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Biomedical subjects

J Wyatt

Publications and source records attributed to J Wyatt.

At least 37 records · Page 2Linked to original sources
PubMed2001

Intramuscular injection of insulin lispro or soluble human insulin: pharmacokinetics and glucodynamics in Type 2 diabetes.

AIM: The aim of the study was to compare the pharmacokinetics and glucodynamics of insulin lispro and soluble human insulin following intramuscular (i.m.) injection in patients with Type 2 diabetes with secondary failure of sulphonylureas. METHODS: Single 15-U i.m. doses of insulin lispro or soluble human insulin were administered to 16 patients in a two-way, randomized, crossover design. Glucodynamic and pharmacokinetic parameters were determined over 6 h after insulin injection using clamp techniques. RESULTS: Insulin C(max) was significantly higher (971 +/- 217 vs. 659 +/- 141 pmol/l, P < 0.001) and T(max) was significantly shorter (46.9 +/- 27 vs. 94.7 +/- 50.1 min, P = 0.002) with insulin lispro. Glucose infusion rate (GIR) curves showed clear separation 20 min after injection and were significantly greater for insulin lispro during the 40-60, 60-80 and 80-100-minute time intervals. Total glucose infused was only approximately 5% larger with insulin lispro during the 6-h follow-up, due to lower insulinaemia at later time points. The glucose R(max) and TR(max) were not statistically different between insulin treatments. CONCLUSION: This study shows that i.m. injection of insulin lispro is followed by its more rapid absorption, which results in stronger metabolic effect in the first 2 h when compared with soluble human insulin under the same test conditions. Diabet. Med. 18, 562-566 (2001)

Blood Glucose↗
PubMed2001

Medical paternalism and the fetus.

A number of developments in the medical field have changed the debate about the ethics of abortion. These developments include: advances in fetal physiology, the increase in neonatal intensive care and the survival rates of premature infants. This paper discusses the idea of selective termination and the effects that these decisions have on disabled people of today. It presents a critique of the counselling services that are provided for the parents of a disabled fetus and discusses how this is viewed from a social perspective. The article ends with an argument that the mother deserves to be autonomous in the decision of abortion. The easiest and most fair way to develop her autonomy is to consider the relationship between a professional and a mother as an expert-expert relationship. Here both parties are considered experts in diagnostic information, treatment options, possibilities, and their history, family roots, philosophy and way of life, respectively.

Abortion, Eugenic↗
PubMed2001

Treatment of type 1 diabetes with insulin lispro during Ramadan.

OBJECTIVE: To compare insulin lispro with regular human insulin with respect to blood glucose control and frequency of hypoglycaemia in patients with type 1 diabetes who wished to fast during the month of Ramadan. RESEARCH DESIGN AND METHODS: Insulin lispro or regular human insulin was given together with NPH insulin, twice daily before the morning and evening meals, for two weeks each in an open-label, randomised, cross-over design, and 64 patients completed the protocol. Blood glucose was self-monitored at fasting morning and evening, and 1-h and 2-h after the post-sunset meal on three consecutive days at the end of each treatment period. RESULTS: The 2-h blood glucose excursion after the post-sunset meal was significantly (p=0.026) lower with insulin lispro (2.50 +/- 0.46 mmol/l) than with regular human insulin (3.47 +/- 0.49 mmol/l). Daily insulin doses did not differ between treatments but compliance with recommended time of injection was better with insulin lispro. Hypoglycaemia incidence (insulin lispro, 15 (23.4%) patients; regular human insulin 31 (48.4%) patients; p=0.004) and frequency (insulin lispro, 0.70 +/- 0.19; regular human insulin 2.25 +/- 0.36 episodes/patient/30 days; p<0.001) were lower with insulin lispro. Five (22.7%) of the episodes during insulin lispro occurred during the nocturnal period compared with 27 (36.5%) of the episodes while on regular human insulin. CONCLUSIONS: Glycaemic control, measured by postprandial glycemic excursions, was improved and hypoglycaemia was significantly reduced with insulin lispro compared with regular human insulin. Patients with type 1 diabetes who insist on fasting during Ramadan may be better managed with insulin lispro.

Adolescent↗
PubMed2000

Transposition of the great arteries, ventricular septal defect and diaphragmatic hernia in a fetus: the role of prenatal diagnosis in helping to predict postnatal survival.

Congenital heart disease and congenital diaphragmatic hernia are frequently associated. The combination of these lesions is predictive of poor postnatal survival. The identification of both lesions during prenatal life may facilitate improved survival in carefully selected cases. We present a case of left-sided diaphragmatic hernia with transposition of the great arteries and a ventricular septal defect (VSD) that survived following repair of both defects within the first six weeks of life.

Adult↗
PubMed2000

Fibrinogen brescia: hepatic endoplasmic reticulum storage and hypofibrinogenemia because of a gamma284 Gly-->Arg mutation.

The proposita suffered from liver cirrhosis and biopsy showed type 1 membrane-bound fiberglass inclusions. The hepatic inclusion bodies were weakly periodic acid-Schiff diastase-positive, and on immunoperoxidase staining reacted specifically with anti-fibrinogen antisera. Coagulation investigations revealed low functional and antigenic fibrinogen together with a prolonged thrombin time of 37 seconds (normal, 17 to 22 seconds) suggestive of a hypodysfibrinogenemia. DNA sequencing of all three fibrinogen genes showed a single heterozygous mutation of GGG (Gly)-->CGG (Arg) at codon 284 of the gamma-chain gene. However, examination of purified fibrinogen chains by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, reverse-phase high-performance liquid chromatography, ion-exchange high-performance liquid chromatography, and isoelectric focusing, failed to show any evidence of the mutant gamma(Br) chain in plasma fibrinogen. This finding was substantiated by electrospray ionization mass spectrometry, which showed only a normal gamma (and Bbeta) chain mass, but a large increase in the portion of their disialo isoforms. We speculate that misfolding of the variant protein causes hepatic retention and the subsequent hypofibrinogenemia, and that the functional defect (dysfibrinogenemia) results from hypersialylation of otherwise normal Bbeta and gamma chains consequent to the liver cirrhosis. These conclusions were supported by studies on six other family members with hypofibrinogenemia, and essentially normal clotting times, who were heterozygous for the gamma284 Gly-->Arg mutation.

Afibrinogenemia↗
PubMed2000

Stillbirths and neonatal encephalopathy in Kathmandu, Nepal: an estimate of the contribution of birth asphyxia to perinatal mortality in a low-income urban population.

We describe a prospective cross-sectional survey over a 12-month period in the principal maternity hospital of Kathmandu, Nepal, where over 50% of the local population deliver. The study aim was to estimate the contribution of birth asphyxia to perinatal mortality in this setting. During 1995, there were 14,371 livebirths and 400 stillbirths, a total stillbirth rate of 27 per 1000 total births. The fresh term (2000 g or more) stillbirth rate was 8.5 per 1000 total births [95% CI 7.1, 10.1]. Ninety-two cases of neonatal encephalopathy (NE) affecting term infants were detected (excluding those due to congenital malformations, hypoglycaemia and early neonatal sepsis). The birth prevalence of NE was 6.4 per 1000 livebirths [95% CI 5.2, 7.8]. There was evidence of intrapartum compromise in 63 (68%) of the cases of NE and 65 (76%) of the stillbirths, but only in 12 (12%) of controls. The cause-specific early neonatal mortality rate for NE was 2.1 per 1000 livebirths [95% CI 1.4, 3.0]. Combining the NE deaths and fresh stillbirths gives an upper estimate for term birth asphyxia perinatal mortality rate of 10.8 per 1000 total births [95% CI 9.2, 12.6], 24% of all perinatal deaths before hospital discharge. This study suggests that birth asphyxia remains an important cause of perinatal mortality in developing countries. The paper discusses the pros and cons of different strategies to reduce birth asphyxia in low-income countries.

Asphyxia Neonatorum↗
PubMed2000

Trends over time in Helicobacter pylori gastritis in Kenya.

OBJECTIVE AND DESIGN: There is increasing evidence to link infection of the gastric mucosa by Helicobacter pylori with the subsequent development of gastric cancer. This study was undertaken to document the progression of H. pylori gastritis in a rural Kenyan population with a moderate gastric cancer risk. METHOD: Biopsy follow-up study of 51 H. pylori-positive patients over an average of 5.5 years. RESULTS: In the study group, the number of individuals with moderate to severe atrophy rose from 17 (33%) to 22 (43%), an annual increase of 1.8% [95% confidence interval (CI) -0.9% to 4.4%]. There was significant progression of atrophy (P< 0.05) in those with low overall scores for graded morphological variables at initial endoscopy. Intestinal metaplasia did not progress; indeed four out of 12 patients initially diagnosed with intestinal metaplasia showed no evidence of it in their follow-up biopsies. CONCLUSIONS: H. pylori gastritis with atrophy may provide a suitable environment within the gastric mucosa for the development of gastric cancer but it is likely that other factors in this population determine further progress towards dysplasia and cancer.

Adult↗
PubMed2000

Patient acceptability of a new 3.0 ml pre-filled insulin pen.

The objective of these two studies was to assess patient acceptance and feature preferences of the new Lilly 3.0 ml pre-filled pen. A total of 701 patients with diabetes mellitus, who required insulin, were treated for 4-6 weeks with the pre-filled pen. Patient acceptance and treatment preferences were assessed by a questionnaire completed at the end of the study period. Patients with type 1 or type 2 diabetes mellitus from South Africa (n = 371) and Croatia (n = 330) were enrolled in the study. The mean age was 51.6 years (range: 18-81), and gender was 359 males and 342 females. Prior to the study, patients in South Africa (SA) had used the Novo Actraphane (Novo Nordisk, Bagsvaerd, Denmark) pen set, and patients in Croatia (C) had used NovoPen 1 or 2 (Novo Nordisk, Bagsvaerd, Denmark) (38.8%), NovoPen 3 (Novo Nordisk, Bagsvaerd, Denmark) (28.8%), B-D Pen (Becton-Dickinson, Franklin Lakes, New Jersey, USA) (18.8%), needle/syringe (10.0%), oral hypoglycaemic agents (2.1%), or unknown (1.5%). The new Lilly 3.0 ml pre-filled pen features that were rated by respondents as good to excellent on a five-point rating scale included: cartridge visibility (C = 94%, SA = 83%), ease of dose correction (C = 92%, SA = 85%), dialling of the dose (C = 89%, SA = 81%), turning of the dose knob (C = 84%, SA = 82%) and attaching needles (C = 92%, SA = 78%). Most respondents (C = 78%, SA = 75%) preferred single-unit versus two-unit dosage increments. Overall, 76% of patients in Croatia and 80% in South Africa preferred the Lilly 3.0 ml pre-filled pen to their previous delivery device; 84% and 87% of patients, respectively, would recommend the pen to another patient. Also, the majority of patients in both trials rated the new Lilly 3.0 ml pre-filled pen as being more convenient and easier to use, and indicated that it represented a significant or modest improvement over their previous insulin injection method. The results of this study confirm that the new Lilly 3.0 ml pre-filled pen is widely accepted and preferred by patients using both reusable and pre-filled devices.

Adolescent↗
PubMed2000

Hypofibrinogenaemia with compound heterozygosity for two gamma chain mutations - gamma 82 Ala-->Gly and an intron two GT-->AT splice site mutation.

We investigated the molecular basis of hypofibrinogenaemia in a woman with a history of recurrent, pregnancy-associated bleeding, and miscarriage. She had a Clauss fibrinogen of 0.9 mg/ml and SDS PAGE of purified fibrinogen showed a normal pattern of chains. However careful inspection of reverse phase chain separation profiles showed apparent homozygosity for a more hydrophilic form of the gamma chain. DNA Sequencing showed only heterozygosity for a CGT-->GGT (Ala-->Gly) mutation at codon gamma82, but further sequencing showed an additional GT splice sequence mutation at the 5' end of intron 2 of the gamma gene. Translation of mRNA containing this intron would result in premature truncation explaining the phenotypic homozygosity of the gamma82 Ala-->Gly substitution. The patient's sister had a mild bleeding disorder with hypofibrinogenaemia and she too was a compound heterozygote for the y mutations. Her nephew had only the novel splice site mutation, while her mother and daughter inherited only the gamma82 Ala-->Gly substitution.

Adult↗
PubMed1999

Predicting abuse-prone parental attitudes and discipline practices in a nationally representative sample.

OBJECTIVE: According to sociological and ecological models of abuse, typically nonabusive parents could behave abusively towards their children under certain circumstances. The purpose of this study was to examine factors that place parents at risk of abusing their children by predicting parents' use of discipline practices and attitudes that may bias parents towards abusive behaviors, which we refer to as abuse-proneness. METHOD: A telephone interview was administered by the Gallup Organization to a nationally representative sample of 1,000 parents. Using a set of theoretically relevant risk factors, multiple regression was used to predict variations in parental attitudes (i.e., attitudes towards physical discipline and attitudes that devalue children) and parental discipline practices (i.e., physical discipline, nonphysical discipline, and verbal abuse). RESULTS: The findings confirmed the importance of examining elements of parental attitudes, history, personality characteristics, as well as religion and ideology in predicting abuse proneness. Child age also was an important predictor in all analyses except predicting parental attitudes that devalue children. The findings suggest also, however, that it may be unduly simplified to regard parents as somewhere on a continuum of nonpunitive to punitive disciplinarians. Social isolation was not a significant predictor in any of the analyses. CONCLUSIONS: Although many important theoretical predictors of abuse proneness were confirmed, many questions arise regarding the diversity of discipline practices that parents use, and the relevance of child's age and social isolation in predicting abuse proneness. Implications for practitioners and future research are discussed.

Adolescent↗
PubMed1999

Energy and substrate metabolism in patients with active Crohn's disease.

The aim of the study was to evaluate the possible contribution of changes in energy metabolism and substrate oxidation rates to malnutrition in Crohn's disease and to assess the effect of enteral nutrition on these parameters. Energy metabolism was evaluated by indirect calorimetry in 32 patients with active Crohn's disease and 19 age- and sex-matched healthy individuals. Measurements were done in the postabsorptive state. Seven out of 32 patients received enteral nutrition via a nasogastric tube. In these patients, resting energy metabolism was determined at d 0 (postabsorptive), 7, 14 (during full enteral nutrition) and 15 (postabsorptive). Resting energy expenditure was not significantly different between patients and controls, whereas the respiratory quotient (RQ) was lower in patients (0.78 +/- 0.05 vs. 0.86 +/- 0.05; P < 0.05). During enteral nutrition in 7 patients with Crohn's disease, the RQ increased on d 7 compared with d 0 and remained high even after cessation of enteral nutrition (d 0, 0.78 +/- 0.03; d 7, 0.91 +/- 0.04; d 15, 0. 84 +/- 0.05; P < 0.05; d 7 and 15 vs. d 0). No effects of enteral nutrition on resting energy expenditure were found. Active Crohn's disease is associated with changes in substrate metabolism that resemble a starvation pattern. These changes appear not to be specific to Crohn's disease but to malnutrition and are readily reversed by enteral nutrition. Enteral nutrition did not affect resting energy expenditure. Wasting is a consequence of malnutrition but not of hypermetabolism in Crohn's disease.

Adult↗
PubMed1999

Use of mitochondrial inhibitors to demonstrate that cytochrome oxidase near-infrared spectroscopy can measure mitochondrial dysfunction noninvasively in the brain.

The use of near-infrared spectroscopy to measure noninvasively changes in the redox state of cerebral cytochrome oxidase in vivo is controversial. We therefore tested these measurements using a multiwavelength detector in the neonatal pig brain. Exchange transfusion with perfluorocarbons revealed that the spectrum of cytochrome oxidase in the near-infrared was identical in the neonatal pig, the adult rat, and in the purified enzyme. Under normoxic conditions, the neonatal pig brain contained 15 micromol/L deoxyhemoglobin, 29 micromol/L oxyhemoglobin, and 1.2 micromol/L oxidized cytochrome oxidase. The mitochondrial inhibitor cyanide was used to determine whether redox changes in cytochrome oxidase could be detected in the presence of the larger cerebral hemoglobin concentration. Addition of cyanide induced full reduction of cytochrome oxidase in both blooded and bloodless animals. In the blooded animals, subsequent anoxia caused large changes in hemoglobin oxygenation and concentration but did not affect the cytochrome oxidase near-infrared signal. Simultaneous blood oxygenation level-dependent magnetic resonance imaging measurements showed a good correlation with near-infrared measurements of deoxyhemoglobin concentration. Possible interference in the near-infrared measurements from light scattering changes was discounted by simultaneous measurements of the optical pathlength using the cerebral water absorbance as a standard chromophore. We conclude that, under these conditions, near-infrared spectroscopy can accurately measure changes in the cerebral cytochrome oxidase redox state.

Animals↗