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Biomedical subjects

B Fowler

Publications and source records attributed to B Fowler.

At least 127 records · Page 7Linked to original sources
PubMed1988

First trimester diagnosis of methylmalonic aciduria.

We have studied methylmalonyl CoA mutase activity in control chorionic villi to establish the potential use of assays performed directly on this tissue for prenatal diagnosis of methylmalonic aciduria. We report the detection of a fetus affected with the apo-mutase deficient form of this condition at 9 weeks' gestation. Methylmalonyl CoA mutase was markedly deficient in chorionic villi, approximately 2.5 per cent of the mean control value. However, incorporation of label from [14C]-propionate into protein was 10 and 40 per cent of the mean control value, respectively, in two portions of the same biopsy, highlighting potential problems in the use of this indirect assay. Normal results were obtained in chorionic villus samples from four other pregnancies 'at risk' for methylmalonic aciduria which were subsequently shown to be unaffected with this condition. The diagnosis in the affected pregnancy was confirmed by demonstration of a marked deficiency of methylmalonyl CoA mutase activity in villi obtained at termination and in cultured fetal fibroblasts. Reduced incorporation of [14C]-propionate label into protein was also found in these tissues.

Amino Acid Metabolism, Inborn Errors↗
PubMed1988

The effects of nitrous oxide on P300 and reaction time.

This experiment investigated the effects of 3 concentrations (15%, 25% and 35%) of nitrous oxide (N2O) on reaction time (RT) and P300 latency and amplitude. Ten subjects responded to visually presented male or female names in an oddball paradigm with accuracy controlled at a high level. The results were analysed on a single-trial basis. Nitrous oxide increased both RT and P300 latency in a dose-related manner and these variables showed a strong between-dose correlation (r = 0.67). Nitrous oxide also decreased P300 amplitude but only up to the 25% dose. The between-dose correlation for P300 amplitude and RT was negligible (r = -0.14). These results suggest that P300 latency is an index of N2O narcosis and are interpreted as indicating that narcosis involves the slowing of stimulus evaluation processes.

Adult↗
PubMed1988

Correlates of amylase and lipase levels in chronic dialysis patients.

Serum lipase and amylase isoenzymes were measured in 44 chronic hemodialysis patients, 16 CAPD patients and 22 normal volunteers. The enzyme levels of the two patient groups were similar and were significantly higher than those of the volunteer group. The ratio of pancreatic to salivary amylase was similar in all three groups. Anuric patients in both dialysis groups had higher enzyme levels than those with residual urine output. Linear regression analysis was done to attempt to identify factors which were good predictors of enzyme levels. Although no such factors were found in the hemodialysis group, in the CAPD group there were significant correlations between the degree of azotemia and the magnitude of enzyme elevations. Further studies are needed to determine the relative importance of oversecretion and underexcretion in the genesis of the amylase and lipase elevations found in dialysis patients.

Amylases↗
PubMed1988

Effect of arteriovenous shunting on plasma vasopressin levels in the anesthetized dog.

Studies were performed in dogs anesthetized with chloralose to establish the plasma arginine vasopressin (AVP) response to 30-minute periods of femoral arteriovenous (AV) shunting at levels of either 10%, 30%, or 50% of control cardiac output. Significant increases in cardiac output, heart rate, and total body peripheral resistance (shunt resistance excluded), suggesting decreased sinoaortic baroreceptor activity, occurred at shunt fractions greater than 10%. There were no significant changes in plasma concentrations of AVP at any level of AV shunting. In separate studies, significant elevations in plasma AVP levels were observed in vagotomized dogs during AV shunting of 50% of control cardiac output. These results indicate that AV shunting less than or equal to 50% of cardiac output does not acutely alter plasma AVP levels in the intact dog and that cardiopulmonary receptors with vagal afferents suppress AVP release that might otherwise occur in this canine model of AV shunting.

Anesthesia↗
PubMed1987

Increased excretion of propan-1,3-diol and 3-hydroxypropionic acid apparently caused by abnormal bacterial metabolism in the gut.

Three patients who died in infancy showed an unusual urinary organic acid pattern with excessive excretion of 3-hydroxypropionic acid but none of the other metabolites normally associated with propionyl-CoA carboxylase deficiency. Propan-1,3-diol was present in the urine in all three cases. In the two patients examined propionyl-CoA carboxylase activity was not deficient in cultured skin fibroblasts. A fourth patient, also severely ill, showed similar urinary abnormalities. Feeding a medium-chain triglyceride-rich diet to this patient increased the ratio of 3-hydroxypropionic acid to propan-1,3-diol and resulted also in the appearance of malonic acid in the urine. These abnormal metabolites disappeared on the administration of neomycin and presumably were produced by gut bacteria.

Aging↗
PubMed1987

Aryl sulphatase isoenzymes of chorionic villi: implications for prenatal diagnosis.

Prenatal diagnosis of metachromatic leucodystrophy (MLD) is based on demonstrating a deficiency of aryl sulphatase A (ASA) in the fetus. To evaluate the place of chorionic villus sampling for prenatal diagnosis of this condition, the properties of ASA were compared in chorionic villi and cultured skin fibroblasts. Considerable differences with respect to pH optimum, Km values and linearity with incubation time were found. These differences can be explained by the presence of aryl sulphatase C (ASC), a major component in chorionic villi and placenta. This isoenzyme was shown to have activity towards p-nitrocatechol sulphate (NCS) thereby interfering in the colorimetric assay most often used to detect MLD (Baum et al., 1959)

Cerebroside-Sulfatase↗
PubMed1987

Krabbe's disease: first trimester diagnosis confirmed on cultured amniotic fluid cells and fetal tissues.

Chorionic villi obtained during the first trimester from a pregnancy at risk for Krabbe's disease were shown to have reduced cerebroside-beta-galactosidase (E.C.3.2.1.46) activity using the artificial substrate trinitrophenylaminolauryl galactocerebroside (TNPAL-galactocerebroside). Assay of this enzyme in cultured amniotic fluid cells following amniocentesis, performed at the patient's request confirmed the diagnosis. Termination of pregnancy was performed and subsequent enzyme studies of the fetal tissues were consistent with the diagnosis of Krabbe's disease, thus confirming that chorionic villi can be used for first trimester diagnosis of this condition.

Amniocentesis↗
PubMed1987

Effects of inert gas narcosis on rehearsal strategy in a learning task.

Two experiments were conducted to examine the effects of 35% nitrous oxide (N2O) on rehearsal strategy while learning a list of words in a free-recall paradigm. In experiment 1, the subjects learned the list while rehearsing the words aloud. Learning was slowed and an analysis of the recorded rehearsal protocols revealed a decrease in the overall rate of rehearsal. In addition, there was a decrease in both the number of words rehearsed together and the proportion of words rehearsed from earlier serial positions in the list. In experiment 2, the subjects were required to follow a different rehearsal protocol which was identical for both N2O and the air-breathing control. They had no difficulty following this protocol, but learning was still slowed. These results demonstrate that rehearsal strategies may be modified by narcosis but can be manipulated experimentally. This is consistent with the hypothesis that strategic variables play an important role in the slowed processing model of inert gas narcosis.

Adult↗
PubMed1986

The concentration of latamoxef achieved in the bile and gallbladder wall of patients with cholecystitis.

This study reports the clinical and pharmacokinetic results following an injection of latamoxef (moxalactam disodium) in patients undergoing cholecystectomy for symptomatic cholelithiasis. Two groups were involved in the study. Group A consisted of 22 patients who received 1 g of intramuscular latamoxef at the time of premedication prior to surgery, and group B consisted of 12 patients each of whom received an intravenous dose of 0.5 g of latamoxef at the time of anaesthetic induction. Latamoxef levels were then measured in peripheral blood, gall bladder bile, common bile duct (CBD) bile and gall bladder wall. Despite a significant difference in the sampling times, inhibitory levels were obtained in the majority of samples in both groups, singularly high levels being assayed in CBD bile. We conclude that an intravenous dosage of latamoxef (0.5 g) given with anaesthetic induction is as effective as 1 g intramuscular dosage given with the pre-medication.

Adolescent↗
PubMed1986

Effects of ethanol and amphetamine on inert gas narcosis in humans.

The effects of ethyl alcohol (1 ml/kg body weight), dextroamphetamine (15 mg), and nitrous oxide (20%) on reaction time were investigated in 6 subjects with a 2-, 3-, and 4-choice serial reaction time task. Each drug was assessed separately and in combination with nitrous oxide. The error rate was held constant. Neither ethanol and nitrous oxide nor amphetamine and nitrous oxide influenced the slope of the Hick-Hyman function, but the former combination increased the intercept while the latter decreased it. The drugs, either alone or in combination, shifted the frequency distributions of the reaction times as a whole, rather than modifying either their shapes or the pattern of the response latencies around an error. These results indicate that the drugs have a common pattern of effects on reaction time and that alcohol exacerbates narcosis while amphetamine ameliorates it. This is interpreted as support for the view that narcosis causes a nonspecific slowing of information processing by decreasing arousal.

Adult↗
PubMed1986

Effects of inert gas narcosis on the vestibular ocular reflex.

A study was conducted to examine the vestibular ocular reflex (VOR) during narcosis. The slow phase velocity of the nystagmus was measured in six subjects by means of electronystagmography during the inhalation of 25% nitrous oxide. It was found that nitrous oxide increased the velocity of the slow phase component of the VOR by approximately 50%. This result indicates that the gain of the VOR is effectively increased during nitrous oxide induced narcosis. It appears that the vestibular end organs and/or the central pathways controlling nystagmus are affected by nitrous oxide and this may be a reason for the disruption in balance associated with inert gas narcosis.

Adult↗
PubMed1985

Heterozygosity for homocystinuria in premature peripheral and cerebral occlusive arterial disease.

Premature arteriosclerosis and thromboembolic events are well-known complications of homozygous homocystinuria due to cystathionine synthase deficiency. It is unknown whether heterozygosity for homocystinuria predisposes to premature vascular disease. We explored the frequency of excessive homocysteine accumulation after standardized methionine loading in 75 patients presenting with clinical signs of ischemic disease before the age of 50:25 with occlusive peripheral arterial disease, 25 with occlusive cerebrovascular disease, and 25 with myocardial infarction. In seven patients in each of the first two groups but in none of the patients in the third group, heterozygosity for homocystinuria was established on the basis of pathological homocysteinemia after methionine loading and cystathionine synthase deficiency in skin fibroblast cultures. Because the frequency of heterozygosity for homocystinuria in the normal population is 1 in 70 at the most, we conclude that this condition predisposes to the development of premature occlusive arterial disease, causing intermittent claudication, renovascular hypertension, and ischemic cerebrovascular disease.

Adult↗
PubMed1985

Improved identification of heterozygotes for homocystinuria due to cystathionine synthase deficiency by the combination of methionine loading and enzyme determination in cultured fibroblasts.

Previous data on tentative identification of the carrier state for homocystinuria due to cystathionine synthase deficiency using methionine loading or measurement of cystathionine synthase activity in tissue extracts are conflicting. We studied the results of standardized oral methionine loading in 20 obligate heterozygotes and compared them with those of determination of cystathionine synthase activity in cultured fibroblasts. Special attention was devoted to our recently reported observation on the small but striking differences in methionine metabolism between healthy pre- and postmenopausal women and men. Fasting and after load peak levels of methionine in serum did not discriminate the carriers from the control subjects. The mean fasting level of total homocysteine was only significantly higher in the group of premenopausal heterozygotes than in the corresponding control group. Nevertheless, the individual values overlapped with the normal range in 4 of 12 premenopausal heterozygotes. After loading peak levels of total homocysteine in 18 out of the 20 obligate heterozygotes exceeded the upper limit of the ranges in the three control groups. Thus, this parameter discriminated 90% of the obligate carriers. Measurement of cystathionine synthase activity in cultured fibroblasts from a skin biopsy identified the obligate heterozygotes to a similar degree (85%). No significant correlation between the measurements of cystathionine synthase activity and the after load peak levels of total homocysteine in the individual heterozygotes was established. Combination of both methionine loading and determination of cystathionine synthase activity in cultured fibroblasts identified all of these carriers.

Adolescent↗
PubMed1985

Recent advances in the mechanism of pyridoxine-responsive disorders.

Pyridoxine metabolism is summarised and speculation on possible defects leading to disease is made. Inherited deficiencies of PLP enzymes, which are known to respond in vivo to pharmacologic doses of pyridoxine are listed. The mechanism of pyridoxine responsiveness in homocystinuria due to cystathionine beta-synthase deficiency is discussed. There is a correlation in most (but not all) cases between the presence of residual CS activity, which is often stimulated by pyridoxal phosphate much more than control enzyme, in cultured fibroblasts and pyridoxine responsiveness in vivo. Exceptional patients have been found and are discussed in the light of more detailed studies on their cell lines. Clearly defined abnormalities of pyridoxal phosphate binding to mutant enzyme have been demonstrated and evidence of reduced intracellular stability of mutant CS and possible modulation by pyridoxal phosphate is presented. Preliminary findings suggest that the tissue level of pyridoxal phosphate achieved following pyridoxine treatment could be one other factor in determining pyridoxine responsiveness.

Cells, Cultured↗