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Biomedical subjects

S Gould

Publications and source records attributed to S Gould.

At least 55 records · Page 3Linked to original sources
PubMed1993

Lethal multiple pterygium syndrome. The importance of fetal posture in mid-trimester diagnosis by ultrasound: discussion and case report.

Lethal multiple pterygium syndrome and its variants provide an opportunity for prenatal diagnosis using mid-trimester ultrasound examination. The case presented here highlights the importance of postural deformity in reaching a diagnosis and illustrates the importance of full ultrasound examination of the fetus even when the well-documented common features of a condition are absent.

Journal Article↗
PubMed1993

Role of respiratory viral infection in SIDS: detection of viral nucleic acid by in situ hybridization.

There is considerable evidence suggesting that respiratory viral infection is involved in the genesis of the sudden infant death syndrome (SIDS), with rates of about 20 per cent of SIDS victims compared to about 13 per cent of controls. Since the techniques used previously are prone to under-reporting from autopsy material, non-isotopic in situ hybridization (NISH) has been used to detect viral nucleic acid in lung in SIDS. Forty-five SIDS cases (30 males) were examined (age range 3 weeks-14 months, mean age 3.9 months). Thirty non-SIDS cases (15 males) were also examined (age range 5 weeks-24 months, mean age 9.0 months). Eleven of 45 (24.4 per cent) SIDS cases were positive by NISH compared to 1 of 30 (3.3 per cent) non-SIDS cases (P = 0.012). There were eight cases of adenovirus type 5, two cases of respiratory syncytial virus (RSV), and one case of parainfluenza virus type 2. The one positive control case was adenovirus type 5. Only lung parenchyma was examined here. Additional examination of the upper respiratory tract may increase the number of positive cases.

Adenoviruses, Human↗
PubMed1993

Expression of the cystic fibrosis gene in human foetal tissues.

In order to examine the onset of the cystic fibrosis (CF) disease process, the expression of the cystic fibrosis gene (CFTR) has been examined in mid-trimester human foetal tissues by in situ hybridization. CFTR mRNA was detected in the epithelia of pancreatic ducts, small intestine, colon, genital ducts, lung and trachea. The majority of these sites of CFTR expression in the foetus are similar to those seen in adult tissues. However, epithelia of the lung, that contain very little CFTR mRNA in the adult, express high levels of CFTR mRNA in the foetus. Since the lung is the major site of pathology and morbidity in CF these findings have implications for treatment.

Cystic Fibrosis↗
PubMed1993

Acute herpes hepatitis in pregnancy.

A 36 year old primigravid woman presented with a "flu-like" illness and premature labour, followed by severe pneumonitis and hepatitis in the late second trimester of pregnancy. Progressive deterioration obliged an elective delivery of twins, stillborn at 25 weeks of gestation. Herpes virus isolated from one placenta, but not from any fetal tissue, was the only indication of a systemic herpes simplex infection in which there were no mucocutaneous lesions seen before or during the illness. There was no history of herpes simplex infection and antibody studies were not helpful initially for a diagnosis that was confirmed in retrospect. Double staining for viral DNA and antigen showed that the virus was present in host monocytes.

Adult↗
PubMed1993

Thromboxane A2 receptor antagonism and synthase inhibition in essential hypertension.

Short-term effects of ridogrel, a combined thromboxane synthase inhibitor and receptor antagonist, were investigated in 16 patients with uncomplicated essential hypertension. After a 2-week placebo period without antihypertensive medication, patients were admitted to the hospital overnight on two occasions 3 weeks apart. On each occasion, they received two doses of either placebo or ridogrel (300 mg) 12 hours apart according to a double-blind crossover protocol. Renal and systemic thromboxane A2 and prostacyclin biosynthesis were investigated by measuring urinary excretion of thromboxane B2, 6-oxo-prostaglandin F1 alpha, and their respective 2,3-dinor metabolites using gas chromatography/mass spectrometry. Responses of platelets to a thromboxane A2 mimetic and to adenosine diphosphate were studied turbidometrically. Blood pressure was measured automatically at 20-minute intervals. Ridogrel reduced excretion of 2,3-dinor-thromboxane B2 and thromboxane B2 compared with placebo (21 +/- 6 versus 279 +/- 28 and 14 +/- 4 versus 39 +/- 9 ng/g creatinine, respectively; P < .0001 and P < .05). Excretion of 2,3-dinor-6-oxoprostaglandin F1 alpha and 6-oxoprostaglandin F1 alpha was increased by ridogrel compared with placebo (184 +/- 20 versus 146 +/- 11 and 86 +/- 9 versus 58 +/- 6 ng/g creatinine, respectively; P < .05). Ridogrel selectively antagonized platelet aggregation to the thromboxane mimetic (P < .0001). Blood pressure did not differ significantly between ridogrel and placebo treatment periods. Thus, in patients with essential hypertension, acute administration of ridogrel reduces renal and extrarenal thromboxane A2 biosynthesis, increases renal and extrarenal prostacyclin biosynthesis, inhibits thromboxane receptor-activated platelet aggregation, but has no effect on systemic arterial pressure.

Adult↗
PubMed1992

Fetal alcohol syndrome and fatty acid ethyl esters.

Fetal alcohol syndrome is the leading known cause of mental retardation. The syndrome, defined as growth retardation, midface hypoplasia, and neurologic dysfunction, represents only part of the spectrum of fetal alcohol effects. The biochemical mechanism of teratogenesis is unknown. In adults, metabolites of ethanol, FAEE, are known to accumulate in major organs. The formation of FAEE is catalyzed by a family of enzymes, FAEE synthases. Our hypothesis is that accumulation of FAEE in the embryo results in fetal alcohol syndrome. We have developed assays for FAEE and FAEE synthase activity using mg of tissue. Using these assays, we have shown the following: Human placenta, mouse placenta, heart, and liver are active in catalyzing the formation of FAEE. One h after maternal ethanol administration on gestational d 14, mouse placenta and fetuses accumulated significant quantities of FAEE. The fatty acid incorporated into FAEE was tissue dependent. Tissues from pregnant animals given ethanol on gestational d 7 showed persistence of FAEE on gestational d 14. We conclude that: 1) human and mouse placentas have significant FAEE synthase activity, 2) mouse heart, liver, placenta, and fetal tissues accumulate significant amounts of FAEE after maternal ethanol exposure, 3) there is tissue specificity for the fatty acid incorporated into FAEE, and 4) FAEE may persist for 7 d in placentas. These results provide a basis for further research into the role of FAEE in the development of fetal alcohol syndrome.

Acyltransferases↗
PubMed1991

Effects of venous hypertension on rabbit free flap survival.

A two-stage project was developed to study the effect of increased venous pressure on blood flow and survival in microvascular free tissue transfers. A rabbit epigastric fasciocutaneous free flap model was used. The blood flow in the rabbit epigastric free flap is 1.07 +/- 0.06 ml/min. The average venous pressure is 8.6 +/- 1.7 cm water. A logarithmic relationship between blood flow and venous pressure was demonstrated, with a statistically significant decrease in blood flow to 20-35% of the control values when the venous pressure rose above 28-30 cm water. This study stands in support of the tolerance by free tissue transfers of pressures below this range. The results further show a positive correlation between increasing venous pressure and free flap failure.

Animals↗
PubMed1991

Activation of erythrocyte aldose reductase in man in response to glycaemic challenge.

Flux via the polyol pathway, which comprises the enzymes aldose reductase (AR) and sorbitol dehydrogenase (SDH), has been implicated in the debilitating complications of diabetes. Previous studies in this laboratory have indicated that erythrocyte AR activities are increased (by 72%) in insulin-dependent diabetic patients. To investigate the mechanism underlying this activation, the response of AR activity to oral glucose challenge was investigated in eight overnight-fasted human volunteers. Glucose consumption led to a transient activation (by 76%: P less than 0.01) of erythrocyte AR, which paralleled the rise and subsequent fall in blood glucose concentrations. It is concluded that erythrocyte AR activity is acutely modulated in response to hyperglycaemia by an as yet unknown mechanism.

Adult↗
PubMed1990

Physiologic effects of acute anemia: implications for a reduced transfusion trigger.

The risks of transfusion-associated infectious disease have led to a reassessment of transfusion practice, which in turn has resulted in a trend toward the reduction of homologous transfusion. This reduction is primarily due to the initiation of hemotherapy at more severe levels of anemia. The optimum threshold for the initiation of transfusion therapy, or the transfusion trigger (TT), is unknown. The purpose of this study is to evaluate the effects of withholding transfusion or lowering the TT to a hematocrit (Hct) of 15 percent in unanesthetized animals. Nineteen adult baboons underwent a laparotomy to simulate surgical stress. Upon their recovery from anesthesia, hemodynamic measurements were obtained, and the animals underwent an exchange transfusion (ET) with 6-percent hetastarch to a final Hct of 15 percent. After ET, hemodynamic measurements were repeated, and the animals were followed for 2 months. There was no morbidity after ET or during the 2-month observation period. After ET, there was a significant increase in both the cardiac output (3.3 vs. 2.5 L/min, p less than 0.001) and the oxygen extraction ratio (59.9 vs. 38.2%, p less than 0.0001). Oxygen delivery fell after ET (18.9 vs. 11.1 cc/kg/min, p less than 0.001), but there was no significant change in oxygen consumption after ET. The unanesthetized animals adapted well to severe anemia and experienced no adverse effects on their long-term survival in this setting, which suggests that the reduction of the TT to a Hct of 15 percent in normal animals is safe. Adoption of this TT could result in a significant reduction in the requirements for homologous transfusion with its attendant risks.

Acute Disease↗
PubMed1990

Accelerated erythropoiesis: the hidden benefit of autologous donation.

The risks associated with the administration of blood products have increased efforts to avoid homologous transfusions. Preoperative autologous donation has received renewed interest as a method of decreasing homologous transfusion requirements. Autologous donations may also stimulate postoperative erythropoiesis. The purpose of this study is to evaluate the effect of an aggressive autologous donation program on postoperative erythropoiesis. Ten adult male baboons were divided into two groups. The autologous group (n = 5) donated an average of 2 units of blood per week for 5 weeks before operation. The control group (n = 5) had no preoperative treatment. All animals then underwent a laparotomy and exchange transfusion with hetastarch to a final hematocrit of 15 percent. The time required to recover to hematocrits of 20 percent (3.3 vs. 5.7 days, p less than 0.01), 25 percent (7.0 vs. 8.8 days, p less than 0.05), and 30 percent (11.1 vs. 17.7 days, p less than 0.01) was shorter in the autologous group. The autologous group had more intense reticulocytosis during the first 4 postoperative days (p less than 0.03). The data show that participation in an aggressive autologous donation program improves the erythropoietic response to anemia in the postoperative setting. This represents a hidden benefit of preoperative autologous donations and suggests that more aggressive donation schedules may be clinically beneficial. Recognition of that acceleration of erythropoiesis by autologous donation could further reduce the need for transfusion of homologous blood.

Animals↗
PubMed1989

Characterization of cis-platinum-induced Sertoli cell dysfunction in rodents.

The present study examined the effects of dosage and frequency of cis-platinum administration on various aspects of Sertoli cell function and its correlation with the status of spermatogenesis in rats 1 and 9 weeks after the initial drug administration. Adult male Sprague-Dawley rats were administered cis-platinum (10 mg/kg) intraperitoneally as a single dose or as five daily doses of 2 mg/kg. Electron microscopic observation of testicular tissues fixed in the presence of lanthanum revealed that cis-platinum administration resulted in leakage of the Sertoli cell tight junctions. This occurred as early as 24 hr after the five daily injections, and persisted at least 40 days. Testicular androgen-binding protein (ABP) content was not significantly affected by either treatment regimen after 1 or 9 weeks of recovery. On the other hand, serum ABP values were significantly elevated after 9 weeks of recovery. In addition, the increased sodium and decreased potassium concentrations in seminiferous tubular fluid noted in cis-platinum-treated animals were also indicative of abnormal Sertoli cell secretory function. Degeneration of spermatogenic cells was noted as early as 5 days after the last drug administration; and partial restoration of spermatogenesis was noted after 40 days of recovery. We conclude that in rats both morphological and biochemical properties of Sertoli cells are affected by cis-platinum administration. These changes in Sertoli cell function may be responsible for the cis-platinum-induced impairment of spermatogenesis in these animals.

Androgen-Binding Protein↗
PubMed1989

Modification of Sertoli cell functions in vitamin A-deficient rats.

FSH binding and cAMP responses to FSH in Sertoli cell-enriched testes were not affected by the vitamin A (retinol) status of the animals. These results indicate that changes in Sertoli cell functions during vitamin A deficiency are independent of FSH-Sertoli cell interactions. Concentrations of serum androgen binding protein (ABP) in vitamin A-deficient rats were consistently higher than those of control animals throughout the study period. The accumulation of testicular fluid after efferent duct ligation, an indication of Sertoli cell secretory function, was normal in vitamin A-deficient rats at least until 70 days of age, but declined thereafter. ABP concentrations in seminiferous tubular fluid of vitamin A-deficient rats increased transitorily during the 70-80-day age period but returned to normal by 90 days. The increment of ABP in seminiferous tubular fluid after efferent duct ligation, and ABP concentrations in interstitial fluid were consistently lower in vitamin A-deficient rats. The higher serum ABP in vitamin A-deficient rats therefore cannot be explained by an increase in the permeability of Sertoli-cell tight junctions or basement membrane.

Androgen-Binding Protein↗
PubMed1989

Ketanserin: an effective treatment regimen for digital ischaemia in systemic sclerosis.

We have studied the therapeutic effects of ketanserin, a specific serotonin antagonist, on digital ischaemia in 11 patients with the CREST syndrome of systemic sclerosis. Ketanserin was administered as a bolus of 10 mg intravenously, followed by an infusion over 72 h and then oral therapy. Skin blood flow as measured by thermography, bolometry, ultrasound Doppler pulses and laser light scattering, showed significant improvement. There was also marked clinical improvement with a reduction in the pain and healing of digital ulceration. These improvements were maintained on oral therapy. In 7 patients detailed studies were performed comparing oral and intravenous ketanserin therapy. When ketanserin was administered as a bolus 10 mg intravenous dose, followed by an infusion at 2 mg/h, steady state was reached by 12 h. Following oral treatment (40 mg tds) therapeutic blood levels were achieved.

Administration, Oral↗
PubMed1989

Unrelenting time.

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Adaptation, Biological↗
PubMed1988

Partial prevention of procarbazine induced germinal cell aplasia in rats by sequential GnRH antagonist and testosterone administration.

The present study examined the feasibility of using a combination of gonadotropin releasing hormone antagonist (GnRH-A) and testosterone in the prevention of procarbazine induced germinal aplasia. Daily injections of GnRH-A or vehicle were given to adult male rats for 21 days prior to procarbazine (PCB) administration and continued until 2 days after the second of two doses of procarbazine (200 mg/kg i.p.) given 1 week apart. One group of rats receiving GnRH-A and PCB was given s.c. two 5-cm testosterone capsule (TC) implants (inside diameter, 3.5 mm) immediately following the second dose of PCB. Eight weeks after the last PCB treatment, more than 99% of the seminiferous tubular cross-sections of rats receiving PCB alone were devoid of spermatogenic activity. Spermatogenesis in PCB injected animals receiving GnRH-A pretreatment alone was abortive but was partially preserved when exogenous testosterone was given following PCB administration. At 16 weeks, spermatogenesis was absent in all PCB treated animals and was only observed in less than 1% of the tubular cross-sections of the PCB treated rats receiving GnRH-A pretreatment alone. On the other hand, active spermatogenesis was noted in 68% of the tubular cross-sections, and complete spermatogenesis was noted in four of the five PCB treated rats receiving both GnRH-A pretreatment and subsequent TC implantation. At the time of sacrifice, testicular testosterone concentrations in animals receiving TC implants were below 10% of normal levels, while both serum and testicular testosterone content were increased in PCB treated animals with or without GnRH-A pretreatment. Concomitantly, testicular androgen binding protein content remained suppressed and serum androgen binding protein was elevated, indicating a prolonged defect in Sertoli cell function. These lesions were prevented by GnRH-A pretreatment. The present study demonstrates that GnRH-A pretreatment and subsequent TC implantation resulted in restoration of complete spermatogenesis in adult male rats given a 400-mg/kg cumulative dose of PCB. It is postulated that GnRH-A may ameliorate PCB induced Sertoli cell dysfunction and/or stimulate the number of spermatogonia to provide more proliferating cells ready for repopulation of the germinal epithelium following PCB injury. The differentiation of these spermatogonia was further supported by exogenous testosterone through certain unknown local mechanisms, resulting in the completion of spermatogenesis.

Androgen-Binding Protein↗
PubMed1988

Disruption of sustentacular (Sertoli) cell tight junctions and regression of spermatogenesis in vitamin-A-deficient rats.

The relationship between the intactness of sustentacular (Sertoli) cell tight junctions and the status of spermatogenesis was examined in rats fed a vitamin-A-deficient diet after weaning (VAD rats). Both serum and testicular retinol concentrations of the VAD rats declined to a nadir by 80 days of age. At this time, it was observed that Sertoli cell tight junctions of the VAD animals were intact and complete spermatogenesis was maintained. Leakage in Sertoli cell tight junctions, as demonstrated by the presence of lanthanum in the adluminal compartment of the seminiferous epithelium, was first observed in 90-day-old VAD rats. Severe regression of spermatogenic cells was noted in 100-day or older VAD animals. These results suggest that severe germ cell loss observed during chronic vitamin A deficiency may result from abnormal intratubular environment due to the disruption of the blood-testis barrier.

Animals↗