Differential expression of lymphocyte function-associated antigen (LFA-1) on peripheral blood leucocytes from individuals with Down's syndrome. We analysed the expression of lymphocyte function-associated antigen LFA-1 on the cell surface of peripheral blood lymphocytes, monocytes and granulocytes from 20 children with Down's syndrome. No differences in LFA-1 expression was found within monocytes or granulocytes from either normal or Down's syndrome children; however, a clear-cut difference was observed on lymphoid cells. Both normal and Down's syndrome lymphocytes displayed a bimodal pattern of LFA-1 staining by flow cytometry, with a predominance of cells with low expression in normal population, and an increased proportion of lymphocytes with high level of LFA-1 expression in Down's syndrome children. This difference correlates well with the abnormal proportion of T cell subsets and inversion of CD4/CD8 observed in a majority of our cases, and therefore, it could merely reflect the increase of certain T cell subsets normally expressing higher number of LFA-1 molecules. Taken together, our results do not support an abnormally increased expression of leucocytes integrins in trisomy 21 cells, and raise some doubt about the suggested role of the abnormal cellular expression of LFA-1 in the pathogensis of secondary immunodeficiency associated to Down's syndrome.


Cytomegalovirus (CMV) infection, CD4+ lymphocyte counts and the development of AIDS in HIV-1-infected haemophiliac patients. After a maximum of 11 years (median 8.3 years) from the time of HIV seroconversion, 25 out of 59 (42%) of CMV-seropositive haemophiliacs had progressed to AIDS, as opposed to eight out of 50 (16%) CMV seronegatives. The age-adjusted relative risk for AIDS among CMV seropositives was 2.4 (P = 0.03). In order to determine how this adverse effect is mediated, the mean rate of decline in serial CD4+ lymphocyte counts was studied. CD4+ lymphocyte counts tended to decline more rapidly in CMV seropositives than in seronegatives (-0.087 x 10(9)/l per annum versus -0.082 x 10(9)/l per annum), but this difference did not reach statistical significance. The average CD4+ lymphocyte count at the time of HIV seroconversion was estimated to be similar in CMV seropositives and negatives, because in HIV-1-negative haemophiliacs the CD4+ counts were virtually identical, after adjustment for age (0.94 x 10(9)/l and 0.97 x 10(9)/l, respectively). The median CD4+ cell count at which AIDS developed was higher in the CMV-seropositive group (0.07 x 10(9)/l) than in the seronegative group (0.04 x 10(9)/l), but this difference did not reach statistical significance. We conclude from these findings that the adverse effect of CMV is not wholly mediated via a more rapid loss of CD4+ cells. We discuss other processes that may be mediated by CMV, such as a functional deficiency of residual CD4+ cells, or dissemination of HIV in other organs, which may be important in determining the earlier onset of AIDS among CMV-seropositive subjects.


"False positive" perinuclear and cytoplasmic anti-neutrophil cytoplasmic antibody results leading to misdiagnosis of Wegener's granulomatosis and/or microscopic polyarteritis. The antineutrophil cytoplasmic antibody (ANCA) test has been shown to be important in helping to confirm the diagnosis and following the clinical course of microscopic polyarteritis and Wegener's granulomatosis. So called "false positive" test results have been reported, but usually in patients without any clinical evidence of these diseases, and the "false positive" result ignored. I wish to report 4 cases, in which a diagnosis of microscopic polyarteritis/Wegener's granulomatosis was considered as part of the differential diagnosis based on the clinical findings. The ANCA test was positive for cytoplasmic staining in 2 cases and perinuclear in 2 others. The combination of a positive ANCA result and the clinical possibility of Wegener's granulomatosis and/or microscopic polyarteritis resulted in the prescription of immunosuppressive treatment, with the consequent mortality of one patient and significant morbidity in two of the other cases.


Combination therapy with nicardipine and beta-adrenergic blockade for angina pectoris. Nicardipine a second-generation dihidropyridine calcium antagonist, has been approved in oral formulation for use in the United States, and is under review for parenteral use. Nicardipine is the most vascular-selective agent of this class currently approved and should, on theoretical grounds, be ideal for combination therapy with beta-adrenergic blocking agents. Studies have shown that the combination of nicardipine and beta-blocking agents offers additional efficacy over monotherapy with either agent alone. The hemodynamic profile of combination therapy appears to be especially favorable in patients with diminished left ventricular function needing therapy with agents of both classes. Adverse effects are few and may be improved compared with other agents of the dihidropyridine class.


Periodicities and transient shifts in anuran (Xenopus laevis, Rana clamitans) oxygen consumption revealed with flow-through respirometry. 1. A custom-designed, computer-controlled, flow-through respirometry system was used to monitor oxygen consumption in aquatic anurans: Xenopus laevis metamorphs and larval Rana clamitans. 2. There was no evidence that animals were stressed in the flow-through respirometer; oxygen consumption rates in static vs open mode fell within the same range and animals were quiescent in the chambers. 3. Diurnal periodicity was pronounced in X. laevis: both mean rates and variability of oxygen consumption were higher during scotophase, although individual differences in the timing of peaks were pronounced. 4. A transient peak in metabolism following introduction of ethanol, with subsequent recovery, was monitored for X. laevis.


Effects of acid Ca2+ Ringer on passive electrical properties and intracellular ion activities in leech Retzius neuron. 1. A significant drop in effective input resistance of the free membrane and an increase in effective coupling resistance in acid Ca2+ Ringer (complete replacement of Na+ with Ca2+, pH 4) compared to control medium has been obtained in leech Retzius neurons. 2. In neutral Ca2+ Ringer (pH 7.2), effective input resistance increased while effective coupling resistance did not change. In acid sodium, leech Ringer (pH 4) effective input resistance increased while coupling resistance decreased. 3. Ten millimolar manganese and 10 mmol tetraethylammonium did not block conductance changes obtained in acid Ca2+ Ringer. 4. Intracellular activity of Na+ decreased, cellular activity of Cl- increased and intracellular K+ activity was unchanged in both acid and neutral Ca2+ Ringer. 5. The main difference was intracellular acidification in acid Ca2+ Ringer while intracellular pH was unchanged in neutral Ca2+ Ringer. 6. We discuss the possibility that in acid Ca2+ Ringer, intracellular acidification in leech neurons may be responsible for accompanying conductive changes.


Granule containing cells in the crayfish third abdominal ganglion. 1. Four of the 850 neuron cell bodies of the crayfish third abdominal ganglion contain large dense secretory granules. 2. The processes of these cells form a neurohemal organ in the dorsal perineurium/neurilemma in the ganglion. 3. None of the immunocytochemically identified peptides accounts for the observed distribution of granules.


Endogenous, photoperiodic and hormonal control of the body weight rhythm in the female European hamster, Cricetus cricetus. 1. Body weight and hibernation rhythms were followed on normal and castrated female European hamsters raised in different conditions of photoperiod and ambient temperature. 2. In the normal females, the photoperiod was more effective than the ambient temperature regarding the control of the body weight rhythm. 3. In the castrated females, testosterone was more effective than oestradiol in suppressing both body weight and hibernation rhythms. 4. In short photoperiod conditions, the existence of endogenous rhythmicity depends upon prior photoperiodic exposure of the animals.


The detection of intracellular bluetongue virus particles within ovine erythrocytes. 1. We report here a simplified method for detecting viruses and other antigenic agents in red blood cells (RBCs). Using a nonionic detergent to prepare cytoskeletons, the interior of RBCs can be scanned rapidly using immunoelectron microscopy. 2. In this study, RBCs from bluetongue (BLU) virus-infected sheep were adsorbed directly onto Formvar-coated, gold electron microscope grids. 3. Cytoskeletons were prepared and then probed using a monoclonal antibody to VP 7, a structural BLU-virus protein and Protein-A gold. 4. Of the ca 32,000 RBCs that were examined from BLU virus-infected sheep, 34 (0.106%) contained labelled BLU virus particles. 5. No labelled particles were observed in any of ca 8000 RBCs taken prior to BLU virus inoculation of sheep. 6. If the antigenic BLU virus particles (which may be viral cores) are in fact infectious, this method of sequestration of virus within RBCs could contribute to the prolonged viremia typical of this arboviral disease, which is known to occur concurrently with circulating neutralizing antibody.


Prostaglandin interacts with steroid sex hormones in the regulation of intestinal zinc transport. 1. The effects of prostaglandins (PGs) E1 and E2, testosterone, 17 beta-estradiol and indomethacin on the intestinal zinc transport rates of male and female rats were compared. 2. PGE1 stimulated Jms (the zinc flux rate from mucosa-to-serosa) of jejunal segments from male rats but inhibited Jms of those from female rats in Ussing chamber experiments. 3. 17 beta-Estradiol inhibited Jms of jejunal segments from male rats, while testosterone stimulated it in those from female rats. However, testosterone inhibited Jms of segments isolated from male rats and 17 beta-estradiol that of those from female rats, while in segments from ovariectomized rats, both of these steroid hormones stimulated Jms. 4. When PGE2 was added to an indomethacin containing medium, Jms significantly increased whereas Jsm (the zinc flux rate from serosa-to-mucosa) decreased further.


Sustained potential shift responses and their relationship to the ECG response during arousal in the goldfish (Carassius auratus). 1. Goldfish, when presented with a 10 sec light-on stimulus against a background of 2 hr of sensory restriction, exhibited sustained potential shift (SPS) activity, of differing polarity, at each of four surface recording sites, on the medulla, cerebellum, optic tectum and telencephalon. 2. Principle components analysis (PCA) indicated that SPS responses from each region comprised superimposed early and late waveforms. At the cerebellar, tectal and telencephalic surfaces, neuronal activity appeared to contribute strongly to the early (less than 2 sec) SPS waveform. 3. While, in response to repeated stimulus presentations, habituation was apparent in the early SPS waveforms recorded from the medulla, cerebellum and telencephalon, an increase in negativity occurred in late SPS waveforms throughout the brain. 4. The tectal SPS response was directly proportional to the telencephalic SPS response both in terms of average SPS amplitudes following the first presentation of the light-on stimulus and in terms of their increasing negativity in response to stimulus repetition. 5. The increasing negativity of the telencephalic SPS was also associated with the habituation of the ECG response over repeated trials. 6. Results are discussed with regard to a possible neuromodulatory role for glia.


Potassium transport in lamprey (Lampetra fluviatilis) erythrocytes: evidence for K+ channels. 1. Unidirectional K+ (86Rb) influx in lamprey red blood cells was studied under different conditions. 2. The influx of 86Rb was markedly inhibited by 1 mM Ba2+ when cells were incubated in saline containing 4 mM K+. In K(+)-free media, the influx rate constant of 86Rb was lower, and 1 mM Ba2+ had no blocking effect. 3. Treatment of the red cells with 0.1 mM ouabain in the absence of external K+ resulted in the appearance of the component of 86Rb influx inhibited by 1 mM Ba2+, quinine, TEA or amiloride. 4. Similar results were obtained in red cells incubated in Na(+)-free media MgCl2-sucrose. 5. The results obtained provide evidence for the existence of K+ channels in the red cell membrane of the lamprey. Under physiological conditions (in the presence of 4 mM K+) the total rate constant for the 86Rb influx in erythrocytes was about 1.9/hr, including ouabain-sensitive (0.6/hr), Ba(2+)-sensitive (1.1/hr) and residual (0.2/hr) components.


The effect of dehydration on brain temperature regulation in Japanese quail (Coturnix coturnix japonica). 1. The effect of dehydration and heat exposure on body and brain temperature was studied in quail exposed to increasing ambient temperatures within the range of 25-40 degrees C. 2. The body-to-brain temperature difference was not affected by increasing ambient temperature or hydration state. A mean body-to-brain temperature difference of 0.96 +/- 0.64 degrees C and 0.85 +/- 0.65 degrees C was found in normally hydrated and dehydrated quail, respectively. 3. The slope of the relation between brain temperature to body temperature (0.77) was significantly lower than 1.0 (P less than 0.001), when the results of the two hydration states were pooled. This indicates increased brain cooling with increased body temperature. 4. Body and brain temperatures of water-deprived quail were significantly higher (P less than 0.05) than those of hydrated birds during exposure to ambient temperatures of 35 and 40 degrees C. 5. Respiration frequency increased during exposure to 35 (four birds) and 40 degrees C (six birds) in the normally hydrated quail, while in the dehydrated quail, respiration frequency increased only in three birds during exposure to 35 degrees C, and four birds during exposure to 40 degrees C, the frequencies were lower during dehydration. 6. Plasma osmolality and chloride concentration were significantly higher in the dehydrated quail (P less than 0.05). 7. The present findings show that dehydration and heat exposure resulted in a relative hyperthermy, and thus implying a reduced evaporative cooling. The quail appears to be well adapted to dehydrating conditions.


Mitochondrial adaptations to chronic muscle use: effect of iron deficiency. 1. The effects of chronic muscle use on mitochondrial structure, enzymes and gene expression is reviewed. The role of iron deficiency in modulating this adaptation is discussed. 2. Chronic muscle use and disuse alter mitochondrial composition and affect mitochondrial subpopulations differentially. This has implications for an understanding of organelle assembly. 3. Iron deficiency decreases mitochondrial functional mass within muscle by reducing the level of heme and non-heme iron-containing components. This alters the metabolic response during exercise and results in a reduced endurance performance. 4. Both iron deficiency and chronic muscle use represent contrasting experimental models for the study of mitochondrial function and biogenesis.


Diet fatty acid composition, age and rat jejunal microvillus enzyme activities. 1. Lactase, sucrase, maltase, trehalase and alkaline phosphatase activities of rat proximal jejunum were measured in 3, 6, 9, 12, 18 and 24-month-old rats fed with diets differing in their fatty acid composition. 2. A drop of 47-53% of the specific enzyme activity was observed with disaccharidases against a decrease of 71% for alkaline phosphatase in the 24-month-old rats compared to the 3-month-old rats. 3. Changes in dietary fatty acid composition, either in the saturated or monounsaturated ratio, or in the polyunsaturated fatty acid composition, did not significantly interfere with this aging effect.


Effects of various fat sources on growth and hepatic mitochondrial function in mice. 1. Five parameters with biophysical meaning for Parks' feeding and growth equations showed that mice fed diets containing hydrogenated beef tallow or beef tallow had lower mature body weight than soybean oil, linseed oil or fish oil-fed groups, and that mice fed hydrogenated beef tallow or fish oil diets had a lower feed efficiency factor than beef tallow, soybean oil or linseed oil-fed groups. 2. Mice fed the diet containing soybean oil or linseed oil had higher carcass fat as a per cent of body weight, significantly different from mice fed hydrogenated beef tallow, which exhibited the lowest carcass fat. 3. The respiratory rate of state 3 and the rate of ATP synthesis of liver mitochondria isolated were highest in the group fed the diet containing soybean oil.


Influence of clenbuterol on the protein digestibility and on nitrogen balance in rats. 1. The influences of a beta-agonist, clenbuterol, on the fecal and urinary nitrogen excretion, the protein digestibility and the nitrogen balance and retention in female Wistar rats of three different weights (70, 150 and 200 g) have been studied. 2. The addition of clenbuterol to the diet did not alter the fecal nitrogen excretion, nor did it change the digestibility coefficient of the protein, irrespective of the age/weight of the animals and the amount of the beta-agonist used. 3. Clenbuterol decreased the urinary nitrogen excretion, especially in older/heavier animals and fed diets with the same dose of the agonist. 4. Nitrogen balance and retention, which, as expected, decrease as the age/weight of the animals decreases, increased significantly with the use of clenbuterol, especially in older/heavier animals. 5. From the results of this study, it can be concluded that, for the range of weight studied, the effect of this beta-agonist does not show on the absorption of proteins at the digestive level; at a metabolic level, however, it does affect the nitrogen retention although, again, to a greater extent in older/heavier animals.


Social stress and atherosclerosis in roosters. 1. Socially stressed roosters fed either plain mash or an atherogenic diet had a greater incidence and severity of aortic atherogenesis than similarly fed non-stressed birds. 2. Results demonstrated a significant atherogenic effect of stress in chickens even in the absence of hyperlipidaemia. 3. Lack of appreciable differences in plasma lipids between stressed and non-stressed birds suggested that the atherogenic effects of stress may be attributable to neuroendocrine responses. 4. Levels of HDLc of plain mash groups were significantly higher than in the atherogenic fed groups. 5. Haemodynamic data showed no treatment-related differences.


Influence of dietary protein concentrations or of duodenal amino acid infusion on cholecystokinin release in goats. 1. Whether dietary protein levels or duodenal infusion of amino acids alters the release of cholecystokinin (CCK) in blood plasma of goats was investigated in three experiments. The CCK determination was done by radioimmunoassay with specific CCK-8 antibody. The male adult Shiba goat, a miniature Japanese native goat, was used. 2. In Experiment 1, four goats were offered a diet containing 4.94 g crude protein (CP)/kg BW0.75 for the first 7 days. They were then given a diet containing 5.86 g CP/kg BW0.75 for 7 days and thereafter 6.79 g CP/kg BW0.75 for the following 7 days. On the last day of each experimental period, blood samples were taken from the jugular vein at zero (before feeding), 30, 60, 120, 240 or 360 min after the feeding of the diet. Plasma CCK levels were not affected by dietary protein levels and time after feeding. 3. Influence of phenylalanine or tryptophan (2 mmol/20 ml) infusion into the duodenum was investigated by a 3 x 3 latin square in Experiment 2. Plasma CCK level was determined at 15 min intervals for 1 hr. Both phenylalanine and tryptophan gradually enhanced plasma CCK concentrations with time after infusion. 4. Branched-chain amino acids such as leucine and isoleucine were supplemented intraduodenally in Experiment 3 as in Experiment 2. No significant change in plasma CCK levels was observed.


Familial increase in plasma glutamic acid in epilepsy. Plasma levels of glutamic acid and leukocyte glutamate dehydrogenase (GDH) activity were determined in patients with primary generalized epilepsy, patients with partial epilepsy and in the first-degree relatives of these subjects. The results show a significant increase in plasma glutamic acid in both groups of patients and their relatives compared to non-epileptic controls. The leukocyte GDH activity in the patients and the relatives was not different from controls. The data support a genetic basis for plasma glutamic acid increase in both primary generalized and partial epilepsy and are compatible with the multifactorial mode of inheritance of these disorders. This is the first study showing a familial plasma glutamic acid increase in epilepsy in a Japanese population.


Structural complexity and evolutionary conservation of the Drosophila homeotic gene proboscipedia. Mutations of the homeotic gene proboscipedia (pb) of Drosophila cause striking transformations of the adult mouthparts, to legs or antennae. We report here an analysis of the gene structure of pb. Coding sequences across a 34 kb interval yield, by alternative splicing, four identified mRNA forms which differ immediately upstream of the homeobox. As a consequence, the homeodomain is expected to reside in four different contexts in the predicted protein isoforms. Mammalian homologs of pb, human HOX-2H and murine Hox-2.8, were identified based on the similarities of their homeodomains (95% identity) and several other conserved motifs. Examination of a collection of pb mutant alleles with antisera directed against the N-terminal region, the center or the C-terminal region of the protein showed that, surprisingly, several partial loss-of-function pb alleles appear to generate partially functional proteins truncated at their C-termini. This suggests that a significant portion of the protein contributes quantitatively to pb function, but is partially dispensable. Finally, evolutionary considerations suggest that pb may be one of several ancient genes which preceded the process yielding the modern homeotic gene complexes.


Expression of Hox-4 genes in the chick wing links pattern formation to the epithelial-mesenchymal interactions that mediate growth. The relationship between the expression of Hox-4 genes in the mesenchyme and the apical ectodermal ridge was investigated in both normal chick wing buds and wing buds treated with retinoic acid. Two conclusions emerge. One is that the activation of Hox-4 domains and the elaboration of Hox-4 gene expression patterns involve cooperation with a signal from the apical ridge. The second is that the domains of expression of 5'-located members of the complex correlate with the maintenance of the thickened ridge which is required for subsequent bud outgrowth.


Comparison of mouse and human HOX-4 complexes defines conserved sequences involved in the regulation of Hox-4.4. We have cloned and sequenced, in both mouse and human, regions of the HOX-4 complex which contain two Abd-B like genes, Hox-4.4 and Hox-4.5 (HOX4C and HOX4D in human, respectively). The high degree of conservation between the homeoprotein sequences extends to non-coding areas, which suggests that the mechanisms of regulation have been conserved. We show that the Hox-4.5/Hox-4.4 intergenic region can be broadly subdivided into three domains based on DNA conservation between rodents and primates. The presence of all these domains in association with sequences located 3' to the transcription termination site are required to mimick the spatial regulation of Hox-4.4 in transgenic mouse embryos. Several highly conserved short sequences located in this region were studied in gel retardation assays for their binding to potential regulatory factors. One such factor is detected in embryonal carcinoma cells but absent from other differentiated cell lines. This specific binding activity is down regulated upon retinoic acid treatment.


Human p68 kinase exhibits growth suppression in yeast and homology to the translational regulator GCN2. The human p68 kinase is an interferon-regulated enzyme that inhibits protein synthesis when activated by double-stranded RNA. We show here that when expressed in Saccharomyces cerevisiae, the p68 kinase produced a growth suppressing phenotype resulting from an inhibition of polypeptide chain initiation consistent with functional protein kinase activity. This slow growth phenotype was reverted in yeast by two different mechanisms: expression of the p68 kinase N-terminus, shown to bind double-stranded RNA in vitro and expression of a mutant form of the alpha-subunit of yeast initiation factor 2, altered at a single phosphorylatable site. These results provide the first direct in vivo evidence that the p68 kinase interacts with the alpha-subunit of eukaryotic initiation factor 2. Sequence similarity with a yeast translational regulator, GCN2, further suggests that this enzyme may be a functional homolog in higher eukaryotes, where its normal function is to regulate protein synthesis through initiation factor 2 phosphorylation.


Conserved immunoglobulin-like features in a family of periplasmic pilus chaperones in bacteria. Detailed structural analyses revealed a family of periplasmic chaperones in Gram-negative prokaryotes which are structurally and possibly evolutionarily related to the immunoglobulin superfamily and assist in the assembly of adhesive pili. The members of this family have similar structures consistent with the overall topology of an immunoglobulin fold. Seven pilus chaperone sequences from Escherichia coli, Haemophilus influenzae and Klebsiella pneumoniae were aligned and their consensus sequence was superimposed onto the known three-dimensional structure of PapD, a representative member of the family. The molecular details of the conserved and variable structural motifs in this family of periplasmic chaperones give important insight into their structure, function, mechanism of action and evolutionary relationship with the immunoglobulin superfamily.


Annexin I and involucrin are cross-linked by particulate transglutaminase into the cornified cell envelope of squamous cell carcinoma Y1. The squamous cell carcinoma line, SqCC/Y1, like natural squamous epithelia, forms a cornified cell envelope during differentiation which can be directly correlated with an increase in particulate transglutaminase activity. When transglutaminase is activated in these cells by calcium ionophore X-537A, annexin I and involucrin become incorporated into the cornified cell envelope and cannot be extracted with solutions containing sodium dodecyl sulfate (SDS) and beta-mercaptoethanol. This effect is specific for annexin I; thus, the amounts of annexins II and IV that were extractable from cells by SDS and beta-mercaptoethanol did not change following treatment with ionophore X-537A. Annexin I could be cross-linked in vitro to itself and to other endogenous proteins by transglutaminase extracted from the particulate fraction of SqCC/Y1 cells. Immunofluorescence studies showed that cross-linked annexin I and involucrin form an envelope-like structure in SqCC/Y1 cells during differentiation that cannot be extracted by EGTA and Triton X-100. The amount of staining of this envelope structure corresponded directly to the particulate transglutaminase activity of these cells. Annexin I monoclonal and polyclonal antibodies were shown to bind to purified cornified cell envelopes from SqCC/Y1. These studies suggest that particulate transglutaminase regulates a function of annexin I during the differentiation of SqCC/Y1 cells by covalently cross-linking this protein into the cornified cell envelope.


Staurosporine induces a neuronal phenotype in SH-SY5Y human neuroblastoma cells that resembles that induced by the phorbol ester 12-O-tetradecanoyl phorbol-13 acetate (TPA). Treatment of SH-SY5Y human neuroblastoma cells with the protein kinase inhibitor staurosporine, induced both morphological and functional differentiation in these cells. The effects of staurosporine were comparable to those induced by the protein kinase C (PKC) activator, 12-O-tetradecanoyl phorbol 13-acetate (TPA), with respect to induction of neuronal differentiation, i.e. neurite outgrowth, inhibition of DNA synthesis, induction and down-regulation of c-myc protein expression, induction of mRNA for both neuropeptide Y (NPY) and growth associated protein 43 (GAP-43) and stimulation of tyrosine hydroxylase expression. Staurosporine failed to translocate PKC to the membrane fraction or to stimulate phosphorylation of the endogenous PKC substrate M(r) 80,000 (p80). Instead, staurosporine inhibited TPA-induced phosphorylation of p80.


Acquired gynetresia in eastern Nigeria.

Acquired gynetresia in eastern Nigeria. A retrospective analysis of 78 patients who presented with acquired vaginal stenosis between January 1980 and December 1989 at the University of Nigeria Teaching Hospital Enugu was carried out. Ritual circumcision was a leading cause of this condition, followed by birth injuries and postoperative injuries. Urinary symptoms such as dysuria and urinary retention, as well as coital difficulty presenting as dyspareunia and apareunia featured prominently amongst the patients. The modified Fenton's operation was used in treating a majority of the patients, with good results. Occasionally more extensive surgery such as the McIndoe operation was used when the lesion was more severe. Recurrence rate was low and 11 women became pregnant during the period of follow up. The problem is of public health dimensions, and community based education to eliminate the etiological factors is recommended.


CA-125 in menstrual discharge in patients with chronic pelvic pain. CA-125 levels in menstrual discharge were determined in 55 patients with chronic pelvic pain to evaluate whether this test would be useful in differentiating between pelvic pain due to endometriosis and other causes. Of the 28 women with endometriosis, 25 (89%) had CA-125 concentration greater than or equal to 72,000 units/ml. The frequencies of elevated levels in Stage I, Stage II and Stages III/IV were 85.7, 85.7 and 92.8%, respectively. When used for the detection of endometriosis, the test had a sensitivity of 89.3% and a specificity of 96.3%. These results suggest that CA-125 in menstrual discharge may be helpful in the evaluation of women with chronic pelvic pain.


Pelvic tuberculosis.

Pelvic tuberculosis. Pelvic tuberculosis was diagnosed in 72 patients analyzed during the years 1979-1989. Twenty-nine percent of the patients were over 40 years of age. The most common complaints were infertility (47.2%), abdominal or pelvic pain (32%) and abnormal uterine bleeding (11%). Only 2 patients had past or family history of pulmonary tuberculosis. The physical examination was normal in 31.6% of the patients. The chest X-ray was normal in 81% of the patients. Blocked tubes were present in 32 of 34 patients who had hysterosalpingograms. Even if the diagnosis can be made from a histopathologic examination, hysterosalpingography is also a very useful aid in establishing a diagnosis. The most common site of infection was the tubes. Reconstructive surgery was performed in nine patients. Only one pregnancy was found in the present study without any medical or surgical treatment of pelvic tuberculosis. In one patient with habitual abortion as a cause endometrial tuberculosis was also found.


Hysteroscopy in the diagnosis of suspected interstitial pregnancy. Three cases are reported in which interstitial pregnancy was suspected on ultrasound scan. The first was managed by scans and laparoscopy, but resulted in rupture of the uterus and hysterectomy at 20 weeks. In the following cases hysteroscopy was used to refute the diagnosis in one patient and confirm it in another within the first trimester. A case is made for the use of hysteroscopy in the assessment of patients with suspected interstitial pregnancy.


Tuberculous vesico-vaginal fistula.

Tuberculous vesico-vaginal fistula. A 32-year-old female with a past history of pulmonary tuberculosis presenting with dribbling of urine per vaginam had a small fistulous opening in the anterior vaginal wall. Chest X-ray showed active tuberculosis. Right hydronephrosis and hydroureter with autonephrectomy of left kidney and vesico-vaginal fistula were demonstrated on intravenous urography. On cystoscopy, the bladder was contracted with two small fistulous openings. Cecocystoplasty and repair of fistulae were successfully done. Histology of bladder wall showed tuberculous cystitis.


Maternal morbidity in developing countries: a review and comments. The incidence and prevalence of postpartum maternal morbidity in developing countries are poorly understood. Methodologic problems, such as lack of standard definitions, misclassification of illnesses, use of nonrepresentative samples, and inadequate validation for self-reported data, tend to compromise existing studies. Available data suggest that serious acute illnesses are common, affecting as many as 20% of mothers who deliver in hospitals in some areas. Providing good antenatal and family planning services should significantly reduce acute and chronic sequelae after parturition.


Level and causes of maternal mortality in Guinea (West Africa). In order to evaluate the level of maternal mortality at Conakry, capital of Guinea (West Africa), a descriptive epidemiological study was made of all maternal deaths occurring between July 1st, 1989 and June 30th, 1990. To ensure that cases of maternal death were recorded as exhaustively as possible, we conducted this study over 1 year in municipal and hospital maternity units, and 3 months in the urban community. One hundred thirty-nine maternal deaths were registered, representing an annual maternal mortality rate of 559/100,000 live births. The main causes of maternal death were abortion, complications linked with hypertension, and postpartum bleeding.


Small for gestational age twins: a retrospective analysis of clinical and acid-base status immediately after delivery. In a retrospective study on 86 twins born between 1971 and 1990, the clinical and acidity status of small for gestational age twins in cases of uncomplicated labor was analysed and compared with the status of appropriate for gestational age twins. No difference was observed in Apgar score and umbilical blood pH between growth retarded and normal twins. The single fact of growth retardation without other factors of risk during labor has no influence on clinical status of small for gestational age twins.


Usefulness of the urinary microalbumin/creatinine ratio in predicting pregnancy-induced hypertension. In 199 normotensive pregnant women at 20 and 30 weeks of gestation, a fasting urinary albumin/creatinine ratio (FU Alb/Cr) was evaluated to predict pregnancy-induced hypertension (PIH). FU Alb/Cr in patients destined to develop PIH was significantly high compared to that in normotensive women. When FU Alb/Cr of more than 16 was considered to represent a positive test result, the negative predictive value was 94% and 96%, respectively. FU Alb/Cr is a useful screening tool for PIH.


Metabolic actions of insulin-like growth factor II in cultured adult rat hepatocytes are not mediated through the insulin-like growth factor II receptor. Short- and long-term regulation of hepatic carbohydrate metabolism by insulin-like growth factor II was studied in primary cultures of adult rat hepatocytes and compared to the metabolic potency of insulin. Insulin-like growth factor II stimulated glycogen synthesis from [14C]glucose, uptake of [3H]aminoisobutyric acid and [14C]lactate formation from [14C]glucose up to three-fold. Basal glycogenolysis was inhibited to about 10%, and glucagon-activated glycogenolysis was blocked completely. The enzymatic activity of glucokinase and pyruvate kinase was induced two-fold, the glucagon-dependent induction of phosphoenolpyruvate carboxykinase was antagonized. Compared to insulin, half-maximal responses required up to 50 times higher insulin-like growth factor II concentrations ranging from 10-20 nmol/l. A similar difference was observed for binding affinity of insulin-like growth factor II to the insulin receptor. The interaction with the insulin-like growth factor II/mannose 6-phosphate (IGF-II/Man-6-P) receptor was examined by studying 125I-insulin-like growth factor II binding and uptake of lysosomal enzymes. The affinity of insulin-like growth factor II to the IGF-II/Man-6-P receptor was considerably higher than for the insulin receptor. Antibodies against the IGF-II/Man-6-P receptor did not affect metabolic responses to insulin-like growth factor II, while binding to its receptor and the receptor-mediated endocytosis of arylsulphatase A were strongly inhibited. Thus, in adult rat liver insulin-like growth factor II appeared to exert metabolic actions not via interaction with its own receptor but through low affinity binding to hepatic insulin receptors.


HLA haplotypes in type 1 (insulin-dependent) diabetes mellitus: molecular analysis of the HLA-DQ locus. The DIME Study Group. In Caucasians the predisposition to Type 1 (insulin-dependent) diabetes mellitus has been shown to associate with HLA-DR3,DQw2 and DR4,DQw8 and with the presence of amino acids other than aspartic acid at position 57 on the HLA-DQ beta chain. In Finland the haplotype-specific absolute risk for developing Type 1 diabetes differs between various DR3 and DR4 positive haplotypes. The aim of our present analysis was to find out whether this variation is attributable to polymorphism at the DQ locus. As part of a nationwide prospective study including 757 serologically HLA genotyped families, we determined HLA-DQ alpha and DQ beta restriction fragment polymorphisms in 17 selected families with important susceptibility haplotypes. Additionally, the DQA1 alleles were determined from 19 haplotypes using sequence-specific oligonucleotide probes, and the DQB1 second exon was sequenced from nine haplotypes. The DR3 as well as DR4 positive haplotypes frequently found in Type 1 diabetic patients showed no variation at the HLA-DQ locus, and they were DQw2 and DQw8, respectively. The absolute risk for Type 1 diabetes for DR4,DQw8 positive haplotypes A2,Cw4,Bw35,DR4 A3,Cw3,Bw62,DR4, A24,Cw7,Bw39,DR4, A2,Cw3,Bw62, DR4, and A2,Cw1,Bw56,DR4 was 35/100,000, 130/100,000, 166/100,000, 196/100,000, and 218/100,000, respectively. The absolute risks for DR3,DQw2 positive haplotypes A1, Cw7,B8,DR3 and A2,Cw7,B8,DR3 were 68/100,000 and 103/100,000, respectively. These results provide further evidence that not only the polymorphism at the DQ locus but also other genes of the haplotypes contribute to susceptibility to Type 1 diabetes.


Different genetic backgrounds for malnutrition-related diabetes and type 1 (insulin-dependent) diabetes mellitus in south Indians. HLA-DRB, -DQA and -DQB genes were studied in ten South Indian malnutrition-related diabetic patients, ten Type 1 (insulin-dependent) diabetic patients and 45 control subjects, by TaqI restriction fragment length polymorphism analysis. The DR7,DQw9 haplotype was found to be frequent in patients with malnutrition-related diabetes (p less than 0.01). The DRw17,DQw2 haplotype was overrepresented in the patients with Type 1 diabetes compared to control subjects (p less than 0.05). In vitro amplification of the polymorphic second exon of DQB genes by the polymerase chain reaction technique was performed on DNA from 10 malnutrition-related diabetic patients, 10 Type 1 diabetic patients and 13 control subjects, as they belong to a new population. Hybridization with sequence-specific oligonucleotide probes for DQB1 alleles showed homozygosity of aspartic acid at position 57 in 7 of 10 malnutrition-related diabetic patients compared to 2 of 10 Type 1 diabetic (p less than 0.05) and 15 of 45 control subjects (p less than 0.05). Homozygosity of non-aspartic acid at position 57 was present in 7 of 10 Type 1 diabetic compared to 0 of 10 malnutrition-related diabetic patients (p less than 0.005) and 3 of 45 control subjects (p less than 0.05). This study has confirmed the association of DQB1 57 non-asp in South Indians with Type 1 diabetes. In addition, our data clearly show that the genetic background of malnutrition-related diabetes mellitus is different from that of Type 1 diabetes.


Dopaminergic mechanisms in the pathogenesis of schizophrenia. The dopamine hypothesis of schizophrenia has been the dominant theoretical construction guiding research and treatment of the schizophrenic disorders over the past generation. This hypothesis, in its simplest guise, posits the presence of a functional alteration in central dopaminergic systems in the brains of schizophrenic patients. Recent findings have resulted in a greater understanding of the complexity of the central dopaminergic systems and have led to revisions of the hypothesis of a simple functional hyperactivity of central dopaminergic systems. These recent data suggest that there may be regionally restricted changes in the function of the mesotelencephalic dopamine system, and that these changes may be in opposite directions. Such changes may be associated with dysfunctions of interactions between distinct dopaminergic terminal field regions, and may be subserved by functional derangements in other transmitter systems or reflect regionally restricted changes in expression or function of distinct dopamine receptors or catecholamine synthetic enzymes. A recent FASEB symposium reviewed new advances in molecular biology, biochemistry, pharmacology, anatomy, and systems neuroscience as they relate to schizophrenia, and discussed the implications of these data for guiding future research and treatment strategies.


Enzymatic and nonenzymatic cross-linking of collagen and elastin. Knowledge regarding the steps and mechanisms related to the intra- and interchain cross-linking of collagen and elastin has evolved steadily during the past 30 years. Recently, effort has been directed at identifying the location and types of cross-links that are found in collagen and elastin. There are two major groups of cross-links: those initiated by the enzyme lysyl oxidase and those derived from nonenzymatically glycated lysine and hydroxylysine residues. The formation of enzymatic cross-links depends on specific enzymes, amino acid sequences, and quaternary structural arrangements. The cross-links that are derived nonenzymatically occur more adventitiously and are important to pathobiological processes. Considerable progress has been made in elucidating the pathways of synthesis for several of the enzymatically mediated cross-links, as well as possible mechanisms regulating the specificity of cross-linking. Although less is known about the chemistry of cross-links arising from nonenzymatically glycated residues, recent progress has also been made in understanding possible biosynthetic pathways and control mechanisms. This review focuses on such progress and hopes to underscore the biological importance of collagen and elastin cross-linking.


FMRFamide-like immunoreactive nervus terminalis innervation to the pituitary in the catfish, Clarias batrachus (Linn.): demonstration by lesion and immunocytochemical techniques. Certain thick FMRFamide-like immunoreactive fibers arising from the ganglion cells of nervus terminalis in the olfactory bulb of Clarias batrachus can be traced centripetally through the medial olfactory tract, telencephalon, lateral preoptic area, tuberal area, and hypothalamohypophysial tract to the pituitary. Following 6 days of bilateral olfactory tract transection, the immunoreactivity in the thick fibers, caudal to the lesion site, was partially eliminated, whereas after 10 and 14 days, it was totally abolished in the processes en route to the pituitary. The results indicate a direct innervation of the pituitary gland by the FMRFamide-like peptide containing fibers of the nervus terminalis.


Adrenergic and dopaminergic regulation of gonadotropin-releasing hormone release from goldfish preoptic-anterior hypothalamus and pituitary in vitro. The involvement of adrenergic and dopaminergic receptor subtypes on in vitro release of radioimmunoassayable gonadotropin-releasing hormone (GnRH) from incubated preoptic-anterior hypothalamic (P-AH) slices and pituitary fragments of sexually mature male goldfish was studied. Norepinephrine (NE) produced a dose-related stimulation of GnRH from P-AH slices, but not from pituitary fragments. The effects of some adrenergic receptor agonists (1 microM) on GnRH release from P-AH slices were tested: phenylephrine (alpha 1-agonist) significantly stimulated GnRH release; clonidine (alpha 2-agonist) and isoproterenol (beta-agonist) were ineffective. Incubation of P-AH slices with phentolamine (alpha 1/alpha 2-antagonist) and prazosin (alpha 1-antagonist), at a concentration of 1 microM, inhibited the release of GnRH induced by NE (60 microM); the alpha 2-antagonist yombibin and the beta-antagonist propanolol were ineffective. None of the adrenergic antagonists (1 microM) tested produced significant effects on spontaneous release of GnRH from both tissue preparations. Spontaneous release of GnRH from both P-AH slices and pituitary fragments was reduced by dopamine (DA) in a dose-related manner. The effects of some DA agonists (1 microM) were tested: apomorphine (D1/D2-agonist) and SKF 38398 (D1-agonist), but not bromocriptine and LY-171555 (D2-agonists) significantly reduced spontaneous GnRH release from P-AH slices in vitro. On the other hand, D2-agonists, but not D1-agonists, significantly reduced GnRH release from pituitary fragments. The effects of DA antagonists (1 microM) were also tested: in P-AH slices, addition of SKF-83566 (D1-antagonist) significantly reduced spontaneous GnRH release; pimozide and domperidone (D2-antagonist) were ineffective when tested alone.(ABSTRACT TRUNCATED AT 250 WORDS)


Cloning, primary structure and regulation of the ARO4 gene, encoding the tyrosine-inhibited 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase from Saccharomyces cerevisiae. In Saccharomyces cerevisiae, two differently regulated 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP) synthase (DAHPS; EC 4.1.2.15) isoenzymes carry out the first step in the shikimate pathway. Mutations in both genes are necessary to cause aromatic amino acid (aa) auxotrophy, since one isoenzyme alone is sufficient to produce enough DAHP for normal growth of the cells. The phenylalanine-inhibited DAHPS is encoded by the previously isolated and characterized ARO3 gene. Here, we report the cloning and characterization of the ARO4 gene, encoding the second DAHPS, which is inhibited by tyrosine. The aa sequence of the ARO4 gene product reveals 76% similarity to the ARO3-encoded isoenzyme and 66 and 73% to the three DAHPS isoenzymes from Escherichia coli. ARO4 gene expression is regulated by the general control system of aa biosynthesis. As in the case of the ARO3 gene, a single GCN4-recognition element in the promoter is responsible for derepression of the ARO4 gene under aa starvation conditions. However, in contrast to the situation in the isogene, ARO3, GCN4 does not contribute to the basal level of ARO4 transcription under nonderepressing conditions.


Proliferating cell nuclear antigen (PCNA) expression in formalin-fixed tissue of non-small cell lung carcinoma. An immunohistochemical study of non-small cell lung carcinoma using PC10, a monoclonal antibody against PCNA, was performed on tissues routinely processed with formalin fixation and paraffin embedding. The PCNA labelling index and mitotic index were determined from sections of these tissues. Tumours showed a high mean PCNA labelling index of 53.3%. The mean mitotic index was 10.3/1000 cells. Inter-examiner agreement of mitotic counting was good. A linear correlation between the PCNA labelling index and mitotic index was demonstrated (r = 0.71, P less than 0.00001). It is concluded that immunohistochemical nuclear labelling with anti-PCNA on routinely processed tissue is a simple technique for the assessment of proliferation in non-small cell lung carcinoma.


[Expression of low-affinity Fc epsilon receptors on circulating monocytes in patients with inflammatory rheumatic diseases]. In patients with scleroderma, high proportions of circulating CD23+ monocytes could be detected by FACS analysis as compared with controls. Supernatants obtained from lymphocytes yielded high amounts of interleukin-4-(IL-4-)like activity. The results suggest that IL-4 contributes to monocyte activation in scleroderma. There were no correlations with serum IgE, or numbers of naive and memory-CD4+ lymphocytes.


Advances in the chemotherapy of gynecologic malignancies. Chemotherapy is playing an ever increasing role in the treatment of patients with the common gynecologic malignancies, including ovarian, cervical cancer, and endometrial cancer. Chemotherapy has its most defined role in the treatment of patients with ovarian cancer where virtually all patients will receive cytotoxic chemotherapy. There are four major areas of research in chemotherapy in gynecologic malignancies. In retrospective studies it has been demonstrated that dose intensity is an important factor in maximizing response rates. Clinical studies are now prospectively evaluating the importance of dose intensity, particularly with the new platinum analogue carboplatin. In addition, it has been demonstrated in endometrial cancer and cervical cancer that patients with poor prognostic features such as high grade tumours and large volume disease have a low probability of cure by standard modalities such as surgery and radiation. In this group of patients combined modality approaches are being evaluated. In addition, regional therapy, either in the form of intra-arterial therapy for patients with cervical cancer or intraperitoneal therapy for patients with ovarian cancer, is being investigated. The primary factor limiting the effectiveness of chemotherapy in gynecologic malignancies is the development of drug resistance. It has recently been demonstrated that several drugs such as taxol, ifosfamide, and hexamethylmelamine have activity in patients who have had previous treatment with platinum-based compounds. In addition, the mechanism associated with the development of drug resistance in ovarian cancer have recently been identified. Clinical trials have been initiated with compounds such as buthionine sulfoximine in an attempt to specifically reverse resistance associated with alkylating agents and platinum compounds.


Characterization of F107 fimbriae of Escherichia coli 107/86, which causes edema disease in pigs, and nucleotide sequence of the F107 major fimbrial subunit gene, fedA. F107 fimbriae were isolated and purified from edema disease strain 107/86 of Escherichia coli. Plasmid pIH120 was constructed, which contains the gene cluster that codes for adhesive F107 fimbriae. The major fimbrial subunit gene, fedA, was sequenced. An open reading frame that codes for a protein with 170 amino acids, including a 21-amino-acid signal peptide, was found. The protein without the signal sequence has a calculated molecular mass of 15,099 Da. Construction of a nonsense mutation in the open reading frame of fedA abolished both fimbrial expression and the capacity to adhere to isolated porcine intestinal villi. In a screening of 28 reference edema disease strains and isolates from clinically ill piglets, fedA was detected in 24 cases (85.7%). In 20 (83.3%) of these 24 strains, fedA was found in association with Shiga-like toxin II variant genes, coding for the toxin that is characteristic for edema disease strains of E. coli. The fimbrial subunit gene was not detected in enterotoxigenic E. coli strains. Because of the capacity of E. coli HB101(pIH120) transformants to adhere to isolated porcine intestinal villi, the high prevalence of fedA in edema disease strains, and the high correlation with the Shiga-like toxin II variant toxin-encoding genes, we suggest that F107 fimbriae are an important virulence factor in edema disease strains of E. coli.


Ability of enteroaggregative Escherichia coli strains to adhere in vitro to human intestinal mucosa. A collection of 44 enteroaggregative Escherichia coli (EAggEC) strains isolated from infants with diarrhea in India and the United Kingdom were examined for their ability to adhere in vitro to human intestinal mucosa and by electron microscopy for production of putative adherence factors. None of the strains adhered to human duodenal mucosa, and six strains tested did not adhere to ileal mucosa; all 44 strains, however, adhered to human colonic mucosa in localized aggregates. Electron microscopy of infected colonic mucosa indicated fimbrially mediated adhesion of the EAggEC strains. Four morphologically distinct kinds of fimbriae, including a new morphological type of E. coli fimbriae consisting of bundles of fine filaments, were identified among the EAggEC strains; this new type of fimbria was observed in 43 of the 44 EAggEC strains. Forty-three of the 44 EAggEC strains were positive with a DNA probe developed to identify EAggEC, and most of the strains belonged to serotypes unrelated to the other major classes of diarrheic E. coli. These results suggest that EAggEC may be a large-bowel pathogen and colonize the colon by a fimbrially mediated adhesion mechanism.


Urease-associated heat shock protein of Helicobacter pylori. Helicobacter pylori urease is an extracellular, cell-bound enzyme with a molecular weight of approximately 600,000 (600K enzyme) comprising six 66K and six 31K subunits. A 62K protein is closely associated with the H. pylori urease, both in crude preparations and after gel filtration; this protein can be removed from the urease by ion-exchange chromatography without inactivating the enzyme. We purified this urease-associated protein and determined its N-terminal amino acid sequence. The sequence is 80% homologous (identical plus conserved amino acid residues) to the Escherichia coli GroEL heat shock protein (HSP), 75% homologous to the human homolog, and 84% homologous to the HSP homolog found in species of Chlamydia. Thus, the 62K urease-associated protein of H. pylori belongs to the HSP60 family of stress proteins known as chaperonins. Evidently this protein, HSP62, participates in the extracellular assembly and/or protection of the urease against inactivation in the hostile environment of the stomach.


Transformed rat pancreatic islet-cell lines established by BK virus infection in vitro. Single-cell suspensions of primary rat pancreatic islet cells were infected with BK virus (BKV) prototype (Gardner) and the naturally occurring BKV strain (TU), isolated from human urine. These viral strains have different sequences in their non-coding control regions which contain promoter-enhancer elements and origin of DNA replication. Uninfected cell cultures disintegrated within 3 weeks, while a varying number of virus-infected cultures were immortalized and a majority exhibited focal areas of 2-dimensional growth. A significantly higher proportion of the BKV (TU)- than of the BKV (Gardner)-infected cultures were immortalized. Large tumor (T) antigen expression was evident in virus-infected cultures from day 4 post infection (p.i.), while insulin secretion decreased steadily during the first weeks of culture. Two cell lines were established from BKV (TU)-infected cultures. Line 5A4 was contact-inhibited, growing as a dense monolayer, while 6A3 demonstrated foci of 2-dimensional growth. Both cell lines have retained their morphology and T-antigen expression for approximately 130 passages. At high passages a low level of intracellular insulin, but no secretion into media, was detected. Based on standard biological tests (reduced serum requirements, growth at low cell density, anchorage-independent growth and tumor induction in nude mice) both cell lines have a fully transformed phenotype, but 6A3 appears to be more malignantly transformed. Since both cell lines were established simultaneously from the same primary cells with the same virus batch, they provide an opportunity to study the transforming mechanisms of BKV in a relative context.


Cardiac involvement in non-specific aorto-arteritis. Cardiac involvement in 75 cases (mean age 21.1 +/- 6 years) with non-specific aorto-arteritis was studied. Detailed clinical examination, echocardiography and cardiac catheterization, including angiography, were done in all the cases, as was coronary angiography. Features of cardiac failure like sinus tachycardia, cardiomegaly, left ventricular third heart sound gallop and pulmonary congestion were detected in 27 cases with reduction of left ventricular ejection fraction (25-48%). Systemic hypertension was seen in 60 cases. Central aortic pressure, left ventricular systolic pressure and left ventricular end-diastolic pressure were increased in 66 cases. Pulmonary hypertension and increased pulmonary vascular resistance were detected in 6 cases. Aortic and mitral regurgitation were seen in 15 and 12 cases, respectively. Three patients had features of dilated cardiomyopathy such as generalized cardiomegaly, systemic and pulmonary congestion but without any cardiac murmurs and with normal central aortic pressure. The coronary angiogram revealed obstruction of the left anterior descending artery in 3 cases and right coronary artery obstruction in another 3 cases. Histopathological studies revealed non-specific inflammatory changes with fibrosis in cardiac musculature and the great vessels.


Estimates of fertility levels in a rural community of Saudi Arabia. There is a dearth of information on fertility levels in Saudi Arabia. In the absence of a reliable vital registration system, fertility level can be estimated from sample surveys. The Gompertz relational fertility model has been fitted to parity data on 923 women from a survey in the Al-Baha region. The estimated total fertility rate was 8.4. Education and age at marriage have strong association with the level of fertility. Those who married at early ages had higher parities, whereas women who had more than primary education reported lower parities.


Laparoscopic salpingectomy using conventional laparoscopy equipment. Laparoscopic surgery has gained wide acceptance in the treatment of ectopic pregnancy. When compared with conventional surgical techniques, the laparoscopic approach reduces perioperative morbidity, hospital costs, length of hospital stay, and recovery time. Laparoscopic surgery, however, often requires special surgical skills and expensive equipment. In this paper we review the literature on the efficacy of the laparoscopic approach to salpingectomy and report a simple technique for such a procedure. Any gynecologist who performs laparoscopic tubal sterilization by electrocautery has the necessary equipment and can develop the skills to carry out this procedure.


Reproductive characteristics and contraceptive method choices of Nigerian women requesting terminal fertility control. A choice of a safe and acceptable contraceptive method is an important concern for women who have completed their child-bearing intentions. This paper focuses on 557 women (mean age 35.9 years, mean number of living children 5.8 +/- 1.4, and mean number of living sons 3.1 +/- 1.3) who indicated some desire to limit childbearing, and were seen at the University of Ilorin Teaching Hospital, Family Planning Clinic in 1986/7. During this period, a wide and free choice of contraceptive methods, including the new subdermal levonorgestrel implant method (NORPLANT) and female surgical sterilization, was offered. Contraceptive method choices of women requesting terminal fertility control are: IUD 56%, injectables 15.3%, female sterilization 11.5%, pills 8.6%, NORPLANT 8.1%, others 0.5%. Comparing terminal and nonterminal contraceptors, almost equal proportions adopted the IUD, 56% vs. 60.5%, while terminal contraceptors adopted the injectables and NORPLANT in significantly higher proportions. Within subgroups by contraceptive method, mean age and mean number of living children and of sons are not significantly different, though younger women tend to adopt the pill. Method choice of NORPLANT and tubal ligation was favoured by previous contraceptive use, but not by spousal approval. Years of education had a positive influence on the choice of NORPLANT. The program implications of these findings regarding selective counselling of terminal contraceptors, provision of long-lasting reversible contraceptive methods, and facilities for surgical sterilizations for men and women are discussed.


Hemoperitoneum from a tubal pregnancy mimicking abruptio placentae: an obstetrical enigma. A case of simultaneous intrauterine and extrauterine pregnancy with hemoperitoneum during labor is presented. The hemoperitoneum from the tubal pregnancy occurred sufficiently late during pregnancy to mimic a placental abruption. The difficulty of diagnosing heterotopic pregnancy is stressed.


Comparison of various therapies for the luteinized unruptured follicle syndrome. A study was initiated to evaluate the prevalence of the luteinized unruptured follicle (LUF) syndrome in a group of 355 women with infertility. The diagnosis was established by carefully observing daily sonograms along with measuring estradiol, progesterone, and luteinizing hormone (LH) levels. Two distinct types of LUF syndrome were identified: mature follicle LUF, in which release of an ovum was not demonstrated after a follicle attained maturity (serum estradiol reached 200 pg/mL while serum progesterone remained less than 2.5 ng/mL), versus premature luteinization LUF, where the serum progesterone increased above 2.5 ng/mL before follicular maturation was attained. The use of either hCG alone or hCG in combination with hMG in a single injection at the time of follicular maturation successfully corrected mature follicle LUF in 21 of 46 patients (46%), whereas ovulation-inducing drugs plus hCG or hCG and hMG corrected LUF in 24 of 25 patients (96%). Clomiphene citrate proved inferior to hMG in that it corrected LUF in 3 of 25 patients (12%) versus 12 of 22 patients (95%) who had undergone hMG therapy. Thus, hMG-hCG therapy is the most efficacious for mature follicle LUF, but because release can occur spontaneously on occasion by an appropriately timed single gonadotropin injection, one could offer the less costly options first. For premature luteinization, speeding up follicular maturation with gonadotropin therapy is effective. Upon failure of this technique, the more costly endogenous gonadotropin suppression followed by hMG can be employed.


Common technical errors in hysterosalpingography. Hysterosalpingograms from 100 consecutive patients referred for in vitro fertilization were reviewed to evaluate the adequacy of visualization of the uterine cavity. In 17 cases the hysterosalpingogram failed to demonstrate the entire uterine cavity. The most common reason for failure was an axial view of the uterus secondary to inadequate traction on the cervix in 82% (14/17) of the cases, followed by obstructed visualization of the lower uterine cavity and endocervical canal by the delivery catheter bulb in 21% (3/17). A speculum left in the vagina obscured visualization of the endocervical canal in 21% (3/17) of the cases. There were no significant differences in the mean number of radiographic exposures between the adequate and inadequate groups (4.7 vs. 5.9). This study suggests that failing (1) to remove the speculum before injecting contrast, (2) to evaluate the lower uterus and endocervix when using an intrauterine catheter, or (3) to place adequate traction on the cervix, may result in inadequate visualization of the uterine cavity and a need to repeat the study.


Some characteristics of azoospermic human semen. Of 260 volume measurements and 265 fructose determinations on 257 azoospermic semen samples, the volume was normal (1-6 mL) in 78%, low in 16.7%, and high in 5.2%. The percentage of azoospermic samples with low volume was greater than that found for samples containing sperm. Mean fructose concentrations were similar in high-volume and normovolemic azoospermic samples, but significantly lower in low-volume samples. There was no correlation between (a) the etiology of the azoospermia and abnormal semen volume or fructose concentration (save for cases of obstruction and/or atrophic seminal vesicles) or (b) semen volume, fructose concentration, and serum LH, FSH, testosterone, or prolactin.


Effects of danazol on coagulant activity in the rat. Coagulation factor activity was evaluated in female rats treated with danazol. Following 30 days of treatment, slight decreases in factor VII and X activities were noted. After 60 days, a prolongation of the prothrombin time, as well as a decrease in factor VII, was noted. The data suggest that in the rodent, danazol has minimal effects on coagulation activity.


The alcohol dehydrogenase polymorphism in natural populations of Drosophila melanogaster: ADH activity variation restriction site polymorphism and the Adh cline. Alcohol dehydrogenase activity has been measured in 186 iso-second chromosome lines--104 from seven Australian populations and 82 from six Chinese populations. Restriction endonuclease variation in the Adh gene region in these lines has previously been described (Jiang & Gibson, 1991). The mean ADH activity of AdhF and AdhS lines was significantly higher in the Chinese samples than in the Australian samples. In each population on both continents the mean activity of the AdhF lines is significantly higher than that of the AdhS lines. Six lines homozygous for a thermostability variant, AdhFChD (detected in four of the Chinese populations), had intermediate levels of ADH activity and protein amount. In a subset of the lines with the highest and lowest levels of ADH, there was a correlation of 0.69 between ADH activity and ADH CRM. None of the restriction site variants was consistently associated with the amount of ADH activity. Associations between BamHI (-7.2), the Adh polymorphism and ADH activity suggest that there are modifiers of ADH 5' to the gene. The deletion (0.2) at position -2.8 on the restriction map (Jiang & Gibson, 1991) was associated with increased levels of ADH activity in AdhS lines from China. Two unique insertions in the gene region were associated with low activity in AdhF lines and a null activity allele had a deletion removing most of exon 2. A single line with a duplication of a part of the Adh coding region and of the 5' regulatory section had relatively high ADH activity. Considering all the data, the main factor affecting ADH activity levels in populations is the frequency of AdhF.


Immunogenicity of deglycosylated zona pellucida antigens and their inhibitory effects on fertility in rabbits. Influence of carbohydrates on the immunogenicity and immunocontraceptive potential of zona pellucida glycoproteins has been investigated in rabbits. Porcine zonae pellucidae, following deglycosylation with trifluoromethane-sulfonic acid, retained significant immunogenic potential, as shown by the ability to generate antibodies which cross-reacted with the heterologous antigen. Antibody response, however, was much stronger against the native zona glycoproteins, thereby suggesting that both carbohydrate and protein moieties contribute to the overall immunogenicity of the zona pellucida antigens. Contraceptive efficacy of active immunization with the deglycosylated zona antigens, when evaluated by mating experiments, demonstrated inhibition of fertility in all immunized rabbits. Normal ovarian functions were disrupted in these animals, as revealed by the reduction in ovarian weights and gross impairment of folliculogenesis. Flushing of the oviducts of the immunized animals yielded a markedly reduced number of ova ovulated in response to hCG administration, none of which were fertilizable. Results collectively suggest that active heteroimmunization with deglycosylated zona pellucida antigens is effective in reducing fertility in rabbits.


Detection of tyrosine hydroxylase and phenylethanolamine-N-methyltransferase messenger RNAs in the mouse adrenal gland and the brain by in situ hybridization. To study the expression of tyrosine hydroxylase (TH) and phenylethanolamine-N-methyltransferase (PNMT) genes in the mouse adrenal gland and the brain, we performed in situ hybridization studies by using several types of complementary DNA probes recognizing coding regions of human TH (THc), the 3'-end of the human region of TH (TH3'), and the coding region of the human PNMT (PNMTc). THc mRNA was detected in the chromaffin cells of the mouse adrenal medulla and brain catecholaminergic neurons including the substantia nigra and ventral tegmental area. TH-immunopositive neurons were located in a similar pattern in adjacent sections. However no positive signals were detected by the TH3' probe. Using the PNMTc probe, the majority of cells in the adrenal medulla demonstrated positive labelling. Although the mouse TH and PNMT genes have not been fully isolated and sequenced, the present study strongly suggests that the sequence of the coding regions of TH and PNMT are similar in human and mouse. The THc and PNMTc probes are particularly useful in investigating the loci of gene transcription in mouse tissues.


HLA-DP distribution in Shanghai Chinese--a study by polymerase chain reaction--restriction fragment length polymorphism. One hundred and four normal unrelated Chinese were typed for HLA-DPA1 and DPB1 alleles by polymerase chain reaction-restriction fragment length polymorphism. Increased frequencies of HLA-DPA1*0201 and DPB1*0501 were found in this Chinese population as compared with those detected in Caucasoids and blacks.


Extensive study of DRB, DQA, and DQB gene polymorphism in 23 DR2-positive, insulin-dependent diabetes mellitus patients. To gain insight into the HLA subregions involved in protection against insulin-dependent diabetes mellitus (IDDM) we investigated the polymorphism of HLA-DR and -DQ genes in 23 DR2 IDDM patients. Results show the following. (1) Fourteen patients (61%) possess the DRB1, DRB5, and DQB1 alleles found in DRw16/DQw5 healthy people. These data contrast with the 5% of DRw16 normally found in DR2 populations and are in agreement with former observations supporting that the DRw16 haplotype is not protective. (2) Nine DR2 patients, i.e., 39% versus 95% in published DR2 controls, possess the DRB alleles found in DRw15 unaffected people. Among them, six patients have also DQA1 and DQB1 alleles identical to those found in DRw15/DQw6 healthy individuals. These data confirm that the DRw15/DQw6 haplotype is protective but indicate that none of the DR or DQ alleles, alone or in association, confers an absolute protection. (3) Our most striking results concern the very high frequency of recombinant haplotypes among the DRw15 patients: 3 of 9. In these three patients recombinations led to the elimination of both DQB1 and DQA1 alleles usually associated with DRw15. This strongly suggests that the occurrence of IDDM in these DRw15 patients is due to the absence of the usual DQ product and thus reinforces the assumption that DQ rather than DR region is involved in the protection conferred by the DRw15/DQw6 haplotype. Finally, analysis of the non-DRw15 haplotypes in heterozygous patients showed that IDDM can occur in the absence of any DQ alpha beta heterodimer of susceptibility.


Polymerase chain reaction--single-strand conformation polymorphism analysis of polymorphism in DPA1 and DPB1 genes: a simple, economical, and rapid method for histocompatibility testing. A new technical trial was carried out to detect polymorphism in HLA-DP genes, based on the diversity in electrophoretic mobility of single-stranded DNA (single-strand conformation polymorphism, SSCP). Genomic DNAs from 31 cell lines homozygous for 2 and 14 different DPA1 and DPB1 alleles, respectively, and from peripheral blood cells of a normal individual homozygous for another DPB1 allele were subjected to polymerase chain reaction (PCR) to amplify the polymorphic exon 2 of DPA1 or DPB1 genes. The PCR samples were denatured by heating in the presence of formamide to obtain single-stranded DNA, electrophoresed in a neutral polyacrylamide gel, and visualized by silver staining. Allelic differences were detected by the distinctive electrophoretic pattern of each single strand, depending on the sequence-specific conformation. Fifteen DPB1 alleles showed 11 distinct electrophoretic patterns, leaving four allelic combinations not distinguished. These four allelic combinations could be further distinguished by using another couple of primers in PCR, with which a part of the exon was amplified, and by subsequent SSCP analysis. The use of four pairs of primers in PCR allowed for discrimination of all the 15 DPB1 alleles tested. Two allelic differences in exon 2 of DPA1 gene could be clearly demonstrated. In addition, putative new alleles of DPA1 and DPB1 genes were detected by SSCP analyses. The PCR-SSCP analysis is simple and rapid, requires neither radioactive materials nor restriction enzymes, and is expected to be a useful tool for investigating the fine HLA-matching required for clinical transplantation of organs.


Effects of growth hormone-releasing factor and feed intake on energy metabolism in growing beef steers: net hormone metabolism by portal-drained viscera and liver. Effects of growth hormone-releasing factor (GRF) and intake on arterial concentrations and net visceral metabolism of hormones were measured in six growing Hereford x Angus steers using a split-plot design with 4-wk injection periods within 8-wk intake periods. Steers were fed a 75% concentrate diet at two intakes and were injected s.c. twice daily with saline or GRF (10 micrograms/kg of BW). Arterial concentrations of growth hormone (GH) were measured on d 1 and d 8 to 10 of injections. Eleven measurements, obtained at 30-min intervals, of arterial concentration and net flux of hormones across portal-drained viscera (PDV) and liver were obtained on d 8 to 10 of injections (six hourly measurements were used for insulin-like growth factor-I [IGF-I] and somatostatin). The area under the GH curve and average and peak GH concentrations were increased (P less than .01) by GRF and were greater (P less than .10) at low than at high intake. Liver removal of GH was not affected by GRF or intake. Arterial IGF-I concentration was increased (P less than .05) by GRF and not affected by intake. Treatments did not affect IGF-I flux across the liver. Arterial insulin concentration was greater (P less than .05) at high than at low intake, in part because of greater (P less than .01) PDV release. Increased (P less than .10) arterial insulin concentration in GRF-treated steers was not attributable to significant changes in PDV or liver net flux. Arterial glucagon concentration was greater (P less than .01) at high than at low intake, in part because of greater (P less than .05) PDV glucagon release and decreased (P less than .10) liver extraction ratio. Effects of intake on arterial concentration of insulin and glucagon were in part due to changes in visceral metabolism, but GRF did not affect PDV or liver hormone metabolism.


Ligand binding to the porcine adipose tissue beta-adrenergic receptor. We measured ligand binding to the beta-adrenergic receptor from porcine adipocytes using tritiated radioligands, dihydroalprenolol (DHA) and CGP-12177 (CGP), and an iodinated radioligand, cyanopindolol (ICP). Binding was measured in a crude plasma membrane preparation. Equilibrium saturation binding was regular for all three ligands; the Kd were approximately 4,000 pM for DHA, 600 pM for CGP, and 100 pM for ICP. Binding was stereospecific with each radioligand. Association of each radioligand was relatively rapid; dissociation was rapid and complete for DHA, initially rapid but ultimately incomplete for CGP, and minimal for ICP. The Kd estimated from kinetic data were approximately 1,000 pM for DHA and 100 pM for CGP. The receptor did not bind phentolamine, an alpha-adrenergic antagonist, except at concentrations greater than 10(-5) M. Propranolol was bound to the receptor with a Ki of approximately 8 nM regardless of the radioligand used. Metoprolol, a purported beta 1-adrenergic specific antagonist, was bound to the receptor with a Ki of approximately 300 nM when the radioligands were CGP or ICP but with a Ki of approximately 1,000 nM when the radioligand was DHA. The Ki for ICI 118,551, a purported beta 2-adrenergic specific antagonist, were approximately 500 nM when the radioligands were DHA or CGP but 125 nM when the radioligand was ICP. Thus, the choice of radioligand can influence the characterization of the beta-adrenergic receptor being studied.


Determination of an antipsychotic agent (ICI 204,636) and its 7-hydroxy metabolite in human plasma by high-performance liquid chromatography and gas chromatography-mass spectrometry. ICI 204,636 (I) is an orally active antipsychotic agent under development for the treatment of schizophrenia in humans. It is partially converted in animals to an active 7-hydroxy metabolite (II). Methods were developed for the simultaneous determination of both analytes in human plasma using high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS). The analytes were extracted from plasma using phenyl solid-phase extraction columns. Quantification by isocratic HPLC was performed in the reversed-phase mode with detection at 250 nm. Extracts were derivatized to trimethylsilyl ethers for quantification by GC-MS using selected-ion monitoring. Both assays were evaluated for consistency of response, precision, accuracy and specificity. Limits of quantification for I and II by HPLC were 15 and 20 ng/ml, respectively; limits of quantification for I and II by GC-MS were 2 and 5 ng/ml, respectively. Both methods were applied to the analysis of clinical samples from oral dosing studies with I.


High-performance liquid chromatography-electrochemical detection of vecuronium and its metabolites in human plasma. A high-performance liquid chromatographic assay coupled with electrochemical detection has been developed for the determination of vecuronium and its three putative deacetylated metabolites in human plasma. A novel solid-phase extraction procedure allowed good recovery of both vecuronium and its metabolites, together with ease and speed of execution. This method was sensitive, reproducible and accurate over the therapeutic range of concentrations of vecuronium and its metabolites, and was applied successfully to a study of the pharmacokinetics of vecuronium in anaesthetized patients.


Correlation of gingival crevicular fluid proteases with clinical and radiological measurements of periodontal attachment loss. Probing attachment loss and radiographical measurements of bone loss were made on 20 untreated chronic periodontitis patients. At a second visit, gingival crevicular fluid was collected on filter paper strips from the deepest accessible interdental probing site of each tooth. Gingival crevicular fluid volumes were determined and the samples eluted into buffer. Protease activities in the resulting eluates were assayed with peptidyl derivatives of 7-amino-4-trifluoromethyl coumarin (AFC). Cathepsin B/L-like activity was determined with Bz-Val-Lys-Lys-Arg-AFC, elastase-like activity with MeOSuc-Ala-Ala-Pro-Val-AFC, tryptase-like activity with Z-Ala-Ala-Lys-AFC, trypsin-like activity with Z-Gly-Gly-Arg-AFC and dipeptidyl peptidase IV-like activity with Ala-Pro-AFC. Total enzyme activities and enzyme concentrations correlated positively with probing attachment loss and bone loss in linear regression analysis. This was true at both a patient level, using mean patient values, and a site level, using either individual patient or pooled patient data. All of these correlations were highly statistically significant for site comparisons. In inter- and intra-patient comparisons the proportion of significant correlations was greater for total enzyme activity than concentration. Clinical and radiological measurements of attachment loss showed generally similar levels of correlation. Total enzyme activities had good specificity and sensitivity as indicators of attachment loss in this cross-sectional study. The results support further investigation of the diagnostic potential of gingival crevicular fluid proteases in evaluation of the periodontal condition.


Mechanisms of early death despite thrombolytic therapy: experience from the Thrombolysis in Myocardial Infarction Phase II (TIMI II) study. Mechanisms of death among patients who died within 18 h of enrollment in the Thrombolysis in Myocardial Infarction Phase II (TIMI II) study were analyzed. Of 3,339 patients enrolled, 32 died within the 1st 4 h and 31 died within the subsequent 14 h. Thirteen of the 63 patients had shock at enrollment; 22 had advanced hemodynamic compromise without shock and 28 initially had minimal to no compromise. Prior infarction was present in 16 patients (25%). Pump failure was responsible for 39 early deaths (62%), ventricular rupture for 10 (16%), arrhythmia for 8 (13%) and complications of therapy for 6 (10%). Nine of 720 patients randomized to immediate intravenous beta-adrenergic blocking agent therapy had an early death compared with 6 of 714 assigned to deferred beta-blocker therapy. Thus, mortality is highest in the early hours after myocardial infarction, even in patients treated with thrombolytic therapy and is most frequently due to pump failure. These results imply that efforts to reduce mortality during this critical time period should be directed at prevention, limitation or palliation of early pump failure.


Influence of histamine receptors on basal left ventricular contractile tone in humans: assessment using the H2 receptor antagonist famotidine and the beta-adrenoceptor antagonist esmolol as pharmacologic probes. Histamine has a positive inotropic action in humans. Recent controversial data have suggested that histamine2 (H2) receptor blockade depresses overall left ventricular systolic performance in healthy volunteers. To explore the possibility that H2 receptors positively influence basal left ventricular contractile tone, 10 normal subjects were studied by using imaging and Doppler echocardiography and calibrated subclavian pulse data in a blinded, randomized, two-period crossover trial with measurements obtained at the end of each 7-day period. Oral drug administration consisted of either the potent H2 antagonist famotidine (40 mg/day) or placebo. Left ventricular circumferential end-systolic wall stress-rate-corrected velocity of fiber shortening (Vcfc) relations were generated over a range of loads with methoxamine. Contractility was assessed by using Vcfc at a common end-systolic wall stress. During each study, data were obtained before and during high dose intravenous esmolol administration to determine the contributions, if any, of sympathetic reflex responses. Famotidine did not alter blood pressure, left ventricular percent fractional shortening, circumferential end-systolic wall stress, stroke volume index, cardiac index, total vascular resistance or ventricular contractile state in comparison with placebo but did decrease heart rate by 3 beats/min (p less than 0.05). With beta-adrenergic blockade, no differences in contractility were evident between esmolol alone and famotidine plus esmolol. Thus, H2 receptor blockade with famotidine does not alter myocardial mechanics or cardiac sympathetic tone, suggesting that in humans basal left ventricular contractile state is not physiologically dependent on the H2-mediated effects of histamine.


Diurnal exposure profile in rats from dietary administration of a chemical (doxazosin) with a short half-life: interplay of age and diurnal feeding pattern. Doxazosin, an alpha-adrenergic blocking agent, has a plasma half-life in male rats of 1-2 h after i.v. administration. Plasma concentrations of doxazosin were measured in male rats receiving the drug mixed in the diet at dose levels from 5 to 40 mg kg-1. Samples taken at 4-h intervals during the light (0700-1900) and dark phases revealed peak concentrations at 0400 which were only about three times higher than the trough concentrations observed ca. 12 h later. The 24-h area under the curve (AUC) values increased disproportionately with dose and with age from 2 months up to 8 months of age; thereafter they were fairly stable to 24 months of age. This age-related effect may have been due to a reduction in clearance and/or a change in the feeding pattern of the rats. Young rats consumed ca. 84% and old rats only 45% of their daily feed during the nocturnal (active) phase. Given the known diurnal rhythms in absorption, protein binding and enzyme metabolising activity, such a change in feeding pattern with age may have wider toxicokinetic implications.


Topically active drugs in the treatment of peptic ulcers. Focus on colloidal bismuth subcitrate and sucralfate. Topically active agents (i.e., colloidal bismuth subcitrate and sucralfate) have proved to be effective in promoting the healing of both gastric and duodenal ulcers and in relieving ulcer symptoms. Sucralfate alone has also been shown to maintain peptic ulcers in remission when taken continuously for a long period of time, whereas successful short-term therapy with bismuth subcitrate is associated with a more prolonged remission of duodenal ulcer disease when compared to H2 blockers. The antiulcer efficacy of these agents is partially counteracted by the need for multiple daily administrations, which requires greater patient compliance than with H2 antagonists. A specific subgroup of patients who might particularly benefit from these drugs are those with duodenal ulcer resistant to H2 blockers, whereas chronic nonsteroidal antiinflammatory drug users with peptic ulcer respond to therapy with site-protective agents as well as to antisecretory drugs.


A review of hospitalized patients with bacterial gastroenteritis. The distribution and clinical management of thirty-two hospitalized patients with salmonella and campylobacter infections were reviewed and the impact of these infections on hospital resources was assessed. Eighteen patients with salmonella infection had an age and sex distribution comparable with the community cases. In contrast, 10 out of 14 (71.4%) patients with campylobacter infection were under 20 years of age though the peak incidence of the infection in the community occurred in the 21-65 years age group (67%). There was no male predominance. The median duration of stay in hospital was 6 days for patients with salmonella infection and 3 days for those with campylobacter infection. Physicians were inconsistent in the treatment of campylobacter infection. Overall the financial impact of managing patients with salmonella and campylobacter infection was considerable (1384 pounds and 779 pounds respectively per patient). A limitation on unnecessarily prolonged hospital stays and the establishment of clear guidelines for the clinical management of these infections are necessary.


Ten years' experience with methicillin-resistant Staphylococcus aureus in a large Australian hospital. The Royal Brisbane Hospital (RBH) is a 1200-bed teaching hospital with acute, general and specialist units for adult patients. Methicillin-resistant Staphylococcus aureus (MRSA) was first detected at the RBH in 1975 and the number of new patients colonized and infected increased from one in 1975 to 720 in 1989, with a peak of 811 in 1987. Virulence may be inferred from blood culture isolates. Between 1979 and 1989 the number of patients with S. aureus bacteraemia increased from 40 to 138 per year. The percentage of these isolates which were MRSA varied from a low of 4% in 1980 to a peak of 37% in 1984 with 28% in 1989. The control attempts, sensitivity patterns, sources of the isolates and their probable impact and importance will be discussed.


Vascular catheter-related sepsis: diagnosis and prevention. Although catheter-related sepsis (CRS) is an important cause of nosocomial infection and the major complication of intravenous catheter use, there is, as yet, no consensus concerning either a useful definition of CRS or the optimal method of catheter management and prevention of infection. Semiquantitative culture of catheter tips is a useful method of diagnosis of CRS but other techniques such as quantitative catheter blood cultures and Gram staining of the catheter have roles in selected patients. The most significant impact on the prevention of CRS is made by the introduction of an intravenous therapy team. The site and method of catheter insertion, type of dressing and antisepsis, catheter flushing and use of prophylactic antibiotics are also important issues. Techniques such as guide-wire exchange and catheters such as triple lumen and total implantable venous access devices have their own infection problems. Many new and interesting approaches to the prevention of CRS are being formulated. To facilitate further progress, a standardized definition for diagnosis, and revised recommendations for prevention of CRS would be helpful.


Evaluation of the efficacy of surgical hand disinfection following a reduced application time of 3 instead of 5 min. The guidelines of the German Society for Hygiene and Microbiology for the evaluation of disinfectants suggest an application time of 5 min for surgical scrub products. In a comparative investigation, which included the more important basic substances and agents, tests were carried out to investigate whether it was possible to reduce the application time to 3 min without losing efficiency in both the immediate as well as the prolonged effect of bacterial reduction. It was found that this could be achieved by certain products, depending on the formula and type of active substance. Thus, a reduced application time of 3 min can be considered for the evaluation of surgical scrub disinfectants for national and international guidelines.


Investigation of an outbreak of nosocomial infection due to a multiply drug-resistant strain of Pseudomonas aeruginosa. A nosocomial outbreak of Pseudomonas aeruginosa infections which occurred in the Urology Service of a large city hospital was studied. A case-control methodology was used to analyse patients' characteristics and the main risk factors of all cases with a positive culture during the period between March 1987 and March 1988. The usefulness of factor analysis in the definition of a case was examined. There were 74 infections of which 35 (47.3%), had a nosocomial origin. The outbreak took place in December 1987, with a peak incidence of infections of 10.5%, compared with a 2.2% frequency during the preceding months (P less than 0.005). Six of the nine infections occurring in that month, were caused by strains resistant to ticarcillin and gentamicin. The epidemic cases had longer hospital stays than the non-epidemic cases (P less than 0.038) and occurred more frequently in a specific area of the hospital (P less than 0.001). The odds ratio for resistance to gentamicin was 15 (P less than 0.018) and that of resistance to ticarcillin, 127 (P less than 0.0001). Our results suggest that inaccurate case definitions may produce misleading conclusions. Factor analysis appears to be a useful analytical tool when defining a case.


Outbreak of infection in two UK hospitals caused by a strain of Klebsiella pneumoniae resistant to cefotaxime and ceftazidime. During an 8-month period, Klebsiella pneumoniae resistant to cefotaxime and ceftazidime were isolated from 18 elderly patients in two closely-situated UK hospitals. Amongst these 18 patients, the organisms were isolated from urine samples of 17, from blood cultures of two and from a wound swab of one. The infected patients were located in nine different wards and several of the patients had been transferred between wards, within and between the two hospitals. All the bacterial isolates belonged to serotype K62, were non-typable or reacted only weakly with bacteriophage, showed similar plasmid profiles and were resistant to tetracycline and trimethoprim, thus indicating they were the same strain. Resistance to cefotaxime and ceftazidime was inhibited by clavulanic acid suggesting the involvement of extended-spectrum beta-lactamase (ESBL) enzyme activity. This was confirmed by analytical isoelectric focusing, which showed that isolates each produced two beta-lactamases with isoelectric points of 7.0(SHV-3) and 7.6 (SHV-1/2) respectively.


A clinical evaluation of glove washing and re-use in dental practice. This study has assessed the durability of four brands of latex gloves, Ansell Medical 'Medi-Grip', Regent 'Biogel D', Surgikos 'Microtouch' and the London Rubber Company 'Supreme', under conditions of repeated washing and re-use in a clinical dental setting. The microbiological effectiveness of 'Hibiscrub' as a decontaminating washing agent was examined simultaneously. Examination by an electrical test for micropunctures in 200 unused gloves of each brand revealed such defects in 6(3%) of Ansell 'Medi-Grip', 3(1.5%) of 'Biogel D', 14(7%) of Surgikos 'Microtouch' and 2(1%) of LRC 'Supreme' gloves. Following repeated clinical use, micropunctures were detected in 18% of Ansell 'Medi-Grip', 10% of 'Biogel D', 75% of Surgikos 'Microtouch' and 56% of LRC 'Supreme'. Microorganisms were isolated from the glove surfaces after 45% of the occasions on which the gloves were washed for 1 min in 'Hibiscrub' (ICI Dental). Eighty-five per cent of these isolates were environmental organisms, but oral streptococci were isolated from 8.4% of the pairs of gloves examined. The high rate of micropuncture development following repeated washing and re-use of latex gloves indicates that they cannot effectively perform their barrier function under such conditions. The microbiological data have also revealed the potential for cross-infection between patients through inadequate decontamination of glove surfaces. For operative dental surgery, the results suggest that heavier, surgical type gloves are to be preferred, and that multiple use of any glove type should be discouraged.


Test models for hygienic handrub and hygienic handwash: the effects of two different contamination and sampling techniques. Two methods for artificial contamination of hands and two sampling techniques to recover the test organisms were compared for their effects on the results of two post-contamination hand treatments: a handrub with two portions of 3 ml of 2-propanol 60% v/v for 1 min, and a handwash with liquid soap 20% w/v for 1 min followed by a 15 s rinse. The two contamination methods involved a short immersion of the hands (up to the middle of the mid-hand) in a suspension of the test organism followed by either air-drying (3 min) or drying by rubbing the hands' vigorously against each other (3 min) in a standardized way. The two sampling techniques consisted of rubbing the fingertips in either 10 ml trypticase soy broth (TSB) against the bottom of a Petri dish; or 100 ml TSB against glass beads contained in a bowl. Sixteen volunteers were randomly allotted to four blocks of four. They carried out the four possible combinations of two treatments and two contamination methods in a series of four tests arranged in a Latin-square design. In addition, the two sampling techniques were compared with each other concurrently by sampling of the right and left hand each with a different one of the two techniques. The alcoholic handrub reduced the release of test organisms significantly (2P less than 0.005) more effectively, by 1.1-1.3 x log10, than did the handwash with liquid soap, regardless of the contamination or sampling method. Whereas the two recovery techniques yielded virtually identical results in corresponding situations, the method of artificial contamination affected the mean reduction factors, strongly.(ABSTRACT TRUNCATED AT 250 WORDS)


Importance of medium and atmosphere type to both slime production and adherence by coagulase-negative staphylococci. Marked differences in both the production of slime and adherence by Staphylococcus epidermidis were observed when comparing four culture media. Slime isolated from a strain cultured in a chemically defined medium (HHW) in air was chemically indistinguishable from that formed in both HHW and synthetic dialysis fluid (SDF) in air with 5% CO2. The presence of a physiological level of CO2 during culture in tryptone soya broth (TSB) prevented production of slime. It was not possible to separate the constituents of slime from those of the culture medium in bacteria grown in TSB in air using DEAE cellulose. Slime production was notably poor in used peritoneal dialysis fluid (PUD). Adherent growth was marked in HHW and SDF but was poor in TSB and PUD when air with 5% CO2 was used. These findings emphasize the advantages in using chemically defined and biological fluids when studying slime production and adherence by S. epidermidis.


Controlled trial of a Y-set dialysis delivery system to prevent peritonitis in patients receiving continuous ambulatory peritoneal dialysis. Peritonitis rates were compared in patients receiving continuous ambulatory peritoneal dialysis (CAPD) via either a Y-set dialysate delivery system or a standard system. Forty patients in each arm of the trial were matched for age (range 20-67 years, mean 49 years), and remained in the study for similar periods (range 3-36 months, mean 14.1 months). The observation time was 564 patient-months for each arm of the trial. There were 22 episodes of peritonitis in nine out of 40 patients using the Y-set and 57 episodes in 21 out of 40 patients using the standard system (P = 0.005 Wilcoxon signed rank test for episodes, P = 0.02 McNemar's chi 2 test for patients). Peritonitis rates were one episode per 25 patient-months in the Y-set group, and one episode per 9.7 patient-months in the standard group. In the Y-set group there were significantly fewer episodes caused by coagulase-negative staphylococci and Acinetobacter spp. There was no difference in the rate of episodes caused by Staphylococcus aureus, streptococci, enterococci, corynebacteria, enterobacteria or pseudomonads. There was no difference in the incidence of catheter exit wound infections. The Y-set dialysis delivery system is effective in reducing peritonitis rates in CAPD patients caused by organisms derived from the commensal skin flora, principally coagulase-negative staphylococci, but does not reduce peritonitis caused by other organisms.