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Biomedical subjects

M R Gray

Publications and source records attributed to M R Gray.

At least 37 records · Page 2Linked to original sources
PubMed1997

Mutation analysis of the gonadotropin-releasing hormone receptor gene in idiopathic hypogonadotropic hypogonadism.

OBJECTIVE: To determine if GnRH receptor mutations occur in patients with idiopathic hypogonadotropic hypogonadism. DESIGN: Patients and controls were studied by molecular genetic analysis. SETTING: A tertiary medical center setting. PATIENT(S): Twenty-four patients with idiopathic hypogonadotropic hypogonadism and 20 controls. INTERVENTION(S): Deoxyribonucleic acid from all individuals was analyzed by Southern blot analysis and denaturing gradient gel electrophoresis. Genomic DNA was digested with restriction enzymes, and Southern blots and denaturing gradient gel blots were constructed. Blots were hybridized with the GnRH receptor complementary DNA probe. The DNA sequencing was performed on samples from two representative patients. MAIN OUTCOME MEASURE(S): Gonadotropin-releasing hormone receptor gene structure was ascertained by comparing fragments from autoradiographs in patients and controls. Individual nucleotides were ascertained from DNA sequencing gels. RESULT(S): No GnRH receptor gene deletions or polymorphisms were identified by Southern blot analysis. New restriction-fragment melting polymorphisms using the enzymes DpnII, RsaI, and HaeIII were identified by denaturing gradient gel blots in patients and controls. CONCLUSION(S): Gonadotropin-releasing hormone receptor gene deletions or rearrangements were not observed in our idiopathic hypogonadotropic hypogonadism patients. Denaturing gradient gel electrophoresis failed to identify single-base differences unique to patients with idiopathic hypogonadotropic hypogonadism, dramatically reducing the likelihood that point mutations of the GnRH receptor gene are present in idiopathic hypogonadotropic hypogonadism.

Adolescent↗
PubMed1997

Congenital absence of the uterus and vagina is not commonly transmitted as a dominant genetic trait: outcomes of surrogate pregnancies.

OBJECTIVE: To determine the inheritance pattern of congenital absence of the uterus and vagina in affected women undergoing surrogacy IVF with this disorder. DESIGN: Retrospective study. SETTING: A hospital-based reproductive endocrinology and infertility center. PATIENT(S): Women diagnosed with congenital absence of the uterus and vagina undergoing IVF with subsequent transfer of embryos to a surrogate uterus. INTERVENTION(S): Questionnaires were sent to all infertility treatment centers performing surrogate procedures. MAIN OUTCOME MEASURE(S): Number, gender, and frequency of congenital anomalies in progeny. RESULT(S): Thirty-two of 53 surveyed programs responded (60%). One hundred sixty-two IVF cycles were performed, and 34 liveborn children were delivered (half female). No congenital anomalies were found, except for one male child with a middle ear defect and hearing loss. CONCLUSION(S): These results strongly suggest that congenital absence of the uterus and vagina, if genetically transmitted, is not inherited commonly in a dominant fashion.

Congenital Abnormalities↗
PubMed1997

The use of capillary electrophoresis as part of a specificity testing strategy for mitoguazone dihydrochloride HPLC methods.

Capillary electrophoresis (CE) has been used as part of a validation experiment designed to prove the specificity of high performance liquid chromatography (HPLC) methods used for analysis of mitoguazone dihydrochloride drug substance. Data regarding accuracy, precision and sensitivity of the CE methods are presented as well as a comparison of results obtained from CE, HPLC and thin-layer chromatography (TLC) analysis of samples stressed under a variety of conditions. It was concluded that, not only were the HPLC methods being investigated specific, but that CE could potentially be used to replace HPLC for the routine assay of mitoguazone dihydrochloride.

Antineoplastic Agents↗
PubMed1997

Effects of intravenous infusion of lidocaine on its pharmacokinetics in conscious instrumented dogs.

In this study, potential alterations in hepatic blood flow, plasma protein binding, hepatic tissue binding, and enzyme activities induced by LD iv infusion of lidocaine (LD) were evaluated using a chronically instrumented dog model. Four conscious female mongrel dogs (19.0-23.5 kg) were each given, on days 1 and 10, a 5-min infusion of a mixture of unlabeled LD at approximately 2 mg/kg and 14C-labeled LD at approximately 25 microCi and, on day 8, a 12-h constant rate iv infusion of LD (approximately 76 microg/kg/min). During LD infusion, there was a 11-79% increase in total hepatic blood flow, mainly due to a 1.6-9.2-fold increase in hepatic arterial flow. Despite similar blood clearance (27.5 +/- 6.0 mL/min/kg vs 27.5 +/- 3.5 mL/min/kg), volume of distribution at steady state (1.38 +/- 0.08 L/kg vs 1.36 +/- 0.17 L/kg), and free fraction values of LD between days 1 and 10 (p > 0.05), intrinsic clearance values were consistently reduced (1224 +/- 859 mL/ min/kg vs 285 +/- 104 mL/min/kg; p = 0.034). Furthermore, hepatic tissue uptake of LD and/or its metabolites was less on day 10 than on day 1 (39.7 +/- 14.5 micromol vs 30.1 +/- 15.1 micromol; p = 0.072). The extent of N-dealkylation of LD to MEGX was unaltered, whereas sequential biotransformation of MEGX was impaired. Hence, these findings suggested that LD infusion led to a reduction of hepatic intrinsic clearance, although the change was not significant enough to alter its conventional kinetic parameters.

Animals↗
PubMed1997

Assessment of cardiovascular changes during laparoscopic hernia repair using oesophageal Doppler.

We have used an oesophageal Doppler to measure aortic blood flow velocity before, during and after induction of carbon dioxide pneumoperitoneum in 10 consecutive patients, mean age 58 yr, undergoing laparoscopic hernia repair. Derived values for stroke distance, minute distance and systemic vascular resistance showed considerable interpatient variation indicating unpredictable haemodynamic responses. Five minutes after insufflation of the abdomen there was a significant increase in mean arterial pressure from 82.5 to 103.6 mm Hg (P < 0.05) but both stroke distance and minute distance decreased significantly (mean 12.0 (SEM 1.4) cm to 9.0 (0.7) cm, P < 0.05; and 747.5 (82) cm min-1 to 596 (49) cm min-1, P < 0.05; respectively) indicating a significant decrease in cardiac output. There was a corresponding increase in the index of systemic vascular resistance from 1092 (747) to 2079 (400) (P < 0.05) which persisted after deflation of the abdomen. Oesophageal Doppler can provide continuous online haemodynamic data with a rapid response to acute changes and may have a role in non-invasive haemodynamic monitoring during laparoscopic procedures in older patients with cardiovascular disease.

Adult↗
PubMed1996

Cost effectiveness of detecting Barrett's cancer.

BACKGROUND: Screening Barrett's oesophagus is controversial owing to a large variation in the reported incidence of neoplastic change and lack of evidence that screening improves tumour prognosis. AIMS: To determine the incidence of Barrett's cancer, its cost of detection, and stage of disease at time of diagnosis. PATIENTS AND METHODS: Data from our surveillance programme have been reviewed to assess the incidence of malignant change, tumour stage at diagnosis, and the cost per cancer detected. RESULTS: 166 patients had annual endoscopic surveillance. Six patients (five men) developed cancer-an incidence of one cancer per 59 male and 167 female patient-years of follow up. The screened group had a significantly earlier stage than a control group of unscreened cancers (p < 0.05). The cost of detecting one cancer was Pounds 14 868 for men and Pounds 42 084 for women. CONCLUSIONS: The cost of screening for Barrett's cancer is high but may be justified on the basis of the high incidence of detecting early stage disease.

Adult↗
PubMed1995

Accelerated gastric epithelial proliferation.

Gastric body mucosal proliferation was quantified and localised under conditions of increased gastrin drive using a variety of techniques. Rats were given omeprazole 400 mumol/kg/day by gavage and after 30 days mean serum gastrin rose 11-fold (p < 0.001). Total mucosal polyamines rose 220% from 15.9 to 50.9 nmol/mg protein (p < 0.001). This was associated with a 238% increase in crypt cell production rate from 0.541 to 1.83 crypt cells/h by vincristine metaphase arrest (p < 0.02). Using computer aided counting of proliferating cell nuclear antigen (PCNA) immunostained nuclei to assess epithelial proliferation in hypergastrinaemia rat stomach: mucus neck cell PCNA labelling was increased by 41% (p < 0.001) and gland cell PCNA labelling was increased by 222% (p < 0.001). PCNA/AgNOR (argyrophilic nuclear organiser regions) co-stained sections were used to assess proliferative activity in cycling and non-cycling cell populations. Data from these experiments suggest that, in addition to increasing the number of mucosal cells in cycle, cell life and cell cycle duration may be reduced in hypergastrinaemia.

Animals↗
PubMed1995

Use of urine albumin measurement as a replacement for total protein.

We have investigated the replacement of urine total protein estimations for the assessment of glomerular permeability, by the measurement of urine albumin excretion using a latex particle enhanced immunoturbidimetric assay. An initial screen was performed using Albustix to assess the sample pre-dilution necessary for immunoanalysis. A total of 167 24-hour urine samples were analysed and urine albumin concentration correlated well with that of urine total protein (r = 0.93) over the range 0-16,800 mg/l. This protocol provides a more cost effective and analytically valid assessment of glomerular permeability.

Albuminuria↗
PubMed1995

Evaluation of a rapid specific ward based assay for creatinine in blood.

We have evaluated a dry reagent stick test for the quantitation of creatinine in plasma employing a whole blood sample. The assay was found to be specific for creatinine and correlated well (r = 0.993) with an established laboratory procedure. The precision found indicated that the method was suitable for use in the diagnosis and monitoring of renal disease.

Clinical Enzyme Tests↗
PubMed1993

Mucosal polyamine metabolism in the columnar lined oesophagus.

Mucosal ornithine decarboxylase activity and polyamine content has been proposed as a possible marker for malignant potential in gastrointestinal mucosa. Polyamine content and histological findings were examined in 107 pairs of endoscopic biopsy specimens taken from gastric fundus, fundic and specialised Barrett's oesophagus and Barrett's adenocarcinoma. The content of putrescine (median nmol/mg protein, range) the primary product of ornithine decarboxylase showed a progressive increase from gastric fundus (0.41, 0.15-1.5); fundic (0.45, 0.01-4.08); specialised Barrett's oesophagus (0.54, 0.01-2.0); dysplastic columnar lined oesophagus (0.56, 0.31-3.1) to adenocarcinoma (1.23, 0.29-8.98). Adenocarcinoma putrescine content was significantly greater than gastric fundus (p < 0.018) and fundic (p < 0.03). Mucosal spermine, spermidine, and total polyamine values were greater in gastric fundus than fundic, specialised Barrett's oesophagus, and dysplastic columnar lined oesophagus (all p < 0.001) suggesting failure to further metabolise putrescine to its higher polyamines in the metaplastic epithelium. Although metaplastic columnar lined oesophagus shows significant differences in polyamine metabolic activity from the stomach the important distinction between specialised and dysplastic columnar lined oesophagus cannot be made by measuring the polyamine content.

Adenocarcinoma↗
PubMed1993

The role of smoking and alcohol in metaplasia and cancer risk in Barrett's columnar lined oesophagus.

Smoking and alcohol consumption predispose to oesophageal mucosal damage and exacerbates gastro-oesophageal reflux. The alcohol and smoking habits of patients with severe oesophagitis (n = 24), Barrett's columnar lined oesophagus (CLO) (n = 58), and adenocarcinoma arising in CLO (n = 23) were studied. There was no significant difference between the age (median 67, 64, and 65 years respectively) or duration of symptoms (median 10 years) in each group. Patients with benign CLO were significantly more likely to be non-smokers and non-drinkers, or both than patients with both severe oesophagitis and adenocarcinoma (p < 0.001). Of those who smoked or drank, patients with CLO had a smoking history of a median 15 pack years (range 2-60 pack years), which was less than both the severe oesophagitis (median 45.5, range 5-150 pack years) (p < 0.01), and adenocarcinoma groups (median 55.25, range 4-200 pack years) (p < 0.001). Patients with adenocarcinoma had smoked for more years in total (median 38.5, range 4-54 years) than patients with CLO (median 29.5, range 6-55 years) (p < 0.01). Patients with severe oesophagitis (median 38.5, range 27-55 years) and adenocarcinoma patients had a similar long history of smoking both of which were greater than CLO patients (p < 0.003). Half of the severe oesophagitis group drank more than 40 units/week and six more than 100 units/week (median 40, range 1-->100 units/week), whereas CLO patients who drank did so more moderately (median 10, 1-100 units/week) (p < 0.02). Adenocarcinoma patients also had a somewhat greater alcohol intake than CLO patients, median 15 (1-100 units/week) (p<0.02). Smoking and alcohol consumption do not predispose to the development od metaplastic columnar lined oesophagus in patients with severe gastro-oesophageal reflux but are strongly associated with the development of adenocarcinoma in patients with established Barrett's oesophagus.

Adenocarcinoma↗
PubMed1993

A novel reconstructive technique for pylorus-preserving pancreaticoduodenectomy: avoidance of early postoperative gastric stasis.

In 30 patients a reconstructive technique was used after pylorus-preserving pancreaticoduodenectomy in which the anastomoses were constructed in the sequence: duodenojejunal, hepaticojejunal (8-10 cm distal) and finally duct-to-mucosa pancreaticojejunal to a separate Roux loop. Indications for surgery included periampullary tumours, (n = 13), carcinoma of the head of the pancreas (n = 10) and chronic pancreatitis (n = 4). No patient required prolonged (> 7 days) nasogastric intubation for primary gastroparesis in the early postoperative period. Postoperative morbidity (17% overall) delayed recovery and return of gastrointestinal function in one patient with a minor biliary leak (closed with 5 days' somatostatin treatment). Other morbidity included gastrointestinal haemorrhage (n = 1), wound infection (n = 2) and respiratory infection (n = 2). There were no pancreatic leaks. One patient died from a subhepatic abscess (mortality 3%). Retrospective investigations, at 3-18 months postoperatively, included endoscopy (normal in 20 patients, none taking anti-ulcer therapy), gastric emptying studies in the first 10 patients (no delay) and bentiromide test in 12 patients considered to have normal pancreatic remnants (all patients > 24% PABA excretion index). All patients who underwent resection for tumour returned to their preoperative weight.

Adult↗
PubMed1993

Enzyme immunoassay--a new technique for estimating hemoglobin A1c.

We describe a method for estimating hemoglobin A1c (HbA1c) with a commercially available enzyme immunoassay system. The method is based on microtiter plate technology, utilizing an antibody raised to hemoglobin, the epitope being the Amadori product of glucose plus the first eight amino acids on the N-terminal end of the beta chain of hemoglobin. The enzyme immunoassay displays good within-batch (CV 2.3-2.4%) and between-batch (CV 2.6-5.0%) precision, and the results were not affected by different types of anticoagulant. The method was linear within the expected range of results and showed good correlation (r = 0.88-0.98) with established methods for estimating glycohemoglobin. Using this method, we obtained a reference interval of 2.8-4.9% (central 95%) for HbA1c in a nondiabetic population. The percentages of hemoglobin that were HbA1c in diabetics (6.86% +/- 2.51%) were significantly greater (P < 0.001) than in nondiabetics (3.46% +/- 0.52%).

Chromatography, High Pressure Liquid↗
PubMed1992

Prospective randomized trial comparing the Shouldice technique and plication darn for inguinal hernia.

The lowest recurrence rates after inguinal hernia repair have been achieved by specialized hernia clinics. The Shouldice repair achieves success through application of a meticulous standardized operation carried out by specialist hernia surgeons. In a trial designed to rule out surgeon-dependent variables, 322 inguinal hernias were randomized prospectively to Shouldice repair or plication darn. Fifteen general surgeons operated on 322 patients. Fourteen surgeons in training not familiar with Shouldice repair received constant supervision for six repairs before independent operation. The mean (s.d.) patient age was 58.3(1.5) (range 20-84) years for Shouldice repair and 57.0(1.2) (range 18-85 years) for plication darn. The sex ratio (M:F) was 17:1 and right side to left side ratio 1.8:1. Six-week complication rates for wound infection (Shouldice repair, 5 per cent; plication darn, 4 per cent) and haematoma (Shouldice repair, 7 per cent; plication darn, 5 per cent) were similar in both groups. There were a similar number of sliding hernias in the Shouldice repair (14) and plication darn (20) groups. After a mean follow-up of 30 (range 24-48) months there were seven recurrences in the Shouldice group and four in the plication darn group (P > 0.05). The recurrences suggest that additional supervision of junior surgeons is required during the Shouldice repair learning period.

Adolescent↗
PubMed1992

Experimental studies of transient mass transfer and reaction in the liver: interpretation with a heterogeneous compartment model.

The uptake and metabolism of lipophilic compounds by the liver were studied by administering a model compound, lidocaine, to the isolated rat liver. Lidocaine was continuously infused into the liver until steady state was reached. Subsequent step changes in the inlet concentration were used to obtain information on rates of cellular uptake and release and to assess the extent of mixing within the organ. A simple heterogeneous model combining mass transfer and enzyme reactions was required to simulate the effluent levels of lidocaine and two primary metabolites, monoethylglycinexylidide and 3-hydroxylidocaine. The rate constants for uptake and release of lidocaine were 1200 and 46 min-1, respectively. The rate-limiting step was intracellular reaction, with a rate constant of 0.49 min-1. Although the rate of lidocaine uptake was fast, it was 50 times slower than the rate of facilitated uptake of galactose, a fact suggesting passive transport of lidocaine between the tissue and the vasculature. The rates of mass transfer of lidocaine and its metabolites differed, but the ratios of the rate of uptake to the rate of release were the same. The results suggested that all three species had an affinity for the cellular region of the liver; concentrations in tissue were approximately five times greater than concentrations in effluent. Because of the large capacity of the organ for uptake of lidocaine and its metabolites, concentrations from washout experiments were controlled by linear mass transfer from the tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗