Efficacy of cimetidine and tri-potassium di-citrato bismuthate (De-Nol) in chronic gastric ulceration: a comparative study.

Sixty patients with benign chronic gastric ulcer were treated in a controlled clinical trial to assess the relative efficacy of cimetidine and tri-potassium di-citrato bismuthate (De-Nol). Patients were assigned at random either to cimetidine or to De-Nol treatment after initial endoscopic diagnosis. Healing was assessed endoscopically after six weeks by an endoscopist who had no knowledge of the patients' treatment. Consumption of analgesic preparations (both for medical and for non-medical reasons), of other anti-inflammatory agents, and of alcohol and cigarettes was recorded. Of the 57 patients who were reassessed at six weeks, 30 had been assigned to De-Nol and 20 of these patients (66%) had completely healed; 27 patients had been assigned to cimetidine and 17 of these (63%) had also completely healed. Those patients who regularly ingested more than four analgesic preparations a day healed less frequently, but this effect was not statistically significant. There was no significant difference between cimetidine and De-Nol in the initial healing of chronic gastric ulceration. The choice of therapy for chronic gastric ulceration will depend on cost, patient acceptance, and data from studies of more complex therapeutic regimens.


Persistent fetal circulation. Two cases with myocardial dysfunction and severe acidosis.

Two neonates with the most severe form of persistent fetal circulation are described. Their presentation mimicked severe congenital heart disease. As well as persistent pulmonary hypertension and right-to-left shunting through the ductus arteriosus, they had poor myocardial contractility and atrioventricular valve regurgitation. Associated acidaemia was extreme. They survived with medical management, and the functional abnormalities resolved.


Photochemotherapy in psoriasis: the first six months in Australia.

The results of the first six months of treatment of psoriasis with photochemotherapy in the Skin and Cancer Foundation's clinic resulted in 30 out of 53 patients being completely clear of psoriasis lesions, 14 showing progressive improvement (and subsequently clearing), four failures, and five withdrawals. The treatment is not a cure, and requires maintenance therapy. It involves the use of large expensive machines to deliver ultraviolet light, and demands careful supervision and control dosimetry.


[Personality-structure in different kinds of bronchial asthma (author's transl)].

The "Giessen-Test" is a psychological test in form of a questionnaire, basing on self-assessment. It was applied in 63 patients with bronchial asthma in order to get their "self-images" and their "ideal-self-images". Except of higher values for depression the "self-images" of the asthmatics resembled very closely those of normals. The ideals ("ideal-self-image") of the patients were uncharacteristic and reflected general trends. In contrast to these findings eleven physicians had a negative conception of asthmatic patients ("foreign image"). Physicians assessed the asthmatics to be disliked ("negative social resonant"), obstinate ("dominant") and depressive. Patients with exogen-allergic asthma, intrinsic asthma and asthma of unknown origin differ from each other only within a few marks. These differences, however, are not sufficient, to allow to coordinate a specific personality-structure with one of the different kinds of asthma.


[Metastases to the bone. Diagnosis, treatment, prognosis (author's transl)].

The prognosis of cancer patients with metastases to the bone has changed little during the past 10 years despite improvement of diagnostic and therapeutic possibilities. A review of the patients treated at the Surgical Clinic of the Erlangen University between 1969 and 1975 showed that out of 78 patients with metastases to the bone only one survived 5 years. In this case a ultraradical method of treatment--hemipelvectomy--was employed. Three groups of comparison were formed; one of them being treated conservatively, the second by palliative osteosynthesis and the third by resection. In the first and second group no patient was alive after 4 1/2 years. The mean survival time was 6,7 months for patients treated conservatively and 11,2 months for those in whom osteosynthesis was used. Patients treated by resection survived 16,3 months on average.


[Familial-hereditary malignant melanoma (author's transl)].

The existence of familial-hereditary malignant melanoma can be accepted for sure. Its frequency is estimated with 1 to 7% of all malignant melanomas. An autosomal-dominant mode of inheritance with reduced penetrance or a polygenetic mode of inheritance are discussed. Patients with numerous inherited, clinical and histological atypical naevi, the so called BK-moles, are reported to have a high incidence of malignant melanoma. Hereditary malignant melanomas begin early in life, have a high frequency of multiple primary lesions and show the coincidence of other malignant tumors in this families. Men are affected as often as women. Five own families are described and a review of the literature is given.


[Ultrasound as a diagnostic procedure in liver disease: results of 3000 sonographic investigations (author's transl)].

3000 sonographic examinations of the liver were performed. The results of 142 sonographic studies were compared with the findings obtained by subsequent laparoscopy and microscopy. In 90% there was good agreement between the sonographic diagnosis and the microscopic findings. Fatty liver (97%) and metastasis (95%) into the liver were diagnosed accurately. 3 hematomas of the liver were found in 150 patients who underwent liver biopsy. Sonographic examination of the liver is usefull in: (1) determining topographic anatomy of the liver before needle biopsy. (2) deciding the next diagnostic step within the catalogue of indications for the morphologic diagnosis of the liver given by the IASL. Ultrasound shortens diagnosis. (3) early diagnosis of hematoma after liver biopsy.


[Complication rate under passive and active cure treatment of cardio-circulatory patients (author's transl)].

A comparison between the rate of complications under preferably passive balneotherapeutic cure treatment in 1967 and under preferably active physical training treatment in 1972 gave no significant difference. In spite of an increasing portion of heart patients the complication rate in the cardio-circulatory system under active treatment showed a slight decreasing tendency. On the contrary there were found differences when comparing the temporal frequency distribution of complications under cure treatment of both years. Indeed both years exhibited the known circaseptan periodicity of cure treatment, the temporal frequency distribution of the maxima and the minima, however, showed the characteristic pattern of reactive periods not but under conventional passive treatment in 1967. By reason of these findings the higher load of modern physical training treatment is supposed to strengthen the influence of interindividual differences in the autonomous reagibility, and thus differences from the conventional mode of cure treatment in the first place appear in the temporal distribution of complications.


[Plasma levels of lidocaine following intramuscular injection by means of an automatic injector (author's transl)].

Plasma levels of lidocaine were determined in either 10 patients following injection into the deltoid and lateral vastus muscle, respectively. We used an automatic injector containing 250 mg of lidocaine in a 10% solution. In the early phase after injection, plasma levels were higher, when the deltoid muscle had been chosen for administration. This was the same result as referred by other authors using normal injectors. Variance of single plasma values was smaller in the vastus group.


[Perforation of sinus of valsalva aneurysms (case report and review of the literature) (author's transl)].

A perforation in a case of sinus of Valsalva aneurysm misinterpreted first as perforated ulcer and later on as myocarditis made us review the literature (76 cases) for patients' history and diagnostic criteria which lead to the diagnosis. Special references were taken to the following subjects: localization of the aneurysms and direction of perforation; age and sex distribution at the time of perforation; ECG-changes and clinical symptomatology before and after perforation, and to diseases which must be taken into account for differential diagnosis.


[Thrombolysis with Urokinase after anaphylaxis caused by streptokinase treatment (author's transl)].

Deep femoral and pelvic phlebothrombosis represents a safe indication for thrombolytic therapy, despite the fact that additionally considered surgical measures have increasingly been brought up for discussion very recently. While numerous studies are being considered for treatment with streptokinase, only sporadically does one hear of reports about therapy using Urokinase. In the case of a deep pelvo-femoral phlebothrombosis we decided to carry out thrombolytic treatment using Urokinase, the originally planned streptokinase treatment having had to be terminated owing to an allergic reaction.


[Reaction of blood sugar and serum insulin to intravenous longterm treatment with Actovegin. Clinical double-blind study (author's transl)].

In a randomised double-blind study involving 20 diabetics and 20 patients with normal carbohydrate metabolism, the influence of a 14 days' course of intravenous infusion of protein-free calf blood extract (0.5 ml Actovegin/kg/day) and equivalent amounts of physiological saline solution on blood sugar and serum insulin was investigated by the oral glucose tolerance test (100 g Dextro-OGTT). In diabetic carbohydrate metabolism Actovegin was shown to improve the glucose tolerance significantly without alteration of the serum insulin, thus possessing antidiabetogenic activities. With normal carbohydrate metabolism, however, the behaviour of blood sugar and serum insulim was not changed by Actovegin.


[Blood sugar self-profiles. Improvement in diabetes control in outpatients (author's transl)].

15 insulin-dependent diabetics who had been hospitalised for evaluation and modification of their treatment regimen were trained to take their own blood samples with 10 microliter glass capillaries. Blood sugar self-profiles were analysed from each patient twice in hospital and afterwards at home. Urine samples were also self-tested for sugar. The profiles were carried out reliably and seem to cause a minimum of trouble to the patient. This method of feedback, with comparison of blood and urine sugar values, increased the patient's understanding and ability to vary his own insulin dosis. The analysis of 3 daily profiles for each patient showed increasing improvement in metabolic control. This also increased motivation to keep to a regimen in which insulin dosage, physical activity, and nutrition are in balance. For the first time daily profiles were introduced which could be carried out under the normal conditions of the patient's daily life.


[Epidemiology of peripheral vascular disease in diabetics (author's transl)].

623 non-selected diabetic outpatients were screened by the Doppler-ultrasonic-method for peripheral vascular disease. Additional angiologic work up was performed to define the location of stenosis and obliteration. 15.9% of the diabetics were shown to have peripheral vascular disease and 57% of those denied claudication. 9% of the patients had signs of mediasclerosis. The predilection of peripheral vascular disease in diabetics for the arteries below the knee (peripheral type) was confirmed in our study. Patients with a pelvic or femoropopliteal type of peripheral vascular disease showed a high frequency of cardiovascular risk factors. An influence of the duration of diabetes on peripheral vascular disease was not evident. In contrast to this, a significant correlation (p less than 0.001) of the peripheral type of peripheral vascular disease-as well as of mediasclerosis--could be demonstrated with the diabetes of long duration. In patients with the peripheral type of peripheral vascular disease significantly more often higher blood sugar volues were found. Thus the quality of metabolic control seems to be of some importance for this form of diabetic macroangiopathy.


In vivo nicking and rejoining of nuclear DNA in ultraviolet-irradiated radiation-resistant and sensitive strains of Dictyostelium discoideum.

Some aspects of DNA repair in several radiation-resistant and radiation-sensitive strains of Dictyostelium discoideum were investigated by using alkaline sucrose gradients to analyze for the production and resealing of single-strand breaks following irradiation with 254 nm UV. All radiation-resistant strains and all mutants assayed that are sensitive to both UV and 60Co gamma rays produced single-strand breaks in their nuclear DNA after a UV fluence of 15 M/m2. Mutants at the radC locus which are sensitive to UV but as resistant as their parental strains to 60Co gamma rays produced many fewer single-strand breaks in their DNA after irradiation with UV. Thus, the radC mutations alter a repair pathway specific for UV-induced DNA damage and presumably affect the activity of a UV-damage-specific endonuclease involved in excision repair. All radiation-resistant strains and all of our mutants sensitive to gamma rays rejoined much of their DNA during a three-hour post-UV-irradiation incubation, suggesting that these strains have at least a partially intact excision repair system.


Interactions between radiation-sensitive mutations in double-mutant haploids of Dictyostelium discoideum.

Haploid strains of Dictyostelium discoideum carrying radiation-sensitive mutations in both the radA and radC genes are more sensitive to UV light irradiation than the "additive" sensitivity of the single-mutant haploids. This synergistic interaction indicates that the radA and radC gene products are involved in two different pathways of repair following UV-induced DNA damage. Double-mutant haploids bearing mutations in both the radA and radB genes have the same sensitivity as the radB single mutant indicating that the radA and radB gene products are involved in the same repair pathway.


Permutation of the DNA in small-headed virions of coliphage P1.

Use of restriction endonucleases Bg/II, EcoRI, BamHI, and HindIII, has established that in small-headed (P1S) virions of coliphage P1, as a population, the entire genome found in big-headed (P1B) virions is represented. In addition, the origin and direction of DNA packaging are identical in P1S and P1B virions.


[Hypsarrhythmia as a cause of recurrent infantile apnoea (author's transl)].

In a seven months old infant with a history of obstructive bronchitis, hypsarrhythmia was found to be the cause of symptoms mimicking pertussis with recurrent apnoea. Morphological cerebral abnormalities could not be detected. Clonazepam showed a prompt and persistent therapeutic effect.


[Joint occurrence of congenital ring constrictions and limb amputations with craniofactial dysmorphia (author's transl)].

A case of an infrequent congenital malformation, partial ring constrictions on fingers and toes and their amputation associated with cleft lip, facial cleft, microphthalmus and hydrocephalus is described. The etiology of the congenital malformation is discussed. Based on the literature, the question is put forward whether an increase in the frequency of this malformation could be connected to the more frequent use of amniocentesis.


[Computed tomography of the trunk in children (author's transl)].

So far whole body CT has not yet been used very often in children. The main reason for this are patient-related factors which impair the recognition of details on the scans such as frequent lack of intra abdominal fat tissue, and so called movement artefacts. The search for tumors is the predominent indication for CT in children. The advantages of CT are discussed and the authors' own measurements of radiation exposure are given.


[Hypertensive emergencies in children with renal hypertension (author's transl)].

Hypertensive emergencies of 10 children with renal hypertension were analysed. Cause of renal disease are chronic renal failure in three, acute renal failure in three, hemolytic uremic syndrome in two, acute post streptococcal glomerulonephritis in one, and renal arterial stenosis in a further patient. Therapy should be started early in the course of the hypertensive emergency, first symptoms are headache and vomiting. Drug of first choice is diazoxide (3-5-(8)mg/kg i.v.). Three  patients developed transitory hyperglycemia after repeated injections of diazoxide.


[Schizophrenia in childhood (author's transl)].

After considerable controversies during the last decades there is no longer any doubt about childhood schizophrenia as a disease, although within German-speaking countries its somewhat wider definition like in Anglo-Saxon child- and adolescent psychiatry is not accepted. The relation of early childhood autism to the nosologic entity of schizophrenia still remains speculative. The etiology of childhood schizophrenia is not known, equally not that of the even less frequent manic-depressive disease. Symptoms, course, and prognosis of childhood schizophrenia which developes between preschool age and the begin of puberty are described in detail.


[The significance of cranial computerized tomography for diagnosis and therapy of inflammatory diseases of the brain and meninges in children (author's transl)].

The significance of cranial computerized tomography (CCT) for the diagnosis and therapy of inflammatory diseases of the central nervous system in children is discussed in connection with five characteristic case studies. CCT is shown to be superior to classical neuroradiological approaches, and to allow important diagnostic insights: 1. the early recognition of diffuse brain edema and the resulting possibility of an early begin of therapy--2. the pathological expansions of the cerebral ventricles of various etiology before a pathological enlargement of the head can be detected, and the size of the ventricles after neurosurgical therapy can be measured--3. the early recognition of space-occupying inflammatory complications.


[Parents of children dialysed at home. Psychological assessment (author's transl)].

Ten married couples with children undergoing home dialysis were examined by means of different tests used in family interaction diagnosis (Joint Rorschach, SIMFAM, Giessen Test, Bales Scale, Expert Rating). The couples showed a similar cooperation as found in a group of psychologically "ordinary" couples, but emotional problems between the parents of home dialysis children were at least as frequent as in a group of psychologically, disturbed couples needing family therapy. The role of the psychologist for the stability testing in parents of children destined for regular dialysis and for psychotherapeutic preparation to home dialysis is described.


[Plasma renin activity in diabetic children (author's transl)].

In 10 healthy and 27 diabetic children aged 11--17 years plasma renin activity was determined in horizontal position (PRA-I) and after stimulation by furosemid and upright position (PRA-II). In diabetic children with or without hypertension and protein-uria, and a normal or only slightly elevated plasma creatinine level normal PRA-I and PRA-II values were found.


Defective reticuloendothelial system Fc-receptor function in systemic lupus erythematosus.

To determine whether reticuloendothelial-system immunospecific Fc-receptor function is abnormal in patients with systemic lupus erythematosus, we studied the clearance of IgG-sensitized 51Cr-labeled erythrocytes by these splenic macrophage membrane receptors in 15 untreated patients. Fc-specific clearance rates were strikingly abnormal in 13 of 15 patients (half-times ranging from 80 to 2256 minutes, P less than 0.001 as compared to controls). Abnormal clearances correlated with immune-complex levels (as measured by the C1q-binding assay) and with disease activity. C1q-binding activity and anti-DNA titers also correlated with disease activity. The correlations of C3, C4, CH50 and factor B with abnormal clearance and disease activity were weaker or nonexistent. The significant correlations among clearance, disease activity and C1q-binding activity suggest that the defect in Fc-receptor function may lead to the prolonged circulation of immune complexes, thereby contributing to tissue deposition and damage.


Respiratory-syncytial-virus infections, reinfections and immunity. A prospective, longitudinal study in young children.

To better understand acquired immunity to respiratory-syncytial-virus infections, we analyzed data from a 10-year study of respiratory illness in normal children who were followed longitudinally from early infancy. Immunity was measured in terms of failure to become infected or reduction in severity of clinical illness upon reinfection. Outbreaks of infections occurred seven times over the 10-year-period. During epidemics the attack rate for first infection was 98 per cent. The rate for second infections (75 per cent) was modestly reduced (P less than 0.001); that for third infections was 65 per cent. Age and history of infection both influenced illness. Immunity induced by a single infection had no demonstrable effect on illness associated with reinfection one year later; however, a considerable reduction in severity occurred with the third infection. These observations suggest that amelioration of illness--rather than prevention of infection--may be a realistic goal for immunoprophylaxis.


Potential effect of self-care algorithms on the number of physician visits.

To assess the potential effect of self-care algorithms on the number of physician visits, actual visits from the Seattle Virus Watch were compared retrospectively with those recommended by clinical algorithms for common illnesses from the book, Take Care of Yourself, by Vickery and Fries. From a total of 3929 illnesses, records indicating the presence of the index symptom for eight algorithms were identified, determining whether the criteria for seeing a physician were met and whether a physician visit was recorded. The number of visits observed was compared to the number of visits recommended by the algorithms. Strict adherence would have increased the number of visits over that observed for five, remained the same for two, and decreased for one of the algorithms. These results indicate that adherence to some commonly promulgated self-care algorithms may increase rather than decrease the number of physician visits.


Reduction to normal of plasma glucose in juvenile diabetes by subcutaneous administration of insulin with a portable infusion pump.

To improve plasma glucose control, we administered insulin via the subcutaneous route in seven ambulatory patients with juvenile diabetes (12 to 17 years of age), using a portable infusion pump at a basal rate with pulse-dose increments before meals. After two to four days, the mean plasma glucose (+/- 1 S.E.) of 94 +/- 5 mg per deciliter was markedly lower than when insulin was given by conventional methods in the patients' usual dose (243 +/- 28, P less than 0.01) or in a total dose equivalent to that administered with the pump (150 +/- 15, P less than 0.01). Maximal fluctuations in plasma glucose were also 50 to 150 mg per deciliter below those observed with conventional treatment (P less than 0.001). Glycosuria was eliminated in six of seven patients during pump treatment. None of the subjects had hypoglycemia. These results demonstrate that plasma glucose can be lowered to normal in ambulatory patients with brittle juvenile diabetes using a portable, subcutaneous insulin infusion system for two to four days. The feasibility and value of the long-term application of this technic need exploration.


Current practice of artificial insemination by donor in the United States.

Of 711 physicians likely to perform artificial insemination by donor surveyed to determine their current practices, 471 responded, of whom 379 reported that they performed this procedure. They accounted for approximately 3576 births by this means in 1977. In addition to treating infertility, 26 per cent of these physicians used the procedure to prevent transmission of a genetic disease, and 10 per cent used if for single women. Donors of semen were primarily from universities, were only superficially screened for genetic diseases, and were then matched phenotypically to the recipient's husband. Most recipients were inseminated twice per cycle. Only 17 per cent of physicians used the same donor for a given recipient, and 32 per cent used multiple donors within a single cycle. Only 37 per cent kept records on children, and only 30 per cent on donors. The identity of donors usually was carefully guarded to ensure privacy and to avoid legal complications.


Chronic cough as the sole presenting manifestation of bronchial asthma.

Six patients with chronic cough, without history of dyspnea or wheezing, had normal base-line spirometry but hyper-reactive airways, as demonstrated with methacholine. Maintenance therapy with bronchodilators promptly eliminated the cough in all patients. Three to 12 months later therapy was discontinued for three days, cough returned, and detailed pulmonary-function studies were carried out. Again, base-line values were normal, but after methacholine one-second forced expiratory volume decreased an average of 40 per cent in the patients as compared to 30 per cent in normal controls (P less than 0.001). The point of identical flow was increased by methacholine to 43.5 per cent of vital capacity in the patients, as compared to 6 per cent in normal controls (P less than 0.001), and the alveolar plateau was 4.8 deltaN2 per liter, as compared to 1.4 in normal controls (P less than 0.01). Specific airway conductance was lowered in patients and controls, but the post-methacholine value was significantly lower in the patients. On the basis of their persistently hyper-reactive airways, inducible diffuse airway bronchoconstriction and excellent response to bronchodilator therapy, these patients appear to have a variant form of asthma in which the only presenting symptom is cough.


Deficits in psychologic and classroom performance of children with elevated dentine lead levels.

To measure the neuropsychologic effects of unidentified childhood exposure to lead, the performance of 58 children with high and 100 with low dentine lead levels was compared. Children with lead levels scored significantly less well on the Wechsler Intelligence Scale for Children (Revised) than those with low lead levels. This difference was also apparent on verbal subtests, on three other measures of auditory or speech processing and on a measure of attention. Analysis of variance showed that none of these differences could be explained by any of the 39 other variables studied. Also evaluated by a teachers' questionnaire was the classroom behavior of all children (2146 in number) whose teeth were analyzed. The frequency of non-adaptive classroom behavior increased in a dose-related fashion to dentine lead level. Lead exposure, at doses below those producing symptoms severe enough to be diagnosed clinically, appears to be associated with neuropsychologic deficits that may interfere with classroom performance.


Epidemic toxoplasmosis associated with infected cats.

In October, 1977, an outbreak of toxoplasmosis occurred in patrons of a riding stable in Atlanta, Georgia; 37 became ill with toxoplasmosis or had serologic evidence by indirect fluorescent-antibody test of acute infection with Toxoplasma gondii (titer greater than or equal to 1:4096 or a positive fluorescent-antibody test for toxoplasma antibodies). Forty-nine additional patrons did not become ill. Two of the three adult cats from the stable were seropositive for toxoplasma, which was also recovered from the tissues of two kittens and four mice trapped near the stable. Patrons who spent most of their time at the end of the stable where a cat had defecated had the highest incidence of infection. Patrons who attended the stable daily had a higher attack rate than those who attended less frequently. No common meals were consumed, and dietary histroy eliminated meat as the source of infection. The data suggest that toxoplasma oocysts were the source of the infection.


Normal human tissues contain RNA and antigens related to infectious adenovirus type 2.

Normal human tissues have been found to contain RNA which hybridises with four regions of the adenovirus type 2 genome, including one which contains the transforming gene(s) of this virus. The RNAs have also been extracted from gorilla organs, but not from those of chickens, suggesting that they are a feature of all normal higher primate tissues. Serological test suggest that these homologous RNAs are translated into proteins connected with essentially normal and virus-infected cell functions.


Radiation-induced chromosome aberrations in nuclear-dockyard workers.

The incidence of chromosome aberrations in peripheral blood lymphocytes of 197 dockyard workers has been followed over a 10-yr period. These workers were exposed to mixed neutron-gamma radiation during the refuelling of nuclear reactors, but most exposures were below the internationally accepted maximum permissible level of 5 rem per yr. There was a significant increase in chromosome damage with increasing exposure; aberration frequency was a linear function of dose and was unfluenced by age and time of blood sampling after exposure.


A novel bacteriophage defence mechanism: the anti-restriction protein.

Bacteriophage T3 and T7 protect their DNA from restriction by producing, as the earliest detectable phage functions, anti-restriction proteins. Although the two phage proteins differ in their chromatographic and antigenic properties, they act by the same mechanism: the anti-restriction proteins inhibit E. coli K12 restriction endonuclease by direct interaction.


[Hypoglycemia in the newborn infant subsequent to hyperplasia of beta cells of the pancreas].

A case of hypoglycemia of difficult control and resistant to treatment due to hypersinsulinism as a result of hypertrophy of beta celis of the pancreas in the newborn perior is analyzed. Based on this case, hypoglycemia of the newborn is discussed, analyzed etiology, pathogenesis, symptomatology, diagnosis and treatment. Emphasis is place on the lack of clear symptoms and signs at this age, on the differential diagnosis, on the entities with which it can be associated or confused, and on the need to make an early diagnosis in order to prevent brain damage.


[Primary prevention of rheumatic fever. Occurrence of beta hemolytic Streptococcus of the A group in 11,314 students in Magdalena Contreras].

A study was made in 11,314 school-age children to determine the prevalence of streptococcus pyogenes group A. The children studied belonged to a low socioeconomic group of one of the political boroughs of the Federal District. The prevalence found was 6.86%. There were no differences in the percentage of carriage according to the school surveyed or the school grade studied. However, marked differences were found when the presence of arthralgias was related to the carriage of streptococcus. Children complaining of artharlgias showed twice as much streptococcus in their pharynx than the ones not carrying it.


[Analysis of fecal mucus in children with prolonged and acute diarrhea].

The fecal mucus obtained from 110 samples in 50 children with diarrhea was studied. Leukocytes were present in 44 cases and 66 samples were negative. Patients with E. coli 0111 did not show fecal leukocytes in contrast with those with E. coli 0119. Patients with shigellosis showed fecal leukocytes of polymorphonuclear predominance, the same as patients with non-thyphoid salmonellosis. But when septicemia was present, either from salmonella or from other enterobacteria, there was a striking increase in percentage of mononuclears. Several patients with negative stool cultures showed fecal leukocytes of polymorphonuclear predominance which suggested residual inflammatory reaction or presence of bacteriologically unidentified invasive E. coli. The index of diagnostic prediction for this test was 73%. Its routine use is recommended in any child with acute or protracted diarrhea, before the initiation of antimicrobial treatment.


Reduced lethality in mice receiving a combined dose of cyclophosphamide and busulphan.

Animals treated with a sufficiently high dose of busulphan die about 14 days later from bone marrow failure. A single, appropriately timed injection of cyclophosphamide can save these mice. The nature of this protection is shown to be the cyclophosphamide induced elaboration of a humoral factor which stimulates haemopoietic recovery.


Granulocyte function in myeloblastic leukaemia.

A study of granulocyte function in myeloblastic leukaemia is reported. Function was assessed by the ability of peripheral blood granulocytes to ingest and kill Candida albicans in bitro. Depressed cidal activity was observed in 11 patients with smouldering leukaemia and in 19 patients with acute myeloid leukaemia. Cidal activity was lowest in the untreated acute disease; this improved during cytoreduction therapy and was maintained when remission occurred. Leukaemic plasma depressed the function of control granulocytes; the possible role of a plasma "factor" is discussed.


The humoral immune response to allografts of foetal small intestine in mice.

The influence of the presence of "passenger leucocytes" on the production of anti-H2 antibodies has been studied in mice receiving allografts of foetal small intestine, adult skin or intradermally injected spleen cells. It was found that the humoral immune response to foetal intestine (a tissue without passenger leucocytes) was identical temporarily to that elicited by skin allografts and these responses differed from that following injection of allogeneic spleen cells in that antibodies to solid grafts took longer to appear. The humoral immune response to small intestine grafts was not evident until several days after the onset of graft rejection as assessed morphologicallymanti H2 antibody production was not observed in thymus deprived recipients of foetal small intestine allografts or allogeneic spleen cells, and this suggests that the humoral immune response to transplantation antigens is thymus dependent.


Colony formation by human haemopoietic precursor cells cultured in semi-solid agar in diffusion chambers.

A technique which allows colony growth of haematologically normal human bone marrow cells is described. The cells are supported by semi-solid-agar-medium inside modified Millipore diffusion chambers implanted in the peritoneal cavity of irradiated mice. After 9 days incubation colonies containing up to 1000 cells are found in these Agar Diffusion Chambers. All haematologically normal patients studied so far produced colonies, the majority with between 10 and 40 colonies per 2 X 10(5) bone marrow cells inoculated. This culture system therefore provides a convenient and reliable clonal assay for human bone marrow cells which, in contrast to the agar colony assay in vitro, does not require a source of Colony Stimulating Factor (CSF).


Liver transplantation in pigs with von Willebrand's disease.

Nine pigs with von Willebrand's disease (vWd pigs) received normal auxiliary livers; in the immediate postoperative period, three pigs died, three survived from 3 days to 3 weeks, and three were killed 5-13 weeks postoperatively. There was an increase in factor VIII (up to 90 u/dl) but with a type of factor VIII that was more labile than normal and that decreased after 2 weeks, probably as a result of liver rejection. There was a slight increase in the levels of the ristocetin-Willebrand factor postoperatively (up to 11%) but this activity was undetectable after 2 weeks. There was no correction of the abnormal bleeding time and platelet retention. When a vWd liver was transplanted orthotopically into a normal pig, the factor-VIII coagulant activity and the ristocetin-Willebrand factor remained normal. The abnormality in porcine von Willebrand's disease is only partially corrected by liver transplantation, which suggests that there also is extrahepatic synthesis of the missing or abnormal plasmatic activity or activities.


Changes in erythroblast morphology as an index of response to cyanocobalamin in patients with megaloblastic anaemia.

Fifty-three patients with megaloblastic anaemia treated with  cyanocobalamin and folic acid have been studied. Repeat marrow examination was found to be of value in assessing response to treatment. The early improvement in marrow morphology in patients with pernicious anaemia was greater with 1000 mug than with 5 mug doses of cyanocobalamin. The effect of folate deficiency in delaying marrow response to cyanocobalamin in patients with pernicious anaemia is described and combined cyanocobalamin and folic acid treatment was found to be more effective than either alone. The response to large doses of cyanocobalamin in folate deficient patients was unrelated to the initial serum vitamin B12 level.


Lack of correlation of lymphoblast cell size with presence of T-cell markers or with outcome in childhood acute lymphoblastic leukaemia.

The proportion of pretreatment bone marrow macrolymphoblasts was determined in a total of 93 children with acute lymphoblastic leukaemia (ALL) in order to assess the validity of cell size as a prognostic indicator. A macrolymphoblast (MLb) was defined as having a diameter greater than 12 mum, and patient samples were divided simply on the basis of whether they had more or less than 10% MLb present at diagnosis. In a retrospective study of a sample of 47 children treated according to Total Therapy Study VII, the continuous complete remission duration, survival and incidence of CNS disease bore no relationship to the cell size distribution present at diagnosis. A second sample of 46 current patients with untreated ALL was examined both for the presence of surface markers for T- and B-cells and for cell size. Bone marrow blasts from 10 of these 46 children formed rosettes with sheep erythrocytes (E)-- a T-cell marker. E-rosette formation was associated with a constellation of adverse prognostic factors, including older age, very high initial WBC counts, organomegaly, and mediastinal enlargement; yet the presence of this T-cell marker was unrelated to cell size. We conclude that pretreatment lymphoblast cell size is not a reliable prognostic indicator in childhood ALL.


Purification and properties of gentamicin acetyltransferase I.

Gentamicin acetyltransferase I is induced 13-fold in R factor resistant Escherichia coli by high concentrations (1 mg/ml) of gentamicin in the growth medium. The enzyme is maximally released from bacteria by osmotic shock in late-log phase, unlike previously studied periplasmic enzymes. Streptomycin sulfate and ammonium sulfate precipitations of shockate followed by affinity and ion-exchange chromatography recover 51% of the induced enzyme with a 360-fold increase in purity (12% of 4400-fold, uninduced). The purified enzyme appears homogeneous by six criteria, the first aminoglycoside inactivating enzyme so purified. Sodium dodecyl sulfate electrophoresis, amino acid analysis, and sedimentation analyses indicate a tetrameric protein of 63000 molecular weight. The protein does not contain tryptophan. Kinetic analyses yield apparent values of: Vmax = 3.4 +/- 0.2 mumol per min mg at pH 8 (optimum), Km (acetyl-CoA) = 3.9 +/- 0.2 muM, Km (gentamicin Cla) = 0.3 +/- 0.08 muM, KI (gentamicin substrate inhibition) = 160 +/- 29 muM. The activity of the enzyme is stable to a variety of conditions, including lyophilization and prolonged storage, and can be monitored by two convenient spectrophotometric assays.


Ionophore A23187. Solution conformations of the calcium complex and free acid deduced from proton and carbon-13 nuclear magnetic resonance studies.

Proton and carbon-13 nuclear magnetic resonance (NMR) spectra have been used to deduce possible biologically relevant conformations of ionophore A23187 as the free acid, and as the calcium complex, in solution. By analysis of coupling constants and dihedral angles obtained from 270-MHz proton NMR, A23187 free acid molecules and individual A23187 anions which comprise the calcium complex are found to differ principally by the rotational state of a carbon-carbon single bond near the benzoxazole ring. Proton Tl relaxation data and measurements of rotational correlation times confirm the dimeric nature of the calcium complex vs. the free acid monomer. Using the deduced pseudocyclic conformation for the A23187 anion, in conjunction with model-building studies, a conformation for the calcium complex is proposed, in which the benzoxazole carboxylate oxygen, the ketopyrrole oxygen, and the benzoxazole (ring) nitrogen atom of each molecule are the major participants in calcium binding. Additional stabilization of the structure is possible through the formation of a postulated hydrogen bond bridge between the pyrrole NH proton and benzoxazole carboxylate oxygen.


Equilibrium binding of magnesium(II) by Escherichia coli tRNAfMet.

Equilibrium dialysis measurements show that tRNAfMet1 in 0.17 M Na+ has one strong Mg2+ binding site, K = 3 X 10(4) M-1, and approximately 26 weak binding sites with K = 4 X 10(2) M-1, with RNA concentration measured in moles of tRNA per liter and T = 4 degrees C. The data fit significantly less well to a model with two strong sites and a large class of weak sites. Binding is noncooperative. Our results differ from previous experiments showing cooperative binding because the binding equilibrium is not coupled to a cooperative conformational change of the macromolecule. Measurements at relatively high Na+ concentrations and low temperature ensure that the tRNA is in the "native" region of the conformational phase diagram for all Mg2+ concentrations.


Conformational changes of transfer RNA. The role of magnesium(II).

Magnesium ions added to tRNAfMET1 selectively stabilize the dihydrouridine helix-tertiary structural region. Low Mg2+ levels have little direct effect on the remaining three cloverleaf helices, but these are prevented from melting independently when their intrinsic Tm is surpassed by the Tm of the tertiary structure. At high Mg2+ concentration the thermal unfolding of tRNAfMet1 is approximately a two-state, concerted transition from the globular native structure to the random coil, in contrast to the sequential unfolding observed without Mg2+. We interpret the kinetics of refolding to mean that the D helix serves as a required nucleus for the rate-limiting step of tertiary structure formation. We found that unfolding of the tertiary structure leads to loss of the tightly bound Mg2+ ions, and showed with a Mn2+-sensitive fluorescent indicator that the rate of Mn2+ release is the same as the rate of unfolding the tertiary structure. Hence the tightly bound divalent ion must be located in a site formed by the tertiary structure-D helix region of the molecule.


Preparation and properties of the repeating sequence polymers d(A-I-C)n-d(I-C-T)n and d(A-G-C)n-d(G-C-T)n.

The repeating sequence polymer d(A-I-C)n-d(I-C-T)n has been prepared using the chemically synthesized oligomers d(A-G-C)4 and d(C-T-G)4 and the DNA polymerase from Micrococcus luteus. The enzymatically synthesized polymer was used as template for preparation of d(A-G-C)n-d(G-C-T)n. Both deoxyribonucleotide polymers were characterized by nearest neighbor analyses, buoyant density measurements in cesium chloride and cesium sulfate, melting temperature, and circular dichroism (CD) spectra. The ribopolymers r(A-I-C)n-r(I-C-U)n and r(A-G-C)n-r(G-C-U)n were transcribed from d(A-I-C)n-d(I-C-T)n, and their CD spectra were compared with those of the respective deoxyribonucleotide polymers.


Mechanism of yeast cytochrome b2 action. I. Thermodynamics and relaxation kinetics of the interaction between cytochrome b2 and oxalate.

Oxalate is the strongest known inhibitor of yeast cytochrome b2 activity. We have used spectrophotometric titration, temperature-jump relaxation, and calorimetry in an investigation of the interaction between enzyme and inhibitor. The titration data are consistent with noncooperative binding to one site per subunit. This conclusion is corroborated by temperature-jump results which reveal a single relaxation phenomenon which obeys second-order kinetics. Further evidence for a simple binding reaction enthalpy estimated from relaxation amplitudes is in good agreement with the value obtained directly with batch calorimetry. The forward and reverse rate constants evaluated from the temperature-jump experiments are, respectively, 1 x 10(4) M-1 sec-1 and 15 sec-1. Although considerably smaller than a diffusion-controlled value, the forward rate constant is characterized by an unusually small activation energy of approximately 3 kcal/mol. This, together with a large unfavorable association activation entropy of -30 eu, suggests that oxalate diffuses freely to the active site, but only a small fraction of the collisions are productive due to severe steric requirements.


Mechanism of yeast cytochrome b2 action. II. Steady-state kinetics of oxalate inhibition.

From a careful steady-state kinetic study it is shown that the inhibition of L-lactate oxidation by cytochrome b2 with ferricyanide as acceptor is of the mixed competitive-noncompetitive type, indicating the formation of an active ternary complex between enzyme, substrate, and inhibitor. With a large excess of acceptor, the simplest formal mechanism consistent with all available data is: E + L equilibrium EL; E + S equilibrium ES leads to EP leads to E + P; ES + L equilibrium ESL leads to EPL leads to EL + P, where L is oxalate, S is L-lactate, P is pyruvate, and E is enzyme. The inhibition kinetics together with the rate constants for oxalate binding to free enzyme (Thusius, D., Blazy, B., and Baudras, A. (1976), Biochemistry, preceding paper in this issue) and recent steady-state experiments on L-lactate deuterated at C-2 (Lederer, F. (1974), Eur. J. Biochem, 46, 393) lead to estimates of some of the elementary rate parameters in the above scheme. As in the case of oxalate (see Thusius et al. reference above), the association rate constant for substrate binding (1.1 x 10(5) M-1 sec-1) is much smaller than a diffusion-controlled value. Our results also imply that dissociation of complex EP to free enzyme and pyruvate is partially rate limiting for the overall reaction.


Soluble tri- and dipeptidases in Escherichia coli K-12+.

As part of a study of the metabolic role of peptidases in Escherichia coli K-12, cell extracts were examined for the presence of three enzymes originally identified [Sussman, A. J., and Gilvarg, C. (1970), J. Biol. Chem. 245, 6518] in extracts of the lysine auxotroph ASO13 by virtue of their activity toward lysine homopolymers. It has now been shown that the activity ascribed to a Co2+-dependent dilysine-specific enzyme is a function of the strain K-12 dipeptidase DP, a metal-dependent enzyme active toward a variety of dipeptides, and that the activity ascribed to a trilysine-specific enzyme is a function of the strain K-12 tripeptidase TP, an aminopeptidase capable of hydrolyzing substrates in the series X-Gly-Gly, X-Gly-X, and X-Leu-Gly (where X is Leu or Met) but devoid of activity toward dipeptides. The third enzyme, an oligopeptidase not previously observed in strain K-12, was found to include among its substrates not only di- and trilysine but other di- and tripeptides that are hydrolyzed by the di-and tripeptidase as well as by aminopeptidases L and AP; the aminopeptidases, however, lack activity toward di- and trilysine. The absence of oligopeptidase activity from extracts of strain AJOO5, a "PEPTIDE-DEFICIENT MUTANT" derived from strain ASO13 by Sussman and Gilvarg, has been confirmed, and strain AJOO5 has been shown to contain all the other peptidases known to be present in strain K-12. Possible functions of the oligopeptidase are proposed on the basis of its observed activity in vitro and of the basis of its observed activity in vitro and of the differences between the growth responses of strains AJOO5 and ASO13 in various media. Some general aspects of peptide metabolism are discussed with emphasis on the use of peptidase-deficient mutants in the study of this problem, and methods that may prove helpful in the isolation of such mutants are suggested.


The control of pyruvate kinase of Escherichia coli. Binding of substrate and allosteric effectors to the enzyme activated by fructose 1,6-bisphosphate.

The binding of various regulatory ligands and substrates to the fructose bisphosphate activated pyruvate kinase from Escherichia coli has been studied at equilibrium. The allosteric activator, fructose bisphosphate, and the substrate phosphoenolypyruvate bind in a cooperative manner to the enzyme. There is one site for each of these ligands per monomer. In the presence of fructose bisphosphate the binding of phosphoenolpyruvate follows an absorption isotherm, i.e., all homotropic interactions of the substrate are lost. In reciprocal experiments, however, both phosphoenolpyruvate and KCl are required in order to facilitate binding of the activator. The allosteric inhibitors of pyruvate kinase, ATP, succinyl-CoA, and GTP compete on the enzyme surface with the binding of the activator, fructose bisphosphate, Inhibitor pairs such as ATP and succinyl-CoA together bring about not cooperative but only additive inhibition of the binding of the activator. The nucleotide substrate GDP and the allosteric inhibitor GTP have in contrast to the activator two seemingly noninteracting sites on each monomer. In the saturating presence of fructose bisphosphate, however, binding of GDP and possibly also of GTP occurs at only one site on each monomer. Magnesium ions inhibit binding of GDP and GTP. KCl which is an activator of the enzyme along with its analogues, such as ammonia, thallium, rubidium, etc., enhances the binding of phosphoenolpyruvate but not of the nucleotides or fructose bisphosphate. The data are analyzed on the basis of a two-site model, where the substrate and fructose bisphosphate bind to one conformation and the inhibitors to the other.


Fluorescence energy transfer measurements between ligand binding sites of the pyruvate dehydrogenase multienzyme complex.

The interaction of the pyruvate dehydrogenase multienzyme complex from Escherichia coli with 8-anilino-1-naphthalenesulfonate (ANS), pyruvate, and acetyl-CoA has been investigated using equilibrium binding, steady-state fluorescence, and fluorescence lifetime measurements. The fluorescnece of ANS is greatly enhanced when bound to the enzyme complex and to the pyruvate dehydrogenase component of the complex. Approximately 22 molecules of ANS are bound to a molecule of the complex with a binding constant of 3.69 muM in 0.03 M potassium potassium phosphate (pH 7.0). Direct and competitive binding measurements indicate that about 42 pyruvate binding sites are present per mole of enzyme complex which has been stripped of thiamine diphosphate; the number of binding sites is reduced to 28,5 in the presence of a saturating concentration of thiochrome diphosphate, a thiamine diphosphate analogue. The dissociation constant for pyruvate to the enzyme complex in the presence of thiochrome diphosphate is 308 muM in 0.02 M potassium phosphate (pH 7.0). Pyruvate, thiochrome diphosphate, and acetyl-CoA all displace ANS from the enzyme complex. In the cases of pyruvate and thiochrome diphosphate, the concentration dependence of the displacements suggests the displacement is allosteric, while in the case of acetyl-CoA direct competition appears to be involved. GTP decreased the effect of acetyl-CoA to the enzyme complex indicate that 24-26 bound acetyl-CoA molecules per complex can be readily displaced by ANS, and the binding of acetyl-CoA to these sites displays positive cooperativity. Fluorescence energy transfer measurements between bound ANS on the pyruvate dehydrogenase enzyme and FAD on the dihydrolipoyl dehydrogenase enzyme indicate, assuming the emission and absorption dipoles are randomly oriented, that these two probes must be at least 58 A apart in the intact complex.


Randomization of membrane lipids in relation to transport system assembly in Escherichia coli.

The distribution of newly synthesized lipid molecules in the pre-existing lipid phase of the membrane was studied in whole cells of the fatty acid requiring Escheria coli strain K1062. The fluorescence probe N-phenyl-1-naphthylamine revealed reversible lipid phase transitions in cells supplemented with cis-delta9-octadecenoate (transition temperature Tt = 14 degrees C; width of the transition deltaT = 13 degrees C) or trans-delta9-hexadecenoate (Tt = 27 degrees C; deltaT = 7 degrees C). Cells were first grown in the presence of cis-delta9-octadecenoate at 37 degrees C and subsequently for various periods in the presence of trans-delta9-hexadecenoate at 37 or 22 degrees C, i.e. above or below the transition of the newly formed lipids. Reproducible phase transitions with single, well-defined Tt values between 14 and 27 degrees C were observed under both conditions. Beta-Galactoside transport induced in a similar experiment before or during a change in the fatty acid composition showed a single change in activation energy at a temperature close to the lipid transition temperature, Tt. Starvation of cis-delta9-octadecenoate-supplemented cells for this fatty acid led to a gradual rise in the transition temperature, due to an increase in the percentage of saturated acyl chains in the membrane lipids. It is concluded that under all conditions investigated a mixed lipid phase composed of newly synthesized and pre-existing lipid molecules is formed in the membrane. Since conserved domains of newly synthesized lipids surrounding simultaneously formed transport proteins could not be demonstrated, the results do not support a membrane assembly mechanism proposed by N. Tsukagoshi and C. F. Fox [(1973), Biochemistry 12, 2822-2829]. It rather appears that newly formed lipid molecules are continuously released from their sites of synthesis into the lipid matrix by a rapid diffusion-controlled process.


Renaturation of a multisubunit multiactivity enzyme complex: recovery of phage Qbeta RNA replicase, EF-Tu, and EF-Ts activities after denaturation in urea.

Phage Qbeta RNA replicase consists of four nonidentical subunits three of which are required for poly(C)-directed synthesis of poly(G): a phage-coded polypeptide and the two host-supplied protein biosynthesis elongation factors EF-Tu and EF-Ts. After denaturation of the enzyme in 8 M urea, poly(G) polymerase activity can be renaturated by dilution of the denatured subunits into a high ionic strength buffer with glycerol. The renaturation reaction has a broad temperature optimum between 11 and 21 degrees. The extent of renaturation is dependent on enzyme concentration: at low enzyme concentrations and 21 degrees renaturation proceeds for more than 3 h with greater than 40% recovery  of activity, whereas at high enzyme concentrations the reaction is complete by 1 h with less than 10% of the poly(G) polymerase activity regained. Activities catalyzed by the elongation factors can be measured while they are part of the replicase complex. Study of rates of renaturation of EF-Tu and EF-Ts dependent activities alone and in the replicase complex revealed that virtually 100% of the EF-Ts activity was recovered more rapidly than could be assayed at temperatures as low as 2 degrees, while the rate of recovery of EF-Tu activity was comparable to that of the poly(G) polymerase activity and was independent of either EF-Tu concentration or the presence of other enzyme subunits. The rate of recovery of the poly(G) polymerase activity was found to be limited by the renaturation of EF-Tu, since the rate was dramatically increased by the addition of undenatured EF-Tu.


The role of 16S rRNA in ribosomal binding of IF-3.

The binding of initiation factor IF-3 to Escherichia coli 30S ribosomal subunits has been found to be inhibited by rRNA ligands such as ethidium bromide, polyamines, and monovalent alkali metals. The order of effectiveness of the polyamines (spermine greater than spermidine greater than putrescine) and alkali metals (Li+ greater than Na+ greater than K+) in inhibiting the ribosomal binding of IF-3 parallels their degree of affinity for the RNA. Furthermore, the binding of IF-3 to 30S subunits chemically modified by photooxidation with rose bengal, nitration with tetranitromethane, and reaction with kethoxal, monoperphthalic acid, and p-chloromercuribenzoic acid was studied. Results obtained after the direct treatment of the 30S subunits with the above chemical reagents or upon reconstitution of 30S particles having a modified rRNA or ribosomal proteins indicate that the IF-3 binding site is preferentially lost when the rRNA becomes modified. It was found that IF-3 could bind normally to 30S subunits lacking protein S1 or proteins S11, S12, S19, and S21 (and perhaps S14) which had been cross-linked to IF-3 in other laboratories.


Mechanism of aminoacylation of tRNA. Proof of the aminoacyl adenylate pathway for the isoleucyl- and tyrosyl-tRNA synthetases from Escherichia coli K12.

The following observations show that the formation of isoleucyl-tRNA catalyzed by the isoleucyl-tRNA synthetase from Escherichia coli K12 involves the initial rapid formation of an isoleucyl adenylate complex followed by the slow, rate-determining, transfer of the isoleucyl moiety to tRNA. (1) The rate constant for the transfer of [14C]Ile from the E-[14C]Ile approximately AMP complex to tRNA is the same as the turnover number for the steady-state isoleucylation of tRNA at pH 7.78 (1.5 s-1) and pH 5.87 (0.34 s-1). (2) On mixing a solution of isoleucyl-tRNA synthetase and tRNA with [14C]Ile and ATP the steady-state rate of isoleucylation is attained in the first turnover of the enzyme, with little or no "burst" or charging that would indicate a slow step after the transfer step. (3) The pyrophosphate exchange reaction in the presence of tRNA is 40 times faster than the overall rate of isoleucylation of tRNA. (4) Similarly, rapid quenching experiments indicate that isoleucyl adenylate is formed prior to the transfer step. The possibility that isoleucyl adenylate formation is a parallel reaction caused by a second active site on the enzyme is ruled out both by the stoichiometry in this rapid quenching experiment and also the overall stoichiometry of isoleucyl-tRNA formation. At saturating reagent concentrations the major species in solution is the E-tRNA-Ile approximately AMP complex. Similar observations are found for the tyrosyl-tRNA systhetase except that at saturating reagent concentrations the rate constants for both tyrosyl adenylate formation and transfer are similar so that both processes contribute to the rate-determining step.


The binding of near-ultraviolet light-induced tryptophan photoproduct(s) to DNA.

To test one possible mode of toxicity of L-tryptophan photoproduct(s) to bacterial cells, we have examined the binding of near-ultraviolet light-treated tryptophan to purified Escherichia coli DNA in vitro. The results show that co-irradiated (or pre-irradiated) [3H]tryptophan binds to purified DNA as assayed by trichloroacetic acid co-precipitation of DNA and 3H counts on cellulose filters. This was supported by co-sedimentation of DNA and 3H photoproduct(s) on CsCl gradients. Hot trichloroacetic acid extraction or enzymatic digestion of DNA prevents filter binding. The binding is most efficient when tryptophan and DNA are co-irradiated. Under these conditions, binding is more efficient with denatured rather than native DNA. From kinetic studies, the binding is DNA-dependent at constant doses of near-ultraviolet light. At a dose of 2.16 - 10(6) ergs - mm-2 we estimate that 100-150 L-[3H]tryptophan equivalents are bound per E. coli genome equivalent. The binding does not occur with another aromatic amino acid such as tyrosine.


The polypeptide chain growth rate in amino acid-starved Escherichia coli determined by a novel method.

The proteins synthesized by arginine-requiring Escherichia coli during growth or arginine starvation were characterized by polyacrylamide gel electrophoresis in sodium dodecyl sulfate to give size distributions. The proteins made during amino acid starvation were smaller than those made by growing cells. This was true for otherwise isogenic rel- ("relaxed") and rel+ ("stringent") bacteria. Also using electrophoretic profiles, the peptide chain growth rate was estimated by a novel method based on comparison of theoretically predicted and observed kinetics of pulse labeling protein chains of different sizes. During arginine starvation, the rate was 2--5 amino acids/s for both rel- and rel+ cells, compared to 20 amino acids/s for growing cells. The results rule out chain growth-rate differences as an aspect of the "relaxed" phenomenon.


Informational complexity of the nuclear and chloroplast genomes of Chlamydomonas reinhardi.

DNA - DNA reassociation kinetics analyzed by hydroxylapatite chromatography have been used to determine the informational content of the Chlamydomonas reinhardi nuclear and chloroplast genomes. The kinetics indicate that nuclear DNA, with the exception of ribosomal cistrons, renatures as a single component with an informational complexity 25 times that of the Escherichia coli genome. The chloroplast genome has less than 0.3% of the informational complexity of the nuclear genome, but is present in about 50 copies in the vegetative cell. Chloroplast DNA shows about a 10-12% zero-time binding component.


Phosphorylation of ribosomal proteins from eukaryotes in homologous and heterogous cell-free systems.

The phosphorylation of ribosomal proteins from eukaryotes in homologous and heterologous cell-free systems has been studied. The ribosomes and protein kinases from yeast (Saccharomyces cerevisiae, strain Bu), wheat (Triticum vulgare) and rabbit (Orystolagus cuniculus) have been used. It has been found that five ribosomal proteins incorporate gamma-32P from ATP during the incubation of wheat ribosomes with wheat protein kinase. When the phosphorylation of isolated wheat ribosomal proteins was examined more phosphoproteins were detected. These data confirm the suggestion that the ribosomal structure affects the phosphorylation. Probably some ribosomal proteins remain hidden for the action of protein kinase. The results from the crossed experiments show that there is no barrier for phosphorylation of yeast ribosomes with liver protein kinase, of wheat ribosomes with yeast and liver protein kinases and of liver ribosomes with yeast and plant protein kinases. The wheat protein kinase does not phosphorylate the yeast ribosomes under these experimental conditions. Some differences in the set of phosphoproteins obtained with various protein kinases have been detected. These data suggest that the ribosomal protein phosphorylation is not highly species specific although it is not universal.


Inactivation by detergents of the proline transport system in membrane vesicles from Escherichia coli and its reactivation by bovine serum albumin.

The proline transport system of membrane vesicles from Escherichia coli was inactivated by a low concentration of detergents such as deoxycholate, dodecyl sulfate and Triton X-100. The addition of a large amount of bovine serum albumin to membrane vesicles which had been treated with one of these detergents resulted in the restoration of the proline transport activity. The restoration of the transport activity by bovine serum albumain was most remarkable with the deoxycholate-inactivated membrane vesicle. 80% inactivation of the transport system with 0.005% deoxycholate was completely overcome by the addition of albumin. The degree of restoration was dependent on the concentration of albumin. Although albumin stimulated the proline transport activity itself, the stimulatory effect could not account for the restoration of transport activity. The binding of deoxy [14C]cholate to the membrane vesicle was roughly proportional to the amount of detergent added. Deoxycholate once bound to the membrane vesicle was removed almost completely by the incubation with albumin. It is concluded that the removal of detergent from the membrane vesicle by bovine serum albumin results in the restoration of the proline transport activity.


Inhibition of dihydrofolate synthetase by folate, homofolate, pteroate and homopteroate and their reduced forms.

Dihydrofolate (H2-folate) synthetase (EC 6.3.2.12) was isolated from Escherichia coli B. A radiochemical assay was developed to determine the activity of H2-folate synthetase in order to study the effects of folate metabolites and antimetabolites which would interfere with the microbiological assay method previously used. The effects of folate and pteroate derivatives on the activity of this enzyme were investigated to determine if inhibition of this enzyme could constitute a site of action for these compounds as chemotherapeutic agents or a site of metabolic regulation. H2-folate synthetase was inhibited by its product, H2-folate, and by the antimetabolite dihydrohomopteroate, with apparent Ki values of 23.4 and 9.2 muM, respectively.


Dimethylaminostyrylmethylpyridiniumiodine (daspmi) as a fluorescent probe for mitochondria in situ.

An investigation has been made on the properties of dimethylaminostyrylmethylpyridiniumiodine (DASPMI), its reaction with isolated pigeon heart mitochondria and its suitability as a vital strain for mitochondria in situ. DASPMI is a low toxicity specific vital stain for mitochondria in living cells. In vitro dye concentrations over 6 nmol/mg protein inhibit fast (state 3) respiration after a preincubation time of more than 5 min in the presence of substrate. No uncoupling was observed. Energization of pigeon heart mitochondria by addition of ATP or various substrated yields an average 8.5-fold increase in fluorescence intensity in relation to DASPMI-stained mitochondria that are under anoxia, substrate deficiency, or under the influence of respiratory inhibitors, or uncouplers. The alterations in fluorescence intensity are not primarily due to ion movements or pH changes. The amount of dye (2.96+/-0.8 nmol) yielding maximal fluorescence response with 1 mg mitochondrial protein remains constant during energization of mitochondria. As indicated by electron microscopic studies the observed changes in emission intensity may be related to changes in the fine structural organisation of cristae. A remarkable difference exists between isolated mitochondria and mitochondria in situ with respect to the reaction to cyanide. According to the reported results DASPMI will be a useful probe for the investigation of mitochondrial activities in living cells.


The 5' ends of bacterial RNA. II. The triphosphate-terminated ends of primary gene transcripts.

Bacterial RNA, Pulse labeled with 32Pi, was digested with pancreatic RNAase. Oligonucleotides containing a triphosphate group at the 5'-hydroxyl, and therefore derived from the original beginning ends of the RNA transcripts, were purified by hydroxyapatite chromatography and analyzed by two-dimensional paper electrophoresis. A broad diversity of species was found, although the distribution among these species was not completely uniform. Possible methods of utilizing these methods in combination with in vitro synthetic techniques are discussed.


Calcium ionophores A23187 and X537A affect cell agglutination by lectins and capping of lymphocyte surface immunoglobulins.

The microtubule-disruptive drugs colchicine and vinblastine alter ligand-induced redistribution of cell surface immunoglobulins and lectin receptors. These effects can be duplicated by treatment of cells with the divalent cation ionophores A23187 and X537A. Ionophore activity was dependent upon the presence of Ca2+ (1.8 - 10(-3)-4 - 10(-4) M) in the culture medium. The K+-selective ionophore valinomycin had no effect on ligand-induced redistribution of surface receptors. It is suggested that A23187 and X537A impair membrane-associated microtubules involved in transmembrane control of receptor mobility and topography. In contrast to the action of colchicine and vinblastine that bind directly to microtubules, it is proposed that ionophores indirectly affect microtubules by raising the concentration of Ca2+ in the cytoplasm to levels that favor microtubule depolymerization and inhibit microtubule assembly.


Ionophores X537A and A23187. Effects on the permeability of lipid bimolecular membranes to dopamine and calcium.

X537A carries dopamine across lipid bimolecular membranes. The rate of transport increases linearly with the X537A concentration and is independent of an electric field across the membrane. The evidence suggests that the permeating species is a neutral 1:1 complex between dopamine and X537A. A23187 does not transport dopamine. The permeability of the membrane to calcium increases as the square of the X537A concentration; the transport of calcium is also increased by A23187. With both ionophores, calcium is probably transported as an uncharged complex. Neither desmethylimipramine nor cocaine alters the transport of dopamine with X537A.


Microtelemetry--the use of integrated circuits in biotelemetry.

Integrated circuits are now in widespread use in such equipment as computers and consumer electronics, where their low cost, high reliability and small size are their principal advantages. In biotelemetry, small size is of particular importance. Here the use of integrated circuits allows systems of considerable complexity to be produced with high reliability in small packages. Commercial integrated circuits with the low power consumption and low voltage operation needed for biotelemetry are now becoming available; some such applications are briefly reviewed. In addition, examples of the use of custom integrated circuits in biotelemetry, and of the use of integrated circuit technology to build unique transducers and assemblies, are described.


Biorhythms in toxicology and pharmacology. II. infradian biorhythms and general discussion.

In man circaseptidian (weekly) rhythm has been established in certain employements where a delayed pulmonary allergic reaction is observed. Circatrigintan (monthly) rhythms related to the biological effects of the rotation of the moon around the earth or of the rotation of the sun around its axis have not been definitely pointed out in man. The demonstration of a circannual (seasonal) biorhythmicity of responses to drugs and toxins requires long runs of observations (5-7 years). However circannual, as well as infrannual rhythms, should not be dismissed as they are consequences of biometeorological factors the actions of which at least for temperature on toxic reactions are admitted. Besides the influences of endogenous factors such as sex and aging perturbate the endocrinological modulations of these biorhythms and complicate the scope of such a research. The cyclic action mechanism of therapeutic and toxic agents appears to be a direct impact on intrinsic enzymatic rhythms of different periods entrained by the physical, chemical and principally psychophysiological factors of man's environment.


The effect of prednisone on the non-stimulated and the stimulated NBT test.

The non-stimulated and stimulated nitroblue tetrazolium (NBT) dye test was studied in five normal adults in sequence, viz. before and at intervals after prednisone was given as one large dose. A negative effect of prednisone on the NBT response was seen. This applied to both the non-stimulated and stimulated NBT test. For the latter five different toxins were used. At the same time a pronounced neutrophil granulocytosis was seen. The depression of the NBT test is present both in the percentage of NBT-stained neutrophils and when expressed in absolute counts of NBT-strained neutrophils.


Ultrastructure of the contractile system of striated skeletal muscle and the processes of muscular contraction. I. Ultrastructure of the myofibril and source of energy.

1) The contractile system consists of thick and thin filaments arranged side by side in a double network of hexagonal cross-section. 2) The thick filaments are principally made up of myosin and the thin ones of actin, tropomyosin and troponin. 3) Myosin is an enzyme catalysing the hydrolysis of ATP; actin increases the specific activity of this enzyme, converting it from a Ca+2 sensitive ATPase to a Mg+2 sensitive ATPase. 4) Hydrolysis of the last phosphoryl group of adenosine triphosphate (ATP) salts is the energy source for muscle contraction. 5) The adenosine diphosphate (ADP) salts, formed by ATP splitting, are rephosphorylated and reinjected into the myofibril.


[Idnetification of DNA methylases in Escherichia coli CK cells].

E. coli CK cell are found to contain metylase which catalyses the incorporation of CH33-groups into tissue and phage DNAs in vitro in the presence of S-adenosyl-L-methionine, the donor of methyl groups. The enzyme was precipitated by (NH4)2SO4 of 30-60% saturation, which increased its specific activity in 1.9 times. Metylase was active both in phosphate and Tris. HCl buffers, pH 6.5-7.5 and did not require Mg2+, EDTA and dithiotreithol. The enzyme recognises certain nucleotide sequences in all the DNAs studied and has more wide specificity as compared with the enzyme from E. coli B. Methylase from E. coli CK developed the highest activity with thymus DNA. Methylase from rat liver nuclei turned to be inactive with bacteriophage DNA.


[Purification, heterogeneity and some properties of T2 bacteriophage lysozyme].

Free T2 bacteriophage lysozyme is isolated and purified from 80 l portion of phagolysate by means of ballast protein and bacterial debris precipitation with rivanol, two-stage fractionation on amberlit IRC-50 and chromatography on CM-Sephadex C-50. Purified enzyme is homogenous under polyacrylamide gel electrophoresis in the presence of sodium dodecylsulphate, it has a molecular weight value similar to that in the literature. A presence of two active enzyme forms (I and II) is demonstrated. They can be separated by means of analytical electrophoresis in polyacrylamide gel at pH 4,5 and of ion-exchange chromatography on Amberlite IRC-50. T2 lysozymes I and II do not differ in their amino acid composition, ORD parameters, and they are not interconversible. Heterogeneity of phage lysozyme is shown not to be an artefact and to be due neither to heterogeneity of the initial phage poluation, nor to aggregation and to oxidation of enzyme SH-groups. The content of alpha-helix regions, as estimated by ORD is higher in phage lysozyme than in hen egg-white lysozyme, which evidences that these proteins are non-homologous.


Physiological significance of the lymphocytic cell coat.

The lymphocytes are coated by an external glycoprotein layer the so-called cell coat. There is some difference between the structure of the cell coat of T- and B-derived lymphocytes. The cell coat represents the chemical basis of some lymphocytic properties, i.e. their homing and electrophoretic mobility and it plays and important role in the expression of antigenicity of lymphocytes and the triggering of blast transformation.


A rosette technique for identification of human mononuclear cells bearing Fc receptors.

A rosette technique has been described which showed some human mononuclear cells to bind chicken red blood cells coated with rabbit anti-chicken erythrocyte antibodies (EA). Intact 7S Ig, but not their F(ab')2 fragments, were found to sensitize chicken erythrocytes; therefore it was concluded that this rosette technique detects cells bearing receptors for the Fc portion of IgG. Among the different parameters of the reaction which were studied, centrigugation at 4 degrees C appeared necessary for obtaining the maximum number of rosettes. Kinetics of rosette dissociation indicated low and heterogeneous binding avidities. Distribution of EA-rosette forming cells among different organs appeared extremely heterogeneous: 8-28% were found in blood, spleen and bone marrow, whereas about 3% were found in lymph nodes and less than 1% in tonsils and thymus; this suggests that EA-rosette forming cells are not restricted to a single subclass of either T or B lymphocytes.


[Correlation of protein synthesis and degradation of messenger RNA in E. coli].

More than 80% of rapidly labelled RNA is found to be bound with cytoplasmic membranes of E. coli and only 17% was discovered in cytoplasmic fraction. 96% of DNA was found in the cytoplasmic membrane fraction. The treatment of E. coli homogenate with sodium deoxycholate resulted in the release of rapidly labelled RNA from membranes. The analysis of membrane-bound rapidly labelled RNA in sucrose density gradient (10-40%) revealed that it sedimented in the polyribosome region. Incubation of E. coli cells with actinomycin D for 10 min at 37 degrees C resulted in the decrease of membrane-bound radioactivity in the polysome region (31% as compared with 55% in the control culture which was incubated for 20 sec with 14C-orotate). The inhibition of protein synthesis with chloramphenicol or puromycin interrupted the decomposition of polysomes in the presence of actinomycin D. The radioactivity of polysomes in these experiments was 50% and 47% respectively and was comparable with the control. Under dialysis of rapidly labelled RNA fraction against buffer with minimal concentration of Mg2+ (0,1 mM) the elimination of the label from the polysome region was observed. The prolongation of the incubation of cells with actinomycin D resulted in the decrease of protein synthetising ability of the membrane fraction. The increase of the inhibition level of protein synthesis by chloramphenicol was shown to result in the increase of the amount of membrane-bound rapidly labelled RNA, which remained stable in the presence of actinomycin D. A number of arguments of the hypothesis on the role of protein in the initiation mechanism of the decomposition of mRNA in bacteria is discussed.


Granulomatous hepatitis caused by B.C.G. injection during immunotherapy of a malignant melanoma.

The authors report a case of granulomatous hepatitis after treatment by B.C.G. in a patient with malignant melanoma. The patient was treated for one year by an association of chemotherapy and lyophilized B.C.G. (Pasteur Institute). Aside from the rarity of the localization the importance of this observation resides in the discovery of B.C.G. after auramine staining in the liver suggesting that the hepatic lesions were linked to the in situ presence of mycobacteria.


Abnormal neuronal differentiation (functional maturation) in mental retardation.

A review is presented of a variety of human pathologic conditions, including some forms of mental retardation, and of experimental situations involving the nervous system proved (with the Golgi method) to be associated with detectable morphologic abnormalities. The postsynaptic elements (the dendritic spines) have been found to be especially sensitive and frequently they are found to be structurally abnormal. Structural abnormalities involving one of the synaptic components could result in synaptic dysfunction which could explain some degree of mental or motor retardation or incoordination. It is hoped that this review will stimulate and encourage the use of the Golgi method in the study of abnormal conditions (clinical or experimental) affecting the nervous system.


Median facial malformations and their implications for brain malformations.

For purposes of identifying craniofacial syndromes which predict brain malformations the face can be regarded as developing from 2 sources. The median and paramedian structures derive from the embryonic segment of the face, termed the frontonasal prominence. The lateral structures of the face derive from the branchial arches. Certain patterns of median plane facial anomalies predict a severe brain malformation, while other patterns, although producing equally grotesque facial malformations, bear little association with a malformed brain. Orbital hypotelorism may occur in a variety of syndromes with microcephaly. When combined in typical patterns with other median plane facial defects, the patient almost certainly has holoprosencephaly, and has a poor prognosis for useful psychomotor development and survival. To the current knowledge of the author, every patient with orbital hypotelorism and total aplasia of the intermaxillary segment has a severely malformed brain. These patients, with only a rare exception, make no useful psychomotor progress and die in infancy. Orbital hypertelorism implies an increased risk of a neurologically abnormal patient, but neither the mental deficiency nor the prognosis for survival are as poor as in hypotelorism. When hypertelorism is combined with certain median plane facial anomalies the patient has the median cleft face syndrome and most likely has normal mentality, or only mild retardation, and has a normal prognosis for survival.


[The reaction of pepsin and pepsinogen with dicyclohexylcarbodiimide].

The reaction of pig pepsin and pepsinogen with 3H-dicyclohexylcarbodiimide (DCC-T) is studied. It is found that about three residues of DCC-H incorporate into pepsin molecule and about four residues--into pepsinogen molecule under the excess of carbodiimide. The incorporation of DCC-T into protein results in a deep enzyme and zymogen inactivation: pepsine retains 20% of the proteolytic activity with respect to hemoglobin, and pepsinogen completely loses its potential proteolytic activity. It is found that a part of DCC-T residues attaches to N-terminal part of pepsinogen, which splits off under the activation of proenzyme in acid medium. It is demonstrated that the interaction of DCC-T with carboxyl groups of dicarbonic amino acids results in the change of isoelectric point of pepsin and pepsinogen.


Cartilage in the face.

Cartilaginous influence in the face begins with the formation of the early chondrocranium and continues into the postnatal life with the persisting derivatives of the chondrocranium, the cranial base synchondroses and the nasal septum, and with the secondary cartilage of the mandibular condyle. A review of available data indicates that the cartilages should be considered as integral parts of a holistic system, and that their role within this system most likely diminishes with age.


A critical analysis of the growth in length of the cranial base.

The basicranium chondrifies and ossifies in a posteroanterior, but ceases growth in an anteroposterior sequence. The synchondroses respond to "built-in" and local influences, show symmetric or asymmetric bipolar growth and cease growth long before synostosis. Individual variations in amount of bone formation occur in them within an overall species pattern. The ethmoid stops elongating early in man and rhesus monkey, but grows until maturity, although least of all the basicranial bones, in other animals. The hypophyseal fossa drifts significantly caudally.


[Morphometry of the juxtaglomerular apparatus of allo-transplanted human kidneys].

Juxtaglomerular appartus of 17 allotransplanted human kidneys was studied by the karyometric method at various periods of existence in the recipient's organism. Kidneys of persons who died of craniocerebral trauma or acute cardiac incompetence served as control. At the early periods (up to 2 months) there was revealed an authentic increase in the nuclear volume of the epitheloid-modified cells of the afferent arteriole and of the Goormaghtigh cells. There was also a tendency to increase in the volume of the macula densa cells. At the late periods the juxtamolecular apparatus persisted in the allotransplanted kidneys with a but little injured parenchyma. Reduction of the juxtaglomerular appartus occurred in case of marked sclerosis and atrophy of the transplant parenchyma.


The priority of malaria eradication programs.

The planning of health activities begins with the setting of priorities--that is to say, the selection and arrangement of the problems to be attacked in an order consistent with their gravity and the possibilities that exist for the adoption of effective measures for their soultion. The assignment of priorities not only implies financial, administrative, and manpower support, but also involves the continuing renewal of health workers' interest in fulfilling the tasks that have been entrusted to them. According to the extent and severity of the problem, priorities may have to be envisaged on a world, continental, regional, or local scale. Ever since the beginning of the present century the Governments of the Americas have accorded high priority to malaria control and, since 1954, to its eradication. In recent years malaria programs in the Americas have been classified into three groups according to their epidemiologic status and prospects for the future. As of 1974, Group I included the 12 political units (countries or territories) in which malaria had been eradicated. These units should give suitable priority to activities for ensuring that they remain free of the disease. Group II was composed of eight units whose prospects of achieving eradication within a short period were good. Here the highest priority should go to efforts designed to eliminate residual foci and to complete the last steps toward ultimate eradication. Group III contained 14 units, the majority of which had part of their territories in the consolidation or maintenance phase. In some of these Group III units malaria eradication could be achieved within a short period if additional funds are found; in others the situation is quite different and eradication cannot be expected in a foreseeable time. The latter units should therefore give high priority to activities that will conserve the gains already made (in those areas which are in the consolidation and maintenance phases) and that will gradually reduce the incidence of malaria in areas that are still in the attack phase. In general, when a malaria program is given high priority by the Government concerned, adequate funds for the campaign can be obtained more redily, either through the regular budget or from international and bilateral agencies.


Biological considerations in the treatment of breast cancer: the "fall out" from clinical trials.

The evolution of the treatment for early breast cancer has now reached a critical period. At long last the conflicting claims of the anatomical and biological approaches towards treatment of this disease are being resolved by the application of prospective randomised clinical trials. The recognition that host factors exist which may place a constraint on the spread of cancer, and that haematogenous dissemination may occur long before the tumour has reached clinical proportions, has shaken the whole basis upon which "radical" cancer therapy is based. Furthermore, experimental work has suggested that lymphadenectomy or regional radiotherapy may produce sufficient disturbance to the immune competence of the host to allow the outgrowth of occult distant tumour foci. Prospective randomised clinical trials designed to determine the most effective local treatment have incidentally produced biological "fall out" which has thrown additional light on the behaviour and nature of breast cancer. It transpires that untreated mediastinal or axillary lymph nodes appear to have little growth potential of their own, or is it likely that they act as a reservoir for further metastatic dissemination. It is at last becoming accepted that irrespective of the extent of local therapy, the outcome for "early" breast cancer is predetermined by the extent of subclinical distant metastases at the time of presentation. In order to improve the results therefore, some form of adjuvant systemic therapy is essential. A number of clinical trials are at present underway designed to explore the most effective means of controlling minimal residual cancer following local ablation of the tumour.


Transmission of hepatitis type B from healthy HBsAg-positive mothers.

Seventeen mothers, all apparently healthy carriers of hepatitis-B surface antigen (HBsAg) during pregnancy, and their children were studied for four to five years to determine the transmission rate of hepatitis-B virus infection. All the mothers had antibody against hepatitis-B core antigen in addition to HBsAg. One of them, a renal transplant recipient, was persistently positive for hepatitis-B-associated e antigen (HBeAg), while the remaining 16, who were detected during screening of healthy pregnant women were positive for anti-HBe. Evidence of infection was found in the child and husband of the woman positive for HBeAg, while none of the 29 children and five husbands of the anti-HBe-positive women became infected.


Role of doxapram in reducing pulmonary complications after major surgery.

In a double-blind study patients given a single dose of doxapram 1-5-2-0 mg/kg combined with morphine postoperatively had a significantly lower incidence of reflex postoperative cough and expectoration of purulent sputum than patients given morphine alone. They also had significantly higher arterial oxygen tensions five days postoperatively. Smaller differences were found with naloxone combined with morphine.


Three-day and ten-day chemotherapy for urinary tract infections in general practice.

The length of a course of antibiotic treatment for urinary tract infection varies with the habits of the prescriber. Many patients do not complete a course of treatment once their symptoms have subsided. In uncomplicated urinary tract infection among women seen in general practice a three-day course of amoxycillin was as effective as a 10-day course of the same drug in the same dose. Relief of symptoms was equal in both groups and bacteriuria was eliminated equally successfully in both regimens.  There was no significant difference between the two groups in the incidence of side effects from the drugs. The financial saving which could accrue from adopting this therapeutic regimen would be significant.


Immunological features in multiple sclerosis.

A clinical and laboratory profile of the immunological system of patients with multiple sclerosis (MS) strongly suggested that many specific immune deficiencies exist in MS. The immunological history showed that patients with MS had had more tonsillectomies, appendicectomies, and childhood infections than matched controls, which suggested that there had been problems in controlling various types of childhood infections. The cell-mediated immune response and the circulating antibody titres were specifically impaired against a variety of antigens. Patients with MS had significantly lower serum antibody titres than controls against many naturally occurring antigens-namely, diptheria and tetanus toxoids, adenovirus, and mumps viruses. Raised serum antibody titres were found against measles and varicella zoster viruses while no difference was found towards other antigens. The delayed hypersensitivity reaction and the immunological memory of patients with MS were also greatly reduced against the mumps skin test antigens. There were normal amounts of circulating T and B lymphocytes, and the phytohaemagglutinin, concanavallin A, pokeweed mitogen, and encephalitogens lymphocyte transformation was not different from that in controls. These results indicated that patients with MS have more infectious problems than normal people and that both their T and B cell systems cannot mount a fully normal immunological response to some viral and bacterial antigens, while they give an increased response to others.


Barbiturate and anticonvulsant treatment in relation to osteomalacia with haemodialysis and renal transplantation.

Among 39 patients treated by regular haemodialysis for four years or more pathological fractures and histological evidence of osteomalacia were significantly more common in those taking barbiturates. Out of 58 transplant recipients surveyed after one year, seven had osteomalacia; four of these had been taking phenobarbitone and phenytoin and one had taken barbiturates alone. Sedatives and other drugs such as phenobarbitone and phenytoin that induce hepatic microsomal enzymes should probably be avoided when possible in patients with chronic renal failure and after transplantation.


Renin concentrations and effects of propranolol and spironolactone in patients with hypertension.

In a crossover study 32 patients with hypertension were randomly allocated to treatment with spironolactone 200 mg/day for two months, propranolol 320 mg/day for two months, and a combination of both drugs at half the dose. Between the treatments placebo was given for two months. Both spironolactone and propranolol lowered the blood pressure significantly in both positions. The initial plasma renin activity (PRA) levels ranged from 0-4 to 5-0 mug angiotensin I l-1 h-1, and there was a close correlation between these levels and the effects of the drugs: with increasing PRA the response to propranolol was better while the opposite was true for spironolactone. Spironolactone reduced the blood pressure more at eight than at four weeks, while no such difference could be shown for propranolol. Spironolactone and propranolol together decreased the blood pressure still further irrespective of the initial PRA. All patients achieved a normal supine blood pressure.


Sterculia bulk-forming agent with smooth-muscle relaxant versus bran in diverticular disease.

Sterculia with and without a smooth-muscle relaxant (alverine citrate) had similar beneficial effects on constipation and reduced the transit times in diverticular disease. Intracolonic pressure, however, varied with the preparation used. Though both preparations relieved the symptoms of diverticular disease, the one containing alverine citrate was more effective. Part of the mode of action of bran may be to relax the smooth muscle of the gut, since its actions were more comparable to those of sterculia plus alverine citrate than to those of sterculia alone.


Metronidazole in prevention and treatment of bacteroides infections after appendicectomy.

The frequency of non-clostridial anaerobic infection was studied in 95 patients who had undergone acute appendicectomy: 49 received prophylactic metronidazole and 46 received placebo. Anaerobic infection did not develop in any of the metronidazole-treated patients, but infections did develop in nine (19%) of the 46 controls. Metronidazole is conveniently administered by suppository to patients who cannot take oral drugs. Five patients with intra-abdominal infections caused by non-clostridial anaerobes were successfully treated with metronidazole.


The treatment of malaria.

At least four doses of quinine followed by a single dose of mefloquine or by a single dose of sulfadoxine-pyrimethamine are two highly effective regimens for chloroquine-resistant falciparum malaria. Mefloquine alone is valuable in ambulant patients. Chloroquine-sensitive falciparum malaria can be treated with a course of chloroquine. Vivax and all other types of malaria should be treated with sequential chloroquine and primaquine. Quinine, by intravenous infusion, is the most effective drug for severe falciparum malaria. The optimum intravenous dose varies between 5 mg/kg and 10 mg/kg administered over four hours. Intravenous or oral quinine should be administered about every 12 hours and the total daily dose of quinine should rarely exceed 20 mg/kg. Intravenous fluid input should be controlled in falciparum malaria to prevent pulmonary oedema. Established renal failure is best treated by dialysis. The value of adrenocortical steroids for falciparum coma has not been established. Fresh blood transfusion may be helpful in small doses for severe anaemia and to replace clotting factors. Anticoagulants, such as heparin, should not be used in falciparum malaria.


Growth of medical laboratory work during 1920-2000.

The volume of work carried out by pathology departments has grown exponentially since they were first opened, and this is likely to continue to the end of the century. Computer diagnosis may modify the process.


Spina bifida and anencephaly: miscarriage as possible cause.

In two retrospective Liverpool surveys the domestic, family, dietary, and medical environments of the mothers of children affected by anencephaly or spina bifida, or both (ASB) were examined. None seemed to be of more than minor importance and the findings of others were therefore examined to see if they suggested a major factor. The most promising lead came from the hypothesis that ASB is usually due to an interaction between twin fetuses or between a fetus and residual trophoblastic material from the previous normal pregnancy, particularly when this is of the opposite sex to the propositus. The sex finding was not confirmed. It was noted that hydatidiform moles, like children with ASB, were usually female and that moles and choriocarcinomas on the one hand and children with ASB on the other occurred in mothers of similar ages, but were to some extent reciprocal in geographical incidence. This suggested that trophoblastic disease might be a factor common to all three and if so then one would expect the frequency of miscarriages to be higher immediately before than immediately after the birth of an ASB child, since mole and choriocarcinoma seldom follow a normal pregnancy. An analysis of published data confirmed that this was almost certainly so. Hence residual pathological trophoblastic material from either a previous miscarriage or a co-twin may interact unfavourably with another fetus to produce ASB and this may be the primary cause of the condition. The hypothesis is consistent with the observed lack of concordance in twins, the high incidence in females, the maternal age effect, and the greater prevalence in social classes IV and V.