Cytotoxic and agglutinating H-Y antibodies in multiparous female mice.

Pregnancy in inbred mice is associated with long-term accceptance of H-Y-incompatible skin grafts (in some "rejector" strain females) and with the formation of cytotoxic and agglutinating H-Y antibodies (in females generally). Yet there is no evident correlation between the two phenomena; postpartum females of nonrejector (H-2k), intermediate rejector (H-2d), and rejector (H-2b) strains all may produce H-Y antibodies, and postpartum H-2b females bearing H-Y-incompatible male skin grafts of long-standing may or may not produce H-Y antibodies depending on the individual recipient. Thus, it remains to be seen whether the presence of H-Y antibodies, as detectable to our sperm cytotoxicity and Protein A-SRBC agglutaination tests, signifies a corresponding presence of enhancing H-Y antibodies in pregnant females, and indeed whether enhancement (with respect to H-Y antigen) may play any part in the survival of the inbred male fetus.


[Effect of the fungal metabolites of Aspergillus flavus and A. niger on the tissue sorptive capacity of the large intestine].

Effects of metabolites of the tiny fungi of Aspergillus flavus and A. niger on the ability of mucuos membrane cells of the large intestine to absorb and exterminate certain dyes has been studied experimentally on guinea-pigs. It has been shown that under these influences, a violation of the cell and tissue metabolism in the large intestine occurs, namely, the absorbtion of the neutral red increased by 1.7 and 1.4 times, respectively, and the processes of extermination of the cells were inhibited by 1.5--1.6 times.


Role of catecholamine degradative enzymes and the adrenergic innervation in determining the cerebrovascular response to infused norepinephrine.

Cerebral blood flow responses to intra-arterial infusion of norepinephrine (NE) at 0.55 microgram/kg/min and 1.1 microgram/kg/min were studied in 3 groups of baboons. The flow was measured by the intracarotid 133xenon clearance technique using a computer program to calculate flow (height over area--H/A) flow (initial slope--is) and cerebral metabolic utilization of oxygen (CMRO2). The normal response to NE was to increase flow without significant changes in CMRO2. Blockade of catechol-o-methyl transferase (COMT) produced vasoconstrictor responses to these same NE doses. Monoamine oxidase blockade abolished the normal vasodilation. Denervation of the cerebral circulation with intracisternal 6-hydroxydopamine produced vasoconstrictor responses with flow (H/A) but not with flow (is). It is concluded that the extra-neuronal COMT enzyme is important in limiting the access of blood-borne NE to cerebrovascular constrictor receptors.


Infectivity of ground-up tick supernates prepared from Theilerai annulata infected Hyalomma anatolicum anatolicum.

Groups of Theileria annulata infected Hyalomma anatolicum anatolicum adults prefed on a calf for 1 to 6 days were separately ground in tissue culture medium-199, supplemented with bovine albumin powder, Fraction-V. Supernatant fluid was collected, made up with additional medium, so that each millilitre represented material from 25 ticks, and was injected subcutaneously into groups of cross-bred male calves. The results indicated that ground-up tick supernate (GUTS) prepared from unfed ticks was not infective, whereas that prepared from 1 to 6 days prefed ticks was infective. GUTS prepared from 3 days prefed ticks appeared to contain highest infectivity and 1 ml of it induced fatal theileriosis.


Case report of heterotopic bone formation in metastatic carcinoma of the colon.

The case of an 83-year-old woman, who was operated on for an adenocarcinoma of the sigmoid colon and died with retroperitoneal matastases, is described. The post mortem examination showed widespread heterotopic bone formation in these metastases. Gastrointestinal cancers and their metastases are liable to calcify and ossify, and they do so more frequently than other malignant epithelial tumors. A search through the literature led to the discovery of 35 other cases of this type. The highest frequency of heterotopic bone formation occurs in cancers of the distal portion of the large intestine and in pulmonary and lymph node metastases. The results of the present case support the view that bone formation derives from the metaplasia of stromal fibroblasts into osteoblasts. The knowledge that gastrointestinal cancers can calcify and ossify has a definite diagnostic relevance for the radiologist and gastroenterologist.


Transurethral treatment of urethral diverticula in women.

Six women with urethral diverticulitis and a history of having had previous operations for diverticula were subjected to transurethral diverticulotomy with a knife electrode. Each patient had multiple diverticula, some compartmented, located in the mid or most proximal segments of the urethra. All patients have been releived of the symptoms and infection during the postoperative period, varying from 1 1/2 to 7 years.


Experimental neurogenic bladder disorder in non-human primates.

These studies indicate that the monkey Macaca nemestrina provides a suitable model to evaluate the neurological mechanism of micturition. This animal has a sacral spinal center for micturition whereby the classification of primary patterns of neurogenic disorder into spinal reflex after suprasacral spinal cord section and autonomous after cauda equina section is validated. Attempts at dissociation of the spinal and vesical neurons by section of the cauda equina were characterized generally by raised rather than lowered tonus, irrespective of previous urinary diversion to prevent inadvertent overstretch of the bladder. No evidence was obtained to indicate that overstretch of the autonomous bladder is followed by loss of tonus but the survival times of the animals after cauda equina section were comparatively short. There was some indication that overstretch may induce coordinated contractility of the bladder when only the peripheral neuron and sympathetic innervation of the bladder are intact. Evidence was obtained that the monkey has a dual innervation of the mid urethra, in which the pressure profile is supported by alpha adrenergic receptors as well as some somatic neural control. The resting urethral pressure profile is preserved after low level section of the spinal cord or division of the cauda equina but is lower in amplitide after  overstretch of the autonomous bladder.


The vesicoureteral hiatus and paraureteral diverticula.

Two ureteral sheaths and the vesical musculature combine to form a watertight ureterovesical junction but the precise anatomy and function of each component are still somewhat contentious. The morphology was studied in postmortem specimens of children with and without paraureteral diverticula and urethral obstruction, and function by deductive reasoning from radiographic and surgical observations in living children. Waldeyer's fascia (the superficial sheath) of the ureter was found to seal the potential space between the tunnel wall and the ureter, and deficiencies were associated with hiatal hernias. The deep sheath provided anchorage of the ureter to the trigone and through the attachments of the superficial sheath to the bladder wall. Both sheaths and the tunnel muscles could be identified clearly and dissected precisely at operations involving the ureterovesical junction to facilitate the surgical procedures.


[A graphic method for the statistical evaluation of metabolic tests].

A graphical method was developed for the statistical evaluation of the results of metabolic tests; this method affords evaluation with due respect to the variance of characters in selected sets and the size of the tested group of animals. In principle, the method is based on the determination of the arithmetical mean and a 95% confidence interval of the selective mean of the values for each parameter of biochemism in each group of animals; these values are then expressed as per cent with regard to a mean reference value. Graphical comparison is enabled for both score and interval estimation of the distribution of a character in the studied group of animals, with a reference interval and reference mean.


[Economic significance of the prevention of losses caused by blood-sucking diptera in grazing dairy cows].

It was was demonstrated in an experiment that the blood-sucking dipterous insects adversely affected the efficiency of cows on pasture; these cows showed a significantly decreased milk yield and milk fat percentage. The experiment was conducted in South Bohemia at Chlum u Trebonĕ where seven species of gnats occurred in considerable abundancy, including the largest populations of Aedes sticticus (Meig.), Ae. cinereus Meig., Ae. vexans Meig. and Ae. punctor Kirby, which represented more than 80% of all gnats, and where gad-flies lived at the same time, represented by 18 species of five genera, chief among which were the species Tabanus bromius (L.) and T. maculicornis (Zett.), forming over 60% of all gad-flies. The experiment with 25 control dairy cows of the Bohemian Spotted breed lasted 62 days (July, August 1977). Diethyltoluamide in a 10% water emulsion was used as repellent with which cows were sprayed (with a special spraying apparatus) in 48h intervals. In the experimental (sprayed) cows, compared with the untreated control cows, milk yield per head per day increased by 6.23%, i. e. 43.56 kg milk, and butterfat percentage increased by 11,81%, representing 3.62 kg per head per day. In conversion to fat-corrected milk (milk with a constant 4% fat content), milk yield increased by 9.69%. In conversion to values per 1000 cows on pasture the net value of milk increased by 709.41 Kcs per day. The return rate of the money expended is 1.31 crowns. The results were statistically significant to highly significant.


[Toxoplasmosis of sheep in the lowland region of Western Slovakia].

The author describes the serological demonstration of toxoplasma antibodies in sheep of ten flocks kept in the lowland region of western Slovakia. The results of serological examination by the complement-fixation reaction (CFR) were positive in different degrees in nine flocks. In the remaining flock the blood of the sheep was not found to contain such antibodies. At the locality L. the author selected a small group of serologically positive sheep from the group of animals to be slaughtered and he studied the CFR values of antibodies in the course of nine months. Toxoplasma strain denoted as H-1 was isolated from the brain of a ram of this group which had a 1 : 256 antibody titre in the blood. This strain was found to be highly virulent for white mice. Toxoplasma antibodies were also identified in the blood of exposed workers, in the blood of dogs, mice and sewer rats. The patho-anatomic picture and isolation of toxoplasma strains from the brain of dead sheep or their foetuses which had the antibodies in the blood before death -- all this demonstrated the occurrence of congenital infection.


[Biochemical and hematological changes in sows during estrus].

After the second and fourth parturition of piglets, ten clinically healthy sows, weaned on the second day of life, were subjected to examination two to three days before heat, during heat (defined by typical changes on the outer genitals and immobilization in the presence of a boar) and two days after insemination. During the morning hours, four hours after the last feeding, blood was taken from V. cava cranialis. Seventeen parameters were determined in whole blood and in the blood serum. In the period of oestrus, compared with the period two to three days before this period and two days after insemination, a marked increase was observed in the concentration of the serum levels of 11-hydroxycorticosteroids, iron, and in the activity of alanine aminotransferase. The activity of aspartate aminotransferase was increased in heat only in comparison with the period of the two days after insemination. The concentration of haemaglobin in whole blood was significantly increased in comparison with the period before oestrus and after insemination. Further, in the heat period -- as compared with the time before it -- a considerable drop was observed in the content of inorganic phosphorus and vitamin A. The possible mechanism of the occurrence of other changes is discussed.


[Dynamics of urea concentration in blood cells of the domestic fowl during early post-incubation ontogenesis].

Urea was determined by means of diacetyl monoxim in the blood cells of 80 cockerels of the initial breed White Leghorn, commercial hybrid Primant. The highest urea concentration was ascertained on the 15th day of life: 392.33 +/- 85 mg per 10(12) blood cells. The content of urea in the blood cells irregularly deceased with the age of the cockerels. The minimum urea concentration was obtained on the 40th day of post-incubation life: 63.40 +/- 56.5 mg per 10(12) blood cells.


[Effect of chorionic gonadotropin administration on the concentration of testosterone in the blood of boars].

In intact boars, intravenous administration of 100 to 6000 I. U. chorionic gonadotropin elicited a pronounced rise in the plasma level of testosterone, depending on the time interval from the administration of chorionic gonadotropin and on the size of the administered dose. In the blood of castrated boars such an application of choronic gonadotropin did not influence the concentration of testosterone. It was inferred that the rise in the levels of blood testosterone in boars after administration of chorionic gonadotropin was specific for testicular incretion and indicated the endocrine reserve of the testes. There is a discussion concerning the importance of the functional testing of the incretion capacity of testes for differential diagnosis different forms o incretion hypogonadism.


[Serum selenium levels in sheep from birth to 90 days of age].

The results of the study of the dynamics of selenium in the blood serum were compared in 31 piglets from birth to the age of 90 days. The analyzed selenium values in the blood serum immediately after birth (0.14--0.20 ppm) provide evidence of the intra-uterine placental passage of selenium. In the period of colostral and milk nutrition, the serum concentrations of selenium showed a statistically insignificant variation, followed by an abrupt drop of the level of the microelement in the weaning period (60th day). The individual values in this period ranged from 0.08 to 0.12 ppm. Towards the end of the study, the level of selenium in the blood serum of the piglets returned to its initial value; this indicates that although the critical period connected with weaning has a transient nature, it should be averted for preventing the occurrence of a selenium-deficit disease; this can be done by adding a supplement of 0.2% solution of sodium selenate or a combined preparation of selenium and vitamin E-Selevit.


[Effects of Mebendazole and Cambendazole on enterohelminths in pigs].

Mebendazole, administered at a dose of 30 mg active substance per 1 kg of feed, was found to have 100% effectiveness on Ascaris suum and Cambendazole, administered at a dose of 1.5 g per 1 kg of liver weight, showed the same effectiveness in the control of Ascaris suum and Oesophagostomum dentatum. The effectiveness of both drugs on Trichocephalus suis and Strongyloides ransomi was low. Mebendazole and Cambendazole can be recommended for mass dehelminthization of pigs in affected stocks. Helminthoovoscopical examination of sows and fattened pigs showed an 88.6% extensity of invasion in sows, and a 28.3% and 33.9% extensity in three- and five-month-old pigs, respectively. Coccidiosis was found in 51.4% of the sows and Balantidium coli had an occurrence rate of 80.7 to 98.2%.


[Devitalization of Bordetella bronchiseptica in vitro using vapors of Persterile and triethyl glycol].

Using the method of bacterial carriers, the devitalizing effect was studied of Persteril and triethylene glycol vapours, acting in vitro, on a 24-hour culture of a mixture of 39 strains of Bordetella bronchiseptica, isolated from the nasal cavity of pigs which came from five stocks suffering from the clinical form atrophic rhinitis. After exposure of the carriers of Bordetella bronchiseptica to the action of spontaneously developing vapours o the mentioned chemicals, the devitalizing effect was determined by bacteriological examination. The vapours of the water solution of Persteril, containing 0.1% of peracetic acid, showed a 90.91 to 93.83% devitalizing effect after 48-hour exposure at room temperature. When the vapours of warmed concentrated triethylene glycol were used, a 98.57 to 100% devitalizingeff ect was obtained after a 72-hour exposure under the same temperature conditions. In experiements performed at a temperature of 37 degrees C, a 24-hour exposure sufficed for obtaining 91.67 to 100% devitalizing effectiveness. There is a discussion concerning the importance of the obtained results and the need for testing them experimentally by a methodically simple and cheap continual disinfection of the air and stable surfaces in premises for pig stocks affected by atrophic rhinitis.


[Resistance of Staphylococcus-aureus strains, isolated from food, to antibiotics].

Resistance to selected antibiotics was studied in 325 strains of Staphylococcus aureus, isolated from foodstuffs. Out of these strains, 50.46% were resistant to penicillin, 15.7% to ampicillin, 4% to streptomycin, 5.2% to erythromycin, 5.8% to chloramphenicol, 18.5% to tetracycline, 18.2% to oxytetracycline, 2.5% to gentamycin, 1.6% to canamycin, 53.5% to colistine and 9.2% to bacitracin. Eighty-five strains (26.15%) were sensitive to all the antibiotics used; 107 strains (32.92%) were resistant to one antibiotic, and 133 strains (40.93%) to two or more antibiotics.


[Pathogenicity of aerobically sporulating microorganisms: Bacillus cereus].

The pathogenicity of the metabolites of B. cereus was determined by bioassays with white mice, chick embryos, rabbits, and kittens. Cell-free filtrates of the cultures of several strains of B. cereus were used for application; in the mice the application was done i. v., i. p. and p. o., in the chick embryos via the allantoic sac, in the kittens p. o. and i. p., in the rabbits via tied-up sections of the small intestine by the loop-test method. It was revealed that some strains of B. cereus produced substances of exotoxin nature under suitable conditions. White mice and chick embryos were the best materials for their detection.


Toxic epidermal necrolysis in a monkey (Macaca fascicularis).

An adult male Macaca fascicularis monkey developed toxic epidermal necrolysis after ingestion of methylmercury. The clinical picture was characterized by the development of large cutaneous bullae with subsequent full-thickness epidermal exfoliation. Areas of sparse pelage were most affected, with the most severe exfoliation occurring on the palms, soles, face and ears. Erosions also developed within the oral mucosa and conjunctivae.


Neutralizing influenza antibodies, IgA and total protein in the nasopharyngeal secretions of subjects vaccinated by nasal route with the inactivated influenza vaccine prepared in the "Stefan S. Nicolau" Institute of Virology.

Intranasal administration of two doses of the inactivated influenza vaccine prepared in the "Stefan S. Nicolau" Institute of Virology was followed by rises in the level of neutralizing secretory influenza antibodies in 82% of the cases. The concomitant study of secretory antibody, IgA and total protein levels, as well as of the serum HAI influenza antibodies demonstrated that their evolution was parallel only in 23% of the vaccinees. The percentage of secretory antibody conversion was similar to the rate of protection conferred by the vaccine.


[Assessment of the results of treating II- and III-stage cervical cancer, parametrial variant, by using different sources of teleradiation].

The data on patients with the parametrial spread of cervical cancer, stage II and III, treated by different types of distant radiotherapy are analysed. An insignificant improvement of the 5-year cure results was noted only in patients in stage II, when treated on modern gammatron machines as compared with the previously used roentgenotherapy, and it may be due to a larger radiation dosage. The number of early and late complications is found to increase. Some methodical recommendations for treatment of these patients are given.


[Quantitative changes in the cellular makeup of the spleen in mice infected with the Rauscher leukemia virus and Brucella abortus].

Changes in the absolute number of splenic cells of mice infected with Rauscher leukemia virus (RLV) and a day later--with living Brucella (BA) were studied. The increase in the absolute number of splenic cells of mice infected with RLV + BA was initially caused by the lymphoid tissue reaction to Brycella and then by the development of leukemia. The number of reticular cells in the spleen appeared to be larger than the control (RLV) within all observation periods; the number of basophilic normocytes amounted to the control, but an increase in the erythroblasts number was noted a week later and reached the control level by the 30th day, practically being unchanged subsequently. In mice receiving RLV + BA there was the increased monocyte, plasmatic cell, megakaryocyte, myeloid series cell count. The shift of splenic granulocytes to the "left", the development of leukocytosis, blood neutrophilia, in particular, lagged 1--2 weeks behind in such mice. The number of normocytes getting into the blood was decreased. All this would result in a significant extension of the lifespan in mice RLV + BA.


[Distribution of 3H-7,12-dimethylbenz(a)anthracene in the rat neuroendocrine system].

Under study was the tritium distribution in tissues of the neuroendocrines system, liver and muscle after intravenous injection into female rats of an aqueous-lipid emulsion containing 3H-DMBA in a dose of 0.05 mci/kg. Thirty minutes following the injection the specific radioactivity of the liver, endocrinous glands, anterior and mediobasal hypothalamus tissues was higher than that of the cerebral cortex, dorsal hypothalamus. Label incorporation into the mediobasal hypothalamus was maintained at a higher level during 12 hours after 3N-DMBA administration than in the anterior and medial hypothalamus, cerebral cortex or muscle. A preliminary injection of adebit or I-DOPA failed to influence the character or rate of tritium uptake by tissues 30 minutes, after the labelled carcinogen was injected. The significance of DMBA retention in the hypothalamus for the mechanism of its action on the neuroendocrinous system is discussed.


A radial immunodiffusion method for the measurement of rat fibrinogen and fibrin degradation products.

The present report describes a technique for the production of monospecific rabbit antiserum to rat fibrinogen and its use in a quantitative radial immunodiffusion assay for measurement of rat fibrinogen and fibrin degradation products. It is a suitable technique for measurement of these parameters in small samples which can be repeatedly obtained from animals the size of rats.


Homozygous.D.

A homozygote for the Rh complex .D. associated with the rare Evans antigen was identified and her family tested: .D./.D. can be clearly distinguished serologically from -D-/-D-. The immune antibody in the serum of the propositus reacts with all cells tested except homozygous -D-, CwD-, cD- and Rhnull cells.


Failure of anti-D immunoglobulin to remove fetal red cells from maternal circulation.

A Rhesus negative female was found post delivery to have circulating cells of fetal origin. The neonate was typed as D-positive. In spite of more than conventionally adequate doses of anti-D immunoglobulin given to the mother, the fetal cell count in the maternal circulation remained unchanged. Further investigation showed the fetus to be a Du variant and to exhibit a diminished reaction with the batch of anti-D immunoglobulin used.


Sibship asymmetries of rhesus blood groups in the presence of maternal antibodies.

The genotypes of the children of R1r, R2r, and R1R2 fathers, and Rh-immunized rr mothers, were examined. R1r fathers had an excess of R1r over rr children, and R1R2 fathers had an excess of R1 r over R2r children. These asymmetries confirm the findings of a previous study. The possibilities of artefactual self-selection, of genotyping errors, and of errors in assigning paternity, were examined and excluded. Alternative models of genetic transmission and of antigenic structure were studied, but no basis for explaining the findings was found or formulated. Three possible biological explanations were formulated including (a) asymmetric segregation of the rhesus genes, (b) selective early fetal loss, and (c) a selective effect upon the performance of sperms bearing different haplotypes. The first of these three appeared unlikely. The data did not provide a basis for supporting or rejecting or differentiating the other two.


Characteristics of different rhesus alloantibodies in lymphocyte dependent (K cell) cytotoxicity to human erythrocytes.

The property of rhesus alloantibodies to elicit antibody-dependent, cell-mediated cytotoxicity (ADCC) against target erythrocytes carrying various Rh genotypes was studied. The killer activity of normal peripheral lymphocytes on human erythrocyte target cells carrying the appropriate antigens elicited by alloantisera was measured by 51Cr release at 18 h. There was no correlation between ADCC and antibodies directed to the antigens present on the surface of different genotypes of Rh-positive red blood cells. The agglutinin titre of different Rh antibodies showed no correlation with the level of ADCC although the degree of cellular cytotoxicity was different with different anti-D sera. Anti-C + D+ E antibody caused higher ADCC than anti-C + D and the lowest cytotoxicity was observed with anti-D and anti-D+ E. This raised the possibility that ADCC was elicited by antibodies directed to other specificities. K cell lysis of human red cells by human peripheral blood lymphocytes in vitro suggests that a similar mechanism may operate in vitro in the destruction of erythrocytes coated by allo or autoantibodies.


Application of microtiter solid-phase radioimmunoassay to the determination of hepatitis B e antigen.

Microtiter solid-phase radioimmunoassay (micro-SPRIA) was applied to the detection of hepatitis B e antigen (HBeAg) in the serum. Antibody against HBeAg to coat the microtiter plate and for radiolabeling was obtained from the serum of asymptomatic carriers of hepatitis B surface antigen by an affinity column of partially purified HBeAg. The micro-SPRIA was sensitive and could be performed without prior concentration of the test serum. HBeAg was detected in 21 (35%) out of 60 serum samples positive for hepatitis B surface antigen, all of which were negative by the conventional immunodiffusion method even after they had been concentrated threefold.


[HBs-antigenemia and the state of cellular and humoral immunity in children with chronic viral hepatitis B].

In chronic virus hepatitis B the causative virus replicates for a long time as manifested by HBsAg persistence. Examinations of 92 sick children revealed changes in cellular and humoral immunity indices. The content of T-lymphocytes (determined according to Bach et al.) was reduced to 31.5 +/- 1.4% in the exacerbation stage (the normal content 50.8 +/- 1.3%), the percentage of O-cells increased, while the number of B-cells according to Mendes et al. did not change significantly. The inhibition of adhesion of A-cells (Halliday et al.--A. F. Blyuger) and "immune" plaque formation (according to A. F. Blyuger) in the presence of HBsAg were also increased maximally in the exacerbation stage. HBs-antigenemia was found to occur most frequently in the exacerbation stage. The content of immunoglobulin G was reduced. An increase in the number of tissue lymphocytes and their blast forms (in the "skin window" sample by Rebuck) was demonstrated. The authors assume that the long-term persistence of HBs-Ag and, consequently, the maintenance of the pathologic process activity are due to a defficiency of cellular immunity factors. The prospects of enhancing cellular immunity in virus hepatitis B in children are discussed.


Malnutrition and gastroenteritis among Jamaican children.

In response to Resolution No. 7 of the Fifth Caribbean Health Minsters Conference of February 1973, the Executive Secretary convened a meeting of a stering committee comprising members of staff of CFNI, the Faculty of Medicine, U.W.I., PAHO, WHO and FAO. Arising from this, it was decided to produce the Strategy and Plan of Action of Combat Gastroenteritis and Malnutrition in children under two years of age. The implementation of that programme was launched in Jamaica in January 1976 by Dr. A.W. Patterson, the Principal Medical Officer of the Ministry of Health and Environmental Control. This preliminary report deals with observations of progess made in the field and the hospitals from the time of initial launching of the programme in Jamaica. Observation covers the time peroid from April 12, to July 27, 1976; and compares favourably with the situation as it exists in the country of Nigeria. Based upon observations, discussions, site visits and data collected, the following preliminary report provides implications for the implementation of strategies related to the SPACGEM PROJECT and the ultimate reduction of malnutrition and gastroenteritis among children under two years old in Jamaica.


[Effect of drugs used for the prevention of urinary calculi recurrence on the growth and metabolism of young experimental animals].

In the animal experiment should be made clear whether several medicaments which stood the test in the prevention of relapses of urinary calculi may be used without any danger also in the infantile carrier of concrements. For this purpose young rabbits high doses of diuretics, kation exchangers, aluminium oxide, extracts of the root of rubia tinctorum, succinimide and diphosphonate were given. Growth and development of the animals were negatively influenced by the medicaments, with the exception of the kation exchanger and the extracts of the root of rubia tinctorum. Numerous animals died under the administration of duiretics. The results of the examinations of metabolism only partly allow general conclusions. The medicamentous long-term metaphylaxis of the urolithiasis in childhood is also to be used like dietetic restrictions under strong indication and permanent control.


[Experience with the anti-androgen cyproterone acetate in the management of hirsutism].

Use of the antiandrogen cyproterone acetate in the treatment of hirsutism.--25 women with hirsutism or hypertrichosis faciei were subject to a "reverse sequential therapy" with cyproterone acetate (Hammerstein's regimen) for 1 to 3 years. In 8 patients, a limited, in 14 patients a satisfactory and in one woman a good result could be recorded. Cycle irregularities and subjective side effects were within a tolerable range. Studies of the hair pattern in 15 patients revealed a higher telogen rate as well as increased diameters of the hair stalks, compared with controls, in the temporal region of the head. These alterations disappeared in the course of the treatment. In the parietal region of the head no significant differences of the hair pattern were found in comparison with the controls and during application of the steroids.


[Heteromorphism of the corynebacteria. III. D- (dark) and C- (clear) cell types and multiseptate specimens].

A population of Corynebacterium diphtheriae may consist of cells with accented (osmiophilic) cytoplasm (cells of the "dark" type, or D type) and cells with cytoplasm having no pronounced osmiophilic properties (cells of the "clear" type, or C type). The divergence of the population into cells of the D and C types occurs at the stage of cell division, the original mother cell being able to divide into 2 or more individual cells belonging to different types (elongated multiseptate cells). At the same time no morphological disturbances in septation may be observed. The ability of each type of cells for division into the corresponding individual daughter cells indicates their being biologically valid. The mixed (D--C) population of Corynebacterium diphtheriae is considered to be a sign of the dissociation of bacterial culture.


[Structural changes in spores under high temperature exposure].

The electron microscopy of ultrathin sections of B. cereus spores showed that no lysis and destructive changes occurred in the main structural components of the spores when heated to 99 degrees C (in distilled water). By the time 99% of the population were destroyed, the spores seemed to preserve the exosporium of the sporoderm, the cortex and the sporoblast intact. Even autoclaving at 120 degrees C for 15 min brought about no visible changes in the ultrastructure of the spores, though it killed the whole spore population.


[Experience in using P. hamadryas for assessing the effectiveness of a peroral vaccination method against plague].

For the first time P. hamadryas were used for studying the effectiveness of oral immunization with dried live plague vaccine. Oral immunization was shown to produce morphological changes in the organs and tissues of the monkeys, which indicated the immune transformation of the organism. The challenge of the immunized animals with the infective agent introduced in aerosol showed the effectiveness of the inhalation and oral methods of immunization. P. hamadryas proved to be a suitable model for the evaluation of the effectiveness of oral vaccination. A more precise quantitative evaluation of the effectiveness of oral vaccination against plague requires further research.


[Pathogenicity of clinical strains of Pseudomonas aeruginosa].

The study of 208 Ps. aeruginosa clinical strains, introduced intraperitoneally into white mice, revealed the statistically significant prevalence of pathogenic cultures (87.5--100%). The pathogenic strains of Ps. aeruginosa were found to have statistically significant differences in their cultural and biochemical properties depending on the kind of clinical material: the strains isolated from blood formed mucoid colonies, the zones of hemolysis and thermolabile or thermostable alkaline phosphatase, and typing could be made in 100% of the isolated cultures; the strains isolated from material of closed cavities formed mucoid colonies and the zones of hemolysis; the pathogenic strains isolated from material of open cavities showed only a tendency towards greater activity in the formation of extracellular sline and greater capacity for the formation of clarification zones on yolk agar as compared with nonpathogenic cultures.


[Use of the A-1 and A-2 elective nutrient media for isolating Ps. aeruginosa].

A total of 327 samples of material obtained from patients with surgical infection and 434 samples taken from various objects of the hospital environment were studied with the use of elective culture media A-1 and A-2. 72 cultures of Ps. aeruginosa were isolated, their biochemical properties and the character of their growth were studied; and the clinical strains were also tested for sensitivity to phages and antibiotics. In 677 cases the capacity of Ps. aeruginosa to proliferate in media A-1 and A-2 was compared with their capacity to proliferate in other culture media (blood agar, serum agar, Levine's medium). The results of this study showed considerable advantages of the elective culture media under study for the isolation of pseudomonades, especially from the objects of the hospital environment.


Effect of D-Trp6-LH-RH on the pituitary-gonadal axis during the luteal phase in the baboon.

An effect of E-Trp6-LH-RH (superactive LH-RH agonist) in the pituitary and ovarian function was examined. Four regularly cycling baboons were used for this study. After determination of control values of plasma levels of LH, oestrogen and progesterone during the entire menstural cycle, D-Trp6-LH-RH was infused subcutaneously for 7 days during the early luteal phase in these four baboons. An infusion of D-Trp6-LH-RH increased plasma LH and oestrogen, but it failed to alter the plasma level of progesterone. From these results, it seems unlikely that 1) D-Trp6-LH-RH has a luteolytic effect, and 2) an increased ovarian oestrogen causes luteolysis in the baboon.


Suppression of the TSH response to TRH by thyroxine therapy in differentiated thyroid carcinoma patients.

Absent response of serum thyrotrophin (TSH) after stimulation with 200 micrograms synthetic thyrotrophin-releasing hormone (TRH) was used as a criterion of adequate suppression of TSH in the treatment of thyroid carcinoma patients with thyroxine. The mean causing total suppression of the response was 223 micrograms of thyroxine per day. At this dose level about 40% of the patients had serum thyroxine concentrations above the upper reference interval and only 10% had elevated triiodothyronine concentrations. In some patients the TSH response to TRH varied between absent and low normal when tested at long intervals. The ideal dose of thyroxine is obviously slightly higher than the smallest one causing total suppression of the TSH response to TRH, i.e. about 250 micrograms a day. The individual dose must be found using the TRH stimulation test because serum thyroid hormone levels cannot be used as a guideline for adequate dosage. In some patients the thyroid remnant of apparently normal thyroid tissue was not totally suppressed although the thyroxine dose was definitely above the level causing suppression of the response to TRH.


Enhanced TSH stimulating effect of TRH by sulpiride in man.

Sulpiride, a specific dopaminergic blocker, was administered im to 6 normal male volunteers (100 mg) alone or in association with L-DOPA (500 mg per os, 90 min before sulpiride) or with TRH (400 micrograms iv in bolus, 30 min after sulpiride) and blood samples were obtained for TSH radioimmunoassay at various intervals before and after the treatments. Sulpiride alone produced a slight increase of plasma TSH levels which was inhibited by L-DOPA pre-treatment. The previous administration of sulpiride resulted in a marked increase of the TSH response to TRH. It is suggested that dopamine and TRH may interact to modulate pituitary secretion of both TSH and prolactin, though the hypophyseal thyrotrophs and lactotrophs show a different sensitivity to the common stimulatory and inhibitory substances.


Effects of methylmercaptoimidazole (MMI), propylthiouracil (PTU), potassium perchlorate (KClO4) and potassium iodide (KI) on the serum concentrations of thyrotrophin (TSH) and thyroid hormones in the rat.

Male Sprague-Dawley rats were given graded doses of methylmercaptoimidazole (MMI), propylthiouracil (PTU), KClO4 or KI in drinking water for 4 days, or the lowest effective dose of each drug for various times. The rats were sacrificed at 1--2 p.m. and serum T3, T4 and TSH concentrations were measured by radioimmunoassays. It was found that administration of 5 mg/l of MMI, 10 mg/l of PTU and 100 mg/l of KClO4 for 4--14 days induced a transient rise in serum TSH and a fall in serum T3 or T4 or in both. The effects of KI were not consistent. In another series of experiments, PTU (10 mg/l) was given in drinking water for 4 days, and then graded doses of T3 or T4 were given iv, or 100 ng of TRH was injected into a tail vein, or the animals were exposed to 4 degrees C for 30 min. The initial high TSH levels were further increased by TRH and cold and decreased by T3 and T4. The PTU-treated animals had goitres after 4 days. We infer that low doses, that is to say 10--100 times lower than previously described, of antithyroid drugs induce a hypothyroidism characterized by an increased TSH level and a decreased serum T3 or T4 level or both. A 4 days' treatment with PTU (40 mg/l in tap water) is a suitable tool for studying the effect of various conditions on TSH secretion.


Effect of two sulphonylureas on the dose kinetics of glucose-induced insulin release in normal and diabetic subjects.

The effect of two second generation sulphonylureas, gliquidone and glibenclamide, on insulin secretion has been studied in the basal state and in combination with glucose infusions in normal controls, patients with mild maturity-onset diabetes, and subjects with normal glucose tolerance but low insulin response. When injected intravenously, gliquidone caused rapid elevation of plasma insulin, peaking at 5 min in all groups, while glibenclamide induced a slow rise in insulin. Insulin response was somewhat smaller than normal in diabetics and low insulin responders. In all groups, 25 micrograms/kg glibenclamide and 200 micrograms/kg gliquidone were equipotent in generating an insulin response at the basal state. Equipotent amounts of sulphonylureas were combined with glucose in fusions at three different dose levels. The glucose-insulin dose relationships, established by giving glucose alone, demonstrated curves that were flatter, and shifted to the right of the control in diabetics and low insulin responders, the changes being more marked in the former group. Addition of sulphonylurea induced a left shift in the dose-response relationships in controls and low insulin responders; under these conditions the effect of glibenclamide was more pronounced than that of gliquidone. The dose-response relation for glucose-induced insulin release was completely normalized in low responders when sulphonylureas were added. In the group of mild diabetics, insulin response to glucose was enhanced by sulphonylureas only to a modest extent, the dose-response curves remaining grossly abnormal.


Drug-induced kinetic perturbations of the marrow blasts in acute leukemia. Effects of the daunorubicin, cytosine arabinoside and 6-thioguanine combination.

Cell kinetic changes induced in the marrow blasts by treatment with a triple cytotoxic regimen including daunorubicin, cytosine arabinoside and 6-thioguanine (DAT) were investigated in 6 previously untreated acute nonlymphocytic leukemia patients. A decrease in the labeling and mitotic indices was consistently observed 24 h after administration of daunorubicin, suggesting a G2 block and a preferential lytic effect on the S-phase cells operated by the drug. Conversely, cytosine arabinoside and 6-thioguanine in combination induced a series of kinetic perturbations variable from case to case; however, three principal patterns of kinetic response were recogized and discussed in detail. Useful information for the planning of a more rational antileukemic therapy can be drawn from a systematic study of the kinetic effects induced by drug combinations.


A modified assay for studies of cultured granulocyte precursors: cryopreservation of stimulating mononuclear cells.

Mononuclear cells (MNC), isolated from peripheral blood of healthy donors, were cryoprotected by dimethyl sulfoxide and stored in liquid nitrogen. Colony-stimulating factor (CSF), produced by cryopreserved MNC, was compared with that of nonfrozen controls in a double-layer agar system with human bone marrow as target cells. Our results indicate that cryopreserved MNC retain their ability to stimulate myelopoiesis-committed stem cells after freezing. In addition, evidence was obtained that CSF of feeder layers changes, depending on the duration of preincubation and cell concentration. In a system where either stimulating or target cells are cryopreserved the dynamics of interactions between normal or abnormal cell lines can thus be studied.


Erythroid repopulating ability of bone marrow cells in polycythaemic mice.

The erythroid repopulating ability (ERA) of femoral bone marrow cells was determined in polycythaemic CBA, C57Bl and Balb/c mice. Polycythaemia was induced by hypertransfusion or exposure to chronic hypoxia in silicone rubber membrane enclosures. The results obtained demonstrate decreased ERA after both types of polycythaemia, with the exception of ex-hypoxic Balb/c mice. A decrease in the number of erythroid repopulating cells in DNA synthesis was found in hypertransfused and exhypoxic CBA mice in comparison to normal values. These studies indirectly indicate the contribution of cells committed to erythropoiesis in measurement of ERA.


Biosynthetic studies and gamma-chain composition in the Greek type of hereditary persistence of fetal hemoglobin and in its association with beta-thalassemia.

Hematological data, biosynthetic studies and gamma-chain structure of three heterozygotes for HPFH Greek type and of two heterozygotes for both HPFH and beta-thalassemia are reported. In the HPFH heterozygotes, hematological data were normal and globin chain synthesis balanced, while subjects carrying both HPFH and beta-thalassemia presented a thalassemic picture and the same degree of alpha/non-alpha-chain imbalance as the beta-thalassemia carrier belonging to the same family. The gamma-chain composition studies showed only the presence of Agamma-chains in HPFH; in the association HPFH/beta-thalassemia also some Ggamma and Tgamma were found. The mechanisms determining the high production of Hb F in the association HPFH/beta-thalassemia are discussed.


The unstable Hb Genova (beta 28Leu replaced by Pro) in an East African Family. Family study and the effect of splenectomy.

A fifth family with the unstable Hb Genova is reported from Kenya, East Africa. This almost certainly represents an independent mutation. The beneficial effect of splenectomy has been carefully assessed in one member of the family.


Reticuloendothelial phagocytic function in children with beta-thalassemia major.

Reticuloendothelial phagocytic capacity (REPC) was determined in 14 children with beta-thalassemia major, by means of technetium 99m sulfur colloid uptake, who had not had splenectomy. No difference was observed in the REPC between patient and controls. The REPC of liver and spleen were evaluated separately by determining the half-time for the clearance of 99mTc from the blood. The REPC of both liver and spleen in patients was expected to be decreased when compared with controls; however, we found that the REPC of the liver was increased in patients and that there was no difference between patients' and controls' spleen values. This suggests that chronic anemia and hemosiderosis do not alter the REPC in beta-thalassemia major.


Identification of an erythrocyte pyruvate kinase variant in a family from Latium with non-spherocytic congenital haemolytic anaemia.

Erythrocyte PK deficiency was detected in a family from Latium in Italy. This PK variant is characterized by normal or increased activity immediately after blood collection, instability to storage, to heat and to urea. Only in the propositus the mutant enzyme exhibited an increased Michaelis constant for PEP, slightly increased inhibition by ATP and an altered optimum pH value. The kinetic anomaly was only partially corrected by activation with F-1, 6-DP and by addition of 2-ME. From these results it can be concluded that in the family observed two distinct erythrocyte PK alterations were demonstrable: instability in the propositus and his father; low affinity for PEP and altered optimum pH value only in the propositus.


Differences between individuals with hemoglobins Istanbul and Saint-Etienne (alpha 2 beta 2 92F8 His replaced by Gln).

The unstable hemoglobins Istanbul and Saint-Etienne have the same amino acid substitution (alpha 2 beta 2 92F8 His leads to Gln). Despite this, there are some clinical and hematological differences between the individual with Hb Istanbul and the one with Hb Saint-Etienne. These are: (1) the clinical course of the patient with Hb Istanbul before splenectomy was more severe when compared with that of the individual with Hb Saint-Etienne; (2) although Hb F was found within normal range in the individual with Hb Istanbul, a high level of Hb F (19%) was observed in the patient with Hb Saint-Etienne. The alkali-resistant Hb found in the former was of adult type and in the latter case it was of fetal type. The possible explanations for these differences are discussed.


Two cases of acute leukaemia in pregnancy.

2 cases of acute leukaemia which developed in the course of pregnancy are reported. The first was a 34-year-old woman who presented with acute myeloblastic leukaemia late in the second trimester and received combination chemotherapy. A normal male infant was delivered. The second patient, aged 24 years, presented with acute lymphoblastic leukaemia early in the second trimester and was treated with the same regime. Pre-eclamptic toxaemia developed at 29 weeks gestation. Intra-uterine death was confirmed 1 week later.


Effect of long term treatment with hydrophilic colloid on serum lipids.

Thirteen patients with essential hyperlipoproteinaemia were treated over periods of 2--29 months with hydrophilic colloid made from Psyllium. Reduction of the increased serum cholesterol levels averaged 16.9 per cent, and the corresponding figure for the increased triglyceride levels was 52.0 per cent. The reduction of cholesterol and triglyceride was statistically significant (p less than 0.0025 and p less than 0.0005 respectively). No significant change in normal blood lipid levels was observed on administration of the Psyllium colloid.


Vaterian diverticula as a cause of acute pancreatitis.

The association of duodenal diverticula and pancreatitis is rare. Various types of such diverticula are reviewed, especially intra- and extraluminal Vaterian diverticula in which common and pancreatic duct terminate. The pathogenesis of the pancreatitis in case of interposed Vaterian diverticula is thought to be mechanical by means of the creation of a closed Vaterian pouch in which higher pressures produce reflux of bile and pancreatic enzymes. Two patients with this particular type of duodenal diverticula are presented.


Neurotoxicity of sodium cyanate. New pathological and ultrastructural observations in Maccaca nemestrina.

The effects of sodium cyanate (NaNCO) on the nervous system of Maccaca nemestrina were studied at 2, 4, and 6 months of administration of the drug. The two groups injected with daily doses of 35 and 25 mg/kg/day of Na-cyanate developed a predominantly demyelinating lesion in the pyramidal tracts of the spinal cord. No neuronal changes were observed in the motor cortex, basal ganglia, midbrain, medulla or anterior horn cells of the spinal cord. There was no evidence of peripheral neuropathy. A comparison between the cyanate induced neuropathy in the rat and in the primate was drawn. Ultrastructurally, both species developed a demyelinating process of central or peripheral myelin characterized by vacuolation of the myelin sheath, removal of myelin debris by macrophages and re-myelination. There was little evidence of axoplasmic damage except for an occasional distended fiber containing abundant dense bodies and whorls of neurofilaments. Oligodendrocytes and Schwann cells were electron microscopically intact and participated actively in remyelination. Maccacas maintained at 15 mg/day and sham animals remained normal clinically and anatomically. The predominantly myelinotoxic effect of cyanate is similar to that produced by other myelinotoxic agents and is attributed to a selective modification of myelin proteins by carbamylation.


Side-effects of prostaglandin synthetase inhibitors.

A short review is given of some of the adverse reactions to prostaglandin synthetase inhibitors. Broadly, these side-effects can be divided into those common to the whole group, and those more or less characteristic of the individual drugs. Among the former, symptoms from the gastrointestinal tract and from the central nervous system are the most conspicuous. Skin reactions, bronchospasm, and serious blood dyscrasias have been reported for several of these drugs and the list of more rare side-effects is long. It is concluded that drugs like phenylbutazone and oxyphenbutazone should not be used for treatment of dysmenorrhea because of the risks of serious adverse reactions. However, even if among the newly introduced compounds none can be said to be free from risks, some seem to have an acceptable ratio between therapeutic efficacy and side-effects.


Prostaglandin synthetase inhibitors. Drugs which affect arachidonic acid metabolism.

Drugs may alter prostaglandin production by acting on the various pathways of arachidonic acid metabolism. The liberation of arachidonic acid from membrane-bound phospholipids, induced by the enzyme phospholipase A2, may be inhibited by mepacrine and the steroidal anti-inflammatory agents. The bio-transformation of the free arachidonic acid, by the enzyme cyclooxygenase, to the unstable endoperoxide intermediates is inhibited by non-steroidal anti-inflammatory agents. Thus, the generation of all the prostaglandin products is prevented. This action can explain the anti-inflammatory, analgesic, antipyretic actions as well as the ulcerogenic properties of these aspirin-like compounds. An alternative metabolic pathway of arachidonic acid, via the lipoxygenase system, can be inhibited by an acetylenic analogue and a newer compound, phenidone. The unstable endoperoxide intermediates can be transformed by blood platelets into the pro-aggregating products, thromboxanes. This pathway can be selectively inhibited by a variety of experimental compounds. Prostacyclin, a potent vasodilator and inhibitor of platelet aggregation is the major product of endoperoxide transformation in blood vessels. Its formation can be inhibited by lipid peroxides. Selective actions on one or more steps in arachidonic acid metabolism can lead to a different profile of the products subsequently generated. Such a diversion of biosynthetic pathways may be an underlying mechanism in certain pathological conditions, perhaps even in dysmenorrhea.


Suppression of uterine activity by prostaglandin synthetase inhibitors.

During hypertonic saline induction, the evolution of intrauterine pressure, the oxytocin response and abortion were delayed in naproxen-treated patients. The PG synthesis inhibitors naproxen, mefenamic acid and ibuprofen decreased the high uterine resting pressure ('tone'), the frequency of contractions but not always the active pressure ('amplitude') in dysmenorrheic patients, with a coincident decrease in pain. The naproxen-sodium treatment decreased prostaglandins F and E in menstrual blood and uterine jet washings by 60--80 per cent.


Endogenous prostaglandins in dysmenorrhea and the effect of prostaglandin synthetase inhibitors (PGSI) on uterine contractility.

The plasma concentration of 13,14-dihydro-PGF2 alpha during menstruation were determined by gas chromatography in 6 non-dysmenorrheic and 10 dysmenorrheic women. Nine out of 10 dysmenorrheic women were found to have increased levels (greater than 50 pg/ml) of the metabolite compared with mean level 25 pg/ml for non-dysmenorrheic women. All 9 women with elevated PGF2 alpha-metabolite levels responded favourably to treatment of dysmenorrhea with prostaglandin synthetase inhibitors. Determinations of PGF2 alpha in the endometrium carried out by gas chromatography-mass spectrometry showed 4 times higher concentrations in 5 dysmenorrheic women compared with 5 non-dysmenorrheic subjects. Treatment of dysmenorrhea with placebo or naproxen 250 mg and 500 mg in 6 patients resulted in decrease in tonus and amplitude of the contractions with a more rapid effect following administration of naproxen 500 mg while no effect was seen in 5 out of 6 patients following administration of placebo.


Prostaglandin synthetase inhibitors and dysmenorrhea. A survey and personal clinical experience.

A survey of earlier published studies on treatment of dysmenorrhea with prostaglandin synthetase inhibitors is given and personal clinical experiences are presented. The time when treatment should start in relation to the onset of bleeding is also discussed. A survey of studies published in English and Scandinavian literature yielded 532 patients. Pain relief was experienced in 64 to 100 per cent of the patients in these studies. The incidence of side-effects has generally been low but in a few studies a high incidence was reported. In the current study 34 patients with prinary dysmenorrhea completed the douule-blind, placebo controlled study on naproxen. The patients were treated for two cycles, 16 with naproxen and 18 with placebo. The mean relief score indicated a "slight to good" pain relief in the naproxen group and "no alleviation" in the placebo group. The difference is statistically significant (p = 0.003). Supplementary medication was much more used in the placebo group compared to the naproxen group (p = 0.01). In the placebo group no change whatsoever was demonstrated in alleviation of interference with every-day life, whereas there was a statistically significant improvement in the naproxen group. No major side-effect was registered. Thus none of the subjects withdrew from the study.


Influence of surface lipids on skin carcinogenesis in rats.

Skin tumours were indeuced in female Wistar SPF-rats by different polycyclic aromatic hydrocarbons, benzo[alpha]pyrene (BP), dibenz[alpha, h]anthracene (DBA), 7,12-dimethylbenz]alpha]anthracene (DMBA), and 3-methylcholanthrene (MCA) being applied on the dorsal skin of 20 rats each. DBA was not carcinogenic under the experimental conditions. DMBA proved the most potent carcinogen, and MCA was more potent than BP. Half of the animals in each group underwent skin-surface lipid extraction (SSLE) before the application of carcinogen. SSLE did not influence the cumulative number of rats with skin tumours during an observation period of 15 months nor the type of tumours induced. The lipid extraction, however, increased the latency period and decreased the rate of tumour development when BP and MCA acted as carcinogens. On the contrary, SSLE enhanced the rate of tumour production by DMBA and reduced the latency period. The role of sebum and its composition in skin carcinogenesis is discussed, and an explanation of the different influence of SSLE on BP and MCA carcinogenesis is discussed, and and explanation of the different influence of SSLE  on BP and MCA carcinogenesis in contrast to DMBA carcinogenesis is sought in differences in metabolic activation of the carcinogens.


Carbonic anhydrase activity in mouse endocrine pancreas.

Histochemical staining for carbonic anhydrase (CAH) was demonstrated in the mouse pancreas. Light microscopically, a strong reaction for CAH was found in the B-cell region of the islets, in blood vessels inside and outside the islets, and in centroacinar cells and ductules. In contrast, no distinct reaction was seen in the peripheral A- and D-cell regions of the islets, or in the cytoplasm of the acinar cells. A weak, irregular staining could, however, be observed in some nuclei of the acinar parenchyma. A newly-developed ultrastructural modification disclosed a distinct reaction in a varying number of the secretory granules of the B-cells, whereas a sparse, irregularly-distributed reaction was observed in the nuclei and cytoplasmic ground substance, and in association to the plasma membranes and microvilli of these cells. The CAH reaction was in all portions of the pancreas abolished by acetazolamide. The specificity of these results is discussed. The findings are suggested to indicate presence of a true CAH activity in the B-cells of the mouse pancreas.


The effect of centrally administered TRH on blood pressure, heart rate and ventilation in rat.

Different doses (3, 16, 80, 400 and 2 000 ng per rat) of TRH or alternatively saline were infused into the lateral ventricle of urethane-anaesthetized rats and blood pressure, heart rate, respiration rate and tidal volume were recorded. A dose of 3 ng TRH caused a significant elevation of blood pressure and heart rate, whereas 16 ng was needed for respiration rate to be elevated. There was no change in respiratory minute volume during the experiment. We conclude that TRH has profound physiological effects and that TRH, given centrally, is a potent hypertensive, chronotropic and tachypnoeic agent.


Thyroid hormones and TSH, prolactin and LH responses to repeated TRH and LRH injections in depressed patients.

Twelve patients with unipolar depressive disorders received 600 microgram of synthetic TRH or LRH, in a random order, for 3 days each. Placebo injections were given as two 3-day courses prior to and between the active treatments. Serum TSH, prolactin (Prl) and LH were measured by radioimmunoassays prior to the experiment as well as immediately before and 20 min after each injection. Serum T4 and T3 were determined by radioimmunoassays before the treatments and 24 h after the first two TRH injections. Serum T4 level in depressed patients did not differ from controls. Serum T3 level in depressed patients was significantly below, and the reverse T3 level was slightly above the normal mean. However, the latter difference was not statistically significant due to the large variation of rT3 levels among the depressed patients. The TSH  responses did not differ from that of controls after the first injection but the responses after the second injection were lower than in a control study. The Prl responses to TRH were sub-normal in seven out of eight patients. Blunted LH responses to LRH were seen in three patients.


Inhibitory effect of charcoal-treated porcine follicular fluid upon serum FSH levels and follicular development in the rhesus monkey.

Injection of charcoal treated porcine follicular fluid into 4 intact, 4 long term castrate and 2 postmenopausal rhesus monkeys brought about a selective decline in serum FSH levels. Luteinizing hormone levels were not significantly decreased. Intraperitoneal injection of 4 ml porcine follicular fluid every 8 hours for the first 4 days of the menstrual cycle led to a decrease in follicle and granulosa cell growth observed at that midcycle. Treatment with porcine serum did not exert this effect.


Luteal phase deficiencies in peripubertal rhesus monkeys: mechanistic considerations.

Short luteal phases in peripubertal monkeys were identified by abbreviated progesterone secretion. Evaluation of the hormonal profiles for LH, FSH, and estradiol revealed that depressed serum concentrations of FSH during the follicular phase and LH and estradiol during the luteal phase were associated with luteal defects. In addition, morphological differences in the corpora lutea of short and normal luteal phases were identified. A mechanism is presented whereby inadequate follicular phase FSH secretion results in abbreviated luteal function.


Prostaglandin F2 alpha and its 13-dehydro analogs: comparative luteolytic effects in vivo.

Prostaglandin F2 alpha (PGF2 alpha) was identified as a luteolytic hormone in sheep (Nature, New Biol. 238, 129, 1972). Attempts to use PGF2 alpha for the pharmacological control of luteolysis in normal cycling sheep met with only partial success due to the rapid clearance of PGF2 alpha from the blood. In addition treated animals showed moderate to severe cardiovascular and gastrointestinal side effects. Accordingly, experiments were carried out to determine whether PG analogs might be more effective as pharmacological luteolytic agents. These compounds, which consisted of a number of the 13-dehydro analogs of PGF2 alpha, were administered to both sheep and monkeys either directly into the ovary or into the systemic circulation to examine them respectively for direct luteolytic activity and for resistance to metabolism. In addition in both the sheep and the monkey smooth muscle activity of the analogs was determined by recording uterine contractions in vivo. Several 13-dehydro analogs including some 16-fluoro derivatives were shown to have luteolytic activity equal to, or in some cases greater than, PGF2 alpha itself. Furthermore most of these compounds showed a marked resistance to the 15-OH-PG-dehydrogenase enzyme in vivo as evidenced by their luteolytic activity when infused intravenously. In terms of uterine contractions, several luteolytic analogs showed markedly diminished smooth muscle activity, and in some cases, complete absence of activity. These results suggest that the receptors governing the luteolytic effect on the one hand, and the smooth muscle effect on the other, possess different structural specificities. Recent studies which we have carried out on the effect of PGF2 alpha on corpus luteum (CL) blood flow support this conclusion. CL capillary blood flow was continuously monitored by means of a miniaturized Geiger-Müller probe inserted through the center of the CL in both the in situ and the autotransplanted ovary of the sheep. Capillary blood flow was measured by the clearance rate of 85Krypton injected periodically into the ovarian artery before and during the induction of luteolysis with PGF2 alpha. It was concluded that the initiation of luteolysis is not dependent on a smooth muscle effect of PGF2 alpha on the capillaries of the CL, a finding which supports the results with the synthetic analogs devoid of smooth muscle activity. More recently, in the primate model used (Macaca fascicularis) we have demonstrated that certain metabolically stable analogs are luteolytic when given intravenously, subcutaneously, or orally. These results demonstrate a rational approach to both drug synthesis and biological evaluation and suggest that a once-a-month contraceptive agent, based on a luteolytic analog of PGF2 alpha, devoid of smooth muscle activity (side effects) and metabolically stable in the bloodstream may become a reality.


Relative quantitation of monoamine histofluorescence in young and old non-human primates.

The relative content of monoamines within identified brain stem neurons in 4 and 20-year old monkeys (Macaca nemestrina) was determined with microspectrofluorometric techniques. Intraneuronal monoamine content was found to decrease with age in the locus coeruleus, substantia nigra and raphe and was found to be reduced further in the locus coeruleus by the presence of lipofuscin granules. These data indicate that intraneuronal monoamine content is reduced in the aged macaque.


Integrated morphology of neuronal catecholamines and neurophysin in the aged macaque.

A new method for the simultaneous visualization of brain peptides and monoamine neurotransmitters was employed to analyze the integrated morphology of hypothalamic catecholamines and neurophysins in young and old monkeys. Immunocytochemical analysis using bovine neurophysin revealed a dual papulation of light and dark stained cells in the paraventricular nucleus in young and old macaques. In general, both populations of neurons stained with less density in old macaques indicating the possibility of a reduced content of neurophysin. Further analysis using specific neurophysin antisera for vasopressin or oxytocin revealed an appreciable decrease in the number of vassopressin-containing perikarya in the 20 year monkey whereas oxytocin-synthesizing neurons did not show a similar change in numbers with age. Qualitatively, terminal innervation patterns of hypothalamic catecholamines remained strikingly constant in spite of marked reductions in dark-stained neurophysin perikarya of the paraventricular nucleus.


Isolation and partial identification of immunoglobulin from T cells.

Using fowl anti mouse (Fab)2 antibody, a protein has been collected from culture fluid and cell lysates of thymoma cells and stimulated thymocytes. This protein did show an immunoglobulin arc on immunoelectrophoresis against abovementioned antibody and against rabbit anti mouse Ig serum. No precipitation lines have been produced by mono-specific anti-mouse gamma, mu and alpha sera. On reduced PAGE heavy and light chains were present. Mobility of the heavy chain was between mu and gamma chains and its apparent molecular weight was calculated at appr. 65,000 daltons. The light chain mobility corresponded to mouse serum kappa chains.


The stimulation of a T cell response in the syngeneic host by the P-815 mastocytoma cell and the isolation of a tumor-associated antigen which has some H-2 antigen characteristics.

Although not obviously immunogenic when developing intraperitoneally or subcutaneously, the P-815 mastocytoma cell induces a significant immune response when injected intradermally into the syngeneic host. In some animals the immune reaction leads to spontaneous tumor regression and survival of the animals, but in most cases the effectively initiated immune-reaction is abrogated by as yet unknown mechanisms. The T cell is identified as the killer cell both in vivo and in vitro during the described period of immune reactivity. By means of two antibodies from two different species, rendered specific for the P-815 tumor cell by in vivo absorption in DBA/2 mice, two distinct antigens have been identified, isolated and partially purified from P-815 cell membranes. One of them is obviously different from H-2 antigens, the other one shows striking similarities with H-2 antigens (molecular weight, lectin binding properties), but does not coprecipitate with H-2 antigens in an indirect precipitation assay, using Staph. aureus Cowan I as the Fc-binding agent.


Comparison of alterations in the histamine-diamine oxidase system during acute intestinal ischaemia in pigs, dogs and rabbits; evidence for a uniform pathophysiological mechanism?

Among various vasoactive substances histamine was also suggested to induce circulatory arrest following superior mesenteric artery occlusion. Thus the involvement of the histamine-diamine oxidase system was studied in intestinal ischaemia using three animal species. In pigs, dogs and rabbits aminoguanidine, the specific inhibitor of diamine oxidase, shortened the survival time after mesenteric infarction. Under these conditions the diamine oxidase activity in the intestinal wall was reduced in animals treated by saline whereas the histamine content was not altered significantly. Plasma histamine levels were increased considerably in the portal vein of pigs during the revascularization period if the animal were pretreated by aminoguanidine. Similar findings were obtained in dogs. It was concluded that in all three species investigated the diamine oxidase protects the organism against the deleterious effects of at least one of its vasoactive substrates-histamine.


B-mode echoencephalography in the normal and high risk infant.

Commercially available high resolution, contact, gray scale imaging systems can now dependably visualize the normal and abnormal ventricular system as well as some other intracranial structures in all newborns. On 25 normal infants and 41 high risk infants, 135 B-mode echoencephalograms were performed. The technique for obtaining these scans is described. The normal lateral ventricle at the midbody in term infants is 0.9--1.3 cm wide (mean, 1.1 cm). Normal ratio of lateral ventricle to hemisphere is 28% (range, 24%--30%). High risk premature infants have a ratio of 31% (range, 24%--34%). The demonstration of hydrocephalus and cystic intracranial masses is reliable and the correlation with computed tomography is excellent. Postoperative or high risk infants can be repeatedly evaluated without radiation, at a lower cost, and more rapidly with ultrasound than with computed tomography. Ventricular size can be closely monitored and shunt failure detected at any early stage.


John Caffey Award: lithiasis due to interruption of the enterohepatic circulation of bile salts.

Bile salts are formed from cholesterol and conjugated in the liver, excreted via the biliary system into the duodenum, reabsorbed in the ileum, stored temporarily in the hepatic bile salt pool, and reexcreted into the biliary system. This normal enterohepatic circulation of bile salts is both efficient and rapid. Interruption of the enterohepatic circulation of bile salts may cause cholesterol cholelithiasis or oxalate urolithiasis. Clinical and radiologic features of pediatric patients with gallstones and urolithiasis secondary to abnormalities of the ileum are reported. The pathophysiology of lithiasis due to interruption of the enterohepatic circulation of bile salts is discussed. This enteric cause is included in the differential diagnosis of cholelithiasis and urolithiasis in infants and children.


Radiographic evaluation of adenoidal size in children: adenoidal-nasopharyngeal ratio.

Adenoidal-nasopharyngeal ratios (AN ratios) obtained by simple linear measurements from lateral skull radiographs are described. The AN ratio reliably expresses adenoidal size and patency of the nasopharyngeal airway. The validity of the ratio as an indicator of adenoidal size was determined by evaluation of measurements of radiographs of 1,398 infants and children and comparison with a subjective visual assessment made by experienced observers in 92 patients. An AN ratio greater than 0.80 was present in 34 of 36 patients (94%) subjectively judged to have enlarged adenoids.


The so-called megaureter-megacystis syndrome.

Megaureter-megacystis describes the appearance of the urinary tract in children with massive primary vesicoureteric reflux and it sequellae. The initial symptoms, radiographic findings, diagnostic misconceptions, and treatment for 22 male children are discussed. Incorrect diagnoses, including obstruction, neurogenic bladder dysfunction, and "megacystis," were made in 16 children; treatment was inappropriate in 14. In only eight boys were diagnosis and treatment prompt and correct.


Pulmonary pseudocysts in newborn infants with respiratory distress syndrome.

Twelve neonates who developed intrathoracic cystlike structures ("pseudocysts") are described. All infants had clinical and radiographic respiratory distress syndrome and all were treated with assisted ventilation. Pulmonary interstitial emphysema preceded the development of the pseudocysts in all cases. The pseudocysts appeared between 0 and 6 days of life (average, 2.4 days), and radiographically documented disappearance occurred in 10 patients at 3--18 days old (average, 7.0 days). Two patients had persisting pseudocysts at 8 and 25 days of age, and no subsequent radiographs. In no case did these structures persist symptomatically or require surgical intervention such as has been described with patients in other series. In two cases, abrupt disappearance of the pseudocysts was accompanied by increased extraalveolar gas in other locations. Eight patients developed radiographic bronchopulmonary dysplasia, which was severe in two of the cases.


Ultrasound of renal sinus: new observations.

Technical factors and diagnostic criteria that permit discrimination among diseases of the renal sinus are described. Because the size of the collecting system changes with the state of hydration, a standard approach permits optimal comparison of examinations performed on different occasions. A fluid challenge is indicated if relative or partial obstruction is suspected. Ureteric compression permits optimal delineation of the collecting system but is indicated only in selected situations. Both tumor and blood clot within the renal sinus appear as echogenic masses without a significant acoustic shadow. Serial ultrasound studies demonstrate the resolution of the blood clot. Both in vivo and in vitro studies of renal stones demonstrate that the acoustic shadow of nephrolithiasis is best seen with low gain and with the stone within the focal zone of the transducer.


Intraarterial vasopressin infusion for treatment of Mallory-Weiss tears of the esophagogastric junction.

Five patients with refractory gastrointestinal bleeding from Mallory-Weiss tears of the esophagus were successfully treated with intraarterial infusions of vasopressin. Although transcatheter embolization has been shown to control the hemorrhage from these lesions, increased experience with and ease of vasopressin infusion suggest that infusion therapy should be the primary treatment method when more conservative measures are inadequate. Embolization techniques may be reserved for cases in which vasopressin therapy is contraindicated or unsuccessful.


Focal spot size and scatter suppression in magnification mammography.

The improved image quality using magnification in film-screen mammography is related to a complicated interplay between focal spot size, x-ray tube output, detector resolution and sensitivity, air gap size, and target dimensions. Preliminary clinical evaluation of magnification mammography indicates that accuracy of diagnosis has been considerably enhanced. Additional technical and clinical evaluations are continuing, as suggested by mathematical modeling, in order to determine the best possible magnification protocols. While a small focal spot (less than 300 micrometers) is highly recommended for both contact and magnification with the film-screen systems, the smallest focal spot sizes (150 micrometers and smaller) may neither be necessary nor the best in all situations of reduced dose magnification mammography.


Esophageal cancer: radiographic chest findings and their prognostic significance.

In 103 patients with a diagnosis of carcinoma of the esophagus, admission chest films were reviewed for abnormal findings attributable to the carcinoma. The presence or absence of these findings was analyzed and correlated with tumor resectability, complications, overall survival, and survival as related to tumor location. Unexpectedly, the group of patients who had normal films had a lower resectability rate (30% vs. 41%). There was no significant difference in survival rates of patients with or without chest film abnormalities (12.4 vs. 11.7 months).


Complications of central venous catheterization.

The complications of central venous catheterization are discussed in a review of experience and of the literature. The anatomy surrounding the subclavian and internal jugular veins is described. Indications and contraindications of catheterization are reported. Common and unusual complications are discussed and illustrated. Laceration of pleura, subclavian artery puncture, hematoma, catheter malposition, fragment embolization, air embolism, venous thrombosis, and infection are included. The radiologist is responsible for recognizing immediate, as well as delayed, complications of central venous catheterization.


A new computed tomographic sign of pancreatitis.

Computed body tomography has become useful in the diagnosis of pancreatic disease. Pancreatitis frequently results in lateral and posterior extension of inflammatory tissue into the pararenal fat planes, which can be visualized by CT. In our series it was associated with clinically diagnosed pancreatitis. Of 100 cases studied for abdominal pathology where pancreatic visualization was optimum, 10 had enlargement of the pancreas with destruction of soft tissue planes extending into the left pararenal space and clinical findings of pancreatitis. Carcinoma of the pancreas was identified in 12; no abnormality was identified in 49; the remaining cases were mixed intraabdominal and retroperitoneal pathology. The value of this sign lies in separating inflammatory processes from neoplastic disease; the sign was not found in normals.


Double-contrast gastrography of the fundus and cardia: normal landmarks and their pathologic changes.

The normal radiographic landmarks of the gastric fundus are the macromucosal (rugal) pattern, the micromucosal (areae gastricae) pattern, and the esophageal rosette. In a comparison of 100 normal double-contrast and conventional barium examinations, the landmarks were most consistently and reliably demonstrated by double-contrast technique. In a group of 36 patients with various types of fundal pathology, double-contrast gastrography demonstrated distinctive changes in these landmarks and led to reliable diagnoses in the majority of patients. Double-contrast gastrography is considered the preferred method for examining patients with suspected abnormalities of the fundus or cardia.


Cholecystokinetic cholecystography: comparison of the effect of intramuscular ceruletide to a fatty meal.

A comparison study of 80 patients using either intramuscular ceruletide or a fatty meal to contract the gallbladder after oral cholecystography is described. The maximum mean percentage reduction of the gallbladder area was significantly greater with ceruletide (59%) compared to a fatty meal (29%). At all time intervals, a 40% or more reduction in gallbladder area occurred in a higher percentage of patients receiving ceruletide, with improvement in cystic and/or common duct visualization occurring at an earlier time than with a fatty meal. There were no adverse effects after gallbladder contraction when large or small calculi were present.


Ultrasound appearance of decidual reaction in the uterus during normal pregnancy.

The sonographic appearance of the decidual changes undergone by the uterus during normal pregnancy is described in 88 ultrasound examinations on 75 obstetrical patients. The relation of these decidual changes to the site of placental implantation and their preferential location in the posterior uterus suggests that they represent a combination of choriodecidual sinuses and prominent draining uterine veins. The decidual reaction is most prominent between 18 and 32 weeks with a decline near term. There is also a wide variation in the extent of decidual reaction during normal pregnancy preventing its use as a sensitive indicator of normal versus abnormal pregnancy.


Lateral wall of the olfactory fossa in determining intracranial extension of sinus carcinomas.

The role of plain skull radiography and pluridirectional tomography in determining anterior cranial fossa extension of paranasal sinus tumors is reassessed. The lateral wall of the olfactory fossa, a thin bony plate forming part of the roof of the ethmoid sinuses, is routinely visualized on plain skull radiography and pluridirectional tomography in the coronal plane and serves as an indicator of intracranial tumor extension. In a series of 47 patients with paranasal sinus tumors, 100% true positive and 3% false negative interpretations of the integrity of the lateral wall of the olfactory fossa were made with pluridirectional tomography. Interpretations with plain skull radiography were 90% true positive and 3% false negative. Assessment of the integrity of the lateral wall of the olfactory fossa by these techniques provides an accurate evaluation of the presence of intracranial tumor extension by this route. Computed tomography in the coronal plane with contrast infusion is a useful adjunct.


Carpal injuries: analytic approach and case exercises.

Radiographic wrist relationships are reviewed emphasizing the posteroanterior view, and analyzing the three normal arcs, principles of parallelism, and overlapping articular surfaces. Use of these concepts, which are not stressed in the literature, enables the radiographic interpreter to easily arrive at a definitive diagnosis and to detect and interpret subtle and complex abnormalities. Case material is included to emphasize major different diagnostic points.


Evaluation of the chronic inhalation toxicity of a manganese oxide aerosol. III. Pulmonary function, electromyograms, limb tremor, and tissue manganese data.

Monkeys and rats were exposed to 11.6, 112.5, and 1152 micrograms Mn/m3 as an Mn3O4 aerosol twenty-four hours per day for nine months. Various evaluations of pulmonary function, electromyographic activity, limb tremor, and tissue manganese levels were conducted. No exposure related effects on pulmonary function, limb tremor, or electromyographic activity were observed. After nine months of exposure Mn levels were elevated in a near dose related manner in kidney, lung, spleen, and blood. However, by six months postexposure there were no differences as compared to the control group in tissue Mn levels which could be attributed to the exposure conditions.


Jejunal mucosa in marasmic children. Clinical, pathological, and fine structural evaluation of the effect of protein-energy malnutrition and environmental contamination.

Seven children suffering from marasmus were investigated clinically, biochemically and morphologically. The fine structure of the jejunal mucosa obtained by peroral biopsy was evaluated. The mucosal changes noted agree with the only other ultrastructural study reported by Brunser et al. (8) and add information on three additional features: an increase in theliolymphocytes, excessive epithelial cell extrusion and abnormalities in the appearances of the mucosal plasma cells, suggesting possible local deficiency in immune function.


The effect of oral pancreatic enzymes on the intestinal flora of protein-deficient vervet monkeys challenged with Vibrio cholerae.

Jejunal bacterial flora in 11 protein deficient vervet monkeys (Cercopithecus aethiops) and four controls was studied. These were the same animals from an investigation previously reported in which it was shown that pancreatic extract modified the course of cholera infection in protein-deficient monkeys. The present study reports in addition that these animals the fluid in the upper jejunum contained significantly increased numbers of bacteria including Enterobacteriaceae compared to its predietary state and to that of the controls. After challenge to these animals with Vibrio cholerae, the jejunal bacterial flora in the protein-deficient animals given placebo remained unchanged, whereas pancreatic extract-treated animals showed a quantitative and qualitative recovery of their jejunal bacterial flora. Pancreatic extract hastened the return of altered intestinal flora to predietary levels.


Changes in nitrogen balance of depleted patients with increasing infusions of glucose.

Depleted patients were maintained on intravenous infusions of amino acids and glucose with constant N intake (173 mg/kg body weight), and three different levels of energy intake (15.4, 37.6, and 58.5 kcal/kg) given sequentially for 4 days each. Changes in N balance were abrupt and maximal in 1 to 2 days. Maximal changes in N balance preceded, and were not dependent on maximal changes in fat and glucose metabolism. N retention increased 1.7 mg/kcal of increased energy balance, during both hypocaloric and hypercaloric intakes, a value similar to that observed in normal adults. No increase in resting energy expenditure occurred with increasing energy intake during negative energy balance. During positive energy balance resting energy expenditure increased by 1 kcal for each 5 of intake. It seems likely that increasing energy restores mainly that portion of lean body mass associated with fat deposition; and rapid restoration of lean body mass requires high N intakes. At zero energy balance, N balance in these depleted patients was only slightly positive at an intake of 173 mg N per kilogram. This is about twice the intake of N required to maintain zero N balance in normal adults.


Juvenile chronic myelogenous leukemia and dermal histiocytosis. In Von Recklinghausen's disease.

A 4-year-old boy with multiple café-au-lait spots and a family history of neurofibromatosis had generalized edema, histiocytic rash characterized by benign histiocytic infiltration, hepatomegaly, and life-threatening infection. Six months later, progessive splenomegaly led to juvenile chronic myelocytic leukemia that eventually proved fata. The case represents an important association of diseases.


Rocky mountain spotted fever in Connecticut: human cases, spotted-fever group rickettsiae in ticks, and antibodies in mammals.

Three parameters were used in 1976 and 1977 to assess the status of Rocky Mountain spotted fever (RMSF) in Connecticut--compilation and review of clinical data on suspected human cases for the 13-year period 1965--1977, examination of tick tissues for spotted fever-group rickettsiae by the hemolymph test and direct immunofluorescence, and analyses of mammalian sera for antibodies against Rickettsia rickettsii. There were six presumptive RMSF cases which probably originated in Connecticut. Four of these cases occurred in areas where the American dog tick, Dermacentor variabilis, abounds. A total of 2994 ticks were examined by the hemolymph test. Rickettsia-like organisms were observed in 67 (2.9%) of 2330 D. variabilis and two (0.6%) of 351 Ixodes sp. near scapularis. Fewer than one-half of these organisms stained positively with spotted fever-group conjugate. Microagglutination tests on 1093 mammalian sera indicated that eight (16%) of 49 raccoons, 14 (2.6%) of 549 white-tailed deer, eight (1.7%) of 470 white-footed mice, and one of two gray squirrels had agglutinins in titers greater than or equal to 1:8 against R.  rickettsii. Spotted fever-group rickettsiae are present at low frequency in inland as well as coastal regions of Connecticut.


Heterochromatin and satellite DNA in man: properties and prospects.

In reviewing the properties of heterochromatin and satellite DNA in man, it is clear that the human genome does not readily lend itself to experimental tests of the postulated functions for satellite DNA. Since the spectrum of known structural properties of vertebrate and invertebrate satellite DNAs are broadly overlapping, an alternative avenue is to experimentally manipulate the heterochromatin of an organism, and then evaluate the generality of the results. When this is done in Drosophila melanogaster, the one organism where such an experimental approach is indeed possible, the results provide no support for most of the popular hypotheses concerning satellite DNA function. They do, however, reveal an important effect on the meiotic system, namely that the position of crossover events can be markedly altered in the presence of heterochromatin known to be rich in satellite DNAs. This effect is not peculiar to Drosophila, since supporting data are readily available from natural situations in both mammals and grasshoppers. In all such cases, the effects are most easily discernible where the heterochromatic blocks are substantial in size, and non-centric in location, situations which do not apply in man. The human system, however, offers other potentials. The ubiquity of naturally occurring heterochromatic polymorphisms, coupled with the extreme sensitivity of the human genome to perturbation, offers some scope for assessing the possible somatic effects of alterations in the amount of satellite DNA.


Prophylaxis against ampicillin-associated diarrhea with a lactobacillus preparation.

The efficacy of a lactobacillus preparation (Lactinex) in preventing ampicillin-associated diarrhea in adult inpatients was studied. In a double-blind procedure, 98 patients were assigned randomly to receive one packet of Lactinex (Lactobacillus acidophilus and L bulgaricus) or placebo four times daily for the first five days of ampicillin therapy. Cases of diarrhea were reviewed independently and classified according to etiology. Complete data were obtained for 79 patients--43 received placebo and 36 received Lactinex. Diarrhea occurred in nine (21%) patients receiving placebo and in three (8.3%) patients receiving Lactinex; the difference was not statistically significant (p = 0.21, Fisher's Exact Test). When the patients with diarrhea unrelated to ampicillin were excluded (50%), the incidence of ampicillin-induced diarrhea in the placebo group (14%) was significantly greater (p = 0.03, Fisher's Exact Test) than in the Lactinex group (0%). Prophylactic administration of lactobacillus preparations may be effective in preventing ampicillin-induced diarrhea; however, prophylactic administration appears to be justified, on a cost/benefit basis, only in patients with a history of antibiotic-induced diarrhea.


Drug therapy reviews: pharmacotherapy of diarrhea.

Gastrointestinal physiology, and the pathophysiology, diagnosis, symptoms and treatment of acute and chronic diarrhea are reviewed. Drugs used in the treatment of diarrhea include opiates (morphine, codeine), synthetic anti-diarrheals (diphenoxylate, loperamide), anticholinergics (atropine, propantheline), adsorbents (kaolin, pectin, cholestyramine resin) and Lactobacillus acidophilus. Chronic diarrhea and acute diarrhea caused by microorgansims, drugs and viruses are described. The management of diarrhea can be divided into three categories: (1) supportive therapy (fluid and electrolyte replacement); (2) symptomatic therapy which improves the consistency of the stool and reduces the frequency of bowel movements; and (3) specific therapy aimed at treating the cause (e.g., antibiotics for bacteria-induced diarrhea) or blocking the cellular mechanisms of fluid and electrolyte loss. Most acute diarrheal conditions can be managed successfully by avoiding oral solids and ingesting carbohydrate-electrolyte solutions. Synthetic antidiarrheals may increase the toxicity associated with bacterial diahhrea.


Pharmacist monitoring of parenteral nutrition: clinical and cost effectiveness.

The effect of pharmacist involvement in total parenteral nutrient (TPN) therapy on patient outcome and cost of therapy was studied. Data from 26 patients who received standard TPN solutions without pharmacist monitoring (Group 1) were compared with those from 26 patients whose TPN therapy was individualized (by use of a minicomputer) and monitored by a pharmacist (Group 2). Six patients from each group who were 35 days of age or younger and who received TPN as the only caloric source for 8 to 20 days were compared for clinical response. Mean duration of TPN therapy increased form 12.3 +/- 9 days for Group 1 to 14.8 +/- 12 days for Group 2, and the TPN use rate for Group 2 was 31% above that for group 1. The mean daily charge for TPN was greater for Group 1 ($72.00) than for Group 2 ($50.18). The pharmacy's mean cost per course of TPN for Group 2 was $44.10 less than that for Group 1. The mean weight gain in Group 1 was significantly less (4 g/day) than that in Group 2 (17 g/day) (p less than 0.05) (for the six patients per group compared). Pharmacist monitoring of TPN reduced the pharmacy's costs and patient charges for TPN and improved the patients' clinical responses to TPN.


Cellular immune deficiency with autoimmune hemolytic anemia in purine nucleoside phosphorylase deficiency.

Immunologic and metabolic abnormalities were studied in a five year old boy with 0.07 per cent of normal erythrocyte purine nucleoside phosphorylase activity. The clinical course is characterized by severe autoimmune hemolytic anemia, a transient neurologic disorder with tremor and ataxia, and minor infectious illnesses. There is severe lymphopenia with decreased absolute numbers of T and B lymphocytes. Mitogen-stimulated blastogenesis is reduced, but response to allogeneic lymphocytes is normal. A monoclonal IgG protein is present. There is hypouricemia, elevated plasma inosine level, hypouricosuria and an increase in the urinary concentration of inosine and guanosine. The pattern of heterozygote distribution in the patient's family is compatible with an autosomal recessive trait in which heterozygotes are identifiable. In addition, the unusual laboratory and clinical manifestations of this patient illustrate the heterogeneity of the clinical syndrome associated with purine nucleoside phosphorylase deficiency.


Calcium binding by a myeloma protein.

We describe a patient with immunoglobulin G (IgG)-kappa myeloma and severe, long-standing, asymptomatic hypercalcemia. Serum nonprotein-bound calcium concentration was 5.2 mg/dl (normal 4.2 to 5.0 mg/dl) at a time when total serum calcium concentration was 17.8 mg/dl. The patient's myeloma protein, IgGCAB, and Fab fragments of IgGCAB migrated more anodally when agarose gel electrophoresis was performed in the absence of calcium ion than when electrophoresis was performed in the presence of calcium ion; 60 other myeloma proteins did not demonstrate such behavior. Purified IgGCAB bound 1.5 calcium ions with a single dissociation constant of 1.2 X 10(-4) M. We speculate that the rare syndrome of myeloma and high protein-bound calcium is due to binding of calcium to variable regions of the myeloma antibody molecules.


Effect of dexamethasone on prolactin secretion in late pregnancy.

It is established that PRL secretion is regulated by estrogens. Glucocorticoids, on the other hand, suppress estrogen secretion during pregnancy and may also inhibit PRL by direct hypothalamopituitary action. In this study PRL and estradiol were determined with specific radioimmunoassays in 14 women during gestational weeks 28 to 34 prior to, during, and following short-term intramuscular dexamethasone administration (12, 8, and 4 mg on three consecutive days) used for prophylaxis of RDS in preterm infants. There were no significant alterations in PRL serum concentrations; estradiol showed a significant drop (P less than 0.001) during all 3 days of treatment, returning to the pretreatment level on posttreatment day 1. The PRL and TSH responses to 200 micrograms of intravenous TRH on day 2 or 3 of dexamethasone treatment in six women during late pregnancy were not inhibited. Short-term dexamethasone treatment with pharmacologic doses does not suppress the physiologic secretion and release of PRL or the release induced by TRH during late pregnancy.


Pregnancy-associated ovarian refractoriness to gonadotropin: a myth.

Ovulation was induced in three of five rhesus monkeys during midpregnancy using human menopausal gonadotropin/human chorionic gonadotropin therapy. No evidence of ovarian refractoriness to gonadotropic stimulation was found. It is concluded that cyclic ovarian function in these primates is suspended during gestation and into the puerperium because pituitary gonadotropin secretion is insufficient to support folliculogenesis.


Deposition of IgA in renal glomeruli of mink affected with Aleutian disease.

The glomerular deposition of immunoglobulin (Ig) was studied in sapphire mink affected with terminal Aleutian disease (AD). Fluorescein conjugated Ig-class specific antiserums were used to evaluate and identify the glomerular Ig. Kidneys of all 28 mink with documented AD had deposits of IgA and beta 1 C in a capillary and mesangial distribution. Only 7 of 28 mink had demonstrable glomerular IgG and/or IgM. In addition, interstitial plasma cell infiltrates in 17 of 19 kidneys stained exclusively with anti-IgA. All antiserums used in this study were evaluated for Ig-class specificity by both gel diffusion and agarose-bead techniques. The striking Ig class restriction demonstrated for glomerular Ig deposition in AD is discussed in light of current knowledge of the pathogenesis of AD glomerulopathy.