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Biomedical subjects

J S Morgan

Publications and source records attributed to J S Morgan.

10 recordsLinked to original sources

Hemodynamic mechanisms of emerging portal hypertension caused by schistosomiasis in the hamster.

A hamster model of schistosomiasis has provided the first opportunity to sequentially examine the early phases of the development of portal hypertension in a natural model of chronic liver disease. Groups of hamsters were infected with 50 cercariae of Schistosoma mansoni and underwent hemodynamic evaluation at intervals of 5, 8, 12 and 20 wk after infection. A progressive rise in intrahepatic resistance (from 4.0 +/- 0.4 to 8.4 +/- 1.0 mm Hg min.ml-1.gm liver weight [p less than 0.01]) appeared to play a major role in the initial stages of evolving portal hypertension. A gradual decline in portal blood flow (from 2.1 +/- 0.3 to 1.3 +/- 0.1 ml.min-1.gm-1 liver weight [p less than 0.01]) was only partially compensated for by an increase in hepatic arterial flow. Accordingly, by week 20, total hepatic blood flow decreased 23%. Liver weight that increased markedly between 5 and 12 wk after infection, as a result of the acute accumulation of obstructing granulomas, stabilized between wk 12 and 20, while a gradual but progressive rise in hepatic collagen content was seen. Portal pressure increased 75% during the study period. Chronic examination of this natural model should help define the pathogenesis of the complications of portal hypertension and contribute to the basis for effective intervention in this disease process.

Animals

Extradural metastases in a case of medulloblastoma.

Extradural metastases in medulloblastoma appear to be rare. We describe a case associated with use of a lumbar drain and propose that in this situation, adjuvant chemotherapy and possibly extension of the radiotherapy field to include the entire sacral epidural fat-space to the lower border of S5, should be considered.

Cerebellar Neoplasms

Somatostatin in portal hypertension.

The effect of somatostatin on portal pressure is mediated by splanchnic arterial vasoconstriction which induces a reduction in portal blood flow and pressure. One of the most important characteristics of somatostatin is that its splanchnic effect is not accompanied by major systemic hemodynamic effects. Somatostatin has been used in several controlled trials to test its potential in controlling acute variceal bleeding. The results remain controversial. Different findings in existing clinical trials may derive in part from distinct protocols for somatostatin administration. Published trials suggest that somatostatin may be as effective as vasopressin in the acute management of variceal bleeding. However, since the efficacy of vasopressin has been questioned, a comparison of two potentially ineffective drugs cannot establish definitively the efficacy of somatostatin in controlling variceal bleeding. The most significant finding of the two published studies has been the lower incidence of minor and major complications with somatostatin when compared to vasopressin. Newer trials in progress may shed new light into the potential use of somatostatin for the treatment of variceal bleeding.

Hemodynamics

Resistance to reinfection in experimental murine schistosomiasis: role of porto-hepatic hemodynamics.

Experiments were conducted to evaluate critically, and independently of the immune system, the possible role of hemodynamic mechanisms in resistance to schistosomal reinfection. The effects of a challenge schistosomal infection were compared in groups of mice which were either previously infected with schistosomiasis, vaccinated with irradiated cercariae, or underwent partial portal vein ligation for the induction of portal hypertension and porto-systemic shunting. Following infection with 60 cercariae, the appearance of portal hypertension preceded by approximately 2 weeks the development of porto-systemic shunting, which reached maximal values 11 weeks postinfection. Such a primary infection conferred on C3H mice an estimated 90% protection to a 2nd infection, measured by the reduction of worm burden. Worm burdens were also reduced in vaccinated and ligated animals as compared to normal controls. The protection amounted to 30% and 56%, respectively, in the C3H strain and 63% and 75-85%, respectively, in the C57Bl/6 strain. Reduction in worm burden in the ligated animals is believed to be due to the extrahepatic porto-systemic vascular shunts. Hemodynamic as well as immunological factors may account for the resistance to reinfection observed in chronic murine schistosomiasis.

Animals

ICI 169,369 selectively blocks 5-hydroxytryptamine2 receptors and lowers portal pressure in portal hypertensive rats.

The contractile effects of 5-hydroxytryptamine on isolated portal veins and superior mesenteric veins of portal hypertensive rats (portal vein constricted) were antagonized competitively by ICI 169,369. The equilibrium dissociation constant of 1-3 nM for ICI 169,369, estimated in the veins, agrees with affinity estimates for arterial 5-hydroxytryptamine2 receptors. The receptors of portal veins of sham-operated rats had the same affinity for ICI 169,369 as the receptors of portal hypertensive rats. The systemic administration of ICI 169,369 to portal hypertensive rats decreased portal pressure from 13.0 +/- 0.4 to 11.3 +/- 0.5 mmHg (p less than 0.01) but did not affect arterial pressure. ICI 169,369 induced nonsignificant changes in both portal venous inflow and portocollateral resistance, as estimated by the radioactive microsphere technique. It is estimated that the combined changes in portal flow and resistance could explain the decrease in portal pressure. The results are consistent with an involvement of 5-hydroxytryptamine, acting through 5-hydroxytryptamine2 receptors, in prehepatic portal hypertension.

Animals

Evidence that the antitumor agent hydroxyurea enters mammalian cells by a diffusion mechanism.

Very little information is available about the process responsible for the uptake of the antitumor agent hydroxyurea by mammalian cells. Therefore we have investigated the transport of hydroxy[14C]-urea into Chinese hamster ovary cells. Using a convenient and reproducible 2 min. assay we found that hydroxyurea was taken up in a linear nonsaturable fashion between 0.01 mM and 100 mM drug. The Km for hydroxyurea uptake was essentially zero and the Vmax appeared to be infinite, suggesting a diffusion mechanism. The observation that intracellular drug concentrations were consistently less than medium concentrations indicated that uptake was not an active process. Experiments performed with the metabolic inhibitor sodium azide, and investigations at different assay temperatures also gave results consistent with a mechanism of drug diffusion. In total, the results obtained in this study are in agreement with the proposal that hydroxyurea enters the cell primarily by a process of diffusion. These observations provide a more complete understanding of the mode of action of this widely used drug.

Animals

Opportunistic strongyloidiasis in renal transplant recipients.

Eight patients with severe strongyloidiasis complicating renal transplantation are reported. Twenty-one additional cases from the English-language literature are reviewed. In this setting, systemic strongyloidiasis is an often baffling illness involving multiple organ systems that is frequently complicated by serious bacterial infection. Bacteremia, meningitis, urinary tract infection, and pneumonia resulting from enteric organisms are common. In order to make the diagnosis, larvae must be sought by direct microscopy of stool, upper intestinal fluid, sputum, urine, or biopsy specimens. Treatment with oral thiabendazole in prolonged or repeated courses is recommended. Effective parenteral therapy is not available. Following treatment, previously parasitized patients must be tested at regular intervals to detect therapeutic failure or reinfection. Screening of patients awaiting renal transplantation for chronic intestinal strongyloidiasis is suggested. Improvement of the observed 52% mortality will depend upon heightened awareness by physicians caring for renal transplant candidates, and upon improved therapeutic regimens.

Adult

Incomplete baroreceptor responses in newborn infants.

Previous studies of the baroreceptor response to a 45 degree head-up tilt in preterm and mature infants during the first 3 days of life failed to demonstrate a significant tachycardia while eliciting a 25% reduction in limb blood flow. In order to determine if maturity or respiratory distress affected the presence of tachycardia after tilting, 34 infants between 28 and 40 weeks gestation, including 15 infants with RDS, were studied serially during their hospitalization in a neonatal intensive care unit. In the first 5 seconds after a rapid (1-second) tilt to 45 degrees, individual infants responded with changes in heart rate (HR) ranging from a fall of 8 beats/min to an increase of 13 beats/min. Individual responses were not predictable on the basis of maturity at birth, age after birth, or presence of clinical respiratory distress. The group as a whole demonstrated a statistically significant increase of 2 +/- 4 beats/min in the first 5 seconds immediately after tilting. This may be compared to a coefficient of variation of +/- 4-5% in the resting HR of the same group of infants. Because of the unpredictability of individual responses and the small magnitude of the response for the group as a whole, it can be concluded that the HR component of the baroreceptor response is poorly developed during the neonatal period.

Gestational Age

Factitious renal stone as a sign of internal conflict about sexual intercourse in an adolescent.

Conflicts about the onset of sexual intercourse have been reported to cause a variety of symptoms. A 16-year-old black female claimed to have passed a stone in her urine. Investigation of her complaints caused some doubt that an organic cause was involved. Social history showed that she had recently begun to have sexual intercourse despite a religious belief that intercourse before marriage was wrong. After an extensive medical work-up, she was discharged with instructions to bring in another stone if passed. A stone subsequently presented by the patient proved to be a piece of lead shot. Those caring for adolescents need to be aware that conflicts about sexual intercourse may present in a number of ways, including urinary-tract complaints.

Adolescent

Work or non-work.

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Technology