the status of the sensorineural auditory function. A descriptive analysis of tympanograms involves a consideration of the amplitude and shape of the tympanogram as well as the location of the peak along the air pressure axis. The differential effect of pathology on tympanogram pressure peak location, amplitude and shape as well as on the acoustic reflex provides the capability for the application of this battery in the differential diagnosis of auditory disorders.


Pathology of the nervous arc of the acoustic reflexes.

A short comment is made on the pathological conditions of the input and efferent arc of the stapedius reflex. The modifications of this reflex during pathological and experimental inpairment of the intermediate portion of the arc, at the brain stem level, in human subjects are analyzed in more detail. The graphic and oscilloscopic records demonstrate a modification of the latency, amplitude and particularly of the speed of onset of the reflex. A concomitant modification of the electronystagmogram and tonal tests of lateralization is also demonstrated. Some abnormal responses observed in cases of facial palsy (efferent arc) as compared with electrogustometry and the problem of eliciting an isolated reflex contraction of the tensor tympani are briefly commented upon.


Impedance changes elicited by electrocutaneous stimulation.

Electrical stimulation of the skin in the cavum conchae is followed by bilateral changes in the acoustic impedance of the ear due to reflex contraction of the stapedius muscle. A stimulator and a special surface electrode for electrical stimulation of the skin have been developed. The apparatus produces square-wave constant-current pulses independent of the electrical impedance of the electrode and the skin, and its hazard-proof. The effect of five independently variable stimulus parameters upon the elicited impedance changes has been examined in order to find a stimulus producing a large and reproducible impedance change without causing discomfort to the subject. Although a pronounced habituation phenomenon tends to mask the cause to effect relation of the various parameters, the results indicate that an appropriate stimulus is a pulse train of 0.5 s duration, consisting of individual pulses of a frequency of 200 Hz and 1 ms duration. The stimulus is applied at 10-second intervals.


Effects of hyperoxia on glutathione reductase activity, membrane proteins, and esterases of rabbit erythrocytes.

Rabbits were exposed to 100% oxygen at pressures of 256 to 1520 mm Hg for up to 5 d and the blood and erythrocytes of these animals were examined for changes that could be related to hyperoxia. Glutathione reductase activity of erythrocytes was reduced 5 to 29% by hyperoxia, whereas that of the plasma was not significantly altered. Significant changes in red and white cell counts, including differential leukocyte count, could not be detected. Electrophoretic analysis of the proteins and esterases derived from plasma and membranes and cytoplasmic fractions of erythrocytes did not reveal changes attributable to hyperoxia.


Some psychological correlates of motion sickness susceptibility.

Four groups of 37 subjects each (highly susceptible men, highly susceptible women, nonsusceptible men, and nonsusceptible women) were obtained from a population of 2,432 college students ranging in age from 18 to 39 years. Susceptibility to motion sickness was determined by scores on a motion sickness questionnaire (MSQ); only individuals with extreme scores were considered for inclusion in the experimental groups. The following tests were administered: Floor Ataxia Test Battery, State-Trait Anxiety Inventory, Menstrual Distress Questionnaire, Cornell Medical Index, Cornell Work Form, Eysenck Personality Inventory, Rotter Internal-External Locus of Control Scale, and the 16 Personality Factors test. Each subject was tested on at least three, but not more than six, of the eight tests. Significant sex differences were obtained on the ataxia battery and the Cornell Medical Index. Susceptible subjects did not differ significantly from nonsusceptibles on the ataxia battery but did differ significantly on all personality tests except the Menstrual Distress Questionnaire (administered only to women) and the Rotter Scale. The generally consistent and significant patterns of results from the psychological tests probably reflect the selection factors used in defining the subject groups; certain personality characteristics are associated with a high degree of susceptibility to motion sickness.


Prolonged weightlessness effect on postflight plasma thyroid hormones.

Blood drawn before and after spaceflight from the nine Skylab astronauts showed a statistically significant increase in mean plasma thyroxine (T-4) of 1.4 microgram/dl and in thyroid-stimulating hormone (TSH) of 4 muU/ml. Concurrent triiodothyronine (T-3) levels decreased 27 ng/dl indicating inhibited conversion of T-4 to T-3. The T-3 decrease is postulated to be a result of the increased cortisol levels noted during and following each mission. These results confirm the thyroidal changes noted after the shorter Apollo flights and show that thyroid hormone levels change during spaceflight.


Voluntary eye movements and alcohol.

Human voluntary horizontal eye-movements are studied prior and subsequent to the ingestion of alcohol. Such movements are important, especially during reading and driving. Infrared monitoring techniques were employed to record eye movements and eye-movement latency histograms were tabulated. Blood alcohol levels were continually monitored. Alcohol increases eye-movement latency but the maximum latency occurred in most cases at different elapsed times from the time of maximum blood alcohol level. In general, a roughly 20% increase in latency occurs subsequent to alcohol. Whether this added delay is a result of a general depression of the oculomotor system or a specific increase in some oculomotor computing element is unresolved. Within the limits of our experimentation, there was no difference between latency change observed in moderate and heavy drinkers.


Sleep at altitude.

The effects of hypobaric hypoxia upon the electrophysiologically assessed sleep of four male and four female subjects--18-29 years old--were measured during two successive nights at 493 torr (3500 m) in a hypobaric chamber. Five subjects experienced varied levels of acute mountain sickness (AMS). Sleep disturbance was primarily manifested as "insomnia" in two subjects experiencing higher levels of AMS. Relatively normal amounts of synchronized sleep were observed at 493 torr, implying the occurrence of sleep hypoventilation.


Cardiac output during sleep at altitude.

The effects of hypobaric hypoxia and sleep, assessed by EEG, upon cardiac output (Q) were studied by impedance cardiography using two male and two female subjects. Three nights were spent at 746 torr (152 m) followed by two nights at 493 torr (3500 m), all in a hypobaric chamber. Relatively normal sleep was observed except in the presence of Acute Mountain Sickness (AMS). The occurrence of normal levels of synchronized sleep implied that sleep hypoventilation occurred. A nadir of Q was observed at about 0500 hours, implying reduced O2 delivery. It was suggested that hypobaric hypoxia, sleep hypoventilation, and reduced O2 delivery may have interacted to produce AMS.


Accidental hypothermia: an experimental study of practical rewarming methods.

Five rewarming techniques, appropriate for first-aid use in the nonhospital setting, were applied to each of nine subjects whose body temperatures had been lowered to 35 degrees C in a stirred tank of 7.5 degrees C water. The rewarming techniques were: a) inhalation of heated, water-saturated oxygen; b) placement of heating pads over areas of high heat transfer; c) combination of methods a) and b); d) hot whirlpool bath; and e) shivering. Inhalation of heated, water-saturated oxygen was significantly better than the shivering control in minimizing temperature "afterdrop" and is, therefore, preferred over the other techniques as it avoids the physiological hazards of the peripheral vasodilation from external rewarming.


Effect of bedrest on circadian rhythms of plasma renin, aldosterone, and cortisol.

Previous studies of normal men after 5 d of bedrest showed that circulatory instability on head-up tilt or standing is preceded by increased plasma renin activity (PRA) at bedrest. In the present study, the circadian rhythms of PRA, aldosterone, and cortisol have been observed in five normal men on a constant diet. In ambulatory controls, PRA and aldosterone increased normally after standing. On the third morning of bedrest, PRA was higher than before, and at noon, PRA was higher than in standing controls. The nocturnal peaks of PRA resulting from episodic renin secretion during sleep were higher after bedrest. Plasma aldosterone was also increased by bedrest. The findings are compatible with the theory that intermittent beta-adrenergic nerve activity during sleep is increased after bedrest, but other factors, such as loss of body sodium and a lower plasma volume, may also be involved.


Comparison of indirect calorimetry and direct heat flow discs results in measuring R+C heat loss in burned patients.

This study was carried out on 17 burned patients. Metabolic heat production, rectal and skin temperatures, and heat exchanges by R+C were measured. It was found that R+C heat loss takes into account 60 to 80% of the increased metabolic heat production. Two methods were used to measure R+C heat loss: calculation by indirect calorimetry and direct measurements by using heat flow discs. The direct relationship which exists between the results of these two methods showed the reliability of the use of heat flow discs for measuring R+C heat loss. This fast-responding techniques may allow the elaboration of a thermal setting system which could modulate ambient air temperature, thus limiting exagerated heat loss due to the skin lesions.


Thermal data from helicopters operating in a sub-arctic environment.

Using automatic and observer-operated equipment for monitoring thermal data, observations have been made during Royal Navy Wessex 5 helicopter operations in a sub-Arctic climate. Measurements were taken in flight of front and rear cabin temperatures and aircrew deep body and skin temperatures. The results indicate that the "arcticised" aircraft used had more than enough cabin heating to alleviate cold stress on the aircrew.


Effect of superoxide dismutase and succinate on the development of hyperbaric oxygen toxicity.

Prolonged exposure to hyperbaric O2 (HBO) causes seizures and eventual death. The precise molecular basis for O2 toxicity is not known but may be due to increased biological production of superoxide anion (O2-). In the present study, superoxide dismutase (SOD), an enzyme that catalyzes the dismutation of O2- to less toxic forms, was evaluated for its ability to protect against HBO-induced seizures and death, and the results were compared to those concurrently obtained with succinate (SUCC), an agent previously reported to protect against HBO-induced seizures. Preconvulsion time and survival time in normal and vitamin E-deficient rats exposed to 100% O2 at 5 ATA were not significantly prolonged by pretreatment with 2 to 20 mg/kg SOD intraperitoneally (ip) or 0.1 to 1.0 mg/kg SOD intrathecally. In contrast, 12 mmol/kg SUCC ip significantly prolonged preconvulsion time in normal and vitamin E-deficient rats and survival time in normal rats. The ability of SUCC to stimulate ATP production may account for its protective role. Reasons for the failure of SOD to protect against O2 toxicity are discussed.


Review of epidemiology in clinical cardiology.

The application of epidemiological techniques to clinical cardiology has led to very significant advances in the diagnosis and treatment of coronary atherosclerosis. However, these epidemiological techniques almost necessitate the use of modern computer technology, including data base management systems, in the application of which medicine has lagged behind other areas. Businessmen have come to rely on computerized methods of data storage, retrieval, and analysis to sell commercial products and manage our finances--while their medical counterparts rely on imcomplete data in forgetful minds beset with bias and emotion to use powerful therapeutic tools in the treatment of patients. Hopefully, the next decade will see a new generation of clinical researchers who will combine epidemiology and computer technology for the improvement of health care delivery.


Organization and operation of civil aviation medicine in the Soviet Union.

The United States of America and the Soviet Union formalized an agreement in 1973 wherein periodic exchanges of information in civil aviation take place. During the period Aug. 21-Sept. 9, 1976, the author and an associate visited the Soviet Union as part of the exchange agreement. During the visit, the following information was covered. The civil ceviation medicine program in the Soviet Union involves preflight physical examinations for aircrew members, including flight attendants, quarterly physical examinations on pilots and flight engineers, and a special central hospital for diagnosis and treatment of problem medical cases occurring in aviation personnel. In addition, prophylactoria (special rest facilities) for flight crew are maintained at major airports. Certain other aspects of Soviet civil aviation medicine include preflight examinations on all children, and the provision at each airport of a designated medical emergency facility.


Hyperbaric oxygenation in the treatment of postencephalitic amnesic syndrome.

The efficacy of hyperbaric oxygenation in the treatment of an amnesic disorder was studied in a young woman with a residual memory impairment 2 years after Herpes Simplex Encephalitis. Quantitative testing of memory was performed under controlled conditions before, during, and immediately following treatment. There was no systematic change in storage and retrieval of either verbal or essentially nonverbal information when testing was performed during hyperbaric oxygenation or after termination of four daily treatment sessions. The findings support recent studies which have indicated a lack of therapeutic effects of hyperbaric oxygenation on the mental efficiency of older demented patients.


Atmospheric pressure and idiopathic facial paralysis (Bell's palsy).

In a statistical study the onset of idiopathic facial paralysis (Bell's palsy) in 241 patients, observed in a 3-year period, is studied in relation to atmospheric pressure. The hypothesis of no association is not rejected. Neither is the hypothesis rejected of uniform distribution of the occurrence of Bell's palsy during the same period.


Stress reactions in organizations: syndromes, causes and consequences.

This study examines the prevalence, causes, and consequences of stress reactions among over 2000 high status members of a large organization in Canada. Five stress syndromes were identified: emotional distress, medication use, cardiovascular disturbance, gastrointestinal disturbance, and allergy respiratory disturbance. The study demonstrates the effects of sociocultural variables on selected stress responses to compare typical symptoms of French vs. English Canadians, and in demographic variables such as age and sex as reflections of stages in the life cycle. Once the sociocultural and demographic effects were isolated, the study revealed a major occupational effect in the distribution of stress syndromes. Managers compared with staff and operations people show a low prevalence of stress reactions. The explanation of this finding led to the evaluation of four possible causes: the maturity effect, the vulnerability effect, the bureaucratic effect, and the power effect. The first two causes assume the objective stressors in the environment are about the same for all occupational groups in the study and the variations in symptoms result from major personality factors held in common among the occupational groups. The second two causes assume that the variations in symptoms result from major differences in the environments of the three occupational groups. Analysis suggests that psychodynamic factors affect the tolerance for stress and the choice of syndrome. The environment, particularly the frustrations and deprivations associated with bureaucracy and the lack of power, activates the defenses against anger and rage that in turn lead to symptom formation. The study concludes with the paradox of the bureaucratic experience. Designed to minimize the uses of power in negotiating work procedures and relationships, bureaucracy requires the mobilization and uses of power to, at a minimum, reduce the risks of falling ill from frustration and anger and, at a maximum, to sense one's impact on events.