[Quantification and statistical analysis of ordinal scale type data in psychiatry (author's transl)]. Observational data from psychiatric patients are usually of the ordinal scale type. Therefore, in the traditional one-rating-per-symptom-and-patient-situation, the resulting score values can be analysed only by applying nonparametric statistical methods. These methods are rather inefficient when--as is usual--there are only four-point-scales for evaluating the symptoms. Moreover, non-parametric methods are not available as of yet to take into consideration the often complex structure of data from psychiatric studies. This leads to the conclusion that the quantification of ordinal scale type data would be very desirable in order that parametric statistical methods could be applied. Such a method of quantification is proposed on the basis of the audiovisual psychiatric rating technique. It is shown that the data resulting from the many-ratings-per-symptom-and-patient-situation can be subjected to parametric statistical methods. In applying the proposed method, therefore, much better use could be made of and a maximum of information could be extracted from the data in psychiatric studies.


N-acetyl-p-amino-phenol (paracetamol, acetaminophen) in the treatment of acute schizophrenia. The hypothesis that schizophrenia is caused by the release of prostaglandin E into the hypothalamus and may sometimes be accompanied by an elevation of temperature was examined by a clinical trial of the prostaglandin E suppressant N-acetyl-p-amino-phenol (paracetamol, acetaminophen). Ten acute schizophrenic patients were included in a double-blind, crossover trial of paracetamol and a placebo, in which each treatment was given for a week. Regular 4-hourly temperatures were recorded in all these cases and in 5 non-schizophrenic patients for comparison. The findings provided no evidence that paracetamol mitigated the symptoms of schizophrenia. The temperatures of the schizophrenics were not elevated more than those of the controls, but the number of cases used was probably too small for this finding to be conclusive.


The feasibility of tracing a sample of school-boys after a lapse of fifteen years. Although the relationship between childhood behaviour and adult adjustment is often presented as established fact, relatively few non-retrospective studies have actually examined this perceived association. This paper presents a description of the attempt to establish the feasibility of tracing children after a lapse of 15 years and suggests that this may present fewer insuperable difficulties than might be imagined.


A specific radio-immunological assay for prednisolone in plasma. A new, specific radio-immunological assay (R.I.A.) for prednisolone in plasma is described. The R.I.A. incorporates a procedure whereby the endogenous interfering hydrocortisone (in de-proteinized plasma) reacts directly with Girard Reagent T, resulting in a derivative which does not cross react with the specific antibody for prednisolone. The assay is sensitive (quantitation levels are in the 5-10 ng/ml range). The specificity compares favorably with that of a high performance liquid chromatographic procedure.


Comparative resistance of San Miguel sea lion virus and vesicular exanthema of swine virus to chemical disinfectants. Two similar calici agents, San Miguel sea lion virus (SMSV) and vesicular exanthema of swine virus (VESV) are susceptible to the virucidal activity of disinfectants of differing formulation. Ten of 12 compounds were effective against six log10 plaque forming units (PFU) of SMSV in a 2-min exposure at 4, 25 and 37 degrees C. However, only seven of these 10 SMSV-positive compounds inactivated VESV under the same conditions of temperature and time. Two compounds were not effective against SMSV in a 20-min exposure at 4 and 25 degrees C, but were effective at 37 degrees C. Two of the three compounds not effective against VESV in a 20-min exposure at 4 and 25 degrees C were also effective at 37 degrees C. The test iodophor compound inactivated SMSV completely but had only minimal inactivating activity against VESV at the three temperatures tested.


[Treatment of urogenital neoplasms in males]. The carcinomas of the male genitourinary tract--prostate, testicle, bladder, kidney and penis--are discussed with regard to incidence, prognosis and therapeutic possibilities. The results of drug treatment, especially for prostatic and non-seminoma testicular cancers, are presented in detail.


[Measurements of blood citrates in neoplasms with bone metastases]. Blood citrate was measured in 49 patients with cancer, with or without bone metastases, and in 53 normal subjects. It is significantly higher (p less than 0.001) in patients with bone metastases than in normal subjects or patients without bone metastases. In normal subjects, blood citrate is higher in summer than in winter and higher in older people. The theoretical and practical interest of these observations is discussed.


[Pseudomembranous colitis caused by antibiotics]. A case of antibiotic-induced pseudomembranous colitis is presented. Following resection of a carcinoma of the colon, an 81-year old man was treated with clindamycin for 9 days and with epicillin for another 9 days. One week after discontinuation of antibiotics the patient developed progressively severe diarrhea. Death from central pulmonary embolism ensued 10 days after the onset of diarrhea. Autopsy revealed severe pseudomembranous colitis of the entire large intestine. Pseudomembranous colitis is often observed as a complication after the administration of different antibiotics. The Anglo-American literature contains several recent reports of clindamycin-induced pseudomembranous colitis. The etiopathology of this drug-induced disease is still unclear. A possible interpretation is an antibiotic-induced change in the intestinal flora. Recent observations suggest that toxin-producing clostridia are responsible for the pseudomembranous colitis.


[Percutaneous splenoportogammagraphy in the study of patients with portal hypertension]. Percutaneous esplenoportogammagraphy in 28 patients with portal hypertension, was carried out; in three patients studies were done before and after a derivative operation; in nine only after operation for portal hypertension and thirteen patients were not surgically treated. Hepatic maximal opacification was obtained in 4.35 seconds. In the operated patients the tecnesium reached right cardiac chambers in 2.91 seconds. In three of the thirteen patients with the test, there were intrahepatic circulatory pattern changes, average spleen-liver was 6 seconds and spleen-heart, 7 seconds, that is, esplenoportal perfussion was poor. In all the operated patients the decreased circulation time spleen-heart and the typical image showed anastomosis permeability.


Selective inhibition of tubulin synthesis by amiprophos methyl during flagellar regeneration in Chlamydomonas reinhardi. Amiprophos methyl (APM) is a strong, readily reversible and highly selective inhibitor of tubulin synthesis in Chlamydomonas reinhardi. The extensive induction of tubulin synthesis that accompanies flagellar regeneration in this organism is prevented by 3 to 10 micrometerAPM. When applied after induction has begun, APM causes a rapid cessation of tubulin synthesis. Translation studies in vitro indicate that the lack of tubulin production in APM-treated cells is not due to a direct inhibition of tubulin messenger RNA translation but rather to a selective depletion of tubulin messenger RNA.


Phagocytosis of light- and dark-adapted rod outer segments by cultured pigment epithelium. Pigment epithelial cells in culture retain their ability to phagocytize rod outer segments. These cells phagocytize rod outer segments isolated from light-adapted rats, or from dark-adapted rats killed after the time at which the lights would normally be turned on. However, they phagocytize for fewer rod outer segments prepared in the dark from the retinas of rats killed before the onset of the normal light cycle. Phagocytosis of dark rod outer segments is variable, but that of light outer segments is reproducible. It is postulated that the effect of light is to synchronize the chemical events that occur at the surface of the rods to prepare them for phagocytosis. These processes also occur in the dark, but more slowly and irregularly than in the light.


Hamster refractoriness: the role of insensitivity of pineal target tissues. Hamsters exposed to short days undergo gonadal collapse followed by recrudescence and insensitivity to the regressive effects of such photoperiods. This refractoriness may be due to exhaustion of the pineal gland or desensitization of its target. Hamsters whose gonads had spontaneously recrudesced were injected with melatonin (25 micrograms per injection) once daily (known to induce regression in intact hamsters) or twice daily (reported to arrest reproduction in pinealectomized hamsters) for 7 weeks. In neither case did refractory hamsters respond to melatonin treatment. The gonads of intact hamsters treated with melatonin for 21 weeks regressed and spontaneously recrudesced along a normal time course. These results indicate that gonadal refractoriness is due to insensitivity of the target tissues of the pineal gland and imply that melantonin participates in photoperiodic regulation of reproduction in the golden hamster.


Epsilon-aminocaproic acid (EACA).

Epsilon-aminocaproic acid (EACA). Epsilon-aminocaproic acid (EACA) is a synthetic inhibitor of the plasmin-plasminogen system. It is the only potent antifibrinolytic agent which is commercially available in the United States. Effective blood levels of the drug are readily obtainable with either oral or intravenous administration, with very high levels of the drug being found in the urine since the drug is greatly concentrated during excretion. EACA has been used in numerous clinical situations to control bleeding and has been claimed to be an effective agent in subarachnoid hemorrhage, genitourinary bleeding from many causes, and in dental surgery in hemophiliacs. It may also be effective in several less well studied situations such as prophylaxis of bleeding episodes in hemophiliacs, control of menorrhagia, gastrointestinal bleeding, obstetrical bleeding and in bleeding following cardiac and thoracic surgery. Major side effects from EACA include hypotension, cardiac arrhythmias, rhabdomyolysis, and generation of thrombi. The incidence of thrombotic events secondary to the inhibition of the fibrinolytic system by EACA is unknown, but may be particularly increased in those patients who have some underlying predisposition to develop thrombosis. The potential benefit from the use of EACA must be weighed against the possible serious complications, particularly the development of widespread thrombi.


Survey on Anisakid larvae in marine fish from fish markets in Jakarta. Anisakid parasites were found in fish commonly sold in the markets of Jakarta. The larvae found were Anisakis type I and Terranova type B. The rate of infection of these two different Anisakid larvae infecting different species of fish was discussed. To date, no human infection has as yet reported in Indonesia. This may be due to the fact that Indonesians do not usually eat raw fish.


Lymph node invasion by Conidiobolus coronatus and its spore formation in vivo. Lymph node invasion with presence of conidia, their replicates, germ tubes, condidia with hair-like projections and hyphae have been observed in a case of entomophthoromycosis caused by Conidiobolus coronatus. This rare occurrence of conidia with hair-like projections that is usually observed in vitro, has been observed in vivo, in the content of an abscess produced by this agent, C. coronatus in the present case. Severe disfigurement and destruction of facial and nasopharyngeal tissues, have also been observed in this case. Response to therapy with oral KI, surgery, combinations of trimethoprim and sulphamethoxazole and steroids though found useful initially, was ineffective subsequently as the disease progressed over 7 years. Findings of lymphatic invasion and the extensive destruction observed in the present case warrants a guarded prognosis. Free conidial reproduction found in lymph nodes may suggest the possibility of this disease being infectious, requiring an active and vigorous treatment schedule and control measures in this infection.


Experimental infection of athymic nude New Zealand mice, nu nu strain with mycetoma agents. Experiments with athymic nude mice "nu nu" strain showed grains of Madurella mycetomi as early as 9 days, and they were well developed by 21 days, after inoculation. Grains were similar to those of humans, in pigment production and tissue reaction.


Cerebral cystic hemangioblastoma.

Cerebral cystic hemangioblastoma. A 26-year-old man having a large left frontal lobe cystic mass due to a 1.5 cm capillary hemangioblastoma acting as a mural nodule is presented. The cerebral topographical location of hemangioblastoma is rare and the reported cases are summarized and analyzed. The distinction between hemangioblastoma and angioblastic meningioma is emphasized by the occurrence of a cystic capillary hemangioblastoma in the cerebrum.


Determination of soluble fibrin monomer complexes by adsorption on immobilized fibrinogen. Determination of fibrin in plasma, also containing fibrinogen, is possible by selective absorption on affinity columns prepared from highly purified fibrinogen. Desorption is complete using 1.0 M potassium bromide, pH 5.3. In addition, the cold-insoluble globulin is desorbed. Therefore, the eluate is checked on microtiter plates by the staphylococcal clumping test which selectively detects fibrin or fibrinogen. The procedure works well with simple laboratory equipment. The diagnosis of fibrinogen-fibrin complexes is demonstrated in some pathological plasmas.


Pseudohyperparathyroidism associated with perirectal adenocarcinomas in elderly female dogs. In 8 elderly female dogs a syndrome of hypercalcaemia and hypophosphataemia was found in association with a perirectal adenocarcinoma. Following removal of the tumour the hypercalcaemia resolved within two days in four of the five operated animals.


Cytotoxicity of butylated hydroxytoluene and butylated hydroxyanisole in cultured heart cells. Butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA) at concentrations of 100 ppm (0.45 and 0.55 mM, respectively) produced a marked leakage of lactic dehydrogenase (LDH) from cultured myocardial and endotheloid cells into the culture medium. At this concentration both BHT and BHA markedly depressed the beating rate of cultured heart cells with maximum inhibition occurring within 1 h after antioxidant exposure. Morphologically the appearance of cells in the presence of 100 ppm BHT and BHA was similar to the appearance of control cells. However, when BHT and BHA concentrations were increased to 1000 ppm (4.5 and 5.5 mM, respectively), marked cell lysis was seen after a 1 h exposure period. The results of this study suggest that both BHT and BHA, in relatively large concentrations, produce injury to myocardial cells in culture.


Rift Valley Fever virus infections in Egypt: Pathological and virological findings in man. Ten strains of Rift Valley Fever virus were isolated from serum samples from acute human cases collected during an epidemic of undifferentiated febrile illness. Post-mortem samples were obtained from two fatal infections. Severe liver necrosis, interstitial pneumonia and myocardial degeneration were seen. Rift Valley Fever virus was isolated from post-mortem samples of liver, cerebro-spinal, pericardial and pleural fluid and from a throat swab. The virus was also isolated from nasopharyngeal washings suggesting that direct transmission from man to man may be possible.


Bladder neck hypertrophy and wide bladder neck anomaly (WBNA). The urodynamic findings of 247 patients with a neurogenic bladder dysfunction were analyzed to evaluate factors which influence the X-ray picture of the bladder neck and urethra. Patients were classified according to the classification of Bors and Commarr, additionally different types of reflex detrusor activity could be differentiated in cases suffering from a supranuclear lesion. As the micturition cystourethrography of female patients with a supranuclear lesion looks similar to the X-ray picture of young girls with a WBNA a second analysis was made to compare the urodynamics of both groups. It is to note that in supranuclear lesions detrusor-sphincter dyssynergia and the type of reflex detrusor activity mainly form the shape of the posterior urethra, neither the duration of the lesion nor the level of spinal cord injury have any influence.


Study of threee urethral pressure recording devices: theoretical considerations. Using a bladder-urethra model, 2 perfusion catheters (open side and open tip) were compared to the balloon catheter. The most accurate results were obtained using the balloon catheter. Based on the law of continuity and Bernouilli's law, the disadvantage of the open side catheter is due to the inconstant diameter of the sum of the side holes. Therefore, the measured pressure is not necessarily identical to the real pressure. The open tip catheter measures the opening pressure and the recorded pressure does not necessarily reflect the pressure at the site of the tip hole. The balloon catheter has elastic and plastic characteristics. Optimum results were obtained only with prestretch of the balloon and with calibration before and after each study. This catheter was the most complicated, but produced the best results and gave rise to the least irritation.


Urethral closure pressure with stress--a comparison between stress-incontinent and continent women. Stress incontinence has been said to occur as a consequence of a low urethral pressure and defective pressure transmission from the abdomen to the urethra due to descent of the bladder neck area. Equipment suitable for dynamic pressure measurements has been used to analyse the losses of urethral pressure that lead to incontinence. The pressure transmission from abdomen to urethra was found to be incomplete in both continent and stress-incontinent women. There was also significant loss of smooth muscle tone in the urethral wall after repeated straining, leading to a still narrower margin between the urethral pressure and the leakage treshold in both continent and stress-incontinent women. The main factor determining the degree of continence or incontinence seemed to be the urethral closure pressure at rest . As long as this pressure is sufficiently high, leakage during sudden stress will not occur.


Pressure transmission to the pre-urethral space in stress incontinence. Pressure transmission from the abdomen to the pre-urethral space has been studied in stress- incontinent women and in some women following pubococcygeal repair for stress incontinence. Pressure was recorded at different levels of the pre-urethral space and simultaneously in the bladder. Simultaneous measurements inside and outside the urethra at different levels above the external urethral meatus showed that an intra-abdominal pressure rise was transmitted via the pre-urethral space to the urethra. Pressure was transmitted almost in full to the surroundings of the lower-most part of the bladder, but outside the functional urethra, transmission was successively more defective along the urethra towards the external meatus. Therefore, a short functional length and a distal maximal pressure plateau in the urethra, as in stress incontinence, is a disadvantage. Pressure losses amount to 1/3 or more. Pressure transmission could be improved to "supranormal" values by establishing firm support for the urethra, thereby allowing a minimum of rotational descent with stress and providing good counterpressure.


Internal urethrotomy of urethral stricture under vision--a five-year report. This report deals with experience with the method of transurethral incision of urethral strictures under vision in 547 patients involving 662 internal urethrotomies between Nov. 1972 and Aug. 1977. Follow-up examinations showed good results in 79, 3% of the patients. Transurethral incision of urethral strictures can be recommended as the method of choice for the treatment of urethral strictures.


[Ureter malformations and renal dysplasia--an embryological concept (author's transl)]. A study was made of 32 cases of single ectopic ureters (without duplication) to assess the abnormalities observed in the corresponding renal parenchyma and to correlate renal status with location of the ectopic uretic opening. Specimens were obtained from 26 nephrectomies and renal dysplasia was found in 22 cases. There was a close relationship between renal anomalies and location of the ureteric opening. The more remote the ectopic orifice from its normal position, the more severe were the associated renal lesions. Dysplasia was always present when the ectopic ureter opened outside the urinary tract (vagina, Gartner's duct, vestibule, seminal tract). Am embryological concept is proposed to explain the association of renal dysplasia with abnormal location of the ureter opening. It is based on the abnormal--premature or late--appearance of the ureteral bud on the Wolffian duct resulting in the abnormal positioning of the bud on the Wolffian duct with the ureter growing into nephrogenic tissue lacking the potential for normal renal development and leading to renal dysplasia.


Ineffectiveness of treatment of urethral syndrome in women. Four hundred ninety-eight episodes of 150 women with female urethral syndrome (lower urinary tract symptoms without definite objective findings) were evaluated. Internal urethrotomy appeared less effective than cystoscopy and dilation. Office dilation with larger sounds appeared less effective than a 16 F sound. Antibacterials and anticholinergics showed no clear evidence of effectiveness.


Time to onset of oestrus after the injection of heifers with cloprostenol. When two injections of 500 microgram cloprostenol are given 11 days apart to unselected cycling heifers the onset of oestrus behaviour is significantly earlier, and more compact, after the second injection than after the first. The time from treatment to the onset of oestrus following this second injection was not significantly different from that obtaining in animals given a single injection on day 8 of the oestrous cycle. It is suggested that the more precise onset of oestrus after the second of two cloprostenol injections is due to the majority of animals being at a comparable stage of the oestrous cycle when the treatment is given. The earlier oestrus after two cloprostenol injections may be due to the greater number of heifers at days 7, 8 and 9 of the oestrous cycle at the time the second injection is given.


[Organochlorine pesticide residues in the eggs from poultry raising farms]. A gas chromatography method was employed to investigate the residual amounts of chlororganic pesticides in a total of 37 average batch samples of eggs taken from 18 large poultry farms. More than two thirds (from 70.3 to 75.6 per cent) of the samples were shown to be free of p'p' DDE, p'p' DDT, and dieldrin, and more than one third (from 35.1 to 43.2 per cent)--of alfa and gamma hexachloran, heptachlor and heptachlorepoxide. In 88,4 per cent of the samples there were found residues of p'p' TDE (up to 0.061 ppm). The egg content showed trace amounts of DDT and metabolites--0.025 ppm, alfa and gamma hexacloran--0.016 ppm, heptachlor--0.006 ppm, heptachlorepoxide--0.01 ppm, and dieldrin--0.002 ppm. These amounts were much lower than the tolerance evaluations postulated by FAO/OMS and those accepted in other countries.


[Effect of the removal of an induced tumor on the immunological reactivity of mice]. An extensive surgical intervention in removing a tumor-bearing limb induce in mice an enhancement of immunosuppression state, developed in the process of carcinogenesis. Rehabilitation of the immunocompetence in such mice proceeds in a more active way than in the control animals, subjected to the analogous amputation of the extremity.


[Supplement of the diet of malnourished geriatric patients with essential amino acids (author's transl)]. A significant improvement in the protein metabolism of twelve malnourished geriatric patients was achieved during a three-week daily supplement of the hospital diet with 9 g essential amino acids (8 classic essential amino acids plus histidine). This was especially evident in the doubled serum concentration of pre-albumin and retinol-binding-protein which may be regarded as highly sensitive parameters of protein metabolism. There was a significant increase of total protein and hemoglobin into the lowest normal range. The immunoglobulins IgG, IgA and IgM, however, remained unchanged for the entire observation period.


[The potassium content of mushrooms (author's transl)]. The potassium content of 410 species (1075 samples) of wild mushrooms ranged between 1.5 and 117g/kg dry wt. It was dependent on species and genus, and on the average was highest in Coprinaceae and lowest in Polyporaceae. A positive correlation was observed between potassium and water content; consequently, the potassium content of the wet wt. showed less variation: it ranged between 0.6 and 14.6 g/kg. In the solid matter of single fruit-bodies (11 species) potassium was distributed as follows: flesh of the cap greater than stem greater than gills or tubes greater than spores. The flesh of the cap contained maximally 1.8 times the potassium of the gills. But due to a correspondingly higher water content, significant potassium differences between fresh weights of these parts of fruit-bodies were uncommon. Potassium was concentrated 20--40-fold in fruit-bodies as compared with the soil.--According to our results mushrooms rank among the most potassium-rich vegetables, appropriate for consideration in diets in chronic potassium deficiency. On the other hand, toxic effects must be considered, especially in cases of renal insufficiency.


[Disturbance due to traffic noise at night]. In order to obtain bases for the establishment of threshold values in the new environmental law, a random sample survey with 1600 persons in urban and rural areas has been made on the degree of disturbance by street traffic noice in the night.


In vitro effect of alpha, beta-unsaturated sulphones of the 5-nitrofuran series on the incorporation of C-labelled precursors into Ehrlich's ascites carcinoma cells. The effect of new 5-nitrofuran (5NF) derivatives on the incorporation of 14C precursors of nucleic acids and protein synthesis into Ehrlich's ascites carcinoma (EAC) cells in vitro has been studied. Of the 32 substances that were tested, 22 markedly inhibited the incorporation of adenine, L-valine, uridine and thymidine. The 5NF derivatives influenced the synthesis of nucleic acids in vitro and the proliferation of EAC cells. The effect of the derivatives depends on the nature and position of the substituents as well as on the spatial arrangement of the whole molecule. Some of the evaluated derivatives showed a weak virostatic effect and induced lysogenicity in E. coli C 600. As most of the tested 5NF inhibited E. coli(rec-) mutants, it can be concluded that the (rec-) gene evidently takes part in the repair of their damage.


[Involvement of thalamic nuclei in the formation of conditional avoidance reflexes in rats. II. Lesions of the midline nuclei]. Lesions of the habenular-paraventricularis-anterior complex of the thalamus caused a total impairment of conditioned avoidance response of hooded rats (Long-Evans-strain) in a jumping test, but not in a simple runway. The change of stereotyped avoidance reactions could be attained very slowly. Running speed was lower and the number of errors much higher using an alternation schedule. Lesions of the nucleus centralis medialis and partly of its surrounding caused less deficits. From the results may be suggested that regulatory interactions between general behavioural activation originating from the brain stem, motivational processes and the analyzer systems are disrupted.


Effects of medial hypothalamic deafferentation on prolactin secretion in pseudopregnant rats. Frontal hypothalamic deafferentation (FHD), which disconnects the anterior hypothalamus from the preoptic area, stops the twice daily surges of prolactin secretion of pregnancy or pseudopregnancy in the rat, and causes rapid luteolysis. Medial hypothalamic deafferentation (MHD), which separates the anterior from the posterior half of the hypothalamus, does not interrupt pregnancy and causes a significant increase in the size of the corpora lutea. To see whether MHD induces an increase in the basal level of prolactin secretion and/or a change in the pattern of prolactin surges, pseudopregnant rats were subjected to MHD or a sham operation on day 3 (day 1 = day of oestrus) and their bloods assayed for prolactin on either day 5 or days 7--8. MHD caused a specific disappearance of the day-time prolactin surge and a diminution in the height of the night-time surge, but no change from the controls in the basal prolactin level. In spite of what thus appears to be a lesser secretion of prolactin than in the controls, the corpora lutea of the MHD rats were larger, and progesterone was secreted at a higher rate and for a longer time, than in the controls. The relation of these findings to the existence of a "surge centre" in the hypothalamus was discussed.


Action of testosterone propionate on the gonadotrophic function of the pituitary gland in the cyclic female rat. Four-day cyclic female rats were injected with 5 mg testosterone propionate (TP) at dioestrus II at 10.00. A blockade of ovulation was observed on the morning of oestrus in most of these animals. No LH surge occurred in the afternoon of pro-oestrus. By contrast the size of follicles exceeding 400 micrometer in diameter did not differ in the afternoon of pro-oestrus in TP-treated and control females. Moreover both the number of follicles and the blood FSH concentration appeared to be higher at 14.00 on pro-oestrus in TP-treated than in control females. The effects of TP in vivo are thus in agreement with the observations which showed that TP caused a blockade of LH release and the maintenance of FSH release in vitro.


The effects of cytochalasin B and colchicine on cell motility and ultrastructure in primary cultures of malignant gliomas. Primary tissue cultures of human gliomas were treated with cytochalasin B (0.5--60 microgram/ml for 90 min). Cell motility was inhibited irreversibly in glial tumour cells, but the effect was reversible on the mesenchymal cells growing in culture in the lower dose range. Cell adhesion was considerably reduced as the dose was increased, as was the capacity for cells to spread on a surface from suspension. Low concentrations of cytochalasin B caused negligible cell death and little disruption of cell ultrastructure. However, increases in dose were accompanied by a greater predominance of rough endoplasmic reticulum and inclusions and aggregation of microfilament bundles. As seen by scanning electron microscopy, cytochalasin B caused the withdrawal of peripheral cell borders, disappearance of ruffles and the breakdown of cytoplasmic lamellae. Charateristic surface blebs and folds appeared in their place. By comparison, colchicine (1--10 microgram/ml) caused a less marked and non-specific reversible reduction in cell motility on both glial and mesenchymal cells. No significant change in cell adhesion or spreading took place even at high doses, although at all concentrations gross disruption of the cell surface took place with changes in ultrastructure characterised by loss of cytoplasmic microtubules and aggregation of 10 nm filaments.


Changes in the sensitivity of dopamine receptors in the nucleus accumbens and in the striatum induced by chronic ethanol administration. Rats of the Sprague-Dawley strain were maintained on ad libitum food and a forced-intake regimen of ethanol for up to 270 days. Bilateral application of dapamine (DA) into the nucleus accumbens of both chronic ethanol rats and rats undergoing withdrawal produced a pronounced increase in coordinated locomotor activity which was 8--10 times higher than that of untreated water control rats. This phenomenon was first observed after 5 months of ethanol treatment and lasted for about 4 weeks after cessation of the treatment. It is concluded that prolonged ethanol administration produces an increased sensitivity of the DA-receptors in the nucleus accumbens and further supports the contention that central catecholamine mechanisms are involved in the mediation of the withdrawal syndrome observed after chronic treatment with ethanol.


The influence of ethanol pretreatment on the effects of nine hepatotoxic agents. The hepatotoxic effects of carbon tetrachloride (0.01 ml/kg i.p.), thioacetamide (50 mg/kg intraperitoneally), paracetamol (0.5 g/kg intraperitoneally), and allyl alcohol (0.05 ml/kg intraperitoneally) as estimated by determination of serum enzyme activities (GOT, GPT, SDH) were enhanced in mice treated with one oral dose of 4.8 g/kg ethanol 16 hrs. previously. Pretreatment of mice with ethanol did not increase the hepatotoxic actions of bromobenzene (0.25 ml/kg intraperitoneally), phalloidin (1.5 mg/kg intraperitoneally), alpha-amanitin (0.75 mg/kg intraperitoneally), and praseodymium (12 mg/kg intravenously) though there was a trend to higher enzyme activities in the case of bromobenzene. In guinea-pigs ethanol also aggravated CCl4-induced liver damage, but only strengthened the hepatotoxic activity of D-galactosamine (150 mg/kg intraperitoneally). Treatment with 4.8 g/kg ethanol did not influence liver glutathione levels in mice but increased aniline hydroxylation in the 9000 x g liver homogenate supernatant of mice and guinea-pigs. A dose of 2.4 g/kg ethanol, on the other hand, neither increased aniline hydroxylase activity nor enhanced carbon tetrachloride-induced hepatotoxicity in mice. It is assumed that the enhanced sensitivity to hepatotoxic agents after treatment with ethanol may be due to an enhanced microsomal activation of these substances.


The ultrastructure of the basilar membrane in the cat. A detailed study of the feline basilar membrane was performed in 13 cochleae with light microscopy and in six with electron microscopy. The distribution of the mesothelial cells and homogeneous ground substance with the filaments was recorded and plotted as a function of length along the cochlear duct. The width, thickness and number of filaments were also measured. In the lower basal turn the basilar membrane was narrowest and its entire thickness was occupied by filaments. In the apical region the width was maximal and the filaments were fewer. The density of the filaments counted in the bundles showed no significant difference along the cochlear duct or across the width of the basilar membrane, but the number of filaments decreased markedly (approximately a ten-fold difference) from base to apex. The number of mesothelial cells increased towards the apex. These morphological characteristics may be related to the different motion pattern of the basilar membrane along the length of the cochlear duct. A discontinuity of the basement membrane was noted in the apical region in all cochleae studied. These gaps seemed to provide structural evidence for the permeability of the basilar membrane in this area. The vas spiralis was present as a blood vessel in two specimens and only in the apical region. Thus, its function as the sole nutritional source for the organ of Corti is doubtful.


Idiopathic hypertrophic subaortic stenosis in the young. Thirty-six young patients with idiopathic hypertrophic subaortic stenosis were studied. Twenty-seven patients were male and 9 female, and their mean age was 11.3 years (range 5 months to 20 years). Twenty-three patients (64 percent) had symptoms, the most common being dyspnea, angina and syncope. Diagnostic difficulties were encountered frequently in younger patients, especially those with right heart involvement, and in asymptomatic patients with murmurs suggestive of other cardiac defects. Patients were classified retrospectively into three groups on the basis of management. The first group consisted of 16 patients who were operated on; 4 of these patients died, 1 operatively and 3 suddenly late postoperatively (at 1.6, 2 and 10 years). The 12 long-term survivors (average follow-up period 6.2 years) have had good relief of symptoms. The second group comprised seven patients treated with propranolol; none of these died. The 13 patients in the third group received no therapy; 7 of these patients died, 6 suddenly and 1 from congestive cardiac failure. Idiopathic hypertrophic subaortic stenosis is a serious disorder that may present at any age and that may be difficult to diagnose. All patients with this disorder should be treated with propranolol; surgical intervention, although it does not totally abolish the risk of sudden death, appears to offer symptomatic improvement in most cases over a long-term follow-up period.


Endocarditis caused by Torulopsis glabrata. A case of Torulopsis glabrata endocarditis involving the mitral valve is reported. Endocarditis developed during convalescence from severe abdominal trauma and was associated with fungemia. Morphologically characteristic organisms were present in the mitral valve.


The effect of the milking process on oxytocic activity in the blood plasma of cows during oestrous. The purpose of this work was to compare the oxytocic activity of plasma in oestrous cows during milking and for the first and second days following oestrous. Oxytocic activity of blood plasma was measured by the in vitro rat mammary cube assay of van Dongen and Hays. During oestrous, signigicantly lower amounts of oxytocin are released into the bloodstream of cows following milking as compared with the control values.


The effect of heparin on the activated partial thromboplastin time. Data from the 1976 and 1977 CAP surveys were analyzed for response of the activated partial thromboplastin time (APTT) to heparin. Different sources and concentrations of heparin were used. The results indicate that the precision of the APTT is more dependent on instrumentation than on partial thromboplastin. This was true for all four of the heparinized specimens evaluated. A single exception was found with the "old" Dade reagent activated cephaloplastin. The mean difference in the activated partial thromboplastin times obtained with differing concentrations of heparin was entirely dependent on the partial thromboplastin reagent used. No significant difference in the results was found when equal concentrations of bovine lung and porcine intestinal mucosal heparin were compared.


Electrical spike activity in the human small intestine. A multiple electrode study of fasting diurnal variations. An intraluminal probe with 10 pairs of bipolar electrodes was used for continuous recording of myoelectric activity along the entire small intestine during 24 hr in 2 normal fasting human subjects. Two types of regular migrating activity were observed: (1) Bands of a great number of spike potentials appearing at hourly intervals migrating through the entire small intestine. This activity corresponds to phase III of the "interdigestive myoelectric complex" described in animal experiments. (2) Bursts of a few spike potentials appearing with minute intervals migrating only through the jejunum. This activity has not previously been demonstrated in man nor in intact animals, but corresponds to the "minute-rhythm" described from in vitro experiments.


Civil liability arising from "wrongful birth" following an unsuccessful sterilization operation. This Article examines the question of civil liability arising, both in tort and in contract, as a result of the "wrongful birth" of a child following an unsuccessful sterilization operation. After a general overview of the concept and background of wrongful birth, the Article deals with tort liability in a sterilization-wrongful-birth action, suggesting in particular that there are four stages in the sterilization process at which a physician's conduct may fall below the standard required by law, and discussing the effect of negligence at each of the four stages. The alternative claim for breach of warranty is then examined, with emphasis on the practical difficulties involved in establishing contractual liability in this type of case. Finally, the Article discusses public policy and assessment of damages issues involved in the wrongful birth action, and evaluates the merits of some of the arguments that have been advanced under these headings--particularly the "overriding benefit" theory--to defeat claims for wrongful birth.


Stability of pediatric liquid dosage forms of ethacrynic acid, indomethacin, methyldopate hydrochloride, prednisone and spironolactone. The stability of liquid dosage forms of ethacrynic acid (1 mg/ml), indomethacin (2 mg/ml), methyldopate hydrochloride (25 mg/ml), prednisone (0.5 mg/ml) and spironolactone (2 mg/ml), which often are compounded extemporaneously, was studied. One or two liquid dosage forms of each of the five drugs was prepared with the pure drug or the powder from a commercial dosage form using aqueous sorbitol or simple syrup alone or with a 10% (v/v) solution of alcohol in water. The dosage forms were stored at 24 C in amber-colored bottles for 21-224 days and assayed by various methods. All solutions studied were stable for at least 84 days. A solution was considered stable if it retained 90% of its drug concentration. Except for the prednisone solution, all solutions were stable for at least 164 days; however, the solution of methyldopate hydrochloride prepared from the pure drug became discolored after 98 days. The liquid dosage forms studied have limited stability but can be used by the pharmacist when extemporaneous oral solutions of these drugs are needed.


Dynamic left ventricular outflow tract obstruction and systolic anterior motion of the mitral valve in the absence of asymmetric septal hypertrophy. Systolic anterior motion of the anterior mitral valve leaflet and asymmetric septal hypertrophy are the principal components of the dynamic subaortic stenosis in hypertrophic obstructive cardiomyopathy. Mitral valve systolic anterior motion without septal hypertrophy or left ventricular outflow tract obstruction has been described, but asymmetric septal hypertrophy is supposedly a consistent feature of dynamic subaortic stenosis. We describe two patients with syncope, chest pain and the typical systolic murmur of hypertrophic subaortic stenosis whose echocardiograms showed mitral valve systolic anterior motion but not asymmetric septal hypertrophy. Normal septal thickness on echo was confirmed by intravenous indocyanine green to identify the right septal endocardium. At catheterization, left ventricular outflow tract gradients were provoked, and neither patient had interventricular septal hypertrophy on biventricular cineangiography. These findings in two cases suggest that mitral valve systolic anterior motion can be the only definable anatomic abnormality associated with symptomatic dynamic left ventricular outflow tract obstruction and that asymmetric septal hypertrophy is not a necessary component of this condition.


Idiopathic thrombocytopenic purpura occurring in a subject previously splenectomized for traumatic splenic rupture. Role of splenosis in the pathogenesis of thrombocytopenia. A 25 year old woman presented with idiopathic thrombocytopenic purpura. She had undergon splenectomy 12 years previously for traumatic splenic rupture. Thrombocytopenia was ultimately resistant to steroid therapy. Howell-Jolly bodies were absent from the peripheral smear and 99mTC-spleen scan demonstrated foci of increased uptake thought consistent with accessory spleens. However, splenosis alone was demonstrated at laparotomy, and all visible splenotic tissue was surgically removed. The patient responded and adequate platelet counts were maintained after discontinuation of steroid therapy. The functional capacity of splenic implants has been previously demonstrated both in animal and man. However, reports linking splenosis to hematologic disease are rare. In the present case, characteristic splenic function was demonstrated by both the the -9mTc-spleen scan and the absence of the typical peripheral blood findings of asplenia. The hematologic response to the removal of the splenotic tissue attests to its importance in maintaining the thrombocytopenic state. In the setting of prior splenectomy for splenic trauma, splenosis may contribute to hematologic disease. Removal of this splenotic tissue may result in hematologic remission.


Lecithin/sphingomyelin ratios centrifuged and uncentrifuged amniotic fluid. The literature suggests that the presence of cellular debris and sediment in amniotic fluid samples may alter the value of the lecithin/sphingomyelin (L/S) ratios, with a loss of as much as 75 percent of the surface-active lecithin1 and consequently a marked change in the L/S ratio. We wish to report our findings on 22 amniotic fluids obtained by transabdominal amniocentesis and analyzed with and without preliminary centrifugation. We find the L/S ratio is indeed unaltered by centrifugation. However, the actual amounts of lecithin and sphingomyelin appear to be lower in centrifuged samples.


Production and origin of estrogen in two true hermaphrodites. Two 46,XX true hermaphrodites with genital ambiguity since birth and gynecomastia were studied. The production rates of estradiol in these subjects, 77 and 71 microgram per 24 hours, and of estrone, 82 and 136 microgram per 24 hours, were approximately twice those of normal adult men. In one of these subjects the plasma production rates of androstenedione and testosterone were measured and found to be 389 and 1,271 microgram per 24 hours, respectively. In this subject all estrone production, 82 microgram per 24 hours, could be accounted for by extraglandular formation from plasma prehormones, whereas 71 microgram of estradiol per 24 hours could not be accounted for by extraglandular formation and presumably arose from glandular secretion. The concentration of testosterone in the testicular portion of the ovotestis of this subject was 465 ng. per gram of tissue, a value comparable to that found in testicular tissue obtained from adult men. In the other subject of this study, who had a malignant gonadal tumor, the plasma concentration of human chorionic gonadotropin was 3,000 ml.U. per milliliter. From the results of this study we conclude that both ovarian and testicular components of the gonads of these two individuals were endocrinologically active, and that their gynecomastia likely developed as a consequence of gonadal estradiol secretion.


Analysis of secretory patterns of prolactin and gonadotropins during twenty-four hours in a lactating woman before and after resumption of menses. Twenty-four hour secretory patterns of prolactin, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were obtained on two separate occasions from a woman with late physiologic lactation. The studies were performed 26 and 34 months after her child's birth. During the initial study, she had amenorrhea, and her child suckled 13 per cent of the 24 hour period (Study 1). At the time of the second study, she had resumed regular menses and her child suckled for 7 per cent of the 24 hour period (Study 2). The average concentrations of prolactin during Studies 1 and 2 were 40 +/- 1.0 (mean and standard error; No. = 72) and 31 +/- 1.4 ng. per milliliter, respectively. The mean plasma prolactin concentration in Study 1 was significantly greater than that in Study 2 (p less than 0.001). The plasma concentrations of LH and FSH were significantly less in Study 1 than in Study 2 (p less than 0.001 and less than 0.01, respectively). It is concluded that hyperprolactinemia and hypogonadotropinemia were endocrinologic correlates of the amenorrhea of late physiologic lactation in this woman.


The relationship of community mental health centers to the professional standards review organizations program. Given the realities of the professional standards review organization (PSRO) program and the necessity for accountability on the part of all health service providers, community mental health centers (CMHCs) should begin now to take an active role in planning their involvement in the PSRO program. The author points out the need for both psychiatrists and nonphysician professionals to become involved. There are many types of mental health services delivered in a given area, and the active involvement of CMHCs can be a major determinant of the shape and direction of this impact.


Splenic artery ligation in distal splenorenal shunts. Splenic artery ligation, a simple surgical procedure expected to decrease splenic flow and portal pressure in patients with cirrhosis of the liver, was performed concomitantly with a distal splenorenal shunt procedure in six patients and as the main surgical procedure in two patients. Immediate cessation of bleeding was achieved in the four patients in whom the splenic artery was ligated to reduce intraoperative bleeding. However, three of the seven patients with previous gastroesophageal hemorrhage rebled from various postoperatively. Symptoms of splenic infarction were observed in six patients, resulting in thrombosis of the splenic vein and/or of the distal splenorenal shunt in four patients and necessitating splenectomy in one. This incidence of thrombosis of the distal splenorenal shunt is much higher than the overall incidence of 5 per cent observed at our institution. It is thus concluded that the splenic artery should not be ligated in cirrhotic patients with patent distal splenorenal shunts, since splenic arterial collateral vessels have already been reduced by the gastric devascularization, an integral component of the distal splenorenal shunt.


Acetate fails to reverse myocardial depression in dogs anesthetized with halothane. Sodium acetate has been shown to reverse the myocardial depression induced by halothane in vitro. The biochemical basis for this restoration of contractility has been located in the glycolytic pathway. The present study was designed to determine whether this antagonistic property of acetate also occurs in vivo. Dogs autonomically blocked with guanethidine, phenoxybenzamine, and atropine were sequentially anesthetized with halothane in O2 and N2O-O2-succinylcholine in a random pattern. All animals were given sodium acetate IV in amounts adequate to produce pharmacologically active levels. Myocardial performance was measured by LVdP/dtmax, LVPDP/dt/KPmax, and Vmax. Halothane effected a significant depression of these myocardial parameters. Acetate did not reverse this depressant effect of halothane. Acetate, a well-established peripheral vascular vasodilator, did decrease left ventricular and aortic pressures.


Brain sodium, potassium, and osmolality: effects on anesthetic requirement. We determined the effects of hyperkalemia, hypernatremia, hyperosmolality and hypo-osmolality on halothane requirement (MAC) in dogs. Hyperkalemia did not change cerebrospinal fluid potassium or MAC. Hypernatremia proportionately increased cerebrospinal fluid sodium and osmolality. MAC concomitantly increased 43%. Serum hyperosmolality achieved by administration of 12 and 25% dextrose increased cerebrospinal fluid osmolality without appreciably altering cerebrospinal fluid sodium or MAC. Infusion of 5% dextraose produced hypo-osmolality of blood and cerebrospinal fluid. Cerebrospinal fluid sodium was diluted and MAC was reduced by 24%.


Acute and chronic changes in intra- and extracellular potassium and responses to neuromuscular blocking agents. The effects of acutely induced metabolic and respiratory alkalosis with reduction of serum potassium concentration as well as chronic total body potassium depletion induced by furosemide treatment were evaluated and correlated with alteration of neuromuscular blockade induced by d-tubocurarine, pancuronium, and succinylcholine in 12 mongrel dogs. Acute respiratory and metabolic alkalosis significantly reduced serum potassium by about 26%, while chronic furosemide treatment (1 mg/kg IV daily for 14 +/- 4 days) significantly reduced both serum potassium concentration (4.16 +/- 0.31 to 3.27 +/- 0.14 mEq/L) and skeletal muscle potassium content (80.9 +/- 5.6 to 58.7 +/- 4.1 mEq/kg). Succinylcholine neuromuscular blockages was essentially unchanged by acute respiratory or metabolic alkalosis or by chronic furosemide treatment, except for more rapid onset of blockade when 0.1 mg/kg succinylcholine was administered during metabolic alkalosis. Acute respiratory alkalosis shortened the duration of neuromuscular blockade induced by d-tubocurarine and pancuronium while acute metabolic alkalosis shortened the duration of pancuronium only and had no effect on d-tubocurarine. Chronic furosemide treatment had no effect on either d-tubocurarine or pancuronium neuromuscular blockage. Potassium concentration gradients between the intracellular and the extracellular compartments may be more important than cellular potassium depletion per se in affecting responses to neuromuscular blocking agents such as succinylcholine, d-tubocurarine, or pancuronium. Serum alkalemia and hypokalemia antagonize the duration of the neuromuscular blocking action of d-tubocurarine and pancuronium but not that of succinylcholine.


Increased sensitivity to succinylcholine in a patient heterozygous for the silent and the fluoride-resistant gene. Increased sensitivity to succylcholine may be due to inherited variants of serum cholinesterase (acylcholine-acylhydrolase, E.C.3.1.1.8). Four different allelic genes at locus E1 controlling human serum cholinesterase have been identified: the normal gene Eu1, the atypical gene Ea1, the fluoride-resistant gene Ef1, and the silent gene Es1. These 4 genes give rise to 10 possible genotype combinations. The sensitivity of some of these genotypes to succinylcholine, as, for instance, homozygotes for the atypical enzyme Ea1 Ea1, is well documented. However, the relation between some of the rarer genotypes and the sensitivity to succinylcholine is less well clarified. The present report represents the 1st case in which a peripheral nerve stimulator has been used to substantiate the increased succinylcholine sensitivity of a patient heterozygous for the silent and the fluoride-resistant gene, and the 2nd published case of prolonged apnea following succinylcholine in a patient carrying the Ef1 Es1 genotype for abnormal serum cholinesterase.


Effect of subanesthetic concentration of enflurane and halothane on human behavior. Ten male volunteers performed 3 tasks before, during, and following administration of 3 levels of alveolar halothane (0.05, 0.1, and 0.2%) for one-half hour each and (on a separate occasion) enflurane (0.15, 0.3, and 0.4%) for one-half hour each. The concentrations of halothane tested representing 7, 13, and 27% of MAC values, respectively; those of enflurane were 9, 18, and 24% of MAC. The tasks were a choice-reaction time test, a digit span test, and a Purdue Pegboard Assembly test. Volunteers also were tested for amnesia with word pairs and a picture. No effects or only slight effects on mental function could be detected at the lowest concentrations of either agent. At higher concentrations both agents impaired function, as indicated by an increase in reaction time, decreased ability to remember numbers, and decreased ability to assemble a simple structural array. Amnesia for word pairs but not pictures occurred at 27% of MAC for halothane and 18% of MAC for enflurane. All test scores reverted to control levels within one-half hour after discontinuing the anesthetic. Our results indicate that subanesthetic but not trace levels of enflurane or halothane can impair mental performance and manual dexterity and produce amnesia. The levels of anesthetic required far exceed those experienced by operating room personnel. However, such levels might be found for several hours in patients following prolonged anesthesia.


Anesthetic considerations for myasthenia gravis and pregnancy. Three pregnant patients with myasthenia gravis are presented and anesthetic considerations discussed. The course of myasthenia gravis is highly variable and unpredictable during pregnancy. Anticholinesterase therapy should be maintained during labor, and the IM route of administration is preferred. Exacerbations very often occur in the immediate postpartum period. Regional anesthesia is preferred for vaginal delivery. In the case of cesarean section, general anesthesia may be preferable. Neonatal myasthenia gravis is a transient syndrome that appears in 20 to 30% of the newborns of myasthenic mothers.


Local anesthetics and tracheal ring ciliary activity. The effects of local anesthetics on ciliary activity were studied using ferret tracheal rings maintained in vitro. Ciliary activity was quantitated visually after exposure to varying concentrations of mepivacaine, lidocaine, procaine, chloroprocaine, and bupivacaine. The recovery of ciliary activity was determined after tracheal rings were washed free of the local anesthetic agent. Mepivacaine was the least toxic, with no effect on ciliary activity at a 1.0% concentration. Bupivacaine was the most toxic, with irreversible damage to respiratory epithelium at a concentration of 0.13%. Lower concentrations caused ciliostasis, with some recovery after removal of the anesthetic. Licocaine, procaine, and chloroprocaine also depressed ciliary activity which, in general, was reversible after removal of the anesthetic.


Blood pressure in the great toe with simulated occlusion of the dorsalis pedis artery. Blood pressure was measured in both great toes using strain-gauge plethysmography in 100 healthy persons aged 18 to 43 before and during successive compression of the dorsalis pedis artery, the posterior tibial artery, and both arteries at the same time. In 54 (27 percent) of 200 feet, successive compression of the dorsalis pedis and the posterior tibial arteries produced no decrease in pressure in the great toe. In 47 of the feet, toe pressure decreased significantly only after compression of the posterior tibial artery, and in 65 of the feet toe pressure decreased significantly only after compression of the dorsalis pedis artery. In 34 of the feet, toe pressure decreased significantly after compression of each of the arteries. Thus in 99 (50 percent) of 200 feet, compression of the dorsalis pedis artery decreased the pressure in the great toe significantly, and in 4 feet the pressure decreased below 40 mm Hg. When both arteries were simultaneously compressed, 69 feet showed detectable blood pressure in the great toe. Attempts to evaluate adequacy of collateral circulation by pressure blanching of the great toe prior to artery compression and then observing capillary refilling time upon release of toe compression proved unreliable.


Evaluation of the Swank IL-201 transfusion filter. The effects of a new transfusion filter (Swank IL-20U) on stored, whole blood have been examined. Six filters were preloaded by passage of two units of outdated, type-specific bank blood, and the effects of filtration on a third unit of 21-day-old blood flowing under 150 mm Hg pressure were measured. Filtration did not significantly alter erythrocyte or leukocyte count, total or plasma hemoglobin, red-cell fragility, and plasma sodium, potassium, albumin, or globulin. Platelet counts were reduced by 33%. Removal of microaggregates, assessed by Coulter counting, screen filtration pressure, total screen protein, wet and dry weight of material retained, and scanning electron microscopy, was shown to be effective over the entire range of particle size. In comparison with other transfusion filters previously examined in this laboratory, the Swank IL-201 filter combines the features of efficient microaggregate removal with moderate blood-flow rate. Compared to its predecessor, the Swank IL-200, this new filter design has improved flow characteristics without loss of microaggregate removal efficiency. In view of the similarity of performance demonstrated for several of the available filters, it seems likely that relative cost will constitute an important determinant of filter selection.


Lumbar sympathetic block with bupivacaine: analgesia for labor. Forty primigravidas were given a bilateral paravertebral lumbar sympathetic block during stage I of labor using 10 cc of 0.5% bupivacaine and 1:200,000 epinephrine on each side. Good analgesia was obtained in 38 patients with maximal effect 7.5 +/- 3 minutes after blockage. Maternal mean blood pressure and pulse were unchanged, fetal well-being was not compromised, and labor progressed rapidly. Twenty-eight patients delivered prior to resolution of the block, while in the remaining 12 patients pain returned before delivery with analgesia having lasted 283 +/- 103 minutes. In the former 28 patients, analgesia for expulsion was provided by pudendal, saddle block, or infiltration analgesia, whereas continuous lumbar epidural or caudal analgesia was utilized when remission preceded stage II. In comparison to continuous lumbar epidural analgesia, the procedure is technically more difficult, generally more painful, and requires a second anesthetic for delivery. It is concluded that bilateral paravertebral lumbar sympathetic block with bupivacaine provides reliable analgesia of long duration with a low incidence of undesirable side effects. However, its primary usefulness is in cases where continuous lumbar epidural analgesia is refused or contraindicated.


Bupivacaine and other amide local anesthetics inhibit the hydrolysis of chloroprocaine by human serum. The rate of hydrolysis of chloroprocaine by human serum was studied in the presence and absence of a number of aminde local anesthetics and their metabolites. Bupivacaine (2.4 microgram/ml) and etidocaine (2.3 microgram/ml) caused 38% and 21% inhibition respectively of the rate of chloroprocaine hydrolysis. Circulating concentrations of these drugs have been reported in this range by several investigators following epidural doses of 150 to 400 mg of either drug. Mepivacaine, lidocaine, and two lidocaine metabolites (glycine xylidide and monoethylglycine xylidide) were only inhibitory at levels much greater than those seen in blood following the usual local anesthetic doses of the parent compounds. Since serum is an important site of chloroprocaine metabolism in man, the probability of chloroprocaine intoxication may be increased when it is administered with local anesthetics such as bupivacaine and etidocaine.


Epinephrine-induced arrhythmias during enflurane anesthesia in man: a nonlinear dose-response relationship and dose-dependent protection from lidocaine. Forty-eight patients undergoing transsphenoidal pituitary surgery under enflurane anesthesia received submucosal injections of 1:150,000 or 1:200,000 epinephrine in saline, 0.5% lidocaine, or 1.0% lidocaine. The threshold doses for ventricular irritability, defined as 3 or more premature ventricular contractions during or in the 3 to 5 minutes following injection, were 1.3 microgram/kg with saline, 2.5 microgram/kg with 0.5% lidocaine, and 4.9 microgram/kg with 1.0% lidocaine. There was no consistent relationship between epinephrine dose and occurrence of ventricular irritability within or among groups. The data show a protective effect of lidocaine against epinephrine-induced ventricular irritability during enflurane anesthesia and suggest a qualitative as well as quantitative difference between enflurane and other volatile anesthetics in their interaction with epinephrine.


Comparison of spread of epidural anesthesia in pregnant and nonpregnant women. Using a standardized epidural anesthetic technic, we compared levels of sensory anesthesia in patients undergoing cesarean section and in nonpregnant women undergoing elective surgery. When equal volumes of local anesthetic solutions were injected (either 15 ml or 20 ml of 0.75% bupivacaine without epinephrine), there was no statistically significant difference in sensory levels in pregnant and nonpregnant patients.


Naloxone fails to antagonize thiopental anesthesia. A study was undertaken to determine the effect in man of naloxone on the central nervous system depression produced by IV thiopental. Eight normal volunteers were given 5 mg/kg thiopental IV. On a separate occasion the same 8 volunteers were given 50 microgram/kg naloxone IV 5 minutes prior to 5 mg/kg thiopental. Naloxone had no significant effect on the rate of return of consciousness following administration of thiopental. Naloxone also had no significant effect on the responses of blood pressure, heart rate, or respiratory rate to thiopental.


Interaction of muscle relaxants and local anesthetics at the neuromuscular junction. The effects on neuromuscular (NM) function of combinations of relaxants (d-tubocurarine, pancuronium, and succinylcholine) and local anesthetics (cocaine, procaine, lidocaine, etidocaine, and a quaternized derivative of procaine, procaine methobromide) were investigated using the rat's phrenic nerve--hemidiaphragm preparation. Combinations of ineffective concentrations of NM blocking agents with ineffective concentrations of local anesthetics caused a greater than 90% NM block. Preliminary administration of ineffective concentrations of local anesthetics significantly ( p less than 0.001) decreased the ED50 of NM blocking agents. The administration of ineffective concentrations of NM blocking agents caused a similar decrease of the ED50 of local anesthetics. Concentrations of d-tubocurarine and pancuronium which alone produced partial NM block had additive effects. These findings suggest that the interaction of NM blocking agents and local anesthetics consists of true potentiation caused by the different sites of action of the two types of compounds at the NM junction. The degree of potentiation may be enough to cause clinically significant NM block in patients who at the same time receive high enough doses of both agents. In vitro the NM block caused by the combinations of local anesthetics and NM blocking agents can be reversed by 4-aminopyridine.


Tracheal pathology following short-term intubation with low- and high-pressure endotracheal tube cuffs. Histologic sections of dog tracheas were taken from 20 dogs anesthetized and intubated for 5 to 7 hours with high-pressure, low-volume Shiley or low-pressure, high-volume Lanz endo-tracheal tubes. Microscopic examination and measurement showed that while the high-pressure, low-volume cuff produced deeper average mucosal erosion, the large-volume, low-pressure cuff resulted in significantly  greater lengths of tracheal mucosa-cuff erosion. Maximal depth of penetration throught the basement membrane was similar in both groups. Grooves in the mucosa were seen in 50% of the high-volume-cuff trachea sections but none of the low-volume-cuff tracheal sections. These findings demonstrate that low-pressure, high-volume endotracheal tube cuffs produce different but significant tracheal damage after short-term intubation when compared to high-pressure, low-volume cuffs.


Chronic rhinitis in the pre-school child. The etiologic role of atopy in chronic rhinitis in 40 infants and pre-school children was investigated and the long-term effectiveness and safety of promethazine studied during six to 48 months. Twenty children were clearly atopic and 16 were not. Four had incomplete laboratory evidence of atopy. In addition to clinical histories and physical findings, the subjects were evaluated by skin tests for common allergens. RAST tests, total IgE levels and absolute eosinophil counts. Promethazine in doses of 3 to 12 mg/kg/day (mean 8 mg) was administered in divided doses, four times a day for perennial rhinitis and on "as required" basis for recurrent and seasonal rhinitis. Side effects included drowsiness and irritability, which led to discontinuance of promethazine in one subject. There was no laboratory evidence of hematologic, renal or hepatic abnormalities. Promethazine was found to be an effective agent for symptom-control of chronic rhinitis in the pre-school child.


Enzymatic hydrolysis of soy protein for nutritional fortification of low pH food. Enzymatic hydrolysis of proteins is an attractive means of obtaining the changes in the functional properties often necessary for incorporating the protein in low pH food, e.g. soft drinks. The main problem associated with protein hydrolysis is the welldel-known formation of bitter-tasting peptides. The bitterness seems to be related to a too high degree of hydrolysis (DH). DH is defined as the percentage of cleaved peptide bonds and serves as the controlling parameter for the hydrolysis process. The choice of hydrolysis parameters is briefly discussed in relation to studies on the hydrolysis kinetics which in many respects can be described by classical enzyme kinetics. Several pilot plant productions of isoelectric soluble soy protein hydrolyzates have been carried out using soy isolate or soy concentrate as the raw material. The preferred enzyme for this type of hydrolysis is Alcalase 0.6 L, a food-grade liquid preparation of subtilism Carlsberg. The chosen hydrolysis parameters are : Substrate conc. : 8 per cent protein (N x 6.25). Enzyme-substrate ratio : 2 per cent. pH : 8.0. Temperature : 50 degrees C. The optimal DH value with regard to taste seems to be 10 per cent, corresponding to about 2 hours' hydrolysis time. The hydrolysis is terminated by the addition of citric or malic acids until pH reaches a value of 4.2. Separation of the supernatant from the unconverted protein is carried out in a continuous, solids-ejecting centrifuge. Preliminary rat trials show a satisfactory nutritional quality of the hydrolyzates. Possible end-uses for soy protein hydrolyzates are briefly discussed.


[Evaluation of soy bean proteins obtained by pressure]. Besides the processes of extrusion and protein fiber spinning, analogous utilization research with a range of protein sources is continuing at an accelerated pace. However, the pressure forming process, an attractive process for producing protein foods, has not received the attention as it merits. The fabrication techniques contribute the advantages of nutritional value, economic and simplicity in manufacture; it can be extend to utilize in the development of useful textured vegetable protein foods. Here, we present a pressure forming process for producing protein foods with soybean grains. In this paper, we evaluated the composition, and the yield of the products obtained by this process; the trypsin inhibitor and enzymatic proteolyse of the products were also studied. The product obtained contents soluble and insoluble proteins of soybean, 45 p. 100 of protein (N x 6,25), 20-25 p. 100 of carbohydrates of which the fibers are included; moreover it contents 6-7 p. 100 of ash and 20-22 p. 100 of fat. It does not content any starch, the oligosaccharides and antinutritional factors were almost eliminated. This product presents in acceptable textural form resembling traditional animal protein foodstuffs; its fonctional and nutritional properties can meet different utilizations in foodstuffs such as dietetic products and protein complements.


[Measure of available and blocked lysine in industrial milks]. The classical methods to measure lysine availability give rise to some difficulties in milks due to the presence of deoxyketose-lysine (DOKL). Six methods, one of which measuring the blocked lysine, are studied. Amino acid chromatography gives a too high value of lysine when it is blocked as DOKL, the latter regenerating lysine during acid hydrolysis. The determined lysine does not correspond to the available one. Fluro-dinitro-benzene is not fully specific for free epsilon-NH2 of lysine and the reducing sugars present interfere during the reaction in converting "nitro" into "amino" groups. Guanidization is a specific reaction between the epsilon-NH2 of lysine and O-methyl-isourea with formation of homoarginine. The homarginine, calculated as lysine corresponds to the available lysine. Reduction with sodium borhydride converts the DOKL to a stable compound which, during acid hydrolysis, does not regenerate lysine and does not form furosine. The recovered lysine corresponds to the available one. Our "in vitro" digestion method with simultaneous dialysis enables the determination of available lysine, as the proteolytic enzymes used do not split up the DOKL binding. The liberated lysine corresponds to the available one. The blocked lysine is measured from furosine after acid hydrolysis. A formula, which makes up the level of furosine formation and for lysine regeneration from DOKL, is established.


[Nutritional study of spun soy proteins]. Most of metabolic studies in man concerning the ability of soya proteins to obtain an equilibrated nitrogen balance have been made with extruded products. Because of the extending development of spun proteins, it seems necessary to study the protein quality of this type of product. A preliminary study in rat (C.E.P. method) was conducted to improve the nutritional value by complementation of the fibers by the way of binder. The metabolic utilization of this protein was evaluated in human subjects during two periods of 10 days. Soya protein cover respectively 78 and 48% of the total protein intake. Under these experimental conditions in which soya proteins constitute an important percentage of the total protein intake, the mean nitrogen balance is near to be equilibrated and the nitrogen utilization does not present any significative difference between the periods. Parallely to the suppression of animal proteins, the introduction of insatured lipids in the diet, has allowed, moreover, to decrease the concentration of the lipidic parameters of the subjects. This study demonstrated the dietetic interest and the ability of the studied product to provide the supplying of the nitrogen balance.


[Utilization of pure proteins and peptides for the study of chemical and nutritional changes suffered by milk during heating]. Milk proteins, and in particular the caseins, undergo during heat treatments (120 degrees C, 20-30 min) physico chemical and nutritional modifications. Using pure proteins (alphas and beta caseins) and peptides, it has been possible to dissociate the effects of heat treatments which, in milk can hide each other. Physico chemical properties of caseins (the ability to bind Ca++ and anionic dyes, acid-basic titration curves, electrophoretic behavior) are strongly altered, while the constitutive aminoacids are less modified. The accessibility of the aminogroups of lysine to the fluorodinitrobenzen and to the O-méthylisourea is lowered with a small rate. Lysinoalanyle interactions between serine and lysine are weak at a neutral pH while the isopeptide bonds epsilonN (gamma glutamyl)lysyle are only produced with more severe conditions as those of sterilization. The digestibility to the proteases is enhanced with low heat treatments then decreases with more severe treatments (120 degrees C-80 min.). Many peptides, which are released from the caseins during heating are issued from low specific split peptidic bonds; these peptides have often stimulating properties on the growth of lactic bacteria.


[Preservation of vitamin B1 and B2 during the preparation of pork meat]. Thiamin and riboflavin seem to resist fairly well to the proceedings of meat products studied here (cooked hams, patties, dry sausages). This result is normal enough to riboflavin, it is less for thiamin which sensitive to nitrite and to heating is well established by the literature. The origin of these observed phenomenons of protection is probably due to the complexation of these vitamins by the meat proteins. A similar phenomenon has been seen before by several authors on milk proteins, eggs and specially sulfhydril groups. This complexation is confirmed by the important release of both vitamins we noted during processing. They are determined much more easily on processed meat products than on raw materials. The nutritional repercussion of the observed phenomenon is difficult to estimate accurately. The vitamins release we find out, make them more available for the organism but it would be compared to the enzymatic decomplexation which occurs in vivo, during digestion, that we did not studied. Nevertheless such an approach would be necessary for the estimation of the practical value of the analytical determinations generally used.


Protein quality and iron availability of intermediate moisture beef stored at 38 degrees C. The longissimus dorsi of a bull and steer were cut into cubes 1.5 cm3 and processed to a water activity (aw) 0.85 by canning in a solution of 9.5 p. 100 sodium chloride, 0.5 p. 100 potassium sorbate and a pre-determined amount of glycerol and water for sixteen hours with continuous tumbling on an end over shaker. After partial drying the intermediate moisture (i.m.) meat pieces were stored at 38 degrees C for periods up to 24 weeks and then freeze-dried before milling and incorporation into test diets fed to rats. Protein quality of fresh cooked beef and i.m. meat stored at 38 degrees C was measured in terms of net protein utilisation (NPU). There was no significant difference in NPU between cooked beef and freshly processed i.m. beef. There were no changes in NPU of i.m. meat from bull up to 9 weeks of storage. After 3 weeks of storage of the meat from the steer however, the NPU fell to 53.0, a level characteristic of cereal protein. This fall in NPU was associated with a decrease in the levels of all essential amino acids (in the protein hydrolysate). Valine and threonine being first and second limiting amino acids. Further storage of i.m. beef after 3 weeks produced a slower rate of decrease in NPU, the value at 24 weeks being 32.1 (61 p. 100 fall). Available lysine decreased by only 15 p. 100 after twenty-four weeks, this measurement under-estimating the fall in protein quality. The decrease in solubility of the meat in SDS/beta-mercaptoethanol on storage was of similar magnitude to that of NPU. Iron availability of i.m. meat, measured by haemoglobin regeneration in rats, showed improved iron availability compared to freshly cooked beef, even though marked changes had occurred in the meat heamatin complexes.


Four new methods of debittering protein hydrolysates and a fraction of hydrolysates with high content of essential amino acids. Extraction of enzymatic protein hydrolysates with azeotropic secondary butyl alcohol (SBA) or aqueous ethanol (AE) or aqueous isopropranol (AI), seems to be an efficient and generally applicable method for removal of bitter compounds. The bitter peptides are concentrated in the alcohol-phase which has an extremely bitter taste. It has a concentration of 40-70 p. 100 essential amino-acids. In the alcohol-phase leucine, isoleucine, phenylalamine and tryptophan were particularly increased. Experiments showed that the bitterness of the alcohol-soluble fraction could be reduced by applying the plastein reaction. A reduction in bitterness of protein hydrolysates could also be achieved by applying hydrophobic interaction chromatography. Of tested gels, hexyl-sepharose was found to be the most effective for debittering of protein hydrolysates.


[Effect of rubomycin and carminomycin on antibody formation during the immunization of mice with various antigens]. The maximum immunodepressive effect of rubomycin and carminomycin was observed when the antibiotics were administered intravenously 24 hours after the immunization. The immune response induced by the sheep erythrocytes or the lipopolysaccharide was equally inhibited by rubomycin. Carminomycin in a dose of 0.5 mg/kg (0.1 of the LD50) to a larger extent inhibited the immune response stimulated by the lipopolysaccharide. Dependence of the immunodepressive effect of the antibiotics on their dose was found when the drugs were administered intravenously or orally.


Effect of hadacidin on growth and adenylosuccinate synthetase activity of Dictyostelium discoideum. The growth of the eucaryotic microorganism Dictyostelium discoideum in liquid culture was completely inhibited by the aspartic acid analog hadacidin (N-formylhydroxyamino-acetic acid). Growth arrest occurred both in chemically defined medium and in complex growth medium containing aspartic acid and AMP precursors such as adenine and adenosine. Although these compounds could not overcome the effect of hadacidin, growth was restored if cells were washed and resuspended in fresh growth medium. Additional experiments showed that D. discoideum contains adenylosuccinate synthetase, the enzyme which catalyzes the synthesis of adenylosuccinate from IMP, aspartic acid, and GTP in the de novo biosynthesis of purines. A partially purified preparation of this enzyme was obtained, and the effect of hadacidin on its activity was studied. We found that maximum inhibition of the D. discoideum activity occurs at a ratio of aspartic acid to hadacidin of 5:1, suggesting that the affinity of the drug for this enzyme is less than for the enzyme from rabbit muscle and plants but greater than for that from Escherichia coli. The effect of the drug can be overcome by a 10-fold excess of aspartic acid, suggesting that the drug acts as a competitive inhibitor. A comparison of the adenylosuccinate synthetase activity levels at various stages of growth showed that its specific activity decreases about 60% as cells enter the stationary growth phase, and decreases about 75% after starvation for 2 h. Further studies showed that in cells treated with hadacidin the rate of uptake of exogenous nutrients is reduced about 75% and that these cells are more resistant to rupture by osmotic shock. While the results of this study are consistent with the proposal that growth arrest is contingent upon inhibition of adenylosuccinate synthetase activity, they also suggest that, as a consequence of this inhibition, some physiological properties of the cell have been altered.


Quantitation of imidazoles by agar-disk diffusion. A simple, reliable, and inexpensive assay for quantitation of the imidazole drugs miconazole, RV 40,500, and RV 41,400 was tested. The assay, similar to a Kirby-Bauer test, was sensitive to less than or equal to 0.2 mug of drug per ml and linear from less than or equal to 0.2 to 10.0 mug/ml. Concentration of inoculum and agar depth in test plates was not as critical as the type of medium, amount of inoculum, or type of drug used.


Enrichment procedures for isolating salmonellae from raw meat and poultry. The combined use of direct enrichment in tetrathionate broth containing brilliant green dye and preenrichment in buffered peptone-water followed by enrichment in tetrathionate broth yielded the maximal recovery of salmonellae from raw meat and poultry samples.


Angiosarcoma with pulmonary siderosis and persistent reticulocytosis. Steroid responsiveness suggests an immune basis. A 35-year old man with cough, hemoptysis, and dyspnea was found to have diffuse pulmonary infiltrates and iron-laden macrophages in the sputum. Pulmonary siderosis was confirmed by transbronchial biopsy. An associated hypochromic anemia required frequent transfusion. Though marrow iron stores were absent, reticulocytosis was maintained. Corticosteroid therapy resulted in cessation of hemoptysis, clearing of the pulmonary infiltration, and a substantial reduction in transfusion requirement. Splenectomy was of no benefit. The patient developed cerebral symptoms with seizures, and rapid deterioration led to cerebral symptoms with seizures, and rapid deterioration led to death. Disseminated hemangiosarcoma was found at autopsy. Steroid responsiveness of the associated pulmonary siderosis suggests that it had an immune basis.


Galactosemia as a result of galactose-1-phosphate uridyltransferase deficiency. This study was designed to determine the activity of galactose-1-phosphate uridyltransferase enzyme in a family (parents and eight children): four of these with clinical diagnosis of classical galactosemia. In two of them a complete transferase deficiency was found, thus confirming diagnosis; the other two, a pair of dizygotic twins, who since birth up to 11 years of age had been on a galactose free diet, showed enzymatic activity consistent with normal heterozygotes, one of them, and with normal homozygotes, the other. The parents and four brothers had the same enzyme activity levels an those found in heterozygotes for galactosemia. Early diagnosis is of utmost importance in classical galactosemia, and we emphasize this point because patients can be treated with dietotherapy and primary prevention is possible through genetic counseling.


Physical illness presenting as psychiatric disease. A study of 658 consecutive psychiatric outpatients receiving careful medical and biochemical evaluation, defined an incidence of medical disorders productive of psychiatric symptoms in 9.1% of cases. The most frequent presentations were of depression, confusion, anxiety, and speech or memory disorders. The presence of visual hallucinations was believed to indicate medical etiology until proved otherwise. Major illnesses presenting with psychiatric symptoms in order of frequency were infectious, pulmonary, thyroid, diabetic, hematopoietic, hepatic and CNS diseases. Forty-six percent of these patients suffered from medical illnesses previously unknown to either them or their physician. A plea is made for careful medical evaluation of psychiatric patients.


Selected isolates of bovine viral diarrhea (BVD) virus propagated on bovine turbinate cells: virus titer and soluble antigen production as factors in immunogenicity of killed BVD virus. Soluble antigen production in a bovine turbinate cell line by 17 isolates of bovine viral diarrhea virus was studied. We showed that the quantity of soluble antigen produced may vary considerably between isolates. Further, the isolate producing the greatest quantity of soluble antigen produced a higher antibody titer in calves than an isolate producing only half as much soluble antigen.


Neuromuscular synapse testing in two cases of suicidal organophosphorous pesticide poisoning. Electromyographic neuromuscular testing was performed for two patients with a very low blood cholinesterase activity due to suicidal poisoning with organophosphorous pesticides. Electromyographic results did not differ significantly from those obtained in healthy nonexposed adults. Neuromuscular synapse functioning was normal, as was determined by electromyography. Neurological signs and symptoms are described in detail.


Surface chemistry characteristics of human umbilical vein used as chronic canine arteriovenous fistulas. Six bilateral loop arteriovenous fistulas from the femoral artery to the femoral vein were constructed in dogs using Dacron-mesh-coated human umbilical vein. Each graft was punctured twice weekly with a 16 gauge needle for up to 36 weeks, and biopsies were done every four to eight weeks. The long-term patency was 83% at 24 weeks. There was no thrombosis from the needle puncture. Serial histologic examination revealed progressive transmural fibrous cell ingrowth and progressive neointimal cell formation. Scanning electron microscopy demonstrated areas of disrupted basement membrane covered with laminar fibrin meshes, probably representing sites of needle puncture. With multiple attenuated internal reflection spectroscopy of the graft lumens, minimal to moderate lipid deposition was observed to a depth of 1 micrometer at 32-36 weeks. No abnormal amounts of minerals were found within the graft walls with energy-dispersive x-ray analysis. Critical surface tensions remained within the biocompatible range of 20-30 dynes/cm. Human umbilical vein possesses many of the surface chemistry qualities of an ideal vascular prosthesis, has excellent long term patency, and is suitable for use where angioaccess with repeated needle puncture is needed.


Bioengineering aspects of the artificial pancreas. In this paper, results of work aimed at the development of artificial beta-cells are presented. An electrolytically driven pump is considered to be a proper device for insulin injection. The transient characteristics of the simplified version of such a pump make it suitable for application in open-loop devices. Methods for electrical control of the injection rate of this pump for application in closed-loop artificial beta-cells are given. An essential component of a closed-loop artificial beta-cell is a glucose sensor. A modified version of the glucose sensor has been developed and its performance is described. Considerations of some control problems related to the artificial pancreas are briefly discussed.


Induction of ornithine decarboxylase in synchronized BHK cells by calf serum after a short period of serum-starvation. Addition of calf serum to serum-starved cultures of synchronized BHK cells induced temporary production of ornithine decarboxylase, irrespective of the phase of the cell cycle of the BHK cells. The induction depended on the duration of serum starvation and on the amount of serum added. In addition, incorporation of 3H-thymidine into the acid-insoluble fraction of BHK cells in the S phase was stimulated by this treatment.


Quantitative cidal activity of hyperbaric oxygen for opportunistic yeast pathogens. Cidal activities of 24-h exposures to 100% O2 and 95% O2 + 5% CO2 were assayed at 1 and 3 ATA. Studied were 21 yeasts isolated from humans: Candida albicans (8 strains), C. tropicalis (3 strains), C. krusei (3 strains), C. parapsilosis (2 strains), C. guilliermondii (2 strains), and one strain each of C. pseudotropicalis, C. stellatoidea, and Torulopsis sp. Generally, these were extremely sensitive to hyperbaric oxygen, although species and strain differences were observed. Indices of kill from 80-100 (total kill) characterized 17 of the 21 yeasts (81%). Hyperoxia (O2 +/- CO2 at 1 ATA) was not lethal. Deprivation of CO2 as a consequence of hyperbaric exposure to 100% O2 enhanced cidal activity for only 2 of 21 yeasts, whereas hyperbaric exposure to the mixture enhanced activity against four yeasts. Cidal activities were not significantly different for the remaining 15 yeasts. This response to deprivation of CO2 is different from that of bacteria, and manifests fundamental differences between procaryotic and eucaryotic cells.


Solubilization of bovine corpus-luteum adenylate cyclase in lubrol-PX, triton X-100 or digitonin and the stabilizing effect of sodium fluoride present in the solubilization medium. 1. Adenylate cyclase activity of the washed 600g sediment of bovine corpus-luteum homogenate was solubilized by Lubrol-PX, Triton X-100 and digitonin. Digitonin was the least destructive of NaF-stimulated activity. 2. NaF, present in the solubilization medium together with MgSO4, increased the percentage yields of soluble activity from untreated 600g sediment and 600g sediment which had been preincubated with p[NH]ppG (guanosine 5'-[betagamma-imido]triphosphate). The stabilizing influence of NaF was most marked with digitonin. However, the highest specific activities of soluble enzyme were obtained with Lubrol-PX as solubilizing agent, since digitonin solubilized more membrane protein than does Lubrol-PX, and less of the activity of the digitonin-dispersed 600g sediment was recovered in the 105000g supernatant. 3. p[NH]ppG also has a stabilizing effect when present during the solubilization, but less so than NaF. 4. Both NaF and MgSO4 alone have a stabilizing effect during solubilization. The greatest amounts of soluble activity were obtained with both agents present in the solubilization medium, there being a synergistic effect.


Acute effect of ascorbic acid on fibrinolytic activity. The acute effect of 1 g oral ascorbic acid on serum fibrinolytic activity was studied in 40 adult males. In Group I (healthy adults) administration of ascorbic acid raised the serum level by about 71%, while the fibrinolytic activity increased to a peak of 137% at 6 h. In patients with CAD (Group II) an essentially similar increase in FA was observed. In Group III, simultaneous administration of ascorbic acid with 100 g fat effectively prevented a fall in fibrinolytic activity and actually raised it by 64% above the fasting level.


Severe and early stenosis of porcine heterograft mitral valve. A patient who had aortic and mitral valves replaced by Carpentier porcine heterografts for bacterial endocarditis developed severe heart failure 18 days after operation. A second emergency operation revealed that the mitral prosthesis had become severely stenosed and calcified. A loud Graham Steell murmur had developed during the 12 hours before reoperation but no distinct murmurs of mitral stenosis had been detected.


A sensitive test demonstrating lupus anticoagulant and its behavioural patterns. The kaolin clotting time of platelet poor plasma was used as a sensitive test for detecting the lupus anticoagulant in mixtures of normal and patients' plasmas. Platelets were found to decrease the anticoagulant effect of a typical lupus inhibitor. Thus, high sensitivity in this test system was achieved by ensuring low platelet concentrations and omitting platelet lipid substitute. In 17 patients with disseminated lupus erythematosus (DLE), 12 had detectable inhibitor by this method, more than would be detected with routine coagulation tests. Mixing patterns were of four distinct types, representing three different modes of anticoagulant behaviour. The pattern (type 3) of plasma mixtures giving longer kaolin clotting times than the individual components could be reproduced in vitro by adding trace amounts of crude thrombin or platelet fragments to a more typical lupus anticoagulant-containing plasma; formation of such a mixing pattern by the plasma of a patient with DLE may therefore indicate activation of the coagulation pathway. Six patients with idopathic thrombocytopenic purpura (ITP) had no detectable inhibitor indicating that anti-platelet antibodies behave differently from the lupus anticoagulant.


Congenital hypofibrinogenaemia and recurrent abortion. Case report. A 26-year-old patient, who had had six consecutive spontaneous early abortions, is presented. The patient had hypofibrinogenaemia. The importance of a normal fibrin network in early pregnancy is discussed.


Fuchs's heterochromic cyclitis: a simultaneous bilateral fluorescein angiographic study of the iris. Twelve patients with Fuchs's heterochromic cyclitis (FHC) were studied with simultaneous bilateral flucrescein angiography of the iris. The flow began a little earlier in the contralateral iris in 4 cases, and simultaneously in both irides in 8 cases. The radial iris vessels were narrow in 7 eyes with FHC and in the contralateral eyes of 2 elderly patients and 1 patient with pigmentary retinal dystrophy and FHC. An ischaemic sector of the iris was seen in 6 eyes with FHC, neovascularisation of the iris in 8 eyes, and fluorescein leakage of the iris vessels was seen in all eyes with FHC. No neovascularisation of the iris occurred in the contralateral eyes, and only minimal fluorescein leakage was seen at the pupillary border of 5 contralateral eyes. The results support the hypothesis of vascular pathomechanism in FHC.


Amino acid sequence of progesterone-induced rabbit uteroglobin. Uteroglobin, a steroid-binding protein of the uterine secretion of the rabbit which is induced by progesterone, comprises two identical polypeptide chains of 70 amino acid residues linked by two disulfide bonds. The primary structure has been determined by using both automated and manual methods of Edman degradation. Overlapping peptides were isolated from tryptic, and CNBr digests. The sequence is not homologous to any known protein except for a small acidic region (residues 22-29) resembling a sequence found in somatotropin. The C-terminal half is relatively basic. Implications for the secondary structure are discussed.


Characterization of DNA-protein cross-links formed by treatment of L1210 cells and nuclei with bis(2-chloroethyl)methylamine (nitrogen mustard). Proteins cross-linked to DNA after nitrogen mustard (HN2) treatment of cells or isolated nuclei were purified in CsCl gradients. The protein-DNA cross-links could be cleaved by incubation in dilute acid and could be stabilized by alkali pretreatment. These results indicate that proteins cross-linked to DNA by HN2 are bound to alkylated purines. Analysis of the DNA-bound proteins on NaDodSO4-polyacrylamide gels showed that primarily large nonhistone proteins are cross-linked to DNA in cells treated with HN2. Very little if any histone is cross-linked to the DNA. Comparison of DNA bound proteins from HN2-treated cells and HN2-treated nuclei showed that in general the same proteins are linked to DNA in both cases, but some qualitative and quantitative differences exist.