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Biomedical subjects

M G Ross

Publications and source records attributed to M G Ross.

At least 163 records · Page 9Linked to original sources

Clinical, biochemical, serological, histological and ultrastructural features of liver disease in drug abusers.

Heroin abusers are frequently found to have abnormal liver function tests and hepatic histology. Hepatitis viruses A, B, and NANB, other drugs or drug contaminants and excessive alcohol consumption are factors thought to contribute. One hundred and sixteen heroin abusers attending a London treatment centre were studied. Sixty two (53%) had a raised aspartate transaminase. This was not explained by current infection with hepatitis A and B, cytomegalo or Epstein-Barr viruses, excessive alcohol consumption (greater than 80 g/day) or concomitant drug taking. Abnormal liver function tests were as frequent in those with markers of current or past HBV infection as those without and there was evidence that both HBV infection and the cause of the abnormal liver function tests were acquired in the first few years of intravenous drug abuse. Liver biopsies from eight patients showed chronic hepatitis with a mild lobular and portal inflammatory infiltrate, fatty change and prominent sinusoidal cells. Electron microscopy showed cytoplasmic trilaminar tubular structures and dense fused membranes in dilated endoplasmic reticulum. These clinical, biochemical, serological, and histological features would suggest a major role for NANB virus infection in the aetiology of hepatitis in heroin abusers.

Adult↗

Intravenous terbutaline and simultaneous beta 1-blockade for advanced premature labor.

Seventeen patients in advanced premature labor (cervical dilatation greater than or equal to 3 cm and effacement greater than or equal to 50%) were randomized in a double-blind protocol to receive metoprolol (a beta 1-adrenergic antagonist) or a placebo in conjunction with intravenous and oral terbutaline (a beta 2-agonist) in an attempt to inhibit the side effects of terbutaline. Both groups of patients had a dose-related increase in heart rate and systolic blood pressure and a decrease in diastolic blood pressure. Laboratory studies revealed significant hyperglycemia, hypokalemia, hypocalcemia, and acidosis during the intravenous terbutaline infusion, all of which normalized during oral terbutaline therapy. There were no significant differences in the cardiovascular or metabolic responses to terbutaline between the metroprolol and placebo patients. The mean delay in delivery was 5.7 days, with 59% of patients having delivery delayed for 48 hours or more. The mean prolongation time was shorter, but not statistically significant, for those patients receiving metroprolol. Despite the use of high-dose terbutaline, there were no significant complications of therapy. There was little efficacy of infusion dosages above 40 micrograms/min or repeated courses of intravenous tocolysis. Although recent reports do not recommend tocolysis in these patients, this study suggests that combined beta-mimetics and glucocorticoids may be the optimal care for patients in advanced premature labor, in particular, those with infants of very low birth weight.

Administration, Oral↗

Bulk flow of amniotic fluid water in response to maternal osmotic challenge.

Amniotic fluid volume is regulated by a complex system of fluid exchanges with fetal and maternal fluid compartments. To assess possible hormonal control of amniotic fluid water exchange with the maternal vascular compartment, we studied the effect of intra-amniotic injections of prolactin, vasopressin, or vasotocin on the amniotic to maternal water flux induced by the acute intravenous infusion of mannitol to the pregnant ewe. This mannitol stimulus increased amniotic fluid osmolality secondary to a shift of free water to the maternal vascular/extracellular compartments. Prior intra-amniotic injection of prolactin but not vasopressin or vasotocin blunted the amniotic fluid osmolar response to maternal mannitol infusion. These results suggest that resorption of amniotic fluid water may occur at the chorioamnion and that amniotic fluid prolactin may have a regulatory function in amniotic fluid volume and osmolar homeostasis.

Amniotic Fluid↗

Acyclovir prophylaxis against herpes virus infections in severely immunocompromised patients: randomised double blind trial.

Twenty patients undergoing allogeneic bone marrow transplantation and 39 patients receiving remission induction chemotherapy for acute leukaemia were entered into a double blind, placebo controlled stratified trial of acyclovir prophylaxis against herpes group virus infections. Within the transplant group intravenous acyclovir 5 mg/kg twice daily given throughout the period of granulocytopenia completely prevented oropharyngeal herpes simplex virus infection compared with a 50% incidence in the placebo arm (p = 0.033). The acyclovir group also had fewer days of fever during the trial and a shorter duration of leukopenia, possibly because of the prevention of herpes simplex virus infections. There was a high incidence of herpes infections after the trial in patients who received either acyclovir or placebo. In the non-transplant group there was also a significant reduction of herpes simplex virus infection in the oropharynx and oesophagus (two out of 19 patients as compared with 10 out of 20; p = 0.018). Herpes simplex virus was isolated in the acyclovir arm within a day after starting the trial in one patient, and the other failure was due to a virus with reduced sensitivity to acyclovir in a patient who had had several previous courses of the drug. The incidence of herpes infections after stopping treatment was low. The influence of acyclovir on excretion of Epstein-Barr virus in saliva in either group was inconclusive. One patient (transplant group) developed a cytomegalovirus infection while receiving acyclovir. Acyclovir provides effective prophylaxis against oropharyngeal and oesophageal herpes simplex virus infection in severely immunocompromised seropositive (greater than or equal to 1/8) patients. In patients given bone marrow transplants this may have the additional benefit of reducing the time to recovery of an adequate blood count and the number of days of fever.

Acyclovir↗

Neonatal metabolic effects of oral ritodrine hydrochloride administration.

Neonatal hypoglycemia and hyperinsulinemia have been reported following maternal ritodrine administration, but no prospective controlled study of the neonatal metabolic and cardiovascular effects of maternal ritodrine is available. We conducted a double-blind prospective study in 35 patients with preterm labor and/or ruptured membranes. Patients in premature labor received ritodrine (max dose, 350 mcg/min) or a placebo intravenously for 12 hours, and then orally (20 mg every 4 hours) until labor ensued. Patients with ruptured membranes received only oral therapy. Only patients who were maintained on oral therapy for a minimum of 12 hours and who were within 6 hours of their last dose of oral therapy were included in the analysis. Glucose and insulin values in cord blood at 6 and 12 hours of age were not significantly different between the ritodrine and placebo groups. There were no hypoglycemic infants in the ritodrine group. Mean systolic and diastolic blood pressure, heart rate and blood volume were similar for ritodrine and control infants. Although premature infants are at high risk for hypoglycemia it appears from this study that chronic oral ritodrine therapy does not significantly affect neonatal glucose homeostasis.

Adult↗

The diagnosis of puerperal ovarian vein thrombophlebitis by computed axial tomography scan.

The diagnosis of puerperal ovarian vein thrombophlebitis by computed axial tomography (CAT) scan is reported. The characteristic finding, ie, a soft tissue mass with a diameter of 2 cm and length of 14 cm, extending from the uterine cornua to the level of the renal vein, can be seen by CAT scan. The near total resolution of the mass on follow-up CAT scan confirmed successful treatment with antibiotics and heparin. Observation of these findings will allow future cases to be definitively diagnosed and treated without invasive procedures.

Adult↗

HLA-B8, immunoglobulins, and antibody responses in alcohol-related liver disease.

Ninety-two British, caucasian, alcoholic patients with liver disese were grouped on the basis of hepatic histology into fatty change, hepatitis with or without cirrhosis, and cirrhosis alone. Men with alcoholic hepatitis with or without cirrhosis showed an increased incidence of the histocompatibility antigen HLA-B8 (P less than 0.02). Increased measles antibody titres were found in patients without cirrhosis with or without hepatitis and were associated with the B8 phenotype in both sexes. Rubella antibody titres and percentage DNA-binding were raised in patients with cirrhosis and showed no association with the B8 phenotype. Concentrations of IgM and IgA were were raised in patients with stetosis and with hepatitis, while in patients with cirrhosis IgG concentrations were also increased. Low titres of autoantibodies were found in all histological groups. It is possible that the development of hepatitis in response to alcohol abuse may be influenced, at least in men, by a gene linked to the B locus. Otherwise, immune processes associated with alcohol-related liver disease are probably secondary phenomena.

Antibodies, Viral↗

Parenteral acyclovir therapy for herpesvirus infections in man.

Acyclovir is a new antiviral agent which is highly active against herpesviruses in vitro and in laboratory animals. Twenty-three cancer patients with cutaneous and/or systemic herpes zoster or herpes simplex infections were treated with parenteral acyclovir. All had received previous specific treatment for their malignant disease and ten had undergone bone-marrow transplantation. The drug seemed to arrest the progress of the infections and was most effective when given early. Although two patients showed transient increases in blood-urea, possibly the result of acyclovir, the drug was remarkably non-toxic in the doses used.

Adolescent↗

Viral exposure and abnormal liver function in haemophilia.

Several studies have recently documented the presence of persistently abnormal liver function tests in asymptomatic haemophiliacs. While the aetiology is unknown it is possible that repeated exposure to agents transmitted in blood products may be important. This study has attempted to determine the prevalence of viral exposure and its relationship to liver function in this multitransfused group of individuals. The prevalence of viral antibodies with the exception of antibody to hepatitis B surface antigen (anti-HBs) and cytomegalovirus (CMV) was normal when compared to that in the general population. Hepatitis B surface antigen (HBsAg) was not detected, but anti-HBs was found in 83% of patients; 50% of patients had abnormal liver function. However, liver function tests were normal in all patients with mild haemophilia and were only rarely abnormal in patients who had no detectable antibody to CMV, Epstein-Barr virus (EBV), and HBsAg. This study demonstrates that multiple transfusions of blood products, that is, cryoprecipitate and factor concentrates, do not increase the risk of exposure to the viruses studied with the exception of hepatitis B virus.

Adolescent↗

Development of concentration thresholds for fetal swallowing and arginine vasopressin stimulation in the preterm ovine fetus.

We previously demonstrated that fetal swallowing was stimulated by intracarotid saline injections in the near term (130 +/- 1 days gestation) ovine fetus. In order to examine the ontogeny of the regulation of thirst-mediated swallowing behavior and arginine vasopressin (AVP) secretion, the present study examined fetal swallowing and AVP secretory responses to hypertonic NaCl and sucrose in preterm (115 days gestation) ovine fetuses. Five fetuses were chronically prepared with thyrohyoid, nuchal and thoracic esophagus, and diaphragm electromyogram (EMG) electrodes, an esophageal flow probe, and vascular catheters. Fetuses received intracarotid injections (0.15 ml/kg) of increasing concentrations of NaCl (0.15-2.55 M), administered at 2-min intervals. The threshold saline concentration for swallowing was defined as the minimum NaCl dose eliciting swallow responses (within 20 s) following 4 of 5 injections at each dose. In 2 fetuses, the threshold dose was 0.75 M (confirmed by 4 of 5 injections resulting in swallows at the next higher dose). In the other 3 animals, no swallowing threshold was observed (i.e., no dose through 2.55 M elicited swallows to 4 of 5 injections). There were no significant increases in AVP secretion. On a subsequent day, equimolar sucrose injections did not affect fetal swallowing activity or AVP secretion. Together with previous reports, these studies indicate that plasma osmolality dipsogenic mechanisms become functional in some ovine fetuses by 115 days gestation, while all fetuses exhibit intact osmotic dipsogenic responses at 130 days gestation. These results further suggest an acute process of development of dipsogenic responsiveness, rather than by gradually increasing sensitivity to osmotic stimuli.

Animals↗

Increased fetal colonic muscle contractility following glucocorticoid and thyroxine therapy: implications for meconium passage.

The incidence of meconium-stained amniotic fluid increases with advanced gestational age and fetal stress, and meconium passage is likely dependent on fetal colonic muscle function. Antenatal hormone exposure improves fetal pulmonary and cardiovascular function. We hypothesized that in utero exposure to steroid or thyroid hormones effect an increase in fetal distal colonic muscle contractility. In a randomized controlled study 126-day (term 145 days) ovine fetuses were treated with a single ultrasound-guided intramuscular injection of 0.5 mg/kg betamethasone (n = 5), betamethasone plus 60 micrograms/kg thyroxine (n = 5), or saline (n = 7). After 48 h, fetuses (128 days) were delivered, distal colon segments were removed, and peak tension responses to bethanechol (10(-8) to 10(-3) M) characterized in vitro. Peak muscle tensions were significantly greater in fetuses exposed to combined betamethasone and thyroxine therapy (989 +/- 190 g/cm2) than in saline-treated animals (509 +/- 91 g/cm2). There was difference in the maximum tension response between betamethasone alone (559 +/- 75 g/cm2) and the saline animals. The bethanechol ED50 values (2.1 +/- 0.5 x 10(-5) M) were not different among the three groups. Antenatal fetal betamethasone and thyroid hormone treatment increases fetal colonic muscle contractility. We speculate that endogenous or exogenous fetal maturational agents may facilitate the passage of meconium.

Animals↗

Maternal plasma hypo-osmolality: effects on spontaneous and stimulated ovine fetal swallowing.

Fetal swallowing is a major route of amniotic fluid resorption, and thus swallowing activity may alter amniotic fluid volume. Near-term ovine fetal swallowing increases in response to plasma and/or cerebrospinal fluid hypertonicity. As maternal hydration status alters amniotic fluid volume, we hypothesized that maternal plasma hypotonicity may alter fetal swallowing activity. Pregnant ewes (130 +/- 1 d; n = 6) were chronically prepared with maternal and fetal vascular catheters, a fetal esophageal flow probe, and fetal thyrohyoid and nuchal and thoracic esophagus electromyogram electrodes. Spontaneous fetal swallowing and hypertonic saline thresholds for stimulated swallowing were determined prior to and following maternal hypotonicity induced with water loading and intravenous DDAVP (arginine vasopressin V2 agonist). Fetal swallowing thresholds were determined with intracarotid injections (0.15 ml/kg) of increasing sodium chloride concentrations (0.15-1.2 M) at 2-min intervals. Maternal DDAVP infusion significantly decreased mean (+/-SEM) maternal and fetal plasma osmolalities (298 +/- 2-284 +/- 3; 295 +/- 2-278 +/- 3 mOsm/kg, respectively) and sodium concentrations (147.3 +/- 0.4-137.5 +/- 0.9; 142.7 +/- 0.8-133.5 +/- 1.0 mEq/l, respectively), suppressed spontaneous swallowing activity and volume (1.1 +/- 0.2-0.6 +/- 0.1 swallows/min; 0.7 +/- 0.2-0.5 +/- 0.1 ml/min, respectively) and significantly increased the osmotic threshold for swallowing stimulation (0.77 +/- 0.08-1.03 +/- 0.09 M NaCl). We conclude that: (1) maternal, and thus fetal, plasma hypotonicity results in suppression of spontaneous fetal swallowing activity and a decrease in volume swallowed, suggesting that spontaneous fetal ingestive behavior results, in part, from tonic dipsogenic stimulation, and (2) under hypotonic conditions, the intracarotid NaCl injection concentration for swallowing stimulation increases. These results suggest that the reset (lower) maternal plasma osmolality during human pregnancy may serve to minimize fetal ingestive and perhaps arginine vasopressin-mediated antidiuretic responses to acute maternal hypertonicity.

Amniotic Fluid↗