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Biomedical subjects

R Marshall

Publications and source records attributed to R Marshall.

At least 19 recordsLinked to original sources
PubMed1992

Suramin: a selective inhibitor of purinergic neurotransmission in the rat isolated vas deferens.

The effects of the putative P2 purinoceptor antagonist suramin on contractile responses of the rat isolated vas deferens to electrical field stimulation and exogenously applied drugs (alpha,beta-methylene ATP and noradrenaline) were investigated. Suramin was devoid of agonist activity in the rat vas deferens. The response of the vas deferens to single pulse field stimulation was characteristically biphasic with a large first component peaking between 260-300 ms after the stimulus followed by a second smaller component peaking at about 650 ms post-stimulus. Suramin (100 nM-1 mM) selectively impaired the first, purinergic phase of the response to single pulse field stimulation but was without effect on the second, noradrenergic component. The response of the vas deferens to trains of electrical field stimuli (10 Hz for 10 s) was also biphasic. Suramin (1 microM-1 mM) reduced the first (less than 1 s) phase of the response by 30%, the second (greater than 5 s) plateau phase by 50% and inhibited the intermediate (2-4 s) phase by 80%. Dose-contact periods of 20 or 30 min respectively were sufficient to achieve equilibration of the inhibitory effects of suramin against the responses to single pulse field stimulation or trains of pulses. Following 30 min incubation with 1 mM suramin, the remaining first and second phase components of the response to trains of pulses were impaired and subsequently abolished by the alpha 1-adrenoceptor antagonist WB4101 establishing their noradrenergic origin. Suramin (300 microM) abolished responses of the vas deferens to alpha,beta-methylene ATP but was without effect on those to noradrenaline. Suramin (30 microM) induced a rightward shift in the concentration-response relationship to alpha,beta-methylene ATP that was associated with a significant 40% increase in the maximum response, but did not modify responses to noradrenaline. The inhibitory effects of suramin (3-300 microM) on responses of the vas deferens to approximate EC50 concentrations of alpha,beta-methylene ATP were reversible on repeated washout for 40-60 min. These results reveal suramin to be a useful pharmacological tool for the study of purinergic neurotransmission in rodent vasa deferentia.

Adenosine Triphosphate↗
PubMed1992

Distinct syndromes of hemineglect.

Hemineglect was assessed in 34 patients with right-hemisphere stroke using a letter-cancellation task and a line bisection task. No significant correlation (r = .39) was found between scores on the two tests. Ten patients who showed neglect on the cancellation task but performed normally on line bisection had frontal or deep lesions. Eleven patients with posterior lesions deviated rightward on line bisection; several of these had minimal or no cancellation deficit. A nonmotor task involving judgment of a bisected line was also performed abnormally by six patients with line bisection shift, suggesting that such shift does not result from a motor response asymmetry. We propose that separable components of the neglect syndrome may be associated with damage to discrete areas of the nondominant hemisphere.

Adult↗
PubMed1992

Gonadal effects of fetal exposure to the azo dye congo red in mice: infertility in female but not male offspring.

The present study describes the relationship between gonadal agenesis and fertility in male and female mice exposed in utero to the diazo dye Congo red (CR). Maternal CR treatment inhibited testicular and ovarian function in the offspring after oral administration of 1 or 0.5 g/kg/day on Gestational Days 8-12. The testes of male offspring from CR-exposed dams were small in size and contained hypospermatogenic seminiferous tubules. However, despite the fact that testis weight was reduced by more than 70% in some males, they displayed normal levels of fertility when mated to untreated females for over 10 months. In contrast, female offspring from CR-exposed dams produced only about half as many litters and pups as the control pairs did under long-term mating conditions. Histological examination of the ovaries revealed that subfertility was correlated with ovarian atrophy. Females lacking maturing follicles were considerably less productive (1.3 litters and 11.5 pups) than treated females with histologically normal ovaries (7.1 litters and 78.1 pups). In summary, prenatal exposure to the dye CR affects the gonads of both male and female offspring, but only the female offspring display reduced fertility.

Animals↗
PubMed1992

Laparoscopic removal of mullerian remnants in a woman with congenital absence of the vagina.

Most women with mullerian agenesis do not have cyclic pain and therefore do not require surgery. When surgery is necessary, we recommend a laparoscopic approach as described in this report because of the decreased morbidity and cost compared with laparotomy. Results from this case suggest that outpatient laparoscopic treatment of this condition is safe and effective. Regardless of the surgical approach used, a preoperative IVP is essential to limit the risk of damage to the urinary tract.

Adolescent↗
PubMed1992

An area analysis of child injury morbidity in Auckland.

The geographical distribution of child injury morbidity in Auckland between 1982 and 1987 was examined. Analysis of total injury, pedestrian injury and vehicle occupant injury, with the census area unit as the basic spatial entity revealed distinct variations in child injury morbidity by census area unit. Morbidity rates were above average in parts of the central urban area and South Auckland and below average on the North Shore. Total injury morbidity and pedestrian injury morbidity rates were strongly correlated with census area unit unemployment rates, which were used as a measure of socio-economic deprivation. Geographical areas with high rates of child injury morbidity, to which injury prevention resources can be directed, were identified. In particular, the results suggest that injury prevention programmes should be targeted at socio-economically disadvantaged communities.

Accidents, Traffic↗
PubMed1992

Myocardial oxygenation in the isolated working rabbit heart as a function of work.

Myocardial O2 consumption (MVO2) was stimulated up to two-fold by either increasing afterload or beta-receptor stimulation in working normothermic isolated rabbit hearts while noninvasively monitoring the O2 delivery or phosphate compounds (total n = 48). Intracellular O2 delivery was estimated with the use of myocardial optical absorbance changes centered at 603.5 and 582 nm that correlate with cytochrome aa3 redox and myoglobin oxygenation states. Phosphate-containing metabolites (ATP, phosphocreatine, free ADP) were assessed using 31P nuclear magnetic resonance spectroscopy. Measurements were made both with intact autoregulation and after maximal vasodilation by 1 microM nitroprusside (NP). When afterload was used to increase MVO2, absorbance decreased at 603.5 nm and increased at 582 nm, consistent with a 10-15% increase in myocardial oxygenation, without an associated change in cardiac phosphate compounds. NP caused a further increase in myocardial oxygenation and venous PO2 consistent with an increase in the O2 supply-to-demand ratio. Increases in MVO2 due to beta-stimulation alone were not associated with changes in 603.5-nm absorbance or phosphate compounds, but in combination with NP were accompanied by increased oxygenation, venous PO2, and cardiac phosphocreatine. KCl arrest caused maximal increases in oxygenation and phosphocreatine. These findings suggest that neither cytochrome aa3 nor myoglobin in the isolated working rabbit heart is fully oxidized or oxygenated, respectively. Furthermore, the oxygenation state of the tissue varied both with afterload-induced changes in cardiac work and with changes in O2 supply/demand.

Adenosine Triphosphate↗
PubMed1992

Hypoxia episodes during sleep in high tetraplegia.

To determine whether oxygen desaturation occurs during sleep in high tetraplegics, 10 neurologically stable male patients (aged 17 to 55 years) with complete motor lesions (C4 to C6) had continuous pulse oximetry recordings and sleep observations on two nights. The patients were studied during admissions for nonrespiratory problems (eg, pressure sores, urinary infection, respite). Lung function tests and daytime arterial blood gases were also measured. Mean forced vital capacity was 46% of predicted, but mean awake PaO2 and PaCO2 were normal (95.0 mmHg and 42.8 mmHg, respectively). Three subjects showed severe nocturnal oxygen desaturation spending greater than 10% of the time overnight with arterial oxyhaemoglobin saturation (SaO2) levels of less than 90%. For the group as a whole, the percentage of time spent under 90% SaO2 correlated with body mass index. Mean overnight SaO2 correlated inversely with body mass index and directly with maximal expiratory pressure, a measure of respiratory muscle strength. Low overnight SaO2 was also associated with higher levels of injury. The pattern of nocturnal oxygen desaturation observed was episodic and was suggestive of obstructive sleep apnoea during rapid eye movement (REM) sleep. Levels of nocturnal oxygen desaturation similar to those observed in the three most severely affected patients have been shown, in other disorders, to be associated with cognitive impairment, cardiovascular disease and increased mortality. Our results suggest up to a third of high tetraplegics may be at risk of potentially serious nocturnal hypoxic episodes.

Adolescent↗
PubMed1991

Cryptosporidiosis in the Isle of Thanet; an outbreak associated with local drinking water.

An outbreak of cryptosporidiosis occurred in the Isle of Thanet during December 1990 and January 1991. A total of 47 cases ranging in age from 2 months to 85 years were identified in residents from the Margate, Broadstairs and Ramsgate areas, with dates of onset of illness from 3 December to 14 January. A case-control study demonstrated a strong statistical association between illness and the consumption of unboiled tap water from a particular source, with evidence of a dose-response relationship. Although no cryptosporidial oocysts were identified in samples of untreated or treated water taken during the investigation, the results were consistent with the view that the source of infection was treated river water which was used to supplement borehole water.

Adolescent↗
PubMed1991

Asexual development of Cryptosporidium parvum within a differentiated human enterocyte cell line.

Unremitting diarrhea with malabsorption is associated with Cryptosporidium parvum infection of the small intestine in patients with AIDS. The lack of a well-defined in vitro model of C. parvum infection has severely hampered research into the biology of cryptosporidial invasion of the host epithelial cell and development of new pharmacologic and immunologic therapies. The adherent human intestinal epithelial cell line HT29 when grown in glucose-free medium develops morphologic and functional characteristics of the small intestine enterocyte and was used to develop an in vitro model of infection. Cryptosporidium oocysts obtained from AIDS patients were applied to a monolayer of cloned, differentiated HT29.74 cells. Cells were fixed and stained to estimate the degree of parasite infection. Schizonts were easily distinguished from the host cell by light microscopy. Twenty-four hours after 10(5) oocysts were added to approximately 10(6) HT29.74 cells, Cryptosporidium infection rates varied from 50 to 120 schizonts per 1,000 cells. Among 14 different experiments, the mean infection rate was 91 (+/- 18) schizonts per 1,000 cells. Electron microscopy at 6 and 24 h confirmed intracellular localization and development of schizonts. The morphologic features of the cryptosporidial schizonts within HT29.74 cells, which included the presence of a dense band and feeder layer, were identical to those described during cryptosporidial infection of human enterocytes in patients with AIDS. Fewer schizonts were observed at 5 days and beyond. Infection of differentiated HT29.74 cells (62 and 65 schizonts per 1,000 cells at 24 and 72 h, respectively) was over five times more efficient than infection of undifferentiated HT29.74 cells (9 and 5 schizonts per 1,000 cells at 24 and 72 h, respectively). In vitro infection of differentiated HT29.74 cells will allow a better understanding of the mechanisms by which C. parvum infects the small intestinal epithelium and will allow a systematic evaluation of new therapeutic agents.

Animals↗
PubMed1991

A 19-year follow-up of tuberculin reactors. Assessment of skin test reactivity and in vitro lymphocyte responses.

Tuberculin skin test reactivity decreases with time such that repeat PPD skin testing may result in reactions of less than 10 mm. This reactivity may be boosted in some individuals with a second tuberculin skin test. The immunologic basis of these observations remains unclear. We studied the relationship between skin-test reactivity and in vitro blastogenic response to PPD in a cohort of 22 individuals (aged 28 to 81 years) known to be tuberculin reactors (induration greater than or equal to 10 mm) in 1970. In 1989, 18 subjects remained reactive to PPD on the first skin test and responded to PPD in vitro (mean incorporation of 3H-thymidine by peripheral blood mononuclear cells, 22,650 cpm). Three subjects reverted (induration in response to PPD less than 10 mm) and lost in vitro reactivity to PPD (mean incorporation of 3H-thymidine, 2,205 cpm). One subject boosted (increase of induration of at least 6 mm to greater than or equal to 15 mm) on the second skin test and showed a concomitant in vitro boost in the blastogenic response to PPD (from 1,008 cpm to 47,837 cpm). In this cohort, interpretation of the two-step tuberculin skin test correlated closely with in vitro proliferative responses. Over a 19-year period, the majority of individuals maintained skin test reactivity and strong in vitro responses to PPD despite a lack of ongoing exogenous exposure to Mycobacterium tuberculosis. The immunologic basis for reversion appears to depend in part on a loss of lymphocyte blastogenic capacity. In the one individual who exhibited the booster phenomenon, repeat antigen stimulation resulted in a dramatic increase in the in vitro blastogenic responses.

Adult↗
PubMed1990

Studies on the potential mutagenicity of p-phenylenediamine in oxidative hair dye mixtures.

An aqueous mixture of p-phenylenediamine dihydrochloride, resorcinol and hydrogen peroxide, incubated for 30 min at 37 degrees C, was not mutagenic in the Ames test and in the mouse lymphoma assay and did not produce chromosome aberrations in human lymphocytes, whereas the same mixture without resorcinol was mutagenic in the Ames test and the chromosome aberration assay, probably due to the formation of Bandrowski's base. The formation of mutagenic Bandrowski's base and other reactive products could be demonstrated by thin-layer chromatography and subsequent Ames testing. Preincubation for 0-7 h of 5 different oxidative mixtures of p-phenylenediamine dihydrochloride and various couplers at 37 degrees C resulted in mutagenicities in the Ames test ranging from 'very strong effects' at 0 or 0.5 h for 2,4-diaminoanisole dihydrochloride to 'not mutagenic' at up to 7 h preincubation time for a recently developed alternative coupler. A comparable ranking of mutagenic potencies of the same mixtures could be obtained by Ames tests with dyed buffalo hair strands, either tested directly on the agar plates or by testing the solvent extracts of the colored strands. The optimal combination without any sign of mutagenic tendency was finally tested in a commercially available hair dye formulation. This complex mixture was also not mutagenic in the Ames test. Our main conclusions are as follows. (I) Oxidative hair dye mixtures of p-phenylenediamine dihydrochloride and non-mutagenic couplers are not mutagenic if tested under normal conditions of use; the formation of mutagenic reaction products (such as Bandrowski's base) can be prevented if the oxidative reaction time is limited to 30 min and if about equimolar proportions of para to meta compounds are used. (II) Optimal non-mutagenic combinations of primary intermediates (such as p-phenylenediamine dihydrochloride) and couplers can be evaluated in the Ames test by either time-dependent preincubation of the mixtures or the described test protocol with hair strands.

Animals↗
PubMed1990

Predictors of Haitian-American infant development at twelve months.

Perinatal and early childhood influences on the development of 66 Haitian-American children were examined as part of an ongoing home visiting program. Although all participants were impoverished, approximately two-thirds lived in an urban setting with some access to social and health services, while one-third lived in a rural farmworkers' community where housing and services were sharply substandard. Measures used to examine the development of infants in these 2 settings included birthweight, household crowding, parental contributions to the child-rearing environment (the HOME), and developmental progress at 12 months on the Bayley Scales of Infant Development. Results showed that the urban sample was advanced on the Mental Development Index of the Bayley Scales. Regression analyses showed birthweight and the HOME score measuring child-rearing environment to be significant predictors of mental development, while psychomotor development was related to birthweight and household crowding. The results indicate that even within this disadvantaged Haitian entrant population, environmental differences exist that influence infant development in subtle but significant ways.

Adolescent↗
PubMed1990

Extracorporeal membrane oxygenation in the neonate.

ECMO is a modified heart-lung bypass system for treatment of moribund neonates. The techniques are described. Our experience with 19 patients reveals a survival rate of 79 percent. In the future, with advances in technology, ECMO may become less invisible and extended to a larger population of newborns.

Extracorporeal Membrane Oxygenation↗
PubMed1989

Influence of environmental factors on the in vitro efficacy of ciprofloxacin against anaerobic bacteria.

The effects of alterations in pH, size of inoculum, addition of human serum, and repeated exposure to sub-minimum inhibitory concentration of ciprofloxacin against anaerobic bacteria were assessed. Increase in the size of the inoculum and human serum had no effect on the minimum inhibitory concentration, whereas decrease in pH and exposure to sub-MIC decreased the activity of ciprofloxacin against Bacteroides fragilis. We tested for synergism of ciprofloxacin with cefoxitin, clindamycin and metronidazole against B. fragilis.

Anti-Bacterial Agents↗
PubMed1988

Acetylcholine sweatspot test for autonomic denervation.

A test for autonomic denervation based on the local sweat response to 0.1 ml 1% acetylcholine administered intradermally, which depends on an intact local sympathetic supply, is described. Diabetic autonomic neuropathy affects the longest fibres first and thus the test was applied to the feet. After painting a standard site on the dorsum of the foot with iodine and starch, acetylcholine was injected intradermally in the centre. The normal response, visible to the eye, is a uniform distribution of dark spots of iodine discolouration at the sites of sweat production. In diabetic autonomic neuropathy this pattern is lost to a varying degree. In a photographic image magnified x 10, the spots were counted in sixty 2.5 cm squares in a grid centred on the injection site. 50 normal volunteers aged 18-69 were tested. No effect of age or sex was found. Five or more squares with less than 6 spots was the definition of abnormal. 24 diabetic men who complained of impotence were investigated with the sweatspot test, a pupil test, and cardiovascular autonomic function tests. 13 had abnormal sweatspot tests with scores up to sixty squares with less than 6 spots. In keeping with the increased length of the sympathetic fibres to the feet compared with those to the iris, there was a 30% false-negative rate for the pupil test if the sweatspot test is taken as standard. Agreement between the cardiovascular tests and the sweatspot test was seen in only 17 patients. The sweatspot test appears to be a more sensitive indicator of autonomic neuropathy than the commonly used cardiovascular tests.

Acetylcholine↗