Adriamycin-cyclophosphamide and adriamycin-cis-dichloro-diammineplatinum(II) combination chemotherapy in patients with advanced cancer. Patients with a wide variety of previously treated, advanced solid tumors were assigned to receive either adriamycin-cis-dichlorodiammineplatinum(II) (cis-platinum) or adriamycin-cyclophosphamide as combination chemotherapy. Hematologic toxicity was prominent but short-lived in most patients; renal toxicity occurred in 14 of 23 patients receiving cis-platinum and frequently precluded further administration of that agent. Of the patients receiving adriamycin-cis-platinum, 37.5% had useful responses, with four of six patients with bronchogenic carcinomas showing partial regression of disease and two patients with embryonal cell carcinoma of the testes showing complete response. In the patients receiving adriamycin-cyclophosphamide, one complete response occurred in a patient with a malignant lymphoma, and the overall response rate was 18%. The combination of adriamycin-cis-platinum merits further study, especially in bronchogenic carcinoma.


Combination chemotherapy for disseminated malignant melanoma with DTIC, vincristine, and methyl-CCNU. Thirty patients with disseminated melanoma were treated with DTIC (250 mg/m2 for 5 consecutive days every 3 weeks), methyl-CCNU (175 mg/m2 orally every 6 weeks), and vincristine (1.4 mg/m2 weekly x 6 and then every 3 weeks). Seven patients died within 3 weeks of the start of chemotherapy. There was a 30% response rate (seven partial and two complete remissions) for all patients and a 39% response for evaluable patients. The median survival was 45 and 18 weeks respectively for responders versus non-responders and 22 weeks for all evaluable patients.


Possibilities, limitations, and technique for the study of regional myocardial perfusion in man by Xenon-133. The theoretical possibilities and the practical limitations of the Xenon-133 (133Xe) method for the study of regional myocardial perfusion in man are discussed. The techniques for data acqusition and processing developed over the past 5 years are described in detail. Illustrative examples of experimental findings are reported. The practical interpretation of the data, at the light of the influence of injection site, initial tracer distribution, constancy of counting geometry, spatial resolution, and Xenon retention in fat, is presented.


Spacer transfer RNAs in ribosomal RNA transcripts of E. coli: processing of 30S ribosomal RNA in vitro. At least three different transfer RNAs are produced by in vitro processing of 30S ribosomal RNA which accumulates in RNAase III- strains of E. coli. Two of these tRNAs, tRNAGlu2 and tRNAIle1, have previously been shown to be "spacer tRNAs"--that is, genes for their synthesis are located in rRNA transcription units between the cistrons for 16S and 23S rRNAs (Lund et al., 1976). The third tRNA whose sequences are contained in 30S rRNA is tRNAAla1B. In addition to the tRNAs, 5S rRNA and several other 4S fragments are produced. Some of these 4S fragments may represent additional spacer tRNAs. One fragment, about 70 nucleotides long, arises from the 5' end of the 17S precursor of 16S rRNA. Four or five other tRNAs are hydrogen-bonded to 30S rRNA as we prepare it; one or more of these tRNAs may also be a spacer tRNA. The enzymes that process tRNAs out of 30S rRNA are associated with ribosomes, but can be removed from them by washing in 0.2 M NH4Cl; the enzymes required for 5S rRNA processing remain bound to the 0.2 M NH4Cl-washed ribosomes. Treatment of 30S rRNA with purified RNAase III produces 6-8S fragments which contain the sequences of tRNAGlu2, tRNAAla1B and 5S rRNA.


The phagokinetic tracks of 3T3 cells.

The phagokinetic tracks of 3T3 cells. This paper describes a technique of visualizing tracks of cultured cells moving on a glass substrate covered with gold particles. It leads to the following observations: -If the tracks of many cells are examined, cell line characteristic track patterns become apparent. -In several cases, second or third generation descendents of 3T3 cells were observed to repeat track patterns of their ancestor cell. -If a 3T3 cell collides with another 3T3 cell or a nonmigrating BSC-1 cell, it forms an outgoing track from the impact area as if the cell was elastically reflected at the target.


Some aspects of the mechanisms by which industrial solvents produce neurotoxic effects. A Short Review is given of the biochemical neurotoxic mechanisms of common industrial solvents of various structures. The acute effects of organic solvents may be caused by their direct action on the nerve cell membrane and energy metabolism, whereas chronic neurotoxic effects may be explained by the formation of chemically and biologically reactive intermediates. The stability of the toxic metabolites appears to correlate with the development of neuropathy although this is structuredependent. The role of reactive intermediates is also emphasized by the potentiating effect of the induction of the cytochrome P-450 complex.


Effects of pyrrol-carboxylic acid derivatives on the growth of coliphages. Effects of 14 pyrrol-carboxylic acid derivatives and analogues (PY-compounds) on the growth of coliphage MS2 using E. coli E102 (Hfr) as the host were measured by the agar double-layer method. Enlargements of plaque size were observed with 7 PY-compounds but increase in plaque numbers was not induced. These enlargements of plaque size were specific to RNA coliphages MS2, GA and qbeta and not found with DNA coliphages delta AC and T4. Furthermore, the interaction between PY-compound PY-10 and the coliphage MS2 was dependent on the host bacterium (indicator strain). When E102 (Hfr) was used, the enlargement was marked, in the case of substrain W1895 (Hfr) it was less, while in the case of substrain W6 (F+) it was undetectable. The one-step growth of the phage MS2 and the production of intracellular phage MS2 were little affected by the PY-compound PY-10. However, the rate of one-step growth was increased in the early stage after infection. Accordingly, the enlargements of plaque size by the PY-compounds might be correlated with an increase in rate of release of phage particles.


[Immediate surgical treatment of penetrating wounds of the heart. Clinico-diagnostic and therapeutic considerations on 2 cases of suture of the myocardium]. The authors, on the basis of their experience on two cases of cardiac tamponade, and from the revision of literature, retain that immediate thoracotomy, followed by re-examination of the pericardial sac and myocardiorrhaphy, represents a treatment preferable to the evacuant pericardiocentesis, confining the latter only to diagnostic conditions and immediate decompression in cases which arrive in unequipped places.


Laboratory techniques for rapid diagnosis of viral infections: a memorandum. This Memorandum evaluates rapid laboratory techniques for the diagnosis of viral infections, especially with a view to their use in developing countries. These techniques comprise the detection of viral antigens by immunofluorescence and immunoperoxidase techniques and methods of viral antibody and antigen determination by the enzyme immunoassay technique. A number of general and specific recommendations are made.


Malaria along the southernmost fringe of its distribution in Africa: epidemiology and control. After more than thirty years of malaria control in northern Transvaal with residual insecticides, malaria prevalence has been reduced to a low level. However, low-grade transmission of Plasmodium falciparum continues, with periodic focal outbreaks after abnormally high rainfall. From October 1973 to September 1976, the operational and epidemiological factors involved in this residual transmission were studied in over 17 000 people of an area of northern Transvaal. Incidence surveys based on the screening of fever cases revealed 42 autochthonous cases of malaria in 1974-75 and 10 cases in 1975-76. Parasite prevalence surveys were not sensitive enough to assess the malaria situation, and serological testing indicated different levels of infection according to the method used. One of the two principal vectors of malaria in Africa-Anopheles funestus Giles-was not detected in the project area, and the A. gambiae group (species A and B) was found in extremely low numbers, so that it could not have accounted for the low-grade transmission in the area. A recently discovered member of the A. funestus group somewhat resembling A. aruni Sobti, and a species hitherto undiscovered in the Transvaal, which is abundant in the area and is indistinguishable from A. flavicosta Edwards, may be involved. Both were found biting man-mostly outdoors during the four hours following dusk, when people frequently gather outside their houses and are thus vulnerable to mosquito bites.


Assay procedures for polyamines in urine, serum, and cerebrospinal fluid. Putrescine (1,4-diaminobutane) and the polyamines spermidine and spermine have attracted interest as possible markers of malignancy and of response to chemotherapy. The assay methods currently in use for these amines are reviewed and compared in respect to sensitivity, reproducibility, and applicability to routine analysis for them in urine, blood, and cerebrospinal fluid.


Comparison of enzyme immunoassay and gas chromatography for determination of carbamazepine and ethosuximide in human serum. Patients' sera were analyzed for carbamazepine and ethosuximide by enzyme immunoassay (x) and gas chromatography (y), and the results were compared. The correlation coefficients were: for carbamazepine, x vs. y 0.94 (n = 93); for ethosuximide, x vs. y 0.99 (n = 30). These results suggest that the two methods could be used interchangeably. Ten serum samples supplemented with carbamazepine (2.5 to 12.5 mg/liter) and ethosuximide (20.0 to 130.0 mg/liter) were analyzed by both methods. The correlation coefficients were: x vs. y 0.99 (n = 10) for carbamazepine and x vs. y 0.99 (n =10) for ethosuximide.


High-pressure liquid chromatography and enzyme immunoassay compared with gas chromatography for determing phenytoin. We compared a gas-chromatographic method for determination of phenytoin with a high-pressure liquid chromatographic technique and with enzyme immunoassay by three instrumental procedures. More than 100 sera from patients being treated with this drug were assayed by all these techniques. The coefficient of variation was the lowest (4.0%) with liquid chromatography, but all methods gave a CV of less than 10%. The correlation coefficients for all methods exceeded 0.97 when compared to gas chromatography. Operation costs varied with the number of tests per batch, reagent costs, and operator labor costs. All assays gave comparable values for the therapeutic range, so it would be plausible to use more than one method in a situation where (e.g.) satellite laboratories handle different quantities of assays. In any of these techniques, interferences from carbamazepine, mephenytoin, phenobarbital, and primidone were negligible.


Aldosterone secretion rate: radioimmunoassay versus double isotope dilution derivative assay. A simple and reliable radioimmunoassay for the measurement of the aldosterone secretion rate has been developed. In this method the urinary pH 1-hydrolyzed aldosterone is acetylated to its 21-monoacetate and purified by a single paper chromatogram. The isolated aldosterone 21-monoacetate is radioimmunoassayed using the N.I.H. antiserum lot 088. From the value obtained and the tritium amount present in the eluate the specific activity is calculated. The following results disclosed the reliability of the method: 1. The values obtained were in perfect agreement with values obtained by a double isotope assay. 2. The aldosterone secretion rate values calculated did not change upon extension of chromatographic steps. 3. Immunochromatographic analysis showed a sharp peak in the aldosterone 21-monoacetate area without significant background immunoreactivity. 4. The steroid concentration measured decreased linearly with dilution of the paper eluate. 5. Identical values were obtained with three antisera, raised against different aldosterone immunogens. In our laboratory no reliable results could be obtained when the conversion to the aldosterone 21-monoacetate was omitted and the specific activity was calculated after radioimmunoassay of chromatographically purified, pH 1-hydrolyzed, aldosterone per se. In that case the values obtained were systematically lower than the double isotope values, a problem which is discussed.


A comparative study of the homogeneous enzyme immunoassay (EMIT) and two radioimmunoassays (RIA's) for digoxin. Our experience with the determination of digoxin in plasma or serum using a homogeneous enzyme immunoassay technique (EMIT) is reported. The day-to-day precision of the EMIT digoxin assay was investigated with different series of calibrators. Coefficients of variation varied from 10 to 25 percent in the range of 0.65--7.0 ng digoxin/ml. The accuracy was established by determining the mean recovery (96 percen) of spiked serum samples (0.0--6.0 ng digoxin/ml). The cross reactivity of structure related compounds: digitoxin, spironolactone (Aldactone) and prednisone were investigated. Amniotic fluid, umbilical cord serum and serum of pregnant patients were examined for false positive reaction. Serum samples of 111 patients from two hospitals, who were treated with digoxin, were analysed by EMIT and 3H-radioimmunoassay (RIA); 38 of these samples were also determined by 125I-RIA. A good correlation was found between EMIT assay and these techniques (r =0.90 and 0.91, respectively).


Supranormal FSH response to gonadotrophin-releasing hormone in oligospermic men with a normal basal serum FSH concentration. Twenty-six men with severe oligospermia (sperm density less than 10 X 10(6)/ml, but greater than O), but normal serum concentration of FSH, as well as normal serum concentrations of LH and testosterone, were given a 250 microgram i.v. bolus dose of synthetic gonadotrophin releasing hormone (LHRH). The serum FSH and LH responses were compared to those of a group of normal men and a group of men with oligospermia or azoospermia and elevated basal serum FSH concentration. The mean FSH response to LHRH of the men with oligospermia but normal basal serum FSH concentration was 911 miu min/ml, nearly three times that of the normal men, 322 miu min/ml (P less than 0.001), though not so great as that of the men with oligo/azoospermia and elevated basal FSH concentration (2890 miu min/ml). Ten of the twenty-six men with oligospermia and normal basal serum FSH had a supranormal FSH response to LHRH. The mean LH response to LHRH of the men with oligospermia and normal basal serum FSH levels was not significantly different from that of the normal men. We conclude that LHRH stimulation can often elicit a deficiency of feedback inhibition of FSH secretion not readily recognizable by measurement of the basal serum FSH concentration.


Diabetes and the heart: coronary heart disease. 1. Diabetics have a greater risk of experiencing and of dying from a CHD event than age matched non-diabetics. 2. The excess risk is particularly notable in insulin dependent female diabetics who seem to lose the usual 'protection' accorded to women. 3. The cause or causes of the excess risk are not known. There are a variety of 'risk factors' observed in diabetics which, in sum, may contribute. 4. At least in insulin-dependent diabetics some cardiac morbidity and mortality may also be due, not to coronary heart disease, but to a cardiomyopathy secondary to intramural obstructive vascular disease and/or disordered myocardial metabolism. 5. No therapy has yet been convincingly proved to reduce (or to increase) the risk of cardiac morbidity or mortality. Nevertheless, in treating diabetics there is an a priori case for using diets designed to lower plasma lipid levels as well as the blood sugar, for early treatment of hypertension and for discouraging cigarette smoking.


The enterohepatic circulation of bile acids in man. The enterohepatic circulation of bile acids may now be described in its broad outlines. Methodology presently available appears sufficient for overall characterization in health and disease. The challenge of the future is to gain insight into the control of the enterohepatic circulation so that new therapeutic approaches to liver, biliary and intestinal disease may be developed.


Histamine-receptor leucocytes (HRL). Organ and lymphoid subpopulation distribution in man. The frequency of lymphoid cells with a membrane receptor for histamine was determined in various lymphoid organs in man using a histamine-rosette assay. Thymus had very low numbers of histamine-receptor cells while lymph node and peripheral blood had increasing percentages. Through a combination of cell separation techniques, we demonstrated that about one third (1/3) of peripheral blood B lymphocytes and macrophages carry histamine receptors. Immature B cells or null cells (E-rosette and membrane-immunoglobulin-negative) do not have this receptor. Only 10% of peripheral blood T lymphocytes formed histamine rosettes. That these histamine receptor T lymphocytes are a subpopulation representing the differentiated suppressor/cytotoxic T cells is suggested by evidence showing complete removal of histamine receptor T lymphocytes on nylon wool adherence columns. Thus, the histamine receptor is expressed on differentiated B and T lymphocytes and may serve as a marker for developed suppressor/cytotoxic T cells in man.


Lymphocyte populations in peripheral blood during normal human pregnancy. The effects of normal pregnancy on peripheral blood lymphocytes were investigated. The frequencies of thymus-derived and bone-marrow-derived lymphocytes in maternal peripheral blood does not vary significantly throughout pregnancy. This observation implies qualitative rather than quantitative alterations in lymphocyte functions to explain the reduced cell-mediated immune responses seen during pregnancy.


Physiological variations of T cells during the menstrual cycle. Peripheral blood T lymphocytes were measured in healthy subjects during the various phases of the menstrual cycle. A significant decrease in T lymphocytes occurred during the menstrual period; T-lymphocyte numbers returned to the pre-levels 1 week after the end of the menstrual period.


Membrane characteristics of adherent cells dissociated from rheumatoid synovial tissue. Synovial tissues from rheumatoid-arthritis patients were dissociated by enzymes and the resulting cells incubated overnight in tissue-culture flasks. The adherent cell population was resuspended with EDTA-trypsin, and morphological examination showed 68--80% non-lymphoid cells, most of which had the appearance of synovial lining cells. The proportion of these cells increased during subsequent culture. Between 40 and 60% of the cells exhibited marked phagocytosis, and less than 14% of the non-lymphoid cells could form EA rosettes. Further culture diminished this Fc-receptor-bearing cell population. Indirect immunofluorescence studies with rabbit anti-human collagen sera revealed membrane staining for 30--60% of the cells; this proportion usually increased to greater than 90% after 6--14 days in culture. Omitting any changes of culture medium resulted in a marked decrease in the proportion of cells staining with anti-collagen sera, whereas the viability and phagocytic ability of the cells did not significantly alter. Subsequent cell passage was followed by an increase in the proportion of cells demonstrating membrane-associated collagen, and this effect was more pronounced when a high concentration (50%) of serum supplement was used. No clear definition could be made as to whether the membrane-associated collagen represents synthesis or phagocytosis of collagen by the cells. Faint membrane staining was also observed with non-immune rabbit serum for 4--20% of the cells after the initial overnight incubation, and this usually dropped to less than 5% during prolonged culture. Rabbit antisera to human albumin, F(ab')2 fragment of IgG or alpha2-macroglobulin also gave similar results, whereas the F(ab')2 fragment of rabbit IgG antibody to human alpha2-macroglobulin was completely negative. More than 99% of the cells commonly exhibited membrane-associated beta2-microglobulin.


The reaction of cells with anti-actin sera in relation to the amount of cellular actin. The staining pattern of anti-actin sera on various cells smeared on glass was compared to the relative amount of cellular actin estimated by SDS-polyacrylamide-gel electrophoresis with subsequent scanning of the gel. Although the cells showed a varying stainability the actin content was fairly constant. Thus, the staining differences reflected changes in the organization of cellular actin rather than actual differences in the amount of actin.


A human-specific mitochondrial antibody its importance in the identification of organ-specific reactions. A previously unrecognized autoantibody, detected by immunofluorescence, reacted with all human organs but gave negative results on tissues from rat, mouse, rabbit, guinea-pig, calf and chicken. From its predilection for mitochondria-rich cells (oncocytes) and its selective absorption with human but not animal mitochondria, it was identified as an anti-human mitochondrial antibody and named AHMA. The antibody is found in about 1% of normal subjects and is mostly of IgG class and of low titres. Its prevalence is increased in primary biliary cirrhosis where it may be associated with the standard non-species-specific AMA used for the differential diagnosis of this disease. The importance of AHMA is mainly in possible confusion with organ-specific reactions in submaxillary duct, parathyroid oxyphil cells and in trying to identify new endocrine cells such as those producing pancreatic polypeptide (HPP) in human tissues. Animals immunized with human hormones develop reactions to human mitochondria and thus produce misleading immunofluorescence reactions when used in low dilutions.


Colony formation by human T lymphocytes in agar medium. An improved method is described for growing human T-lymphocyte colonies in agar medium containing phytohaemagglutinin (PHA) and sheep red blood cells (SRBC). Cluster and colony growth was obtained when blood mononuclear cells were plated directly in the agar-medium (one-step procedure) or after incubation of cells in liquid medium with PHA (two-step procedure). In the one-step procedure approximately 1 per 100 cells plated formed a cluster containing four to fifty cells. In the two-step procedure 1 per 20 cells plated formed a cluster or a colony (more than fifty cells). The proliferating cells were shown to be sheep-erythrocyte rosette-forming cells (E-RFC). Optimal proliferation was dependent on the presence of phagocytic cells in the cell suspensions cultured. No growth occurred in cultures depleted of E-RFC. Detailed studies of the cycle, velocity sedimentation, and density of the cells plated showed that the majority of cluster- and colony-forming cells were small non-cycline lymphocytes with a sedimentation velocity of 4 mm/hr, and a density between 1-069 and 1-077 g/cm3.


Histopathological and immunohistological changes in the rabbit lung after experimental exposure to a purified enzyme of Micropolyspora faeni. Rabbits were exposed intratracheally to enzyme 1, a highly immunogenic esterase isolated from Micropolyspora faeni. A single exposure to active enzyme 1 induced no histologically or immunohistochemically detectable changes in the lungs of experimental animals, while signs of focal interstitial and perivascular inflammatory reactions were evident following a course of three exposures to the enzyme. Interstitial pneumonia with characteristic generalized vasculitis and perivasculitis was produced following seven or nine inoculations. An enzymatically inactive preparation of enzyme 1, even by repeated administration, proved ineffective in eliciting pneumonia. Intracellular antigen within macrophages/histiocytes was demonstrated in the lungs of all experimental animals, including those which had been exposed to inhibited enzyme. Repeated exposure to the enzymatically active preparation resulted in the deposition of immunoglobulin and complement in association with vascular endothelia and in the walls of small- and medium-sized blood vessels; both immunoglobulin and complement could also be demonstrated within macrophages/histiocytes. On the basis of these findings it is concluded that (1) Farmer's lung-like interstitial pneumonia may be produced in rabbits by exposure to a purified, enzymatically active derivative of M. faeni, (2) an important pathogenic principle of the disease may consist in the rapid vascular deposition of immune complexes (type III reaction), and (3) damage by direct enzyme action may prove to contribute significantly in eliciting tissue damage by (an) ancillary mechanism(s) not yet understood.


Impaired antibody responses in alloxan diabetic mice. Alloxan diabetic BALB/C mice with high hyperglycaemia levels (larger than or equal to 600 mg/100 ml) when immunized either with T-dependent (SRCB) or T-independent (TNP-LPS) antigens show a significant decrease in the number of specific PFC when compared with normo-glycaemic controls. Moderate diabetes (greater than 350 mg/100 ml) does not affect the immune response and in some experiments a slight increase of anti-SRBC plaques was seen. In transfer experiments primed spleen cells of either diabetic or normal doners gave much better responses when transferred to normal rather than diabetic X-irradiated recipients. In Mishell-Dutton (MD) cultures anti-SRBC response of CBA spleen cells was moderately reduced only when the blood glucose level of cell donors exceeded 500 mg/100 ml. Glucose added to MD cultures of normal spleen cells diminished significantly the number of SFC when in concentrations exceeding 600 mg/100 ml. The data indicate that in diabetic animals B-lymphocyte function may be affected but give no clear-cut answer to whether this is also true for T-helper cells. Disabled lymphocytes, whatever population they represent, may partially recover when transferred into normo-insulinic milieu. It may be inferred that under conditions tested neither hyperglycaemia nor excess of corticosteroid accounted significantly for the impaired humoral responses in diabetic animals. These experiments imply, however, that in hypoinsulinaemia the lack of saturation of insulin receptors on the lymphocyte, and possibly also macrophage, membranes renders these cells functionally inactive presumably due to accumulation of cyclic AMP in the cell membrane.


Migration inhibition factor and the blood clotting system: effects of defibrination, heparin and thrombin. Heparin is not suitable as an anticoagulant in the leucocyte migration test used to demonostrate the presence of migration inhibition factor (MIF) due to a rapid disappearance of the response after even a short storage of the blood. The use of defibrinated blood is highly recommended and defibrinated blood can be stored for at least 90 min without any diminution of the response. The change in response when using heparinized blood is not due to any direct effect of heparin, because heparin has no effect when added to defibrinated blood. However, heparin, added together with thrombin, is capable of abolishing the MIF effect completely. The basis for this phenomenon is most probably the binding of the heparin-antithrombin cofactor (AT III) to a complex with heparin and thrombin. The activity of MIF requires the presence of AT III, its esterase-inhibiting activity probably being crucial, in order to express MIF activity on macrophages. This mechanism forms a link between certain cellular immune reactions and the blood-clotting system.


Blood lymphocyte subpopulations in breast cancer patients following radiotherapy. Both T and non-T lymphocytes decreased immediately following radiotherapy in breast cancer patients. The relative depletion of non-T lymphocytes, however, was more marked than that of T cells. 3 years later the number and the proportion of non-T lymphocytes was higher than immediately after radiotherapy, while T lymphocytes were still depressed. The proportion of cells with membrane-associated Ig was higher in patients 3 years following radiotherapy than in non-treated patients and healthy controls. There was no difference in the proportion of T and non-T lymphocytes between patients with and without metastases, respectively.


Crossreactivity with sporozoites, exoerythrocytic forms and blood schizonts of Plasmodium berghei in indirect fluorescent antibody tests with sera of rats immunized with sporozoites or infected blood. IFA studies are reported using plasmodial antigens from three different stages of the life cycle of Plasmodium berghei: sporozoites (SP); exoerythrocytic schizonts in rat liver (EEF); and parasitized rat erythrocytes (SCH = schizonts). Two series of specific sera were applied: sera from adult rats with a blood-induced infection (series A) and sera from rats immunized against sporozoites by mosquito bites and protected against parasitaemia by chloroquine (series B). In series A antibody titres with all three antigens were seen, but those with SCH were generally the highest. Superinfection with parasitized rat blood did not change the titre. In series B sera, collected from rats after a single exposure to infected mosquitoes, showed only titres with SP from day 3 onwards, but after a second exposure titres to all three antigens developed. Crossreactivity with the heterologous antigens in series B was clearly less than in series A. Anti-P. berghei sporozoite antibodies did not crossreact with P. vivax sporozoites. Rats of series A were resistant to a challenge of parasitized blood and could also inhibit the development of sporozoites. Rats of series B were protected against a challenge of sporozoites but not of infected blood. The results are discussed.


Immunobiology of primary intracranial tumours. II. Analysis of lymphocyte subpopulations in patients with primary brain tumours. Circulating peripheral blood lymphocyte subpopulations were analysed in patients with primary intracranial neoplasia. Patients with tumours of glial origin demonstrated a significant depletion of E-rosetting lymphocytes whereas the quantitative lymphocyte profiles of patients with non-glial brain tumours were normal. The number of immunoglobulin and Fe receptor-bearing cells was not significantly altered in any group of patients: however, the EAC-RFC subpopulation was increased in those with malignant gliomas. Two hypotheses are suggested to explain these observations: first, the presence of cross-reacting antibody between T cells and brain (glial) cells, and secondly, the proliferation of EAC-RFC in response to malignant degeneration.


The effect of renal transplantation on middle molecules in plasma and urine. The plasma level and urinary excretion of middle molecules were determined in 5 patients with chronic uremia undergoing renal transplantation. The results demonstrate that after successful transplantation, the uremic middle molecules disappear rapidly from plasma while being excreted in the urine. The reduction in plasma level of middle molecules after transplantation is more rapid than the reduction in creatinine concentration.


Presence of creatine phosphokinase brain band in the serum of chronic renal disease patients. The almost universal presence of the isoenzyme creatine phosphokinase brain band (CPK-BB) in the sera of patients with chronic renal insufficiency and serum creatinine above 4.5 mg/dl is noted. It is absent in patients with severe acute renal failure and in transplanted patients with normal renal function. The source of the enzyme may be nerve tissue and may represent neuronal cell damage in uremics over a period of time.


18F scintigraphy in the early diagnosis of osteonecrosis of the femoral head in chronic hemodialysis and transplantation. Osteonecrosis of the femoral head results in an increased uptake of 18F due to a reparative reaction in the necrotic area and its surroundings. Twenty hemodialysis and twenty-seven post-transplant patients were studied serially. In the hemodialysis group, nine patients had positive scintigraphs and eleven had negative studies. All were asymptomatic. In the transplant group, twelve were positive and fifteen were negative. Four patients with positive scans later developed unequivocal clinical and radiographic evidence of osteonecrosis. Patients with negative scans have been asymptomatic and without radiological abnormalities. Age, sex, duration of dialysis, bone mineral densitometry, total steroid dose, duration of hospitalization after transplantation, and serum chemistries were not different in positive and negative patients. All patients on alternate-day steroids have negative scans. A positive 18F scintigraph antedates the occurrence of clinical and radiological findings of osteonecrosis.


Dysfunctional uterine bleeding in adolescence. Dysfunctional uterine bleeding is one of the most frequent urgent gynecologic problems of the adolescent. Its diagnosis is by exclusion. Dysfunctional bleeding is managed expectantly with the anticipation of ovulation, individualization of therapy and continuous observation. In severe cases, hormal hemostasis and 3 months of cyclic therapy are indicated. In a small percentage of patients dysfunctional bleeding may persist and be associated with serious chronic disturbances.


Protriptyline plasma levels and antidepressant response. Twenty-one depressed outpatients were treated for 4 wk with 20 mg/day of protriptyline. Protriptyline plasma in individuals after 4 wk ranged from 22 ng/ml to 167 ng/ml. There was a negative correlation (-0.50, less than 0.05) between the severity of depression measured by the Hamilton Rating Scale (HRS) and the wk 4 protriptyline concentration. Patients with plasma levels above 70 ng/ml (wk 4) had better outcomes measured by the HRS (p less than 0.05) and the Zung Self-Rating Depression Scale (p less than 0.05) and had greater percent decreases on both scales (p less than 0.05) during treatment than those with lower plasma levels. An upper limit to the therapeutic plasma level range beyond which response to treatment was less satisfactory was not demonstrated in this study.


Effect of beta adrenoceptor antagonists on baroreceptor reflex sensitivity in hypertension. High-pressure baroreceptor reflex sensitivity (BRS) was estimated by measuring the reflex heart rate response to pharmacologic elevation of blood pressure (phenylephrine, 150 to 200 microgram intravenously) in 18 patients with essential hypertension on two occasions: after a 4-wk placebo period and after 9 wk of incremental doses of oral timolol (20, 40, and 60 mg daily). On placebo, measurements were performed both before and after propranolol (0.2 mg/kg intravenously). The level of cardiac vagal inhibition, estimated by the heart rate change after atropine (0.04 mg/kg intravenously), was similar in placebo and on timolol, thereby permitting comparisons of BRS. BRS on placebo (before and after propranolol) correlated with BRS on timolol ( r = 0.87 and 0.90, p less than 0.001), attesting to the reproducibility of BRS measurements. BRS was unchanged by either short-term (propranolol) or long-term (timolol) beta adrenoceptor inhibition. Results were similar in responders (n = 10), whose mean arterial blood pressure on timolol fell by 10 mm Hg or more, and in nonresponders. The findings do not provide evidence for a change in gain of the baroreceptor reflex arc under conditions of short- or long-term beta adrenoceptor inhibition.


Pathophysiologic and pharmacokinetic determinants of the antihypertensive response to propranolol. The tendency for patients with essential hypertension to differ markedly in antihypertensive response to propranolol could arise from pathophysiologic or pharmacokinetic differences between them. This possibility was investigated in 23 men with mild to moderately severe essential hypertension. At each of three propranolol doses, 40 mg, 80 mg, and 320 mg daily, approximately a 20-fold range in steady-state plasma propranolol concentrations was observed. Clinical response however was unrelated to plasma propranolol: oral dose ratio, since patients with higher plasma levels were less sensitive to the existing plasma drug concentration. When falls in blood pressure and plasma propranolol concentration were compared overall, a biphasic dose-response relationship was noted, with a first component at plasma propranolol concentrations of 3 to 30 ng/ml and a second at concentrations above 30 ng/ml. Only patients with increased sympathetic nervous system activity and high plasma renin activity (PRA) had substantial falls in pressure at propranolol levels of 3 to 30 ng/ml. Cardiac beta adrenergic receptor blockade, not suppression of PRA, seemed to be the antihypertensive mechanism. This relation of pretreatment sympathetic nervous activity and PRA to antihypertensive response existed only at lower plasma propranolol concentrations. With a propranolol dose of 320 mg daily, both plasma norepinephrine concentration and PRA were unrelated to the clinical response.


A multicenter trial of sulindac in osteoarthritis of the hip. Sulindac (cis-5-fluoro-2-methyl-l-[(p-methyl sulfinyl)-benzylidene]-indene-3-acetic acid) is a new nonsteroidal antirheumatic drug recently evaluated in a double-blind trial of 91 patients with hip osteoarthritis. Consecutive patients with documented flare following previous drug withdrawal were randomly assigned to one of 3 treatment groups: (1) sulindac given twice daily, (2) sulindac given 4 times daily, and (3) placebo. The dosage of sulindac, 100 to 300 mg daily, was adjusted according to patient global response and tolerance at 3- to 7-day intervals over 3 wk. Of 15 efficacy measurements evalulated, there was no difference between sulindac given 2 or 4 times daily, but differences were disclosed between one or both sulindac treatment groups and placebo in 11 of the 15 efficacy measurements (p less than 0.05, less than 0.01). The frequency of adverse reactions was of the same order for each treatment group. These included gastrointestinal upset, rash, and dizziness, usually transient and mild to moderate in severity. Serial laboratory studies revealed no evidence of renal, hepatic, or hematopoietic toxicity.


Renal clearance and tissue accumulation of gentamicin. Multiple-dose studies of gentamicin pharmacokinetics were performed in 2 treated patients. After the final dose, serum and urine concentration declined in biphasic fashion with beta half-lives of 87 and 173 hr. Recovery of the total dose administered required urine collection for at least 10 to 20 days after the last dose. A two-compartment model was used to describe the biphasic decline in serum concentrations, to simulate all measured concentrations during treatment, and to predict the amount of gentamicin in the tissue compartment. Analysis of autopsy tissues yielded the predicted amount of drug. A linear two-compartment model adequately quantitates gentamicin disposition until about 4 days after cessation of therapy when gentamicin renal clearance begins to decline because of tubular reabsorption.


Selected case histories and epidemiologic examples of human mercury poisoning. To illustrate the various clinical pictures resulting from toxic effects of mercury and its compounds, highlighted literature excerpts have been prepared and arranged in a logical sequence. Particular emphasis is placed upon early diagnosis and prevention of epidemic outbreaks involving intoxication through organomercurials.


Mechanism of B-cell activation and self-non-self discrimination. The evidence for the one, nonspecific signal hypothesis, which states that the B lymphocytes are activated by nonclonally distributed receptors which are not the Ig receptors, has been summarized. Even though protein A is a polyclonal B-cell activator, it does not exert its effect by interacting with the Fc part of Ig receptors. One consequence of the one, nonspecific signal concept is that thymus-dependent antigens cannot activate or tolerize B cells. It was shown that B cells from animals tolerant to a thymus-dependent protein antigen could be activated by polyclonal B-cell activators to produce antibodies against the tolerogen. Experimentally induced tolerance did not differ from tolerance to self antigens, since LPS and PPD induced autoantibodies capable of lysing autologous red cells and isotope-labeled autologous and syngenic spleen cells. Thus B cells cannot discriminate self from non-self, whereas T cells have been shown to possess this ability.


Structure of HL-A A and B antigens isolated from cultured human lymphocytes. From these data, a model was prepared which summarizes schematically our present knowledge of the structure and orientation of the HL-A antigenic molecule in the lymphocyte membrane (Fig. 3). It seems likely that the heavy chain spans the membrane, with the hydrophobic region inserted in the membrane and the hydrophilic C-terminus inside the cell. This C-terminal region bears one (possible two) SH residue which has the potential for forming interchain disulfides. Whether or not these are actually formed physiologically remains an interesting question. There is the attractive possibility that whatever the physiological functions of HL-A antigens are, structurally these molecules provide the potential for signaling from outside the cell to inside the cell because they span the membrane. It is even conceivable that this function might be expressed via the opening and closing of disulfide bridges.


Oral health status of institutionalized elderly Cape Coloreds from the Cape Peninsula of South Africa. A study has been conducted to assess the oral health status and need for dental treatment among elderly Cape Coloreds resident in homes for the aged in the Cape Peninsula of South Africa. This paper describes the prevalence of diseases of the mouth with special reference to denture-induced lesions and white lesions of the oral mucosa. Dental caries was the most prevalent oral lesion (27.2%). The most common conditions of the soft tissues were leukoedema (24.4%) and leukoplakia (4.4% for the tongue; 20.4% for the remainder of the oral mucosa). Leukoedema and leukoplakia showed statistically highly significant correlations with tobacco habits. Men more commonly had a tobacco habit than women (P less than 0.002) and leukoplakia, leukoedema and depigmented lesions of the lips were significantly more common in men than in women. No significant difference could be proven statistically when the frequency of irritative fibrous hyperplasia in females was compared with that in males.


From hospital to community care: the change in the mental health treatment system in California. In 1968 California enacted a law transforming its state hospital centered mental health services to a single system of patient care based on local community responsibility. The 1968 law was not the cause of radical change in California, but rather the culmination of a process that began three decades earlier. The 1963 federal regulation enabling former mental patients to become eligible for categorical aid through public assistance programs and the development of psychoactive drugs were two necessary catalysts that provided the opportunity ot maintain many formerly hospitalized mental patients in the community and to avoid lengthy hospitalization of others.


Medical data base system with an ability of automated diagnosis. We carried out an experiment on a medical information system in which a clinical data base is combined organically with computer programs for automated diagnosis. In this system, the parameters for automated diagnosis are devised to be renewed as the contents of the data base (patient's information) increase. This system can be regarded as a data base possessing a kind of diagnosing ability which grows up with time. We have named this system "Intelligent Data Base". The algorithm for computer diagnosis used in this study is based on maximum likelihood method, and each likelihood is weighted with a prior probability of each disease. The discrimination efficiency of this method is logically equal to that of the Bayes rule. First 27 cases were learnt by the system and correct diagnosis was obtained in 78% of the cases. When cases for learning increased to 82, the percentage of correct diagnosis was improved to 95%.


Kidney in lupus erythematosus.

Kidney in lupus erythematosus. The pathologic abnormalities present in patients with SLE have been classified as follows: minimal lupus nephritis, mild (focal) proliferative lupus nephritis, severe (diffuse) proliferative lupus nephritis, and membranous lupus nephritis. Changes in individual patients from one form of nephritis to another are observed infrequently. Pathologic evidence of activity is usually present in patients with hematuria, although it may be found in patients with no evidence of clinical renal disease. Complement components and titer of antibody to native DNA may be helpful in estimating disease activity.


Henoch-Schönlein nephritis.

Henoch-Schönlein nephritis. Henoch-Schönlein nephritis now appears to be an immunologically mediated disease, common in children but rare in adults, and initiated by unknown antigen or antigens. We have reviewed this form of nephritis with particular attention to immunological changes, occurrence in adults and prognosis. Assessment and treatment are made difficult by varying diagnostic criteria, especially in adults, and lack of controlled data.


Heroin addiction and renal disease.

Heroin addiction and renal disease. In this paper, renal involvement secondary to other medical complications of heroin addiction is discussed. We review 12 published studies totalling 102 heroin addicts with renal disease. Of these, in only 40 patients could other discernible causes of renal disease be excluded. The existence of 40 reported cases of renal disease from a population of more than half a million is insufficient data upon which to postulate the existence of a type of renal disease unique to heroin addicts.


Air contrast studies of the colon in inflammatory bowel disease. The purpose of this review is to evaluate the role of double-contrast examination of the colon, in the detection and differential diagnosis of colitis. The emphasis is on correlation with endoscopy, (twelve color endoscopic photographs are included with the corresponding radiographs illustrating the spectrum of abnormalities in ulcerative and granulomatous colitis), differential diagnosis between ulcerative and granulomatous colitis (the double-contrast technique allows for accurate examination of the rectum and careful mapping of the extent and nature of disease in an involved segment. This facilitates the differential diagnosis between ulcerative and granulomatous colitis), and detection of early changes (in ulcerative colitis, the early stage of mucosal edema results in a finely granular mucosa on double-contrast study. In granulomatous colitis, small, shallow, "aphthoid" ulcers are frequently seen as the earliest lesion). The accuracy of the double-contrast technique is assessed by review of series comparing the radiologic and endoscopic findings. This is compared to the accuracy of the conventional enema. Some of the important technical considerations necessary for good double-contrast studies are discussed, as well as some of the potential pitfalls in interpretation.


Tunnelling in radiation chemistry.

Tunnelling in radiation chemistry. This review is devoted to the radiation chemistry of frozen systems with emphasis on the recent theoretical and experimental investigations suggesting tunnel character of trapped electron transfer to scavenger molecule.


Transfer of episome F'lac+ and chromosomal trp+ genes from Erwinia amylovora to Salmonella typhimurium. The F'lac+ episome of Escherichia coli origin was transferred by conjugation with frequencies of 10(-7) to 10(-5) from Erwinia amylovora to 14 out of 15 Salmonella typhimurium trp female parents. The chromosomal trp+ genes were transferred with frequencies of 10(-7) to 10(-6) only to one trpB and 2 trpD female parents, which have a point mutation in the 2nd and fourth structural genes, respectively, of the tryptophan operon. The transferred male trp+ genes became integrated at the selected sites of the S. tryphimurium chromosome. The resulting Trp+ hybrids were phenotypically stable, lacked a cryptic trp allele selected against in the female parent, had high genetic homology values in the tryptophan region, and showed biochemical reactions and pathogenicity typical of S. typhimurium.


Advances in the morphological diagnosis of bone tumours: cytology, cytochemistry, acrylate embedding and electron microscopy (author's transl). An exact morphological diagnosis of bone tumours is the prerequisite for selective treatment. In a given case this may present great difficulties, partly because of the rarity of a tumour group and thus lack of experience, partly faulty removal of the specimen and unsatisfactory further technical handling. Progress can be expected only by widening the spectrum of methods by using modern morphological tests. In a programme using imprint cytology, cytochemistry, rapid section, histochemistry, paraffin, non-decalcified embedding in acrylate and electron microscopy it was demonstrated in 78 cases of bone tumour (seen over a period of two years) that with these tests, especially cytology, cytochemistry and non-decalcified acrylate histology, significant improvement can be obtained in the morphological diagnosis of bone tumours. In addition, new lights on cytogenesis and pathogenesis of these tumours and possible points of attack of cytostatic treatment are provided.


[Immunopathological findings in herpes gestationis (author's transl)]. Herpes gestationis occurred in a 26-year-old woman during the last weeks of her second pregnancy. Within 8 days of the delivery the disease had progressed to such an extent that systemic treatment became necessary. Whereas pre-delivery treatment had consisted exclusively of local desinfection, and steroid and antibiotic ointments, treatment after delivery also included systemic use of prednisolone. After treatment for 3 weeks the skin changes had disappeared except for minimal pigmentation. Using immunofluorescent microscopy a complement activation in the dermo-epidermal junction and in adjacent clinically healthy skin could be demonstrated: There were massive linear depositions of C3, C1q and C4. In the basal membrane of the epidermis IgM could be demonstrated as an unusual finding. Further immunopathological features were found in the form of an immune complex vasculitis which could be shown during the active phase of the disease.


[Integrated teaching of morphological sciences in medical training]. To provide more information to participants in the Second Meeting of the Textbook Committee of PAHO/WHO for the teaching of the Morphological Sciences in the Medical Schools of Latin American, a survey was held of the departments of those sciences, in 150 Latin American schools to acquire updated information on the academic organization, the work schedule of the teachers, the levels of integration of the instruction, use of textbooks by students, and the degree of familiarity with the PAHO/WHO Testbook Program and its coverage. The results of the survey, presented in detail in this document, demonstrate the persistence of most of the problems discussed in the First Meeting of the Committee (1969), which makes it necessary to reconsider the integrated teaching of the morphological sciences and the strategies for attaining it. The document also analyzes the development of the morphological sciences and of integration in them.


[Endosseous blade implantations in the edentulous patient and the prosthetic superstructure]. Our suprastructures for blade vent implants are purely tissue-borne constructions. The retainers fixed to the denture base (Dolder jacket or Gilmore rider) are attached to the implant bar to guide the movement of the saddles. In addition, this is to counteract lifting to the dental replacement by the tongue or the muscles of the floor of the mouth. Cases in which this therapeutic method was applied are presented.


[Study of gastric secretion in white rats with a chronic gastric fistula on endotoxin exposure]. The author carried out a study on the stomach secretion in white rats endotoxin shock, induced by venous adminsitration of endotoxin, obtained from Escherichia coli. Stomach fistula was made on the rats in advance and the stomach juice was collected under the condition of chronic experiment. The amount of stomach juice was estimated in mililiter per hour as well as the content of free hydrochloric acid, total aidity and electrophoresis of proteolytic enzymes. There was a statistically significnat lowering of the amount of stomach juice, diminuation of free hydrochloric acid and of total acidity acidity as well as diminution of complete disappearence of its proteolytic activity in the rats after endotoxin action.


[1-glutamine and dipropylacetic acid as subsidiary psychotropic agents in the treatment of psychiatric in-patients. Effect on the neuroleptic consumption]. In a division of the neuropsychiatric hospital of Racconigi, with acute and chronic inpatients, the use of 1-glutamine and N-dipropylacetic acid as subsidiary psychodrugs, after one year follow-up, showed to have reduced the whole administration of neuroleptics, without diminishing the therapeutic efficacity. This administration, during the four sampler months (December, March, June and September), face with the sames of the preceding year, has been lesser than 29,04% (lesser than 38,21%, if we take into consideration the last two months). Such result has been confirmed by a corresponding diminution of orphenadrine, the drug used to counteract the neuroleptic syndrome, which during the last two months considered in this research, respectively subsided of 28,57% and 36,36%.


Production of antisera against electrophoretically separated relaxin and immunofluorescent localization of relaxin in the porcine corpus luteum. Antisera to porcine relaxin were produced in rabbits injected with different fractions that had been separated by polyacrylamide gel electrophoresis (PAGE). Analyses by agar double immunodiffusion demonstrated that the different fractions of relaxin separated by PAGE have similar antigenic sites and the individual fractions are indistinguishable from one another by this procedure. Antiserum to porcine relaxin inhibited the interpubic ligament forming ability of the hormone in vivo. Indrict fluorescent antibody studies demonstrated that the hormone was localized only in the corpus luteum of the pregnant sow ovary. Large ovoid or polyhedral cells, assumed to be granulosa lutein cells, exhibited the heaviest fluorescence.


The effect of glucose on the acute uptake and efflux of calcium-45 in isolated rat islets. The effect of glucose on acute 45Ca uptake and efflux in collagenase-isolated islets was studied using a double-isotope incubation technique with [3H]sucrose as an extracellular marker. Both 45Ca uptake (0-70 min) and efflux (0-80 min) were measured in either 3 or 20 mM glucose. Calcium-45 uptake and efflux were biphasic demonstrating a rapid phase (0-1 min) followed by a slow phase. Glucose (20 mM) increased the rate constant for slow-phase 45Ca uptake 7-fold and had no effect on the rapid phase. Suppression of insulin release by D2O (100%) did not affect glucose-induced 45Ca uptake indicating that this increased uptake occurred independent of insulin release. Rapid-phase and slow-phase 45Ca efflux rate constants were unaltered by 20 mM glucose and inhibition of insulin release by D2O did not influence 45Ca efflux. The rapid-phase movement of 45Ca may represent a rapidly exchangeable calcium pool at the cell membrane whereas the slow phase may be transmembranous calcium movement, as has been reported for calcium transport in HeLa and kidney cells.


Serum gonadotropins in rats fed a low-valine diet. Female rats fed a low-valine diet from the time of weaning have been shown to have delayed puberty compared to growth-matched controls. To explore the mechanism of this delay, serum LH and FSH were measured in rats fed the low-valine diet and in growth-matched control rats at several ages prior to puberty. Hormonal determinations at each time point were made both in the basal state and after LHRH administration or castration. After age 27 days, the mean basal serum FSH was lower in the low-valine group than in the control group. The mean serum levels of LH and FSH after oophorectomy were significantly lower in the low-valine group than in the control group, although the mean serum levels of LH and FSH after LHRH administration to intact animals were similar in both groups. The combination of impaired response to castration with unimpaired pituitary response to LHRH suggests that the low-valine group had a hypothalamic defect which accounts for their delayed sexual maturation when compared to growth-matched animals.


Application of ovine luteinizing hormone (LH) radioimmunoassay in the quantitation of LH in different mammalian species. A sensitive double antibody radioimmunoassay has been developed for measuring luteinizing hormone (LH) in various African mammalian species, using rabbit anti-ovine LH serum (GDN 15) and radioiodinated rat LH or ovine LH. Serum and pituitary homogenates from some African mammals (hyrax, reedbuck, sable, impala, tsessebe, thar, spring-hare, ground squirrel and cheetah, as well as the domestic sheep, cow and horse and laboratory rat and hamster) produced displacement curves parallel to that of the ovine LH standards. The specificity of the assay was examined in detail for one species, the rock hyrax. Radioimmunoassay and bioassay estimates of LH in hyrax pituitaries containing widely differing quantities of pituitary hormones were similar. In sexually active male hyrax mean plasma LH was 12.1 ng/ml and pituitary LH 194 microgram/gland, but in sexually quiescent hyrax mean plasma LH was 2.4 ng/ml and mean pituitary LH 76 microgram/gland. Intravenous injection of 10 microgram of luteinizing hormone releasing hormone increased mean LH levels in hyrax from 0.9 ng/ml to 23.2 ng/ml by 30 min. Conversely, im injection of 250 microgram testosterone induced a fall in LH levels in male hyrax from 1.7 ng/ml to 0.7 ng/ml 6 h after administration. Although the specificity of the assay for quantitating plasma LH in other species was not categorically established, there was a good correlation between plasma LH concentration and reproductive state in the bontebok, impala, spring-hare, thar, cheetah, domestic horse and laboratory rat, suggesting the potential use of the antiserum in quantitating LH in a variety of mammalian species.


Somatostatin inhibition of pancreatic glucagon release from monolayer cultures and interactions with calcium. The effects of somatostatin (SRIF) on glucagon release have been studied in the monolayer culture of newborn rat pancreas. It was found that SRIF inhibited glucagon release rapidly and in a dose dependent manner at concentrations of 1-1000 ng/ml. SRIF inhibited glucagon release under basal conditions and after stimulation by arginine, 3-isobutyl-1-methylxanthine (IBMX), high Ca++ concentrations, ionophore A23187 and Ca++, and Ba++. SRIF inhibited ionophore-induced glucagon release over 60 min when a low concentration of A23187 was used (0.1  microgram/ml) but not when a high concentraion (10 microgram/ml) was used. The stimulant effect of 10 microgram/ml A23187 was, however, inhibited by SRIF during short periods of incubation. The per cent inhibition of arginine-stimulated glucagon release due to SRIF remained unchanged when the Ca++ concentration in the medium was varied from 1-10 mM. It is concluded that SRIF promptly inhibits glucagon release under basal conditions or when stimulated by a variety of agents. Thus, the action of SRIF appears to be basic to the granule release process and not specifically antagonisitc to any particular stimulants. Further, as SRIF inhibits release due to raised cytosol Ca++ (e.g., ionophore-Ca++ or high Ca++ experiments) the action is probably at a late point in the release mechanism.


Spontaneous expulsion of a migrating infantry missile impacted in the duodenum and the common bile duct, 32 years after wounding. 32 years after the injury, an infantry bullet was found to extrude into the duodenum, with its sharp end impacted in the common bile duct. After several previous endoscopic examinations (duodenoscopy, ERCP), endoscopic removal was planned. In the meantime, the bullet was expelled per vias naturales, leaving a biliodigestive fistula.


Phenylbutazone and the horse--a review.

Phenylbutazone and the horse--a review. The clinical uses and side-effects of phenylbutazone in man, horses, and other animals are reviewed. The blood dyscrasias commonly described in man have not been reported in the horse, although several of the more minor side-effects have occasionally been seen (e.g. water retention, depression, transient staggering and phlebitis). Despite the lack of documented evidence, the toxicity of phenylbutazone in the horse is considered to be lower than that in man. This may be associated with the lower dose rates normally used, the more rapid plasma clearance rate and the comparatively younger age of most horses under treatment. The following guidelines for the use of phenylbutazone in practice are put toward. It should only be used under strict veterinary control and then only if there are clear clinical indications. It should not be given if there are signs of gastro-intestinal ulceration, clotting defects or any cardiac, renal or hepatic dysfunction. Dose rates should be kept to a minimum and the drug withdrawn immediately if any side-effects occur or if there is no clinical response within 4 days. If prolonged therapy is necessary, periodic haematological analyses should be carried out.


Structural studies of the Shigella flexneri variant X, type 5 a and type 5 b O-antigens. Previous studies of different Shigella flexneri O-antigens indicate that their O-specific region is composed of oligosaccharide repeating units containing a basic tetrasaccharide structure, to which alpha-D-glucopyranosyl groups and O-acetyl groups may be attached to different positions. Structural studies of O-antigens from variant X, type 5a and type 5b lend further support to this assumption. These antigens contain terminal alpha-D-glucopyranosyl groups, one each per repeating unit in X and 5a, two in 5b. The location of these groups in the repeating unit has been determined.


Macromolecular synthesis and energy level in a mitochondrial conditional yeast mutant, tsm-8. Mitochondrial DNA, protein and ATP syntheses persist at non-permissive temperature (35 degrees C) in the mitochondrial, conditionally rho- petites forming yeast mutant, tsm8. Protein and ATP syntheses, however, are diminished during prolonged incubation at 35 degrees C in non-fermentable substrate. Mitochondrial RNA synthesis decreases rapidly to a residual constant level of about 10% of the initial value after the shift to 35 degrees C. The decrease is reversed by returning to permissive conditions. Evidence is presented that this temperature-induced decrease in mitochondrial transcription rate is effected by a mutationally altered regulatory process rather than by temperature sensitivity of mitochondrial RNA polymerase. It is concluded that rho- petite formation in mutant tsm8 is not effected by complete inhibition of macromolecular and ATP syntheses but is correlated with a reduction in mitochondrial transcription.


Effect of rifampicin on the infectivity of RNA bacteriophage f2. RNA bacteriophage f2, treated in vitro with rifampicin, loses infectivity dramatically. Rifampicin interacts with phage RNA, binding to a few specific sites. Inhibition of phage RNA infectivity occurs at 10-100 times lower molar excess of rifampicin than inhibition of infectivity of intact phage particles. Thus the phage capsid acts as a barrier, diminishing interaction of the drug with phage RNA.


Somatic antigens of Shigella. Structural investigation on the O-specific polysaccharide chain of Shigella dysenteriae type-2 lipopolysaccharide. The O-specific polysaccharide obtained from Shigella dysenteriae type-2 lipopolysaccharide by mild acid hydrolysis consisted of N-acetylgalactosamine, N-acetylglucosamine, D-galactose, D-glucose, and O-acetyl group in the ratio of 2:1:1:1:1. A number of oligosaccharides were obtained by deamination of the N-deacetylated polysaccharide and by Smith degradation of the both native and O-deacetylated polysaccharides. The identification of oligosaccharides along with methylation analysis and chromic anhydride oxidation showed that the polysaccharide was built up of the repeating pentasaccharide units whose proposed structure is given below: (see article) Serological properties of Sh. dysenteriae O-specific polysaccharides are discussed.


The genetic control of molybdoflavoproteins in Aspergillus nidulans. A xanthine dehydrogenase I half-molecule in cnx- mutant strains of Aspergillus nidulans. The cnx- group of mutants of Aspergillus nidulans lacks xanthine dehydrogenase (xanthine: NAD+ oxidoreductase, EC 1.2.1.37) and nitrate reductase (EC 1.6.6.3) activities and are thought to be defective in the synthesis of a molybdenum-containing cofactor, 'cnx', common to xanthine dehydrogenase and nitrate reductase [Pateman, J.A., Rever, B.M., Cove, D.J. and Roberts, D.B. (1964) Nature (Lond.) 201, 58-60]. The cnx cofactor has a role in maintaining the aggregated multimeric structure of nitrate reductase [MacDonald, D.W., Cove, D.J. and Coddington, A. (1974) Mol. Gen. Genet. 128, 187-199]. We report here that, in cnx- mutants grown under conditions inducing xanthine dehydrogenase I, a species cross-reacting with antisera to the native enzyme and of half its molecular weight is present, together with cross-reacting molecules of similar molecular weight to the native enzyme. This suggests that the cnx cofactor has a role in maintaining the aggregated structure of xanthine dehydrogenase I. Both cross-reacting species are capable of passing reducing equivalents from NADH to a tetrazolium salt, showing that the cnx cofactor is not necessary for enzymic activity towards NADH.


The primary structure of a non-histone chromosomal protein. The primary structure of the calf thymus non-histone chromosomal protein HMG-17 has been determined. The sequence was determined mainly from data provided by the peptides obtained by cleavage with staphylococcal protease. Additional information was obtained from peptides produced by cleavage with trypsin and alpha-protease (from Crotalus atrox venom) and by partial acid hydrolysis. The protein is 89 amino acid residues in length, and has molecular weight of 9247. The N-terminal two-thirds of the molecule is highly basic, 22 of the first 58 residues being lysine or arginine, whereas only seven residues are aspartic or glutamic acid residues. In contrast, the C-terminal region of the molecule has an overall negative charge, only four of the last 31 residues being basic, whereas seven aspartic and glutamic acid residues are present. The protein is also characterised by a region of high density of proline residues, there being six proline residues between residues 31 and 40. A region of 19 residues sequence similarity with the trout-specific histone, H6, is noted together with some smaller regions of sequence similarity with histones H1 and H5.


Mapping of 23-S rRNA at the ribosomal peptidyl-transferase center by photo-affinity labeling. Photo-sensitive peptidyl-tRNA's were used to scan the environment of the peptidyl-transferase center of the ribosome. The specificity of the previously described labeling in the 18-S fragment of 23-S rRNA by Boc-Phe(N3)-Phe-tRNA (4-azido-N-t-butoxycarbonyl-phenylalanyl-phenylalanyl-tRNA) was demonstrated by the ability of the covalently anchored molecule to serve as donor substrate in peptide bond formation. Labeling patterns were also obtained with Boc-Phe(N3)-Phe-Phe-tRNA bound at the acceptor site and with Boc-Phe(N3)-(Gly)n-Phe-tRNA (n = 2,4). The results indicate that subsequences within the 18-S fragment of 23-S rRNA are located close to the acceptor site as well as along the path where the peptide moiety adheres to the ribosome. Identification of the labeled sequences is expected to shed light on the spatial arrangement as well as functional role of rRNA in the peptidyl transferase center.


Limited proteolysis of elongation factor Tu from Escherichia coli, Multiple intermediates. Limited proteolysis of native elongation factor Tu (Mr 44 000) by trypsin occurs in at least three distinct steps. The first intermediate arises through cleavage at a site about 65 residues from the amino-terminal end of the protein. It is functionally active [Jacobson, G. R. & Rosenbusch, J. P. (1976) Biochemistry, 15, 5105-5110] and is partially protected from further degradation by the antibiotic kirromycin. The second step converts this intermediate to one of similar size (Mr 37 000) which now is partially inactivated. It is likely to be identical with the intermediate described by Arai et al. [(1976) J. Biochem. Tokyo, 79, 69-83]. In the third step, the partially inactive intermediate is cleaved without any apparent change in the functional properties tested. The resulting two trypsin-resistant fragments have molecular weights of 24 000 and 14 000, and remain associated under nondenaturing conditions. When either of these polypeptides, after isolation in 8 M urea, is allowed to renature, no significant reactivation of GDP binding is observed unless the isolated fragments are mixed before renaturation. These results show that the two fragments are structurally and functionally interdependent.


Effects of disopyramide and aprindine on arrhythmias after acute myocardial infarction. The incidence of ventricular arrhythmias after myocardial infarction was compared in a double blind study of disopyramide (33 patients), aprindine (34 patients) and placebo (31 patients). Total ventricular arrhythmias were less frequent in the aprindine group than in the disopyramide group (P less than 0.05) or than in the combined disopyramide and placebo groups (P less than 0.05). The incidence of life-threatening arrhythmias and of ventricular arrhythmias in high risk patients was also reduced by aprindine compared to disopyramide (P less than 0.001) or placebo (P less than 0.001). It is concluded that aprindine is effective in reducing ventricular arrhythmias and that further investigations on its preventive use after the onset of myocardial infarction are justified.


The antihypertensive effect of pindolol (Visken) alone and combined with clopamide (Brinaldix). After a two week washout period 25 patients with moderate to severe essential hypertension were treated with pindolol. In 12 patients the reduction in blood pressure was excellent and treatment with pindolol was continued. In 13 patients treatment was supplemented subsequently with clopamide and 12 patients had a satisfactory result. Side-effects were few and mild.


Distinct properties of Thy-1 antibodies elicited in rats by immunization with mouse brain. Rats are known to possess antigenic determinants related to the Thy-1.1 allele. Immunization of rats with brain homogenates from mice carrying either the Thy-1.1 or the Thy-1.2 alleles resulted in the production antisera which were cytotoxic for thymus cells of both strains of mice. Lymph node, spleen and cortisone-resistant thymus cells were refractory to the cytotoxic effect of rat anti-mouse brain sera. Peripheral lymphocytes were fully capable of absorbing the cytotoxic activity of the sera on thymus cells, although the concentration of the antigen on their cell surface was considerably less than on thymus cells. Blocking experiments with allo- and xenoantisera to Thy-1 antigens suggested that the antigen detected by rat anti-mouse brain sera is related to the Thy-1 system. The Thy-1 specificity detected by rat antisera seems to differ from previously described Thy-1 antigens in that it attains a high concentration on thymus cells but is relatively deficient in its expression on peripheral T cells.


The antipyretic effect of flurbiprofen.

The antipyretic effect of flurbiprofen. Flurbiprofen, like its predecessor ibuprofen, possesses antipyretic properties in the endotoxin-fevered rabbit. Comparison of flurbiprofen and ibuprofen at varying dosages, reveals that flurbiprofen is at least 15 times more potent in this species. In goats, flurbiprofen is more potent than in rabbits. Flurbiprofen inhibited the pyrogenic effect of intravenously administered leucocytic pyrogen, but it did not alter the release of leucocytic pyrogen from peritoneal exudate cells in vitro. Moreover, flurbiprofen did not inhibit endotoxin-induced release of endogenous pyrogen in vivo. Incubation of leucocytic pyrogen with flurbiprofen did not alter its pyrogenic poteny. These results suggest that the antipyretic activity of flurbiprofen is due neither to interference with endogenous pyrogen synthesis and release, nor to inactivation of circulating endogenous pyrogen.


Relationship between the ventromedullary clonidine-sensitive area and the posterior hypothalamus. The connections between the areas 'S' which have been previously described as the ventromedullary sites of the action of clonidine and the posterior hypothalamus have been investigated. Superficial electrocoagulation of the left area 'S' suppresses the pressor response to electrical stimulation of the homolateral part of the posterior hypothalamus. Although such medullary lesions cause a significant reduction of the mean arterial pressure, the contralateral hypothalamic stimulation can still increase blood pressure. Clonidine it self applied topically (8 micrograms/kg) to the ventral face of the brain stem decreases the blood pressure response to liminal hypothalamic stimulation. It is concluded that efferent pathways, which are involved in vasomotor regulation, originate in the posterior hypothalamus and run through the ventrolateral part of the brain stem. The mechanism of the blocking effect of clonidine on these pathways is discussed.


Mesenteric hemopoietic colonies: occurrence in BALB/c mice after transplantation of syngeneic normal or leukemic hemopoietic cells. Intraperitoneal (ip) inoculation of BALB/c mice with syngeneic hemopoietic cells results in the formation of 'Mesenteric Hemopoietic Colonies' (MHC). In lethally irradiated mice actively growing erythroid, myeloid and megakaryocytic, or mixed colonies form and soon become confluent. It is therefore concluded that in mice the mesentery is a suitable site for growth of hemopoietic cells. The mesentery might play an important role in the recovery of the hemopoietic system in lethally irradiated mice, being the primary site of proliferation of stem cells and/or CFU before their migration to bone marrow and spleen. Bone marrow and spleen cells from animals infected with Rauscher Leukemia Virus (R-MuLV) also produce MHC and spleen colonies after ip injection into lethally irradiated mice. In addition to the undifferentiated cells in the MHC, cells with limited differentiation and/or retarded maturation were identified. The cytologic pattern of the majority of cells in MHC was of mixed type.


Coupling of fructose-1,6-P2 to aminated agarose by Schiff base reduction. Affinity chromatography of yeast aldolase. Fructose-1,6-P2 was immobilized by sodium borohydride reduction of the Schiff base formed with aminated agarose (AH-Sepharose 4B). The coupling occurs with high yield (25 mumoles immobilized fructose-1,6-P2 per ml packed gel) at neutral pH and room temperature. Schiff base reduction thus provides a convenient and mild coupling prodecure for sugar phosphates preserving their labile phospho ester bonds. As exemplified by a new isolation procedure for fructose-1,6-P2 aldolase from yeast, sugar phosphates insolubilized in this manner may be used for affinity chromatography of the corresponding enzymes, provided that contaminating unspecific phosphatases are removed in a preceding fractionation step.


Regulation of glucose transport in Aspergillus nidulans. Pyruvate and acetate inhibited the uptake of glucose by Aspergillus nidulans; although there were significant variations in glucose uptake rate, the intracellular concentration of acetate was almost identical in biotin-supplemented, normal and deficient cells. The in vitro activity of glucose-binding protein was not affected by biotin, avidin, acetate or acetyl-CoA.


Activation of complement by trypanosomes. Factors exhibiting anti-complementary activity released from trypanosomes after incubation at 20 degrees C were described. The active material was shown to consume the first component of bovine complement. While the anti-complementary factor(s) from T. lewisi could activate bovine, human and guinea pig complement, the factor(s) from T. congolense was observed to activate bovine complement, but not guinea pig and only slightly human complement. The roles of complement activating factor(s) of trypanosomes in the pathology of the disease are discussed.


Synthetic identification as a hexapeptide of alpha substance-IB inducing sexual agglutination in Saccharomyces cerevisiae. For the identification of a peptidyl principle inducing sexual agglutination in the yeast, 2 supposed hexapeptides (1a, b) were synthesized by the conventional method. The 1a (H-Arg-Gly-Pro-Phe-Pro-Ile-OH) revealed complete identity with the natural peptide in TLC, MS and biological property on agglutination. The 1b showed the sexual agglutinability in the same degree as 1a, though distinct differences were observed in the chemical data. Both 1a and 1b had a strong bitter taste.


Effects of bilateral lesions of the nuclei habenulae on plasma thyroxine levels in Japanese quail. Electrolytic bilateral lesions of th nuclei habenulae were made in male, adult photostimulated quail. Habenular destruction led to a marked decrease in the plasma thyroxine level (40%), whereas sham operated birds did not differ from controls. This result appears to be somewhat different from those obtained in mammals and the mechanisms of habenular-thyroid interrelationships are unknown.


Establishment of serum based essentiall free of proteolytic activity for the culture of mouse pancreatic islets. The present study demonstrates that a) serum based culture medium degrades 125I inhibits its proteolytic activity leading to the recovery of more insulin secreted by islets cultured in the presence of high glucose concentration alone or with glucagon; c) aprotinin also favoured the accumulation of secreted insulin by protecting the hormone from a residual degradative capacity of the hear treated serum.


Correlation between the susceptibility of E. coli to phagocytosis and their ability to invade HeLa cells in vitro. The susceptibility of several strains of E. coli to phagocytic killing by polymorphonuclear lencocytes and the ability of the same strains to invade HeLa cells were studied. It was found that only the strains resistant to killing by leucocytes were able to penetrate and multiply within HeLa cells.


Inhibition by verapamil of ionophore-mediated calcium translocation. Verapamil and other organic calcium-antagonists inhibit the A23187-mediated translocation of calcium from an aqueous into an organic phase.


In vitro mutagenicity of the soil nematicide 1,3-dichloropropene. The cis- and trans-isomers of 1,3-dichloropropene have been tested in the Ames mutagenicity assay system on Salmonella typhimurium tester strain TA 1535. Both isomers have been found to be mutagenic even without microsomal activation.


Intracellular localization of calcitonin in the C cells of the rat. Specific localization of C cells at the electron microscope level was achieved by an indirect immunoperoxidase technique. The hormone is present in the electron dense granules. The presence of granules apparently devoid of calcitonin was also detected.


Eye lens development and gamma crystallins in Discoglossus pictus (Anura). The ontogeny and localization of the gamma crystallins in Discoglossus pictus lens development has been determined. Using antibody specific for amphibian gamma crystallins in the immunofluorescence technique, it was found that gamma crystallins first appear in primary lens fibre cells in the lens rudiment, and continue to be restricted to the fibre area as lens development progresses. Thus the role of gamma crystallins as indicators of a differentiated state remains constant in amphibian evolution, having been demonstrated in the most archaic anuran superfamily, as well as in others more recently evolved.


The enterohepatic circulation of conjugated bile acids in healthy man: quantitative description and functions. A multicompartmental model describing the enterohepatic circulation of conjugated bile acids in man under steady-state conditions is proposed. The model encompasses conjugation; deconjugation and reconjugation; dehydroxylation; sulfation, desulfation and resulfation; dehydrogenation; and stereoselective rehydrogenation. A dynamic description of the enterohepatic circulation and a brief description of bile acid functions in health and dysfunctions in disease are also discussed.


Primary amides of bis-(2-carboxyphenyl)-disulfides with antimycotic activity. A series of bis-amides of 2,2'-dicarboxydiphenyldisulfides with monosubstituted N-alkyl groups (substances I leads to XXVI) or N-aralkyl groups (substances XXVI leads to XLII) was prepared and examined for in vitro antifungal activity. The substances were obtained by condensing the chloride of 2,2'-dicarboxydiphenyldisulfide with suitable amines. The fungistatic activity of the products was tested in vitro against the following four strains: Candida albicans, Candida tropicalis, Saccharomyces cerevisiae, Trichophyton mentagrophytes. The results obtained summarised in Tables I and II amplify the structure-antifungal activity relationships of this class of compound. The most active compounds proved to be bis-(N-n.heptyl-2-carboxami-dophenyl)disulfide (XX) and bis-(N-beta-4Cl-phenylethyl-2-carboxamidophenyl)disulfide (XXXV).


Effect of inhibitors of prostaglandin synthesis and metabolism on ovum transport in the rabbit. Several drugs known to affect prostaglandin synthesis, release, or metabolism have been tested for their effects on ovum transport in the rabbit after systemic or local administration. Acceleration of transport was obtained with several drugs; among the most effective were benzydamine, a blocker of thromboxane production, and L11204, an inhibitor of prostaglandin metabolism.


[Disorders in automatism and atrioventricular conduction during Luciani periods]. In isolated perfused hearts of rabbits and in spontaneously active preparations of the Purkinje fibers, conditions for occurrence of Luciani's periods were studied. Hypoxia, inhibitors of energy metabolism, inhibitor of the membrane Na+, K+ - ATPase ouabain, and acetylcholin were shown to induce primarily disturbances of the intracardiac conduction up to complete atrioventricular blockade in isolated hearts, periodic asystolia of ventricles occurring under these conditions only. With the aid of microelectrode recording of transmembrane potentials, Luciani's periods were found to be a periodic suppression of the Purkinje fibers' automatism. As distinct from the ventricles, no Luciani's periods occur in atria which indicates functional stability of the nomotopic pace-maker of the heart: the sino-atrial node.


Age and parity influences on maternal mortality: United States, 1919-1969. Comparisons of crude and standardized rates of maternal mortality show that changes in age and parity distributions of births had some influence on maternal mortality trends for the years 1919-1969 in the United States. Changes in the age and parity distributions of births for cohorts of U.S. women also influenced crude cohort maternal mortality rates to some extent.


Mortality in nineteenth century America: estimates from New York and Pennsylvania census data, 1865 and 1900. Given the lack of information on mortality in the nineteenth century United States, it seems appropriate to apply techniques which have been created for mortality estimation for developing nations with inadequate vital registration data, to the historical American experience. Two such related sets of techniques are the brass, Sullivan, and Trussell methods and the technique here called the Surviving Children Method, which utilizes the age structure of surviving children and the number of children ever born to women in various age or duration of marriage categories. Both techniques estimate child mortality. Coale and Demeny model life tables are used to extend child mortality estimates to adult mortality. The techniques are applied to census manuscript samples from seven New York counties in 1865 and seven Pennsylvania counties in 1900, both censuses having information on children ever born. The estimates confirm a drop in mortality between 1865 and 1900 in New York and large differentials between native and foreigh-born populations as well as between rural and urban populations.


The size-density hypothesis in Great Britain: analysis of a deviant case. Recent studies have found size of territorial units to vary inversely with population density, the only exception to this regularity being Great Britain, where size and density were found to be unrelated. The present research accounts for this anomaly by demonstrating Britain's historical conformity to the size-density relation. The size-density hypothesis is further supported by direct test, made possible by a recent reorganization of british counties. Results show that reorganization has restored the expected inverse relation between size and density and has restructured the size and density of counties in a manner precisely specified by underlying theory.


Epithelium of the human palatal tonsil used for new test antigen in  IIF examination (for pemphigus, pemphigoid antibodies and ANA). The author presents the results of IIF examinations for pemphigus, pemphigoid antibodies and antinuclear antibodies (ANA) on the epithelium of the human palatal tonsil obtained by tonsillectomy in patients with chronic hypertrophic tonsillitis. Tonsil epithelium is more sensitive to intercellular antibodies (IC Ab), and antibodies of the basal membrane zone (BMZ Ab) than sample tissue of the monkey esophagus, while its reaction to ANA is the same or even weaker than monkey esophagus.


Gastro-intestinal blood loss during administration of indoprofen, aspirin and ibuprofen. The acute effect of three non-steroidal anti-inflammatory drugs, ibuprofen, acetylsalicylic acid (ASA) and indoprofen, on faecal blood loss was investigated in 15 subjects by means of 51Cr-labelled erythrocytes. Ibuprofen (900 mg/day for 5 days) and indoprofen capsules and tablets (300 mg and 600 mg/day for 5 days, respectively) slightly increased the amount of blood eliminated in faeces. The increase was of the same order of magnitude for both doses of indoprofen. ASA (1,500 mg/day for 5 days) caused about a 6-fold increase in blood loss. Four days after withdrawal of ASA, faecal blood was still about twice as high as in faeces of subjects given ibuprofen and indoprofen. The method appears sensitive and reliable for comparison of the immediate effect of anti-inflammatory drugs on gastro-intestinal mucosa.


Mefenamic acid compared with ibuprofen in the treatment of rheumatoid arthritis. A randomized double-blind within-patient study of mefenamic acid compared with ibuprofen was performed on forty patients with rheumatoid arthritis. It was concluded that mefenamic acid and ibuprofen had an analgesic and anti-inflammatory effect which was not significantly different in the dosages employed. Apart from six complaints of drowsiness of ibuprofen with two complaints on mefenamic acid, the side-effects were similar.


Diclofenac (Voltaren) for the treatment of osteo-arthrosis: a double-blind comparison with naproxen. A double-blind, between-patient, comparative trial of diclofenac (Voltaren) and naproxen was carried out in 30 patients suffering from osteo-arthrosis of the hip or the knee. The drugs were given twice daily, morning and evening, during a period of two weeks. The daily dose was 100 mg for Voltaren and 500 mg for naproxen. The results indicate that Voltaren brought relief of pain and stiffness in a greater number of patients than did naproxen. The same finding was made regarding the influence on the range of joint movements, the difference reaching statistical significance. Voltaren appeared also to be better tolerated since the number of patients reporting side-effects was smaller and the complaints of less severity.


A double-blind parallel study of acetylcysteine-isoproterenol and saline-isoproterenol in patients with chronic obstructive lung disease. A double-blind parallel study in patients with asthma compared the safety and efficacy of saline-isoproterenol (SI) and acetylcysteine-isoproterenol (AI), when administered at home as an aerosol, over a one-week period, using a conventional nebulizer compressor. Measurements of pulmonary function revealed statistically significant differences between the two therapies for FEV1 and FVC in favour of AI. In the group treated with AI, the average sputum viscosity after six days of treatment was significantly less than pre-treatment values, or when compared to the results with SI treatment. No serious side-effects were reported during treatment with either therapy. These results indicate that acetylcysteine combined with a bronchodilator, such as isoproterenol, may be safe and of significant value in the treatment of patients with asthma who are also sputum producers.


Clinical trial comparison of two sustained release forms of amitriptyline. A double-blind between-group trial was carried out in 50 depressed patients to compare the efficacy of two sustained release forms of amitriptyline--Lentizol and Tryptizol 75. Patients received either Lentizol 50 mg or Tryptizol 75 75 mg each evening for the first week of the trial, and these dosages were then doubled for a further four-week trial period, with the proviso that dosage for individual patients could be maintained at, or altered to, original level where considered necessary by the investigator. Lentizol gave equivalent therapeutic effect to Tryptizol 75 despite the fact that overall dosage was one-third less than in the case of the latter.


A comparison of lomotil and imodium in acute non-specific diarrhoea. A multicentre trial was conducted to compare Lomotil and Imodium in the treatment of acute non-specific diarrhoea in general practice. A total of eighty-three patients contributed to the study and were randomly allocated to one of the two treatments. No statistically significant differences were found betwwen the drugs in their efficacy and speed of action in alleviating diarrhoea or in their palliative effect on nausea/vomiting and abdominal pain when present.


Topical treatment of eczema with triamcinolone acetonide benzoyl-beta-amino-isobutyrate: a double-blind comparison with betamethasone dipropionate. The results are reported of a double-blind study of the topical efficacy of triamcinolone acetonide benzoyl-beta-amino-isobutyrate (TBI), in 21 patients with symmetrically paired lesions of acute eczema. The effects were compared with those of betamethasone dipropionate. On the indication chosen, the two corticosteroids were equally efficacious; tolerance, also, was the same for both substances.


Effects of cimetidine and poldine on nocturnal gastric secretion in duodenal ulcer. Cimetidine inhibited nocturnal secretion of acid but only slightly inhibited the nocturnal secretion of pepsin in patients with duodenal ulcer. Administration of cimetidine (200 or 400 mg), together with an anticholinergic drug (poldine), augmented the inhibition of the nocturnal secretion of acid and of pepsin. The combination of an H2-receptor-blocking drug with an anticholinergic drug will have therapeutic application in the management of duodenal ulceration.


[CK MB versus total CK in the estimation of myocardial necrosis. Comparative kinetic analysis and evaluation of an immunological method]. It has been suggested that the adoption of a relatively specific marker of the myocardial cell, such as creatine kinase MB isoenzyme, can yield improved accuracy in estimating infarct size by serial serum sampling and compartmental analysis. Nevertheless, current methods for the evaluation of isoenzyme activity are cumbersome and unsuitable for clinical use. We have therefore employed a new test for the rapid determination of CK MB activity, based on the immunological inhibition of M subunities. In 19 patients not submitted either to intramuscular injection or to repeated defibrillations, a good correlation was found between indexes of necrosis based on MB and total CK determination (r = 0.94), with the cumulative MB release amounting to 16 +/- 4% of total CK. Significant differences were observed in 3 patients submitted to external cardiac massage (MB = 9 +/- 1% of total CK) thus suggesting a considerable extracardiac source of total CK due to the trauma of the skeletal muscle. The comparative kinetic analysis shows substantial differences between the two isoenzymes, not only concerning the greater disappearance rate of CK MB but, more significantly, related to a faster release of this isoenzyme from the myocardium, which has not been previously reported. The good correlations found between maximal appearance rate and cumulative enzyme release (r = 0.86) suggest that the former may represent an index of the rate of degradation of cellular membranes. Practical implications of these data are discussed.


Effect of cholestyramine on the symptoms of reflux gastritis. A randomized, double blind, crossover study. Bile acids have been proposed to be important in the pathophysiology of the syndrome of "bile reflux gastritis" after surgery. To examine the role of cholestyramine, an ion exchange resin that binds bile acids, on symptoms of this syndrome, we did a randomized, double-blind crossover study on 16 patients. No differences in frequency of abdominal pain, nausea, vomiting, or bitter taste were observed among cholestyramine (4 g, three times daily for 3 weeks), placebo, and routine (dietary restriction and ad libitum antacid) treatment periods. We conclude that this regimen of cholestyramine was ineffective in symptomatic treatment of bile reflux gastritis.


Ulcerative colitis in a patient with anti-B lymphocytotoxin and hypogammaglobulinemia. Lymphocytotoxins (LCT) have been recently reported in the serum of patients with inflammatory disease of the bowel, but up to now these antibodies have shown no specificity for B or T lymphocyte subpopulations. A 32-year-old patient with chronic ulcerative colitis, primary hypogammaglobulinemia and a very low number (0.5 to 1.5%) of B lymphocytes in peripheral blood is described. The presence in the serum of a LCT reacting specifically with B cells was demonstrated by cytotoxicity and direct immunofluorescence experiments. Intestinal immunofluorescence studies indicated a dichotomy between blood and gut immunoglobulins, and showed a heterogeneous distribution of plasma cells of the three major classes from the jejunum to the rectum. The significance of the association of hypogammaglobulinemia, chronic ulcerative colitis, and anti-B LCT is discussed. To explain the dissociation between blood and gut immunoglobulins, it is suggested that the intestine was, in this patient, a privileged site for differentiation of B cells.


Correlation between titer of antibody to hepatitis B core antigen and presence of viral antigens in the liver. Liver specimens of 31 autopsied cases of liver cirrhosis who had had detectable levels of antibody to hepatitis B core antigen (anti-HBc) inthe serum were stained for hepatitis  B core antigen (HBcAg) and hepatitis B surface antigen (HBSAg) by the direct immunofluorescence method. Their premortem serum samples were tested for HBSAg, antibody to HBSAg (anti-HBS) and anti-HBC. Persistent hepatitis B virus (HBV) infection as judged by circulating and/or liver HB antigens was identified in 18 patients, and all of them revealed a high titer of anti-HBC ranging from 2(11) to 2(16) by the immune adherence hemagglutination method. In contrast, anti-HBC titer of the remaining 13 patients without detectable HB antigens was less than 2(9), and the geometric mean titer of anti-HBC of the patients with persistent HBV infection was significantly higher than that of the patients without (13.9+/-1.55 versus 7.23+/-1.30; t test, P less than 0.001). A combination of circulating anti-HBS and hepatic HB antigens was found in one patient, whose serum revealed an anti-HBC titer of 2(12). On the basis of these results, a high titer of anti-HBC in the serum (immune adherence hemagglutination titer of 2(11) or more) seems to be a reliable indicator of persistent HBV infection in the liver.


Symptomatic treatment of diarrhea with bismuth subsalicylate among students attending a Mexican university. Students attending a Mexican university who developed diarrhea were randomly treated with bismuth subsalicylate or a placebo. One hundred and eleven were given 30 ml each 1/2 hr until eight doses (total dose of active drug 4.2 g) were given and 58 students received twice this dose (8.2 g of active drug) over the 3 1/2-hr treatment period. The number of unformed stools was significantly decreased in both bismuth subsalicylate treatment groups compared to the placebo controls for the period 4 to 24 hr after therapy. A reduction in diarrhea was additionally noted for the duration of the 48-hr surveillance period for the students receiving the higher dose of active drug. Subjective relief within 24 hr of therapy of the symptoms of diarrhea, nausea, and abdominal pain or cramps was reported with a significantly increased frequency in the bismuth subsalicylate group. The most pronounced effect of the treatment occurred in the United States students with diarrhea who had recently arrived in Mexico. This appeared to be related to the favorable effect of bismut subsalicylate on the course of toxigenic Escherichia coli infection. Students with shigellosis did not experience a prolonged illness in either treatment group.