Protein degradation during the differentiation of eukaryotic cells: studies on the sporulation of Saccharomyces cerevisiae and on the formation of the neuromuscular junction in the chick embryo.

The role of protein degradation in cell and tissue differentiation has been investigated during the sporulation of Saccharomyces cerevisiae and during endplate formation in developing avian muscle. The results suggest that a variety of proteolytic processes as enzyme inactivation, degradation of mitochondrial membrane constituents and removal of embryonic cell surface proteins exert stringent controls over the sequence of differentiation in eukaryotic cells.


Proteolytic and transhydrogenolytic activities in isolated pancreatic islets of rats.

In homogenates and subcellular fractions of pancreatic islets of Wistar rats we could demonstrate three groups of protein degrading enzymes. The proteinases of group 1 are characterized by both trypsin-like and carboxypeptidase B-like specificities with slightly acid pH optima (pH 5.5-6.5) and seem to play important roles in the conversion of proinsulin into insulin. The properties suggest that these enzymes localized in the secretion granule/mitochondria fraction are related to the tissue cathepsins. Group 2 enzymes are thiol-depending proteinases with a pH optimum at 7.0 occuring mainly in the cytosol and to a lesser extent in the fraction of nuclei and cell debris. Group 3 represents the thiol protein oxidoreductase with a pH optimum of 7.0. This enzyme degrading disulfide bonds could also be important in the formation of the disulfide bonds during protein folding after synthesis.


The effect of LH-RH infusion on serum LH, FSH and testosterone in boys with advanced puberty, delayed puberty and hypogonadotrophic hypogonadism.

LH-RH injection and infusion studies were performed in advanced puberty, delayed puberty and hypogonadotrophic hypogonadism. No differential diagnosis could be made between delayed puberty and hypogonadotrophic hypogonadism using LH-RH injection. In the LH-RH infusion studies evidence was obtained that stimulation of the pituitary during 4 h results in continuously rising LH levels in advanced puberty and in delayed puberty while in hypogonadotrophic hypogonadism the secretory capacity of the pituitary is gradually exhausted. This phenomenon can be used in the differential diagnosis between delayed puberty and hypogonadotrophic hypogonadism. Though the FSH data point in the same direction they are not useful in this connection as the overlap between the different categories was considerable.


Effect of pyridoxine on plasma levels of HGH, PRL, and TSH in normal women.

The effect of chronic administration of pyridoxine (vitamin B6) on HGH, basal and TRH stimulated PRL and TSH levels was studied in seven healthy female volunteers. HGH and TSH basal levels remained unaffected. Basal PRL and TRH stimulated PRL and TSH levels were slightly reduced without statistical significance (P greater than 0.05). The results indicate, that stimulation of the hypothalamic dopaminergic pathway by pyridoxine is highly variable and unpredictable. Therefore it seems meaningless to recommend vitamin B6 for the treatment of hyperprolactinaemia.


Prostaglandin-stimulated gastric mucus secretion in man.

In 6 healthy volunteers, following intragastric instillation of a prostaglandin analogue pentagastrinstimulated gastric secretion of acid, pepsin, and glycoprotein N-acetylneuraminic acid (NANA) was assessed. There was only a slight and statistically insignificant inhibition of acid output while pepsin secretion remained entirely unaffected. On the other hand, gastric mucus (NANA) secretion was significantly increased dependent on the prostaglandin dose administered. It is concluded that prostaglandins in addition to their well-known gastric acid inhibitory action may exert mucus stimulating properties and thus may have a direct protective effect on the gastric mucosa.


In vivo vs in vitro response time of trancutaneous PO2 electrodes. A comparison of four devices in newborn infants.

Four devices for transcutaneous PO2 (tcPO2) monitoring have been applied simultaneously in 16 infants. Both during a maximal change in PaO2 and during physiological PO2 variations, the in vivo response time of the electrodes did not show the differences observed in vitro. We compared A, a prototype of the electrode by Huck, Lübbers and Huch (25 micrometer Telfon membrane) ; B, the commercial version of A by Hellige--Draeger (25 micrometer Telfon); C, the Radiometer TCM I oxygen monitor (25 micrometer polypropylene); and D, the Roche macrocathode electrode (6 micrometer Mylar), at 44 degree C. In vitro the 50% response times were 2.9 (A), 4.4 (B), 3.7 (C), and 7.4 (D) sec. The rates of tcPO2 changes at the midpoint of the response curves were 3.8(A) 2.0 (B), 3.0 (C), and 1.7 (D) kPa/sec. In vivo during a sudden change from hyperoxemia (FIO2 1.0) to normoxaemia the respective rates were 0.6 (A), 0.8 (B), 1.1 (C), and 1.0(D) kPa/sec. The in vivo 50% response times were 53.3 (A), 51.1 (B), 46.2 (C) and 45.3 (d) kPa/sec. The in vivo 50% response time were 53.3 (A), 51.1 (B), 46.2 (C), and 45.3 (d) kPa/sec. The in vivo 50% resonse time were 53.3 (A), 51.1 (B), 46.2 (C), and 45.3 (D) sec. The lag time between PaO2 and tcPO2 was about one third of this overall response time. The response to more physiological variations of PaO2 (periodic breathing) was not different among the tested electrodes in terms of damping and of delay of the tcPO2 deflections. In a steady state the correlation of tcPO2 44 degree C vs PaO2  was close (r = 0.98) with all devices up to 6.1 kPa (456 torr).


Effects of positive end-expiratory pressure on renal function.

The effects were studied positive end-expiratory pressure (PEEP) on renal function in eight patients with acute respiratory failure, requiring mechanical ventilation. On application of PEEP + 10 cm H2O, central venous pressure increased, systolic blood pressure decreased, urine flow and PAH-clearance were reduced, while inulin clearance remained stable. There was a marked increase in fractional sodium reabsorption and a concurrent decrease in fractional osmolal excretion. Fractional free-water clearance and the ratio UOsm/POsm did change.


Ovarian follicular apparatus and hormonal parameters in patients with primary and secondary amenorrhea.

Correlation between ovarian follicular apparatus and hormonal parameters such as serum gonadotropin and urinary estrogen levels was investigated in patients with primary and secondary amenorrhea. Serum gonadotropin levels were elevated in amenorrheic patients without ovarian follicles or with follicles of low developmental stage and pituitary responsiveness to LH-RH in these patients were marked compared with patients with follicles of high developmental stage or normal ovulating women in the follicular phase of the menstrual cycle. The 24-hour urinary excretion of total estrogens was low in patients without follicles or with follicles of low developmental stage and ovarian responsiveness to exogenous gonadotropins was quite low in comparison with patients with highly developed follicles or normal control subjects. Thus, serum gonadotropin and urinary estrogen measurements and LH-RH and gonadotropin loading tests are diagnostic of the presence or absence and the state of development of ovarian follicles in the diagnosis and treatment of primary and secondary amenorrhea.


The effects of longacting paracervical block anesthesia on the abortifacient efficacy of intra-amniotic PGF2alpha and hypertonic saline.

A comparative study was conducted to evaluate the effects of repeated, longacting paracervical blocks on the abortifacient efficacy of intraamniotic prostaglandin F2alpha (PGF2alpha)-40 mg initially and an additional 20 mg after 24 hours--and hypertonic saline augmented with intravenous oxytocin, for patients at 16 to 20 weeks' gestation. Patients were randomly assigned to the 2 abortion procedures, and one half (50) of the patients induced with each procedure received serial, longacting paracervical blocks. For those patients aborted with saline, the rates of complications, side effects, incomplete abortion, and cumulative abortion were similar for patients whether they did or did not receive paracervical blocks. Among the PGF2alpha-treated patients who were administered paracervical blocks, there was a significant reduction in the rates of gastrointestinal side effects and incomplete abortion and a significant differences in the cumulative abortion rates. Within 32 hours of the initial PGF2alpha, instillation, 98% of the patients who received paracervical blocks aborted compared to 70% of those who did not receive paracervical blocks. Although the cumulative abortion rates of PGF2alpha-treated patients with paracervical blocks and saline-treated patients were similar, the rate of incomplete abortion for the PGF2alpha-treated patients was significantly lower. Additional studies will be necessary to evaluate the safety and advantages of using paracervical block anesthesia as an adjunct to midtrimester abortion procedures.


Comparison of extra-amniotic instillation of rivanol and PGF2alpha either separately or in combination followed by oxytocin for second trimester abortion.

Second trimester abortion was induced in 92 women by extra-amniotic instillation of Rivanol and/or PGF2alpha followed by intravenous oxytocin after 24 hours. All instillations were made via a catheter with a balloon filled with 30 ml and left in place until abortion, but never for more than 24 hours. Induction was started by Rivanol alone (n = 23), PGF2alpha alone (n = 23), Rivanol combined with PGF2alpha (n = 23), or Rivanol combined with half dose PGF2alpha (n = 23) and the patients were allotted to the different groups in a random manner. The Rivanol solution was instilled as a single dose but PGF2alpha was instilled every 2nd hour for 24 hours. The mean induction-abortion time was similar in all 4 groups but a number of patients given PGF2alpha alone or in combination with Rivanol aborted earlier than patients induced by Rivanol alone, during the period before intravenous oxytocin was administered. Gastrointestinal side effects were equally common after Rivanol as after PGF2alpha. With the methods and doses used in the present investigation PGF2alpha alone or combined with Rivanol with subsequent oxytocin had no over-all advantage over Rivanol.


HLA-B 12 and HLA-B 27 antigens and susceptibility to the corneal allograft reaction.

Our series comprised 100 penetrating corneal transplantations: 36 cases with HLA-B 12 and/or B 27 antigen in the recipient and, as controls, 64 cases without these antigens. The cornea was vascular in 44% of the HLA-B 12/B 27 group and in 40% of the controls. In the HLA-B 12/B 27 group AR developed in 13 of 36 cases, 36%; but in the control group only in one case (2%). In vascular and avascular cases the incidence of AR was equal. Among the high-risk cases of the HLA-B 12/B 27 group with definite mismatching of B 12 or B 27 antigens, 9 of the 14 recipients had developed AR. Six further recipients of this group had untyped grafts, and AR occurred in 4 of the 6, but in none of the 16 cases that were matched for B 12 or B 27 antigens. The value of a compatible graft, at least to the carriers of HLA-B 12 and/or B 27 antigens, is thus confirmed.


Failure of an elbow endoprosthesis.

In a patient with a severely damaged elbow, the complication of gas gangrene could be controlled without amputating the arm. However, massive bony defects resulted in a flail elbow joint and an attempt to fit a specially designed endoprosthesis replacement failed. Four years post-injury, the flail joint was fused by three bone grafts on three separate occasions. These experiences are reported and discussed.


Urinary tract infections caused by Proteus mirabilis in children. The antibody response to O and H antigens and Tamm-Horsfall protein and bacterial adherence to uro-epithelium.

Sera from seven girls with acute symptomatic pyelonephritis and nine children with acute symptomatic cystitis caused by Proteus mirabilis were analysed for antibodies against the bacterial O and H1 antigens and the Tamm-Horsfall protein. An increase in antibody levels against O antigen and Tamm-Horsfall protein was noted only in patients with acute pyelonephritis indicating that antibody determinations can be useful in differentiating between upper and lower urinary tract infection caused by Proteus in similarity to those caused by E. coli. In contrast no difference in adhesive ability was noted comparing Proteus strains causing acute pyelonephritis or cystitis.


Bacteriology of the chronically discharging middle ear.

Suitable bacteriological techniques revealed anaerobic bacteria in 38 (33%) of 114 chronically discharging middle ears. The genus Bacteroides was cultured from 25 ears. Aerobic bacteriology showed the predominance of staphylococci, facultative enteric gramnegative rods, diphtheroid bacilli and Pseudomonas species. Anaerobic bacterial cultures were always mixed with aerobic bacteria. 12 ears were culture-negative, and 9 of the 108 Gram-stained smers revealed no bacteria. No significant difference in bacteriology was noted between ears with or without local antimicrobial treatment, or between profusely draining or only moist ears. The ears with postoperative recurrent infection or with clinical suspicion of cholesteatoma grew anaerobes significantly more often, and were seldom sterile. Because anaerobic bacteria are frequently associated with chronic otitis media, their characteristics with regard to susceptibility to antimicrobials and to air must be remembered in the choice of therapy.


Long-term prophylaxis with methenamine hippurate in girls with recurrent urinary tract infections.

Twenty girls, aged 5-12 years, with recurrent urinary tract infections, were treated with methenamine hippurate, Hiprex, for a period of 12 months. The number of infections per patient per year was reduced from 3.1 to 0.7 (p less than 0.001). After prophylaxis was stopped this number increased to 1.4 which is a significantly higher incidence than occurred during treatment (p less than 0.05). A few girls complained of the taste but no side-effects were observed. Methenamine hippurate is a useful alternative in long-term prophylaxis against recurrent urinary tract infections in girls.


Reliable diagnosis of the major type of cystic fibrosis with fibroblast cultures. A double blind study.

A double blind study has been carried out to demonstrate that the most common type of cystic fibrosis (CF) can be reliably diagnosed with skin-derived fibroblast cultures. Alkaline phosphatase (AIP) activity has been measured in 6 normal controls, 12 CF-heterozygotes and 6 CF-homozygotes before and after stimulation with Tamm-Horsfall-glycoprotein (THP), isoproterenol and theophyline ("THP-induction test"). The mean AIP-activities after THP-induction were 8.8, 12.7 and 34.6 for the three different genotypes respectively. There was no overlap between the values of CF-homozygotes on the one hand, and the values of CF-heterozygotes and normal controls on the other hand. All 24 specimens were correctly diagnosed in the present double blind study, indicating the very high degree of reliability of the THP-induction test in the detection of the predominant type of cystic fibrosis with fibroblast cultures. Normal controls and CF-heterozygotes could not be discriminated on an individual basis, but as a group the CF-heterozygotes displayed higher AIP-values.


Fine morphology of the advancing front of cholesteatome--experimental and human.

The fine morphology of the advancing front of the cholesteatoma and the mucocutaneous juction of implanted skin in the feline bulla have been investigated. Inflammatory cell infiltration was frequently observed at the advancing front and the mucocutaneous junction. It is suggested that this frequent inflammation at this junction is due to the lack of a tight seal. In the advancing front, epidermal migrating cells appear to be lower spinous cells (or "suprabasalar" cells) rather than basal cells. It appears that the slender cell processes of the migrating cells make the initial attachment to the fibrin and/or basement membrane left behind by the degenerated epithelial cells as a result of inflammation and migrate along these structures, using them as a guide. Implanted skin in the cat's bulla failed to develop a pearl formation but frequently developed an epiboly, in which case the epidermis receded and was partly replaced by mucous membrane, and its stroma was heavily invaded by mucous epithelium, resembling tubular glands.


Paradoxical enhancement of tolbutamide-induced insulin release by diazoxide in a patient with islet cell hyperplasia.

A case of islet cell hyperplasia in a ten year old black male with symptomatic fasting hypoglycemia was documented histopathologically. Provocative studies with glucose, tolbutamide, glucagon, and diazoxide were performed to test the insulin response of hyperplastic islets. The islets responded to glucose, glucagon, and tolbutamide. Diazoxide potentiated the tolbutamide-induced insulin response, and this effect of diazoxide was not blocked by propranolol. In the diagnostic work up of islet cell hyperplasia, dizoxide may paradoxically potentiate tolbutamide-induced insulin release, a finding which may falsely suggest progression of the disease.


Child abuse: a literature review.

The following is a summary of a recently published review of Swedish and international literature concerning children exposed to abuse and neglect or manifesting failure to thrive. The review is the first report appearing from the so-called PRU group in Uppsala--Psycho-social Risk Children in Uppsala. The group is a multidisciplinary team engaged in a research project about Uppsala children exposed to mental, social and physical risks in their homes. The project is financed by the Save the Children Fund, which has also contributed to the printing costs of the book. Various professions are represented in the research team, namely social work, family therapy, child psychiatry, child psychology, paediatrics, and sociology. The complete review was published in the autumn of 1977 under the following title: Dagmar Lagerberg/PRU-gruppen: Föräldravåld mot barn. En litteraturstudie (PRU group: Child abuse by parents. A literature review). A second main report, presenting the aims, material, methods, and results of the project, is planned for publication in 1979.


Rapid identification of group A, B, C and G beta-haemolytic Streptococci by a modification of the co-agglutination technique. Comparison of results obtained by co-agglutination, fluorescent antibody test, counterimmunoelectrophoresis, and precipitin technique.

A rapid modification of the co-agglutination (COA) technique for grouping A, B, C and G beta-haemolytic streptococci was developed. The results are obtained within three hours after inoculation from primary plates of 0.5 ml broth. This method was compared to the fluorescent antibody test (FA) and counterimmunoelectrophoresis (CIE), two other rapid methods available for serological grouping of streptococci. Of 71 recently isolated streptococcal strains from clinical sources, 70 were correctly grouped in COA, 63 in FA and 68 in CIE. With commercial reagents COA compared favourably in accuracy to the other methods and can be recommended for routine serological grouping of beta-haemolytic streptococci in the clinical laboratory.


The effect of colostrum and colostral antibody SIgA on the physico-chemical properties and phagocytosis of Escherichia coli o86.

A hydrophilic effect of human colostrum and colostral antibody SIgA binding on Escherichia coli o86 has been demonstrated by hydrophobic interaction chromatography on Octyl-Sepharose and partition in a polymer two-phase system containing dextran, poly(ethyleneglycol) and poly(ethyleneglycol)-palmitate. Furthermore, antibody SIgA binding reduced the negative surface charge of the E. coli bacteria. The reaction between centrifuged but not further purified colostrum and bacteria yielded a complex which, compared to bacteria alone, showed decreased negative and increased positive surface charges, the latter being sensitive to pepsin. Binding of SIgA or colostrum to E. coli showed no definite effect on the attachment to and phagocytosis by polymorphonuclear cells in vitro. The effects observed are discussed in relation to the structure of SIgA.


Density gradient centrifugation in urografin of Moraxella and Kingella cells and appendages.

Purification of fimbriae (pili) by density gradient banding in Urografin medium was attempted. Moraxella nonliquefaciens and Kingella kingae fimbriae were of higher density than their cells of origin, but fimbrial fractions obtained by homogenization and differential centrifugation still banded together with presumed outer membrane fragments and some whole cells in Urografin gradients. The cellular density of genetic variants with different fimbriation/competence levels was also studied. For one strain of M. nonliquefaciens and two strains of K. kingae, cells harvested from agar plates tended to show several bands on isopycnic density gradient centrifugation, with slightly higher general density of fimbriated variants than non-fimbriated. A single density band could be observed with cells from log phase broth cultures of selected strains which showed no distinct difference between fimbriation or competence variants of each strain. Cells of M. nonliquefaciens and M. bovis showed comparable buoyant densities, whereas those of K. kingae had a higher density.


Acid-soluble nucleotides of Acholeplasma (Mycoplasma) laidlawii A.

A study was made of the acid-soluble nucleotides present in Acholeplasma (Mycoplasma) laidlawii A during growth. The nucleotide pool of this organism is meagre, both qualitatively and quantitatively. The main nucleotides are uridine mono- and diphosphates, and none of the more complex nucleotide compounds, such as uridine diphosphate (UDP) sugars or sugar peptides, required for cell wall formation, were detected. The nucleotide composition of A. laidlawii A is compared with that of the Streptococcus L-form.


Phagocytosis of 32P-labelled E. coli by human polymorphonuclear cells (PMN). Adaptation of a method.

A system for the study of phagocytosis by human polymorphonuclear cells (PMN) is presented. The leucocytes are harvested from heparinized whole blood by the Bøyum method and transferred to glass tubes to yield glass adherent monolayers of leucocytes, approximately 80% of which were PMN. A strain of E. coli labelled by 32P served as test organism.


Analysis of amines and other bacterial products by head-space gas chromatography.

A gas chromatographic (GC) head-space technique is presented, which is suitable for the analysis of volatile products in bacterial broth cultures. This is exemplified by studies on Clostridium septicum, Klebsiella pneumoniae and Proteus mirabilis. The media were acidified or made alkaline and after heating, samples of the gas phase above the media were directly injected into the gas chromatograph. A gas chromatograph equipped with dual columns and flame ionization detectors was used, employing Porapak Q and Chromosorb 103 as stationary phases. Analysis of acidified media, using Porapak Q, gave chromatograms representing acidic and neutral volatile products, while when analysing samples made alkaline, using Chromosorb 103, alkaline and neutral compounds could be detected. Interest was particularly concentrated on the analysis of bacterial amines. P. mirabilis was found to produce isobutylamine and isopentylamine, which were identified by mass spectrometry and GC retention times C. septicum produced ethylamine. The GC head-space technique described constitutes a means for rapid identification of microorganisms. It is adaptable for use on a routine basis in the clinical microbiological laboratory.


Rabbit polymorphonuclear leukocyte chemotactic factor generated in vivo by Bacteroides fragilis lipopolysaccharide. I. Isolation and physico-chemical characterization.

By chromatographic separation on Sephadex gels a peptide, termed the lipopolysaccharide-induced chemotactic factor (LPS-CF), has been isolated from inflammatory exudate. The exudate was obtained from Teflon chambers implanted subcutaneously in rabbits 3 h after LPS from Bacteroides fragilis ss. fragilis had been injected. Three chemotactic peaks were eluted by fractionation of the exudate on Sephadex G-200 columns; one major peak with molecular weight of approximately 16,000 and two minor peaks with molecular weights of approximately 68,000 and 7,000. Refiltration of the major peak on G-75 showed the same elution profile as that found on G-200 columns. By addition of 8 M urea to the elution fluid only the major and the low molecular weight peaks appeared. The molecular weight of the major chemotactic peak was calculated to 16,000 on Sephadex gels, and also using SDS-polyacrylamide gel electrophoresis and equilibrium centrifugation. The chemotactic factor was quite heat-stable and was also non-dialyzable, and freezing and thawing as well as storage at 4 degrees C for several weeks did not impede its activity. This chemotactic factor is probably identical to the cytotaxic fragment split off from C5 upon interaction with LPS.


Chlamydia trachomatis from men with non-gonococcal urethritis. Simplified procedure for cultivation and isolation in replicating McCoy cell culture.

Chlamydia trachromatis was cultivated on replicating McCoy cells without the addition of antimetabolites. A further technical modification was centrifugation of the specimens at room temperature at 4000 g, thus making it possible to use the method in any microbiological laboratory. C. trachomatis was isolated from 36 of 81 patients (44.4%) with non-gonococcal urethritis. This rate compares well with reported isolation rates using antireplicative agents and higher centrifugation temperatures.


Influence of phenylbutazone on leukocyte chemiluminescence and function.

The effect of phenylbutazone on human leukocyte chemiluminescence, phagocytosis and intracellular killing of bacteria has been examined. A marked reduction of chemiluminescence and intracellular killing of bacteria was observed. The effect on phagocytosis was less pronounced. High drug concentrations nearly abolished light emission, and concentrations equivalent to those obtained in plasma during therapy caused a 25--30% reduction. The effect occurred within less than 10 minutes. No permanent effect upon resting cells was observed. Phenylbutazone reduced the effect of sodium azide on leukocyte chemiluminescnece, indicating that the drug might also inhibit myeloperoxidase dependent chemiluminescnece. Whether these impairments of leukocyte function also take place in vivo resulting in enhanced susceptibility to infection remains unknown.


Immunosuppressive effect of human pregnancy zone protein on H-2 incompatible mouse heart allografts.

Human pregnancy zone protein (PZP) given intraveneously, significantly (p less than 0.001) prolonged the survival of heterotopic A/J heart transplants in A.CA recipients, compared to untreated control recipients, recipients treated with phosphate buffered saline and recipients treated with a control preparation from male serum. The results support the hypothesis that PZP protein exerts an unspecific immunosuppressive effect in vivo.


Tricyclic antidepressants in the treatment of depressions. A double-blind clinical comparison of clomipramine (Anafranil) and amitriptyline.

The clinical efficacy of oral clomipramine and amitriptyline treatment (50--125 mg/day) was compared over a period of 2 months in 72 depressive patients visiting a psychiatric out-patient clinic. Both drugs were equally effective as measured by the Hamilton Rating Scale for Depression. According to a nurse's independent evaluation of 13 items the two drugs were equipotent in relieving depressive symptoms and no statistically significant differences between the treatment groups were found in the global evaluation by the investigator and the patient. A trend in favour of clomipramine was, however, seen in several parameters. The declines in the Hamilton Rating Scale scores and the nurse's evaluation scores were highly significant during the first 2 weeks of treatment (P less than 0.001) in both groups and the scores continued to decrease during the 2nd month of the study. The most common unwanted effects were dryness of the mouth and fatigue. The frequency of side effects was 51% in the clomipramine group and 43% in the amitriptyline group. The side effects were generally mild and transient and called for discontinuation of treatment in only one case in each group.


Clinical effects and drug concentrations in plasma and cerebrospinal fluid in psychotic patients treated with fixed doses of chlorpromazine.

The clinical effects of chlorpromazine (CPZ) administered in accordance with a double-blind design in one of three doses (200, 400 or 600 mg) were examined in 44 psychotic patients. The relationships between the effects and the CPZ concentrations in plasma and cerebrospinal fluid (CSF) were analyzed. The antipsychotic and side effects were rated according to the CPRS and the Simpson and Angus scale. CPZ concentrations were measured by a mass fragmentographic method. Treatment with CPZ resulted in a significant reduction of morbidity scores, without any clear dose relation. The final outcome was more favourable in women than in men. Extrapyramidal side effects but not somnolence were positively dose related. The antipsychotic effects tended to be positively related to the dose of CPZ in mg/kg as well as the CPZ concentrations in plasma and CSF. The greatest number of significant correlations between the CPZ concentration in CSF and the morbidity scores were seen after 2 weeks of treatment. The results indicated marked clinical improvement with CPZ concentrations above 1 ng/ml in CSF and 40 ng/ml in plasma. After 4 weeks of treatment the correlations between the CPZ concentrations and the clinical improvement were still positive but the coefficients were lower than at 2 weeks and only occasionaly significant. Extrapyramidal symptoms were significantly related to the CPZ concentrations in plasma and CSF. Somnolence was significantly related to the CPZ concentrations in CSF.


Delirium tremens: a double-blind comparison of diazepam and barbital treatment.

The effect of diazepam and barbital in the treatment of delirium tremens and other acute conditions related to alcohol abuse was evaluated in a double-blind trial. 91 patients participated in the study, 44 in the diazepam group, 47 in the barbital group. The choice of diazepam rather than chlordiazepoxide was motivated by its major anticonvulsive properties. Barbital was given by the oral route, diazepam as intramuscular injections. Different ways of drug administration to patients with delirium tremens are discussed. It is concluded that the two different ways used in the study probably did not have a noteworthy influence on the results. All patients were excluded who had taken psychoactive drugs before admission. Nevertheless a considerable part of the patients had diazepam, but not barbital, in the blood before treatment was initiated. This may give support to the use of barbital as a "special purpose drug" in the treatment of these conditions. The patients were divided into three diagnostic categories, according to the severity of the clinical condition. No difference between the two drugs tested was found in the milder conditions, but barbital was found superior to diazepam in the treatment of fully developed delirium tremens.


Amipaque as contrast medium for intraosseous phlebography.

The degree of pain produced by Amipaque 260 and Isopaque 260 at intraosseous phlebography in patients with varicose ulcerations in the ankle region was compared. Amipaque produced less pain than Isopaque. No complications or side-effects occurred during the observation period of about one year.


Stereotactic gamma irradiation of basilar artery in cat. Preliminary experiences.

Irradiation of the basilar artery of cats by stereotactic technique was performed with doses varying from 100 to 300 Gy in a gamma unit. Histologically, vascular lesions such as vacuolization, degeneration and desquamation of the endothelium and hyalinization and necrosis of the muscular coat predominated, whereas reparatory reactions were relatively sparse. Thrombosis was completely absent.


The pathogenesis of Pott's paraplegia and the effect of surgical intervention in its course and prognosis.

14 cases of Pott's disease of the spinal column treated by surgery is described. The operation was performed by an anterior approach and evacuation of abscess, removal of granulation tissue, seguesterated bone and disc material achieved. Any mechanical compression by bony ridges, dense fibrotic tissue or fibrotic posterior longitudinal ligament was removed making it possible for anti TB treatment to have full effect. Stability of the spine was achieved by means of anterior bone grafts which accelerated bony fusion and eradication of the disease. It is stressed that this type of radical surgery in Pott's allows for histological diagnosis, corrects the deformity thus preventing future cardio-respiratory complications, prevents paraplegia of late onset, and shortens the duration of hospital stay allowing the patient to return to his previous occupation.


Antihypertensive treatment with pindolol in one or two doses. A comparative trial.

A comparative trial was carried out in 21 patients on the antihypertensive effect of pindolol given once or twice a day. A change-over design was employed, with two treatment schedules and four treamtnet periods of six weeks each. No statistically significant difference was found in BP lowering effect between one and two daily doses. It is unlikely that a switch from pindolol twice daily to the same amount once daily will crease the BP by more than at most 1.0 mmHg systolic and 2.2 mmHg diastolic, or decrease it by more than 2.7 and 1.0 mmHg, respectively. It is concluded that pindolol given once daily can be recommended.


Salmon calcitonin in the acute treatment of moderate and severe hypercalcemia in man.

The effect of i.v. infusions with salmon calcitonin was evaluated in the treatment of acute hypercalcemia in 12 patients. Clinical improvement and a less critical level of serum calcium were achieved within 24 hours for eight of the patients, for another two after treatment for 48 hours. In malignant conditions (six patients) calcitonin was less effective, which could be evaluated within 24 hours. In addition to rehydration, the rapid onset of action and the lack of side-effects make calcitonin a drug of first choice in the treatment of acute hypercalcemia.


Effect of food on the bioavailability of bendroflumethiazide.

Bendroflumethiazide (BFT), 10 mg, was given orally to eight subjects after fasting overnight and together with a meal. Concentrations of the diuretic in plasma and urine were determined by GLC. As judged by AUC and urinary recovery of BFT, the bioavailability of the diuretic was not influenced by concomitant intake of a meal.


Verapamil and pulmonary hypertension.

We report on the effect of verapamil in 12 patients suffering from pulmonary hypertension. The drug caused a slight, but statistically significant decrease in mean pulmonary artery pressure and in the work performance by the right ventricle. The mean pressure of the right atrium, the end-diastolic pressure of the right ventricle, the pulmonary arteriolar resistance, the cardiac index and the stroke volume were not significantly changed, however, and there was a wide spread of the values observed. In some patients the drug exerted a marked negative inotropic effect, with a concomitant increase in the pulmonary arteriolar resistance.


Absorption and side-effects after peroral administration of sustained release iron tablets. Ferro-Retard compared with Ferronicum and Duroferon Duretter.

Study I. In 13 iron deficient patients the absorption from 100 mg ferrous sulphate (Ferro-Retard) after 3 and 5 hours was comparable to the absorption from 176 mg ferrous gluconate in rapidly disintegrating tablets (Ferronicum). Study II. (a) The serum iron elevation in 14 blood donors with normal Hb after administration of ferrous sulphate (100 mg Fe2+) in Ferro-Retard or Duroferon Duretter seemed to be equal when tested on the 4th day after donation of 450 ml blood. (b) The iron absorption, measured by the elevation of serum iron 5 and 8 hours after administration of sustained release tablets, proved to be better on the 11th and especially on the 16th day than on the 4th day after donation. Study III (side-effects). In a study on 113 subjects the total number of complaints was unusually high both before and after administration of placebo, rapidly disintegrating and sustained release ferrous sulphate tablets. The selection of participants and other methodological factors have probably been of importance. Hence, comparisons between different studies of side-effects should always be carried out with caution.


Lidocaine and the quarternary ammonium compound QX-572 in acute myocardial infarction. A comparative study.

Patients with suspected or proven acute myocardial infarction complicated by ventricular arrhythmias not corrected by lidocaine therapy (bolus dose 100 mg followed by infusion 2 mg/min) were treated either with an increased dose of lidocaine (bolus dose 50 mg followed by infusion 3 mg/min) or with 600 mg N,N-bis dimethylammonium chloride (QX-572, Astra, Sweden) as an i.v. infusion during 30 min (3 patients) or 60 min (13 patients). In the lidocaine group the arrhythmias were controlled in 6 out of 15 patients, in the QZ-572 group in 12 out of 16, a difference that is not statistically significant. However, the frequency of side-effects was significantly higher (p less than 0.001) in the QX-572 group (15 out of 16 patients). They were also more severe, including pronounced tachycardia and hypertension. It is concluded that despite the high antiarrhythmic effect of QX-572, an increase of the lidocaine dose would be safer and preferable in the clinical situation studied.


Haematologic effect and Shwartzman reactivity of radiodetoxified endotoxin.

Comparative experiments were made in rabbits with Escherichia coli O89 endotoxin and endotoxin detoxified by ionizing radiation (60Co-gamma, 5 Mrad). Radiation significantly weakened the leukopenia and thrombocytopenia provoking effect of endotoxin. Radiodetoxified endotoxin decreased the fibrinogen level only slightly and caused insignificant changes in reptilase time. The complement level was decreased less by the detoxified than by the parent endotoxin. Even the local Shwartzman phenomenon inducing capacity of radiodetoxified endotoxin decreased significantly, particularly when it was used for preparation and provocation, too.


Heat-stable enterotoxin produced by Shigella flexneri.

Filtrates and ultrasonics extracts of Shigella flexneri showed rapid permeability factor (PF) test and proved positive in suckling mice and ligated rabbit loop tests within 4 hr. Delayed PF was not detected and the rabbit loop dilatation test read after 18 to 24 hr, the mouse pad oedema reaction, the test for elongation effect of CHO cells were also negative. In the delayed PF test a strong "blanching" effect was observed. A filtrate of an Ent-Escherichia coli strain was positive only in the rapid PF test, while filtrate and ultrasonic extract prepared from the Ent+ E. coli strain showed a positive reaction in all tests for enterotoxins (ST and LT) including the rapid PF test. Ultrasonic extracts of a S. flexneri and an Ent- E. coli strain concentrated by freeze-drying were fractionated on Sephadex G-100 column. S. flexneri fractions of 60--70ml were positive for rapid PF, dilation capacity in suckling mice, and the blanching effect in the delayed PF test. No positive reaction was found in the delayed PF test and in CHO cell culture. Similar fractions of Ent- E. Coli carried substances responsible for the rapid PF and the blanching effect, but without suckling mice positivity.


Diploid formation of Candida tropicalis via protoplast fusion.

Haploid auxotrophic mutants were produced from Candida tropicalis, and protoplast usion was induced by polyethylene glycol. The resulting nutritional complementation was due to heterokaryon formation and, at a much lower frequenty, to spontaneous diploidization. During cultivation, heterokaryotic clones regularly gave rise to heterozygous diploids from which, in turn, haploids could be isolated. The technique of protoplast fusion gives an opportunity for genetic analysis of this and similarly asexual fungal species.


Unique features of heat-stable enterotoxin of Shigella flexneri.

Sephadex G-100 fractions of ultrasonic lysate of Shigella felxneri were compared to the fractions of Escherichia coli lysates of Ent- , LT+ ST+, LT+ and ST+ strains. The range of molecular weight of S. flexneri ST fractions was the same as that of E. coli LT fractions. Rapid PF activity was associated with the ST peak in the case of S. flexneri, and followed the LT activity in the E. coli (LT+ ST+) fractions, and appeared in the same molecular weight range in the case of Ent- E. coli lysate. Cross neutralization could be demonstrated between S. flexneri ST and E. coli LT. Antigenic relationship between shigella ST and choleragen seemed to be less expressed and rather unilateral.


[Unequal breast-nourishment as pretended cause of differences of features at twin-brothers (author's transl)].

A theological polemical treatise of 1709, as a source for the general history and this history of civilization and especially of ethics, is exploited to declare some scientifical matters of fact. The conception, developed by the author by reason of the different behaviour of twins as adults, the nourishment assimilated in earliest youth would decide the future of man, is analyzed and compared with the modern state of knowledge of the twin-research. On the confrontation of the notions "nature" and "nurture", which can be traced back to Shakespeare, in Galton, the originator of the twin-research, is referred to.


Dose-independent pharmacokinetics of digoxin in humans.

Nine healthy male volunteers received single 0.5, 1.0, and 1.5 mg. doses of intravenous digoxin in a randomized three-way crossover study. Multiple venous blood samples were drawn during 35 hours after each dose, and all urine was collected for 6 consecutive days. Concentrations of digoxin in serum and urine were determined by radioimmunoassay. Over-all mean values for kinetic variables were: distribution half-life, 0.35 hours; elimination half-life, 27.9 hours; volume of distribution, 5.46 liters/Kg; total clearance, 2.51 ml./min./Kg. The mean projected cumulative urinary excretion of digoxin was 70.1% of the dose; mean renal clearance of digoxin was 1.71 ml./min./Kg., not significantly different from creatinine clearance (1.50 ml./min./Kg.). None of the identifiable pharmacokinetic variables was significantly influenced by dose, suggesting that digoxin disposition is dose-independent in healthy individuals.


Role of exercise stress testing in healthy subjects and patients with coronary heart disease. Controversies in cardiology--I.

The value of the exercise stress test in the evaluation of clinically healthy subjects and patients with coronary heart disease is not limited to the isolated interpretation of abnormalities of the S-T segment. Other measurable parameters which are of diagnostic and prognostic importance include: (1) a decrease in systolic blood pressure during exercise; (2) the appearance of complex ventricular arrhythmias of low exercise heart rates; (3) the appearance of inverted U waves during or after exercise; (4) the patient's maximal exercise capacity; and (5) new auscultatory findings postexercise. The reliability of the exercise test as a diagnostic tool is futher enhanced by proper patient selection and careful attention to exercise techniques. Subjects with labile ST-T wave changes during standing hyperventilation, fixed ST-T changes at rest, and intraventricular conduction defects are not ideal candidates for "diagnostic" stress testing and the examining physician must rely more heavily on nonelectrocardiographic findings. The criteria used to define an abnormal S-T response will vary according to the lead system used. However, in both symptomatic and asymptomatic subjects the appearance of marked degrees of S-T depression at low exercise heart rates significantly increases the probability of finding advanced coronary disease, particularly if the S-T depression is seen in multiple monitoring leads and is of prolonged duration postexercise.


Hemagglutination tests for syphilis antibody.

In a study of serodiagnosis of syphilis, the authors compared the specificities and sensitivities of two hemagglutination tests, a sheep-erythrocyte test (MHA-TP) and a trukey-erythrocyte test (TPHA), with those of the Fluorescent Treponemal Antibody-Absorption (FTA-ABS) test. In tests of sera from 935 patients without syphilis, the MHA-TP, TPHA, and FTA-ABS tests were reactive for 0.96, 0, and 1.3% respectively. The false-positive results were usually transient and not associated with underlying illness. For the 68 patients with syphilis, the MHA-TP test was as sensitive as the FTA-ABS test in all stages except untreated primary disease. The TPHA test appeared to be undersensitive, and testing of follow-up sera from persons with latent syphilis showed unexplained conversion of false-negative TPHA results to reactive results. Reproducibilities of the two hemagglutination tests were comparable. The MHA-TP test is a valuable confirmatory test for syphilis. Further study is needed before the use of the TPHA test can be recommended.


Alcoholism and women.

Alcoholism, the most prevalent form of drug dependence, has become a problem for large numbers of women. The research literature on alcoholism in women is reviewed, with suggestions for treatment and future research. The greater stigma placed upon female intoxication has made it difficult to obtain reliable data and has contributed to the tendency to ignore the problem altogether. Furthermore, the greater stigma has resulted in guilt because the woman alcoholic is likely to share society's opinion of herself, and this stigma/guilt/shame factor is viewed by the authors as one of the main difficulties in recovery. Certain recurring characteristics among alcoholic women are listed, and the impact on children is briefly discussed. Treatment suggestions include offering women alternatives during rehabilitation.


Comparison of basal gastric acid and pepsin output in controls vs. active peptic ulcer disease (PUD).

Quantitative basal and pentagastrin stimulated acid and pepsin outputs were determined in a group of 15 patients without peptic ulcer disease (PUD) and in 11 patients admitted to hospital with endoscopically proven PUD (two gastric and nine duodenal). While there were statistically significant differences in both acid and pepsin outputs in both the basal and maximally stimulated states, only the basal pepsin output clearly separated the groups in this small preliminary study. No patient produced more than 100,000 pU./hr. in the basal state unless an active peptic ulcer was present; no patient with an active ulcer produced less than 100,000 pU./hr.


Physicochemical determinants of incompatibility and instability in injectable drug solutions and admixtures.

Several physicochemical conditions or phenomena most commonly causing incompatibility, instability or related difficulties in parenteral drug solutions and admixtures are reviewed. The following factors involved in chemical incompatibilities are reviewed: concentration, pH, acid-base character, reduction-oxidation, photolysis, epimerization, temperature, dextrose catalysis and hydrolysis. The following factors involved in visual incompatibilities are discussed: pH, acid-base character, solvent system, color change, complexation, adsorption and adherence, dissolution rate, salting-out and leaching, and foaming. Pharmacists may recognize, predict and avoid parenteral imcompatibilities based on their experience, an understanding of physicochemical principles and reference to pertinent publications.


Drug therapy reviews: chronic hepatitis.

The classification, clinical course, etiology and treatment of chronic hepatitis are discussed. The clinical manifestations of chronic hepatitis are of limited diagnostic use. Diagnosis must be made by liver biopsy. The disease is classified as chronic persistent or chronic active hepatitis. The prognosis for chronic persistent hepatitis is excellent, and no treatment is required. Chronic active hepatitis may progress to cirrhosis and is associated with a poor prognosis if untreated. Recognized causes of chronic active hepatitis are hepatitis-B virus infection, post-transfusion hepatitis not associated with hepatitis-B virus, and certain drugs. For drug-induced hepatitis, discontinuation of the medication is indicated. For other types of chronic active hepatitis the recommended treatment is prednisone 10 mg and azathioprine 50 mg daily.


Drug therapy reviews: clinical pharmacology of antiepileptic drugs.

The absorption, distribution, biotransformation, excretion and clinical pharmacokinetics of antiepileptic drugs are reviewed. Six guidelines for the therapeutic use of these drugs are given: (1) when therapy with an antiepileptic drug is initiated or when dosage is raised or lowered, the new steady-state drug serum concentration and the full effect of the dosage change will not occur for five elimination half-lives; (2) a loading dose is usually necessary to immediately achieve a steady-state serum drug concentration equal to the usual maintenance steady-state serum drug concentration; (3) the choice of dosage intervals for antiepileptic drugs is determined in part by the range of fluctuation in drug concentration between doses that is acceptable; (4) addition of a drug to an existing antiepileptic regimen may raise or lower the serum concentration of prior drugs by inhibition or induction of their metabolism; (5) if possible, make only one change at a time in an antiepileptic drug regimen; and (6) antiepileptic drugs should not be given by the i.m. route in emergency situations.


Computer-assisted eye examination. VII. Final evaluation of the refractor. III system for subjective examination after reducing software and hardware errors.

Eighty patient-volunteers were refracted by the computer-assisted Refractor III system and the results were compared with those obtained by the usual manual method. For the distance prescription 95% of the results were satisfactory. For the near add all were satisfactory. Relative validity of the system was also measured objectively by repeatability data. System test differences and test-retest manual-examination data were found comparable, indicating that the validity of the system is similar to that of the manual method. Further developments are expected to improve reliability, simplify maintenance, and extend testing so that the system will be an economical and useful instrument in eye clinics.


Membrane potentials and the energetics of intestinal Na+-dependent transport systems.

The transmembrane chemical gradient for Na+ that most living cells maintain represents an energy source which is not sufficient to account for observed cellular sugar or amino acid gradients. This short review summarizes the literature pointing to the above conclusion, and described experimental evidence from a variety of model systems which indicates that the membrane potential can provide an additional driving force. Ordinarily, solute leak pathways compromise the full gradient forming capability of the Na+-dependent concentration systems and obscure the extent to which membrane potentials are important. When these "leaks" are experimentally controlled, solute gradients are established that identify the membrane potential as a quantitatively very important energy input. Furthermore, if the electrochemical gradient for Na+ is the sole source of energy, an extremely high efficiency of energy transduction must occur during gradient-coupled transport. An experimental approach is described here which can provide clues to the mechanistic role for membrane potentials in intestinal Na+-dependent sugar transport.


Effect of toxigenic Escherichia coli on myoelectric activity of small intestine.

When exposed to cholera toxin (CT), distal ileal loops of the rabbit small intestine showed an alteration in myoelectric activity. This alteration was defined as the migrating action potential complex (MAPC). The purpose of this study was to determine, using myoelectric recording techniques, the effects of live toxigenic Escherichia coli (TEC) on motility. Live TEC, live nontoxigenic E. coli (NTEC), and culture filtrates of these organisms were studied. Live TEC and its filtrate induced MAPC activity similar to that of CT. Live TEC induced a mean of 3.8 MAPCs/h, significantly greater than induced by live NTEC. TEC filtrate induced a mean of 14.2 MAPCs/h, significantly greater than NTEC filtrate. Heating the TEC filtrate to 100 degrees C before use resulted in a significant decrease of MAPC activity. This experiment demonstrated that live TEC and its culture filtrate altered ileal myoelectric activity. The effect may have been mediated by a heat-labile enterotoxin. This study suggests that alterations in small intestinal motility may be important in the pathogenesis of TEC diarrhea.


The control of sodium excretion.

The kidneys of a normal man filter approximately 24,000 meq sodium/day, reabsorb about 23,900, and yet can make a 1--2 meq change in 24-h urinary sodium excretion. The control of urinary sodium excretion, therefore, depends, first, on ensuring that the bulk of the sodium is reabsorbed, a function which is carried out in the proximal tubule and ascending loop of Henle. Second, it depends on adjusting the reabsorption of the small quantity of sodium which is delivered into the collecting duct so that the amount excreted in the urine is that required to maintain sodium balance. The bulk reabsorptive mechanisms can be considered as buffers to prevent large fluctuations in the amount of sodium delivered to the collecting duct, thus facilitating the fine adjustments of reabsorption which are made at this site. In conditions other than extreme salt loading or deprivation, changes in sodium reabsorption in the proximal tubule and loop of Henle probably have little, if any, effect on urinary sodium excretion. Sodium reabsorption in the proximal tubule and the collecting duct appears to be influenced by unidentified circulating substances.


Choline acetyltransferase activity in rat heart after transplantation.

Choline acetyltransferase (CAT) catalyzes the biosynthesis of acetylcholine according to the chemical equation: Acetyl-CoA + Choline in equilibrium Acetylcholine + CoA. To demonstrate the neuronal relationship of this enzyme, CAT activity was measured in hearts to which the extrinsic innervation was completely interrupted by extirpation of the heart from a donor animal and transplantation in a heterotopic position into the recipient's abdominal cavity. After the animals were killed at 8 days, enzyme activity in the transplanted hearts was measured and compared with that of the recipient. Choline acetyltransferase activity decreased 98% in the right atrium of the transplanted denervated hearts, 94% in the SA node, 87% in the left atrium, 80% in the right ventricle, and about 50% in the interventricular septum and left ventricle. These data show that sectioning the extrinsic parasympathetic innervation to the heart results in variable decreases in CAT activity, a finding which confirms that CAT activity is related to the extrinsic cholinergic innervation. The extrinsic (preganglionic) component of the parasympathetic system is nonuniform and supplies predominantly the specialized regions of the heart with conduction tissue. The residual enzyme activity is related to intrinsic (postganglionic) parasympathetic neurons. The intrinsic component is uniformly distributed to both specialized and contractile regions of the heart.


On editing the Journal: Ave atque vale.

Dr. Braceland discusses his 13-year tenure (1965-1978) as Editor of the American Journal of Psychiatry, noting that he took office during a period of social turmoil that in many ways resembled the decade of the Journal's founding 134 years ago. He describes the advantages and disadvantages of the peer review system he introduced to the Journal and states that this approach is essential in a time of ultraspecialization. He reviews the crafts of editing and writing for medical journals, both of which are brightened by clarity and brevity. As to the future of medical journals, he considers reports of their demise premature, while acknowledging the problems they face. Dr. Braceland briefly considered a "rocking chair" approach to his retirement from the Editorship, but the Editor Emeritus will instead continue to provide whatever assistance he can to his colleagues.


Prediction of imipramine antidepressant response by a one-day dextro-amphetamine trial.

This study provides additional evidence that there is a moderate association between the acute activation, euphoria, and antidepressant responses to dextro-amphetamine and the antidepressant response to imipramine during a four-week trial. Comparison of the responses of 13 patients to dextro-amphetamine on two different days during a double blind trial indicated that differences in dextro-amphetamine response are consistent, replicable characteristics of individual depressed patients. The variables of sex, diagnosis, diurnal mood variation, platelet MAO activity, and MMPI scale scores were of minimal assistance in revealing factors that might be associated with activation or antidepressant responses to dextro-amphetamine in this small patient group. The authors suggest the need for larger-scale studies in this area.


[Spontaneous delivery during respirator therapy. A case report (author's transl)].

Following a short presentation of the physiological changes in respiration of pregnant women, we report our own experience with the development and therapy of a case of pneumonia during the last month of pregnancy. In this case, the spontaneous birth of a healthy child occurred after four days of mechanical ventilation. We discuss the advantages and disadvantages of waiting for spontaneous birth, taking under consideration the conditions previously described.


[Scanning and transmission electron microscopic studies of the development of the joint surfaces (author's transl)].

The late embryonic and post partum development of the rat knee-joint has been studied by the transmission and scanning electron microscope. Undergoing a transformation in the sense of functional adaption to extrauterine life there is a final breakdown of the mesenchym cell layer (interzone) which separates in the embryo the anlagen of the bones. Its is followed by an accelerated growth of the collagen-containing intercellular substance which finally forms the surface.


[Demonstration of intrastriatal types of synapses and axon-collaterals by experimental isolation of fundus striati from all extrastriatal connections (author's transl)].

After columnar isolation of the cat's fundus striati with a survival time of 2 days or 2 or 4 weeks all axospinous boutons (type I, III And iv) and most axo-dendritic (or axo-somatic) boutons (type II, VI and VII) undergo dark degeneration. All specimens of axo-somatic (or axodendritic) type IX bouton (containing large, round vesicles in a clear axoplasm) and most specimens of type V bouton (with pleomorphic and some dense core vesicles) are unaltered. Many type VIII boutons (dindritic terminals containing scattered, small, sphrical vesicles suspended between the filaments of many microtubules in clear dendroplasm) are almost preserved, in the fundus more than in the caudate nucleus. After 2 or 4 weeks, some perikarya and many dendrites have undergone an electron-dense retrograde degeneration resulting from interuption of the efferent axons of the large striatal cells. The type IX synapses are interpreted as intrinsic between the small spiny and the large efferent striatal neurons; the type V as intrastriatal axon-collaterals of the large efferent neurons and the type VIII as dendritic terminals of intrastriatal Golgi type II nerve cells (possibly dwarf cells).


[On a nerve in the foramen thyroideum (author's transl)].

On the right half of the larynx of a 35-year old man a branch of the ramus externus nervi laryngei superioris was described that entered the inner larynx without vessels through a foramen thyroideum. A foramen thyroideum that appears in adults in more than a quarter of the cases is considered on the one hand as a remaining cleft between the fused cartilagineous skeletal elements of the forth and fifth viszeral arch and on the other hand as a occasionally remaining opening on account of a vessel or nerve running through. In more than half the cases vessels and nerves together pass through a foramen thyroideum and in a further third vessels only. If, in the case described, a nerve only passes through the foramen, this nerve, in human beinges, cannot be the nerve of the fifth veszeral arch on account of phylo-and ontogenetic considerations.


[Intelligence : individual differences, genetic factors, environmental factors and interaction between the genotype and the environment (author's transl)].

The authors undertook a review of published work on the sources of variation in individual differences in intelligence. They should : 1) that methods of quantitative genetics concerning intelligence are not applicable to human populations ; 2) that the results of studies on adoptions and on twins do not permit one to estimate the respective roles of environment and heredity ; 3) that this division of variance had no heuristic value in the study of human intelligence.


[Sensitivity in vitro of opportunist yeasts (Candida albicans and Torulopsis glabrata) to flucytosine and concordance curves (author's transl)].

The authors report the results of a study with 100 strains of C. albicans and 50 strains of T. glabrata: the objectives of this experiment were to exhibit the primary and secondary resistance of the clinical isolates of fungi against flucytosine (5-FC) :another objective was to establish the concordance curves for 5-FC, by mean of MIC measurements and inhibition diameters by disk plates diffusion, determined simultaneously for the same strains. These curves make it possible subsequently to determine the MIC of 5-FC for the fungi strains by means of the inhibition zones. The last objective of this study was to compare the results achieved in different medium and growth conditions in order to choose the best possible technical conditions for MIC and antifungigramme determination.


Skin grafting and graft rejection in goats.

As part of a study to define the major histocompatibility complex of the goat and to show certain aspects of its biological function, a skin-grafting technique is described which might also be applicable for similar studies in other ruminant species.


In vivo transfer of an Escherichia coli enterotoxin plasmid possessing genes for drug resistance.

Experiments were conducted to study transfer of an enterotoxin (Ent) plasmid from a porcine enteropathogenic Escherichia coli to an E coli K12 strain in the intestine of newly weaned pigs. The Ent plasmid carried genes for resistance to tetracycline, streptomycin, and sulfonamides, thereby permitting a selection for tetracycline-resistant exconjugants in the feces of the pigs. In vivo transfer of the Ent plasmid was demonstrated to occur when the pigs were given large oral inocula of donor and recipient cultures, 1 hour apart. Differences in extent of transfer were not detected in pigs given antibiotic-free feed compared with littermates on feed containing oxytetracycline at 50 g/ton. In one experiment, tetracycline-resistant Ent- exconjugants were found which appeared to have received an R plasmid from an enteropathogenic type of E coli resident in the intestine.


Morphologic evaluation of IgM cells of the canine small intestine by fluorescence microscopy.

Biopsies of small intestine from 7 dogs were examined by fluorescence microscopy to determine the number of IgM-containing cells in the lamina propria. Biopsies were taken from duodenum, jejunum, and ileium. (Cell counts were made by 2 persons to demonstrate reproducibility.) There were 452.24 +/- 60.09 cells per mm2 in the duodenum 572.68 +/- 62.13 cells per mm2 in the jejunum, and 107.47 +/- 59.57 cells per mm2 in the ileum. All sections were cut at 6 micrometer. The ileum had fewer cells than either duodenum or jejunum (P = 0.000038 and 0.00001, respectively), whereas duodenum and jejunum did not differ significantly in numbers of cells (P = 0.17528). Quantifying autofluorescent cells in the same sites showed no significant differences among the 3 tissues (P = 0.24697). The autofluorescent cells differed in intensity and morphology from the IgM cells. These two observations tend to support the contention that the autofluorescent cells did not bias the IgM cell counts at the 3 sites. Total autofluorescence (cells, collagen, and vessels) was higher in the ileum than in either the jejunum or the duodenum (P = 0.04967 and 0.03050, respectively). However, all 3 categories counted (IgM cells, autofluorescent cells, and autofluorescent structures) had significant dog-tissue interactions. This will necessitate determining normals for each age-sex-breed category of dog studied.


Immunochemical study of canine intestinal, hepatic, and osseous alkaline phosphatases.

Partially purified alkaline phosphatase (ALP) from canine intestine, liver, and bone were injected into rabbits to elicit anti-canine intestinal, hepatic, and osseous ALP antibodies, respectively. The antibody formed a soluble enzyme-antienzyme complex when directly interacted with the ALP antigen. In order to form an insoluble complex, it was then necessary to interact the initial soluble complex with the goat anti-rabbit gamma-globulin antibody in the 2nd step. Antiintestinal ALP antibody was highly specific and did not cross react with canine hepatic, osseous, splenic, and renal ALP. Antiliver and antibone ALP antibodies, on the other hand, did cross react with hepatic, osseous, splenic, and renal ALP, but not with the intestinal ALP.


Origin of serum alkaline phosphatase in the dog.

The origin of canine serum alkaline phosphatase (ALP) was investigated by various means. On the basis of electrophoretic migration, neuraminidase treatment, thermal denaturation, and chromatographic fractionation, canine serum was found to contain ALP principally of hepatic origin. There was evidence of only a minor portion of ALP being of osseous origin. Intestinal ALP was not detected in canine serum when monitored by immunochemical technique, L-phenylalanine inhibition, and thermal denaturation.


Diagnostic evaluation of canine serum alkaline phosphatase by immunochemical means and interpretation of results.

Sera of several canine patients contained an isoenzyme of alkaline phosphatase (ALP) that resembled intestinal ALP with respect to heat inactivation, L-phenylalanine inhibition, and sensitivity to anti-canine intestinal ALP antibody, but differed with regard to the electrophoretic migration. The electrophoretic mobility of the isoenzyme was slightly cathodal than that of hepatic ALP, and its migration was reduced, similar to that of hepatic isoenzyme after neuraminidase treatment. This isoenzyme, which could be corticosteroid induced, was in the sera of numerous dogs with hepatobiliary disorders and was different from the hepatic isoenzyme that appeared in the sera of dogs with acute hepatitis, based on anti-canine intestinal ALP antibody interaction, heat inactivation, and electrophoretic migration.


Comparisons of the complement-fixation, indirect fluorescent antibody, and card agglutination tests for the diagnosis of bovine anaplasmosis.

Results of complement-fixation (CF), indirect fluorescent antibody (IFA), and card agglutination (CT) tests were statistically compared, using 380 serum samples obtained from 140 cattle which were disease-free or naturally or experimentally infected with Anaplasma marginale of Colombian origin. The IFA test was significantly the most sensitive for detection of amimals infected with anaplasmosis (97%); the CT test and the CF test were less so (84% and 79%, respectively). However, the most efficient test for identifying noninfected animals was the CF test (100%), and the CT and the IFA tests were less efficient (98% and 90%). A linear regression analysis performed on the average IFA and CF titers of 10 calves artificially infected with A marginale during a 20-week period showed significant regression coefficients for both tests. The regression line for the CF titers decreased below the sensitivity threshold at 14 weeks after calves were inoculated, whereas the regression line for the IFA titers continued above the sensitivity threshold 20 weeks after inoculation. The CT test also detected antibodies until the end of the observation period.


Airway hyperreactivity and peripheral airway dysfunction in influenza A infection.

We studied 39 consecutive college students with documented nonpneumonitic influenza A/Victoria/3/75/H3N2 infection to examine alterations in pulmonary mechanics and airway reactivity to cholinergic challenge, and to assess the effect of the antiviral agent amantadine on these changes. Thirty-six of the 39 subjects (92 per cent) demonstrated diminished forced flow rates and decreased density-dependent forced flow rates while breathing a helium-O2 mixture as compared to an air mixture. On initial evaluation, there was no significant difference in forced flow rates or density dependence between a group of 18 subjects treated with amantadine and 21 subjects given a placebo. However, the placebo group demonstrated further decreases in density dependence 7 days after initial presentation, whereas the amantadine group demonstrated a significant increase in density dependence (P less than 0.05), which suggested an accelerated improvement in peripheral airway dysfunction in the treated group. After inhalation of carbachol aerosol, 25 subjects showed a significant (P less than 0.05) increase in total respiratory resistance that was prolonged and independent of hay fever history. Airway hyperreactivity gradually diminished during a 7-week period in both groups. There was no significant difference in the initial degree of hyperreactivity or in the rate of improvement between groups. These data suggest that nonpneumonitic influenza infection may be associated with both an inflammatory response predominantly in the peripheral airways and transient bronchial hyperreactivity. By means of its antiviral effect, amantadine may arrest the proliferation of virus and associated inflammatory response in peripheral airways, but airway hyperreactivity presumably related to initially damaged airway depithelium is not attenuated by inhibition of viral replication after infection has been established.


Acute pulmonary edema in Plasmodium falciparum malaria.

This report describes a patient who developed acute pulmonary edema as a complication of Plasmodium falciparum malaria. Hemodynamic evaluation revealed a pulmonary artery wedge pressure of 3 mm Hg and a cardiac index of 4.6 liter per min per m2. The patient exhibited an acute decrease in serum colloid osmotic pressure from 25.1 mm Hg to 16.8 mm Hg. These findings suggest that pulmonary edema in this patient was the result of altered capillary membrane permeability.


[Pediatric bibliometrics. III. World circulation of pediatric periodicals (author's transl)].

Circulation of pediatric journals through the main twenty international index on medical bibliography is analized.


Hypothermia: pathophysiology, clinical settings, and management.

Hypothermia, defined as a core temperature less than 35 degrees C, is frequently not recognized, in part because of the inadequacy of standard thermometers. This entity has multiple causes and unique pathophysiologic consequences that complicate diagnosis and treatment. Understanding of the physiology of thermoregulation is important in light of recent advances in therapy using core rewarming. Pathophysiology, etiology and management of the hypothermia syndrome are reviewed.


Gentamicin in 1978.

For a decade gentamicin has been used extensively because of its antimicrobial efficacy and the relatively low prevalence of clinical toxicity. Recently the more frequent appearance of resistant organisms, reports of increased nephrotoxicity and ototoxicity, and the development of newer aminoglycoside antibiotics have raised doubts about the continued use of this agent. This paper reassesses the role of gentamicin. It is clear that an appreciation of the pharmacokinetics and the clinical use of gentamicin as well as an understanding of the patterns of toxicity in animals and humans can lead to more efficient treatment with this antimicrobial agent. Despite ample competition from a number of newer aminoglycoside antibiotics, gentamicin will probably continue to be used widely in the near future.


Cannabis, 1977.

Recent advances in development of immunoassay methods for marijuana constituents in body fluids provide a rapid means of detection for forensic purposes and a useful research tool for accurate quantitation of dose-response relation. Therapeutic possibilities of cannabis, such as reduction in intraocular pressure and bronchodilatation, may stimulate development of synthetic cannabinoid derivatives that meet acceptable standards of safety and effiicacy for treatment of glaucoma and asthma. Cannabis use may have harmful short- and long-term impacts on health. Potentially serious short-term effects include predisposition to angina during exercise in patients with coronary artery disease. Even in healthy subjects, marijuana smoking decreases peak exercise performance, possibly because of its chronotropic effect with achievement of maximum heart rate at reduced work loads. Although no conclusive evidence exists for long-term biologic consequences of chronic cannabis use, preliminary evidence, suggesting impairment in pulmonary function and immune responses, requires further investigation with large-scale epidemiologic studies.


[Intolerance to cow's milk protein. A complication of acute gastroenteritis (author's transl)].

Eight cases of acute gastroenteritis, two caused by enteropathogenic "E. coli", with secondary cow's milk protein intolerance were studied. Diagnosis was established clinically and by means of intestinal biopsy, before and after a milk challenge. The role of acute gastroenteritis as a trigger of cow's milk protein intolerance and other factors contributing to the appearance of that complication are discussed. The mechanisms leading to intractable diarrhoea in a situation of prolonged gastroenteritis are also commented.


[Klebsiella pneumoniae infection in immunosuppressed mice treated with gentamicin (author's transl)].

Experiments have been established in order to study the antagonistic effect of cyclophosphamid treatment on the antibiotic activity of gentamicin in vivo. An immunodepressive state in mice (50 % reduction of neutrophil polymorphonuclear) was obtained with a 5 day treatment of cyclophosphamid, at the dose of 15 mg/kg. The mice were inoculated intraperitoneally with 10 LD50 of Klebsiella pneumoniae. Antibiotherapy was applied in 2 ways differing with the dose of gentamicin given twice a day by subcutaneous route (either 2.5 or 25 mg/kg) and with the time at which treatment was started (either at 1 or at 2 h after bacterial challenge). The gentamicin activity decreases in immunosuppressed mice when antibiotic is applied with a low dose (2.5 mg/kg), 1 h after infection challenge. This effect disappears when gentamicin is given with high doses (20 mg/kg) or when antibiotherapy is delayed (2 h after infection challenge). In this case, mortality is important and close to non immunodepressed mice.


[Isolation of a cytolytic strain of hog cholera virus from IB-RS2 cells (author's transl)].

An infectious agent, able to induce a definite cytopathic effect in pig kidney cell monolayers, was isolated from the IB-RS2 cell line. Immunofluorescence, seroneutralization and ultracentrifugation studies have permitted to identify this agent as hog cholera virus (HCV). Representative HCV-strains being devoid of pathogenicity in tissue culture, the practical and theoretical interest of such an isolation is discussed.


Changing patterns in paediatric surgical care.

The increased use of day facilities for children undergoing surgery and the provision of a paediatric home nursing team has resulted in a change in overall care of surgical children in hospital in Southampton. The ratio of day patients to inpatients has fallen from 1 : 2 in 1970 to 1 : 1 in 1976 and the early discharge of inpatients has resulted in a fall in the average inpatient stay of 6.6 days in 1970 to 5.7 days in 1976. I am sure that Alex Simpson Smith, who experienced a traumatic hospital admission at the age of 3 years and who always had the interests of children at heart, would have appreciated and actively encouraged these changes in hospital practice if he had been alive and with us today.


[Sero-immunological research by immunofluorescence of rats bilharziosis in Guandeloupe. Epidemiological interest, comparative studies in various biotopes (author's transl)].

A sero-immunological survey by immunofluorescnece has been conducted on 94 rats (R. rattus and R. norvegicus) captured in Guadeloupe, in there different biotopes where the presence of S. mansoni carriers had been reported. These biotopes are those of the "Grand Etang" (Great Pond), the fresh-water mangrove and its back-mangrove area, and the Beaugendre valley. The post-mortem performed on the rats revealed that 92 % of those carrying. S. mansoni eggs of full-grown worms, had a rate of antibodies superior to 40. The rates of antibodies obtained, as well as the percentages of S. mansoni-parasited rats vary according to the biotopes. Two hypotheses can account for these variations: a smaller or greater adaptation of the S. mansoni stock to the rat; a change in the comportment of rats  which would thus be more or exposed to reinfestations.


[Density gradient ultracentrifugation method of studying sibiromycin interaction with linear and circular DNA].

Sibiromycin added to linear chromosomal E. coli DNA in vitro leads to the decrease of bouyant density in neutral CsCl density gradient. This decrease is a linear function of sibiromycin/DNA ratio and amounts to about 32 mg/ml at the ratio equal to 0.1. Binding sibiromycin does not change the degree of hydration of DNA as revealed by centrifugation in metrizamide density gradients. When added to the covalently closed or open circular DNA of PM-2 phage, sibiromycin decreased the bouyant density of these DNA species to a similiar extent. The antibiotic does not induce single-strand breaks in DNA in vitro as follows from the results of ethidium bromide-CsCl density gradient centrifugation of covalently closed PM-2 DNA.


[2 types of auxotrophic mutants occurring by insertion of the ampicillin transposon into the chromosome of E. coli K-12].

Insertion of transpozone TnI determining ampicillin resistance into the E. coli K-12 chromosome resulted in formation of auxothrophic mutants of 2 types. The mutants of the first type carried thermosensitive mutation resulting in auxotrophy with respect to isoleucine at a temperature of 43 degrees C. Such mutants occurred with high frequency (up to 14 per cent with respect to the number of the survived cells with the chromosomes carrying inserted TnI) and had capacity for reversion to the phenotype of the wild type. The mutants of the second type occurred with a frequency 20--180 times lower than that of the mutants of the first type and did not reverse to the phenotype of the parent bacteria. It was found that the chromosome of E. coli K-12 possessed at least 7 sites available for transpozone TnI insertion.


[Antibiotic sensitivity of the H- and O-forms of bacteria in the genus Proteus].

Proteus strains isolated from the gastro-intestinal tract of children not older than 1 year were characterized by resistance to oxytetracycline, chlortetracycline, benzylpenicillin and erythromycin. The strains were more sensitive to neomycin, monomycin and streptomycin. Antibiotic sensitivity of Pr. mirabilis and Pr. vulgaris strains increased on transfer from H- to O-form. Inverse dependence of the urease activity of the strains on their sensitivity to tetracyclines was noted.


[Effect of hydroacridine derivatives on the sensitivity of polyresistant strains of Staphylococcus aureus and Escherichia coli to antibiotics].

Sensitivity of 4 clinical strains of Staph. aureus and E. coli to 13 hydroacridine derivatives and their combinations with antibiotics, such as benzylpenicillin, ampicillin, semi-synthetic penicillins, streptomycin, chloramphenicol, tetracycline, chlortetracycline, monomycin, oleandomycin and erythromycin was studied. The highest bacteriostatic effect was observed on the use of perhydroactidine derivatives with benzylpenicillin or ampicillin with respect to polyresistant penicillinase-producing strains of Staph. aureus, resistance of which to these antibiotics was decreased 250--1000 times. Under the effect of the above compounds the staphylococcal resistance to chloramphenicol, tetracycline, chlortetracycline, oleandomycine and erythromycin decreased 2--66 times. The combinations of hydroacridine with the antibiotics, except 10-amino-trans-syn-trans-perhydroacridine had no effect on the resistance of the E. coli strains. The results of the combined effect of the above substances were associated with their chemical nature, the bacterial type and possibly the character of the strain resistance.


Comparison of three techniques for the detection of antibodies to double-stranded DNA: immunofluorescence on Trypanosoma gambiense, immunofluorescence on Crithidia luciliae and radioimmunoassay using the Farr technique.

Three techniques for the detection of antibodies against double-stranded DNA were compared: two immunofluorescent (IF) techniques using either Trypanosoma gambiense or Crithidia luciliae as antigen and a radioimmunoassay (RIA) based on the Farr technique. The IF on T. gambiense or C. luciliae gives very similar results but the reaction on C. luciliae is easier to read and to interpret. The use of C. luciliae permits the swift elimination of the two main causes of errors: antibodies against the nucleus of Trypanosomidae and antibodies reacting with the base of the flagella. The RIA appears as a very sensitive test since six sera gave a positive reaction with the RIA and a negative reaction with the IF on C. luciliae. However, the RIA gives in nine cases false positive reactions and in four cases false negative results. Those last four sera contained specific antibodies with low avidity for double-stranded DNA.


[Chemotherapy of experimental lactational mastitis in mice].

More severe mastitis on infection with Proteus was shown on a standardized model of experimental lactation mastitis of mice caused by Staphylococcus, Proteus and their mixture. Significant differences in the morphological pictures of the staphylococcal and Proteus mastitis were noted. A pronounced effect was observed with the use of kanamycin in combination with fuzidin in treatment of experimental mastitis of various etiology.


[Delayed local reaction (DLR) after BCG vaccination in mice. I.--Description (author's transl].

Mice injected subcutaneously in the hind footpad with BCG vaccine subsequently develop a local reaction. This local reaction could be divided into three stages: a first characterized as an acute inflammatory reaction, a second as an active granulome formation, and a third as a chronic long lasting inflammatory reaction. The second stage is mainly formed by the appearance of a typical histiolymphocytic granuloma. The intensity of the delayed local reaction (DLR) is measured by the swelling of the injected footpad. This reaction does not occur after injection with irradiated (gamma or UV) BCG in normal mice, nor after injection of living BCG in Nude mice, indicating a T-cell immune response which develops during the in vivo multiplication of this intracellular bacteria. When the lymphoproliferation response in draining node was measured, a direct correlation was found with the intensity of the DLR, and the 125IUdR incorporation into DNA after injection of living BCG or after an irradiated BCG inoculation. The intensity and the rapidity of the onset of this DLR depend upon the dose of viable BCG inoculated in the mouse. When the DLR reached its peak, a linear dose relationship was observed in C57Bl/6 and in NCS mice.


[Pharmacokinetics of semisynthetic cephalosporins for parenteral use on surgical patients].

Pharmacokinetics of 4 cephalosporanic antibiotics for parenteral use, i. e. cephaloridine, cephradine, cephazoline and cephacetryl was studied in surgical patients with normal function of the kidneys and liver. The first 3 drugs were well absorbed after intramuscular administration, their maximum serum levels being achieved during the first hour. High blood levels of cephacetryl were determined after its intravenous administration. When cephaloridine, cephradine and cephazoline were administered in equal doses, it was found that the first 2 drugs did not practically differ with respect to the values of the serum levels, the rate of elimination from the blood, the rate and level of excretion with the urine. Cephazoline was characterized by higher blood levels and slower elimination from the blood.


[Possibilities of preventing cardiotoxic complications in chemotherapy with carminomycin].

Carminomycin chemotherapy of the patients with malignant tumors is often complicated with cardiopathy which is sometimes assymptomic and registered only electrocardiographycally. Chemotherapy on the background of reparative regeneration stimulators from the series of synthetic pyrrimidine derivatives, such as methyluracyl for oral use and a soluble salt of methyluracyl for parenteral administration significantly decreased the rate of the cardiotoxic complications and promoted a decrease in their level. The use of methyluracyl and its soluble salt did not decrease the therapeutic effect of carminomycin. Methyluracyl and its soluble salt may be recommended for prophylaxis of cardiotoxic complications in chemotherapy of malignant tumors with carminomycin.


Erythrocyte surface: novel determinant of drug susceptibility in rodent malaria.

To study the role of the erythrocyte membrane in the process of chloroquine accumulation, surface polypeptides were digested with a nonspecific protease from Streptomyces griseus. This treatment activated a saturable process of chloroquine accumulation with an affinity and a specificity similar to those of mouse erythrocytes infected with Plasmodium berghei CS (chloroquine susceptible). Studies of competitive inhibitors of chloroquine accumulation yielded the following approximate values for K(i): amodiaquine, 2 x 10(-7) M; quinacrine, 5 x 10(-7) M; quinine, 2 x 10(-6) M; and mefloquine, 2 x 10(-5) M. Lack of a substrate requirement distinguished this process from the one used by P. berghei and permitted the protease to be used in studies of infected erythrocytes. Protease treatment of erythrocytes infected with P. berghei CR (chloroquine resistant) produced a dramatic transformation. Instead of describing a sigmoid curve, the process of chloroquine accumulation became saturable and substrate dependent, with a K(diss) of approximately 10(-8) M; i.e., protease-treated erythrocytes infected with P. berghei CR now behaved similarly to those infected with P. berghei CS. Coating the erythrocyte surface with albumin completely inhibited the protease-activated process of chloroquine accumulation. These findings are presented as evidence that erythrocyte surface components determine the affinity with which chloroquine is accumulated and thereby determine whether or not the malaria parasite will be susceptible to the drug.


Two transport systems for tetracycline in sensitive Escherichia coli: critical role for an initial rapid uptake system insensitive to energy inhibitors.

Escherichia coli sensitivity to tetracycline involves transport and accumulation of the antibiotic within the cell by two different uptake systems: an initial rapid uptake, which occurs over the initial 6 min of contact of the cell with tetracycline, and a slower uptake system, which continues indefinitely and whose rate of uptake is 1/10 that of the rapid system. Only the slow uptake system is blocked by inhibitors of energy-driven systems; it appears to be particularly dependent upon energy from oxidative phosphorylation. Although both uptake systems lead to accumulation of intracellular tetracycline and contribute to the cell's sensitivity, the rapid uptake system appears to be the more important. While these studies confirm active transport of tetracycline into the cell, they demonstrate that a critical uptake system which appears insensitive to metabolic inhibitors occurs initially.


Mode of incomplete cross-resistance among pipemidic, piromidic, and nalidixic acids.

Spontaneous mutants with various patterns of resistance to pipemidic acid (PPA), piromidic acid (PA), and nalidixic acid (NAL) were isolated from Escherichia coli K-12. Most mutants were less resistant to PPA than to PA and NAL, and some mutants resistant to PA and NAL were hypersusceptible to PPA. As for the mutants tested, resistance to the drugs was conferred by mutations at nalA and new nal genes designated as nalC and nalD, both of which were located at about 82 min on the recalibrated map. Resistance to PA and NAL was due to decreased sensitivity of the bacterial DNA synthesizing system to them and insufficient drug transport, whereas resistance to PPA was only due to the former.


Inhibition of cell division of Escherichia coli by a new synthetic penicillin, piperacillin.

The mechanism of the action of piperacillin against Escherichia coli was investigated. This drug converted cells to filaments, but did not show lytic action in a range of concentrations below 25 mug/ml. In some of the filaments, stretched constrictions with various diameters were observed. Addition of piperacillin to a synchronous culture inhibited cell division immediately at any stage of the cell cycle. The results of morphological examination of synchronous cultures show that the percentage of filaments with a stretched constriction corresponds to that of normally septated cells before addition of the drug. Furthermore, peptidoglycan synthesis and cross-linking were not inhibited by this drug. It is likely that this drug inhibits only septum formation, but not the growth of wall, and that stretched constrictions are a result of longitudinal growth of septation caused by the drug. Examination of affinity of the drug to penicillin-binding proteins shows that protein 3 is the most sensitive, proteins 2 and 7 are moderately so, and protein 1 is sensitive only to high concentrations of the drug.


Isolation of Klebsielleae from within living wood.

Previous studies from this laboratory have documented the presence of coliform bacteria emanating from wooden reservoirs containing finished drinking water. Coliforms were identified as Klebsiella pneumoniae and Enterobacter spp. In the present report, evidence is presented which suggests that the origin of these coliforms is from the wood used to construct the reservoirs. In liquid expressed from freshly cut redwood, total bacterial counts in the range of 10(5) to 10(6)/ml were commonly observed. When present, coliform counts were over 10(3)/ml of expressed liquid. E. agglomerans was the most prevalent coliform present, but Klebsiella was isolated from freshly cut logs. Citrobacter freundii was also occasionally isolated. No fecal coliform-positive Klebsiella were obtained from any of the samples. Highest total bacteria and coliform counts were observed in sapwood specimens. Coliforms were present throughout sapwood as evidenced by contact plating serial sections of freshly cut wood. Scanning electron micrographs illustrate the presence of bacterial colonies within sapwood tracheids. Other wood species also contained coliform bacteria but in numbers lower than found in redwood.


Fumitoxins, new mycotoxins from Aspergillus fumigatus Fres.

Extracts of cultures of Aspergillus fumigatus isolated from silage were lethal to chicken embryos. Using this test and thin-layer chromatography, four UV-absorbing toxins, designated as fumitoxins A, B, C and D, were isolated. Analysis and mass spectrometry of crystallized fumitoxin A, the most abundant in the extract, established its molecular formula to be C31H42O8. Infrared, UV spectroscopy, and chemical reactions suggested that fumitoxin A is a steroid. Fumitoxins appear to be clearly different from the previously described toxins recognized in A. fumigatus.


Modification of M-FC medium by eliminating rosolic acid.

Eliminating rosolic acid from M-FC medium improves the MFC procedure by allowing higher fecal coliform colony recoveries with greater ease in counting. Samples of unchlorinated and chlorinated domestic sewage, creek, lake, and river water were analyzed for fecal coliforms by standard procedures. Results of 200 comparisons of fecal coliform counts on M-FC medium without and with rosolic acid showed that higher counts were obtained 71% of the time when rosolic acid was excluded without an overgrowth of background colonies. Results from analyzing chlorinated sewage showed that eliminating rosolic acid improved the recovery of fecal coliform bacteria by 49%. A total of 1,675 blue colonies and 766 nonblue colonies were verified. Of the 1,675 blue colonies, 1,566 were confirmed as fecal coliform bacteria, for a verification of 93.5%. The percent verification of nonblue colonies as noncoliform bacteria was 84.2% (644/766).


Isolation of citrate-positive variants of Escherichia coli from domestic pigeons, pigs, cattle, and horses.

Twenty-seven isolates of citrate-positive variants of Escherichia coli were obtained from domestic pigeons, pigs, cattle, and horses. With the exception of citrate utilization, all isolates closely resembled typical E. coli in their biochemical reactions. These isolates were multiply resistant to antibiotics in in vitro susceptibility tests. Transfer experiments of multiple-drug resistance to the E. coli K-12 strain showed that all citrate-positive isolates from domestic pigeons, pigs, and cattle, resistant to three or more drugs, carried R plasmids showing temperature-sensitive transfer.


Significance of the inactivation of transport in thermal death of Escherichia coli.

Cells of Escherichia coli ML308-225, harvested from the exponential phase, were heated in 50 mM potassium phosphate, and the loss in viability and inability to transport lactose, proline, and alpha-methylglucoside was compared. After cells were heated at 48 degrees C for 15 min, there was a 16% loss in viability and a similarly small reduction in the steady-state accumulation of lactose at 25 degrees C. The initial rates of lactose and proline transport were severely inhibited by heating at either 48 or 50 degrees C, but substantial recovery occurred within 5 to 7 min at 25 degrees C. Heating at 50 degrees C for 15 min caused an 86% loss in viability, but only a 53% decrease in the steady-state accumulation of lactose and only a 24% reduction in the initial rate of alpha-methylglucoside uptake. Twice as much alpha-methylglucoside was accumulated at 50 degrees C as at 25 degrees C. Although alpha-methylglucoside phosphate leaked from the cells at 50 degrees C, the concentration retained within the cells was about 500 times that externally, when only about 14% of the cells were viable. Overall, these results indicate that cells made nonviable by heating at 50 degrees C still have significant membrane integrity.


The dynamics of utilization review: a case study of 44 Massachusetts hospitals.

Utilization review programs have existed on a national basis for over a decade, but relatively little is known about the patients who are scrutinized and what actions are taken to correct unnecessary use. In the fall of 1976, 44 of the 122 Massachusetts hospitals participated in a two-week in depth study of their utilization review activities. Over 22,000 admission and extended stay reviews were performed during this time period, and of these, 2,120 patients' continued stays in the hospital were questioned. In five admission review cases and 79 extended stay review cases, the UR committee formally terminated continued health insurance benefits, and in 12 admission reviews and 74 extended stay reviews, questioning by the UR committee led the attending physician to discharge the patient earlier than would have otherwise occurred. Ninety-four percent of the terminations occurred in Medicare patients and the median age of these patients exceeded 80 years. For medical patients, a disproportionate share of all those cases questioned and of those terminated occurred in chronic illness categories, such as cancer, heart failure, and organic brain syndromes. A higher than expected percentage of surgical cases questioned by the UR committee were in neurosurgical, cardiovascular and orthopedic procedure groups. The frequency with which UR committees identified and acted upon cases suggests that effective self-policing is occurring. A large portion of the utilization problem, however, may be related to the unavailability of appropriate sub-acute care for patients with chronic medical illness or surgical procedures which require long postoperative rehabilitation and recuperation.


Malumfashi Endemic Diseases Research Project. II. Malariometry in Malumfashi, Northern Nigeria.

Prior to longitudinal studies into the effects of malaria upon the immune response, nutritional status and haematological indices in young children in northern Nigeria, the degree of malarial endemicity in the area has been established. Field work was carried out in the wet seasons of 1976 and 1977 and the dry season of 1977 (April). Seasonal variation in transmission has been demonstrated. Age-specific parasite prevalence rates and splenic indices confirm previous studies that this northern part of the Guinea savannah belt of West Central Africa is an holoendemic area.