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Biomedical subjects

G White

Publications and source records attributed to G White.

At least 19 recordsLinked to original sources
PubMed1996

Different types of Na+ and A-type K+ currents in dorsal root ganglion neurones innervating the rat urinary bladder.

1. Whole-cell patch-clamp recording in combination with axonal tracing techniques was used to examine the electrical properties of afferent neurones innervating the urinary bladder of the adult rat. Individual bladder afferent cells were labelled by Fast Blue (FB), injected into the bladder wall. 2. Passive and active electrical parameters at room temperature (20-22 degrees C) in FB-labelled bladder afferent neurones were comparable with those in unlabelled neurones. Unselected dorsal root ganglion (DRG) neurones as well as bladder afferent neurones exhibited two different types of action potential: high-threshold humped spikes in small-sized neurones and low-threshold narrow spikes in large-sized neurones. 3. The majority (70%) of bladder neurones which were small in size expressed high-threshold tetrodotoxin (TTX)-resistant Na+ channels and slow-inactivating A-type K+ channels (KA), which were available at the resting membrane potential, whereas large-sized DRG neurones had low-threshold TTX-sensitive Na+ channels and fast-inactivating KA channels, which were almost completely inactivated at the resting membrane potential. 4. Half-maximal conductances of activation of TTX-resistant and TTX-sensitive Na+ currents were obtained at -10.3 and -25.3 mV, respectively. The TTX-resistant and TTX-sensitive Na+ currents were half-inactivated at -25.3 and -56 mV, respectively. 5. In the TTX-resistant neurones, the transient outward K+ current (A-type current, IA) with half-maximal conductance at -40.8 mV was half-inactivated at -77.5 mV, and exhibited slower decaying kinetics (mean decay constant (tau), 240 ms) than the IA current recorded from the large-sized TTX-sensitive neurones (mean tau, 20 ms). 6. These results suggest that the majority of bladder afferent neurones have high electrical thresholds for spike activation due to the TTX-resistant Na+ current and the slow-inactivating IA current, which reflect the large population of unmyelinated high-threshold C fibre afferents that innervate the urinary bladder.

Action Potentials↗
PubMed1996

Optical changes in unilamellar vesicles experiencing osmotic stress.

Membrane properties that vary as a result of isotropic and transmembrane osmolality variations (osmotic stress) are of considerable relevance to mechanisms such as osmoregulation, in which a biological system "senses" and responds to changes in the osmotic environment. In this paper the light-scattering behavior of a model system consisting of large unilamellar vesicles of dioleoyl phosphatidyl glycerol (DOPG) is examined as a function of their osmotic environment. Osmotic downshifts lead to marked reductions in the scattered intensity, whereas osmotic upshifts lead to strong intensity increases. It is shown that these changes in the scattering intensity involve changes in the refractive index of the membrane bilayer that result from an alteration in the extent of hydration and/or the phospholipid packing density. By considering the energetics of osmotically stressed vesicles, and from explicit analysis of the Rayleigh-Gans-Debye scattering factors for spherical and ellipsoidal shells, we quantitatively demonstrate that although changes in vesicle volume and shape can arise in response to the imposition of osmotic stress, these factors alone cannot account for the observed changes in scattered intensity.

Lipid Bilayers↗
PubMed1996

Clinical experience with a bifurcated endovascular graft for abdominal aortic aneurysm repair.

PURPOSE: The purpose of this study was to test a transfemoral system of bifurcated endovascular graft insertion for aortic aneurysm repair. METHODS: Bifurcated endovascular grafts were inserted through bilateral femoral artery cutdowns in 41 patients. The results were assessed by completion angiography and follow-up computed tomography. RESULTS: The second half of the study included more aneurysms 6 cm or larger (p < 0.05) and more instances of short proximal neck (p < 0.05), proximal neck angulation (p < 0.05), and iliac angulation (p < 0.05). Despite the increasingly challenging anatomy, the results were better in the second half of the study as illustrated by the lower overall combined morbidity/mortality rate (15% vs 50%) and higher overall success rate (85% versus 65%). The mortality rate for the series as a whole was 7.5%. Mean follow-up was 18.8 months for the first 20 patients and 10.9 months for the second 20. The commonest complication in the first half of the study was graft thrombosis (n = 5). This complication was absent from the second half of the study because of routine adjunctive stenting. Two patients died of complications of endovascular repair. In both cases aneurysm rupture on the third postoperative day was associated with coagulopathy and angiographic signs of perigraft leak. CONCLUSION: Aneurysm exclusion with a bifurcated endovascular graft was feasible in a wide range of patients, but when the aneurysm was not entirely excluded from the circulation, the risk of rupture persisted.

Aorta, Abdominal↗
PubMed1996

A prospective study of anatomico-pathological changes in abdominal aortic aneurysms following endoluminal repair: is the aneurysmal process reversed?

AIM: The aim of this prospective study was to analyse early anatomico-pathological changes in abdominal aortic aneurysms (AAA) following endoluminal repair to determine if the natural history of continued expansion of AAA is reversed. MATERIALS AND METHODS: Sixty-seven of 85 patients undergoing endoluminal AAA repair between May 1992 and August 1995 had their operations prior to the end of February 1995 and were potentially available for follow up at 6 months or longer after operation. Excluded were: patients with failed endoluminal repairs (n = 14), patients who died within 6 months of operation (n = 5), patients with anastomotic AAA (n = 1), leaving 47 patients in the study group. Based on contrast enhanced CT performed preoperatively, within 10 days of operation and 6, 12 and 18 months after operation patients were divided into two groups: those in whom the AAA maximum transverse diameter (MTD) decreased Group I (n = 39) and those in which it increased Group II (n = 8). The following parameters were analysed: diameter of the supra coeliac aorta, MTD and the dimensions of the proximal and distal necks of the AAA plus extravasation ("leak") of contrast into the aneurysmal sac. RESULTS: Leak of contrast was seen in 0 of 39 patients in Gp I and 5 of 8 patients in Gp II. Patients in Group I experienced a progressive diminution in AAA mean MTD. The diameters of the proximal and distal necks increased but there was no shortening of the length of the necks in this group. In Group II the AAA MTD was dependent on whether or not the aneurysmal sac was isolated from the circulation. The diameter of the proximal and distal necks increased irrespective of this fact. CONCLUSION: We conclude that in early follow up AAA which diminish in diameter following endoluminal repair remain isolated from the general circulation. Co-incident with this decrease in AAA diameter, the proximal and distal necks increase in diameter but do not undergo any shortening in length. This paradoxical increase in neck diameter, was not progressive in the period of follow-up.

Aged↗
PubMed1995

Topical non-steroidal anti-inflammatory drugs and admission to hospital for upper gastrointestinal bleeding and perforation: a record linkage case-control study.

OBJECTIVE: To evaluate the relation between topically applied non-steroidal anti-inflammatory drugs and upper gastrointestinal bleeding and perforation. DESIGN: A case-control study with 1103 patients admitted to hospital for upper gastrointestinal bleeding or perforation between January 1990 and December 1992 (cases). Two different control groups were used, with six community controls and with two hospital controls for each case. Previous exposure to topical and oral non-steroidal anti-inflammatory drugs and ulcer healing drugs was assessed. STUDY POPULATION: The population of 319,465 people who were resident in Tayside and were registered with a Tayside general practitioner between January 1989 and October 1994. A record linkage database containing all data on hospital events and dispensed drugs between 1989 and 1992 was used for this population. MAIN OUTCOME MEASURES: Unadjusted and adjusted odds ratios of exposure in those admitted to hospital compared with controls. RESULTS: Significant unadjusted associations were detected between all three classes of drug and upper gastrointestinal complications. The significant association detected for topical non-steroidal anti-inflammatory drugs was no longer evident in analyses which adjusted for the confounding effect of concomitant exposure to oral anti-inflammatories and ulcer healing drugs (odds ratio = 1.45; 95% confidence interval 0.84 to 2.50 with community controls; 1.06; 0.60 to 1.88 with hospital controls). CONCLUSION: In this study topical non-steroidal anti-inflammatory drugs were not significantly associated with upper gastrointestinal bleeding and perforation after adjustment for the confounding effects of concomitant use of oral anti-inflammatories and ulcer healing drugs.

Administration, Oral↗
PubMed1995

Benzodiazepine site inverse agonists can selectively inhibit subtypes of the GABAA receptor.

Using the two-electrode voltage-clamp technique, we have evaluated the effects of several inverse agonists on GABA current amplitude in Xenopus oocytes. Oocytes were injected with cRNA coding for primate alpha 1, alpha 2, or alpha 3 subunits in combination with beta 1 gamma 2, beta 2 gamma 2, or beta 3 gamma 2 subunits. In the presence of CGS 8216, we observed greater inhibition in alpha 1 beta 1 gamma 2, alpha 1 beta 2 gamma 2, alpha 1 beta 3 gamma 2, and alpha 3 beta 1 gamma 2 subunit combinations than in other subunit combinations (p < 0.022). DMCM also showed subunit selective inhibition (p < 0.035) whereas FG 7142 did not (p > 0.075). The above findings indicate that drug structure, alpha subunits, and beta subunits interact to influence the magnitude of inhibition of GABAA R subtypes.

Animals↗
PubMed1995

Alpha subunits influence Zn block of gamma 2 containing GABAA receptor currents.

The two-electrode voltage-clamp technique was used to evaluate Zn block of current activated by gamma-aminobutyric acid (GABA) in Xenopus oocytes injected with cRNA coding for alpha 1 beta 3 gamma 2, alpha 2 beta 3 gamma 2, or alpha 3 beta 3 gamma 2 subunits of the GABAA receptor (GABAAR). cDNA coded for the human form of alpha 1, alpha 2, beta 3 and gamma 2L subunits. alpha 3 subunit cDNA was obtained from an African green monkey library. Zn significantly inhibited the current evoked by application of GABA. Maximal inhibition was greater in alpha 2- and alpha 3- containing GABAARs than in alpha 1-containing GABAARs (51 +/- 1% and 53 +/- 2% vs 19 +/- 2%, respectively). The IC50 for Zn was smaller in alpha 1 than in alpha 2 or alpha 3 GABAARs (1.2 +/- 0.3 microM vs 7 +/- 1 and 9 +/- 1 microM, respectively). Zn shifted the concentration-response curve of GABA to the right in a parallel manner. These data suggest that Zn reduces the amplitude of current evoked at gamma 2 subunit containing GABAARs through an allosteric mechanism.

Alprazolam↗
PubMed1995

Idiopathic CD4+ T-lymphocytopenia in HIV seronegative men with hemophilia and sex partners of HIV seropositive men. Multicenter Hemophilia Cohort Study.

Persons with hemophilia or other HIV-1 risk factors may be more likely to have idiopathic CD4+ T-lymphocytopenia (ICL). We determined the frequency of ICL in prospectively followed cohorts of HIV-1 seronegative hemophilic men and seronegative female sex partners of HIV-1 infected hemophilic men, and examined factors potentially associated with ICL. Seven of 304 (2.3%) seronegative hemophilic men and one of 160 (0.6%) female partners met the ICL definition, but the condition resolved for two of the men and for the sole female partner. All five men with persistent ICL had lymphocytopenia (< 1,200 total lymphocytes/microliters) and < 300 total CD4+ lymphocytes/microliters; only one had a low CD4+ percentage. On the most recent measurement, 14.5% of the 304 seronegative hemophilic men had lymphocytopenia. Compared with matched hemophilic controls, men with persistent ICL more often had a history of liver disease (3/5 cases, 0/21 controls, P = 0.007) or splenomegaly (3/5 cases, 4/21 controls; P = 0.04), but not severe hemophilia, greater clotting factor concentrate exposure, high alanine aminotransferase levels, hepatitis B virus antigenemia, or detectable hepatitis C virus RNA in plasma. All five cases and 20/21 controls had antibodies to hepatitis C virus present in their serum. In this cohort of hemophilic men, ICL was related to lymphocytopenia associated with liver disease rather than selective loss of CD4+ lymphocytes.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Transfemoral insertion of a bifurcated endovascular graft for aortic aneurysm repair: the first 22 patients.

The purpose of this study was to evaluate and optimize a system of transfemoral bifurcated graft insertion for endovascular repair of infrarenal aortic aneurysm. Grafts were inserted through bilateral femoral arteriotomies in 22 patients. Placement was guided by fluoroscopy. Results were assessed by completion angiography, with computed tomography scanning or duplex ultrasonography at 1, 3 and 6 months. The first 11 insertions were complicated by failed insertion in two cases, proximal leakage in one, graft limb thrombosis in five and wound infection in one. The second 11 insertions were complicated by retrograde leakage around the distal graft orifice in two patients. One of these was associated with aneurysm rupture, leading to the sole mortality of the series. There were no instances of graft migration or embolism. In conclusion, the lessons learned during the first 11 insertions were responsible for the improved results apparent in the second 11 insertions. When applied in properly selected patients, transfemoral insertion of a bifurcated graft is a reliable method of isolating an aortic aneurysm from the circulation.

Aortic Aneurysm, Abdominal↗
PubMed1995

Endoluminal repair of atypical dissecting aneurysm of descending thoracic aorta and fusiform aneurysm of the abdominal aorta.

A 62-year-old male patient was admitted with acute dissociation of the descending thoracic aorta and an infrarenal abdominal aortic aneurysm (AAA). Investigation revealed that the thoracic dissection probably had arisen retrogradely in the posterior wall of the AAA and extended superiorly to the left subclavian artery as a blind sac. Implantation of an endoluminal graft device below the renal arteries enabled simultaneous treatment of the AAA and the thoracic aortic dissection. The patient had an uncomplicated recovery. Postoperative aortography and computed tomography demonstrated normal flow through the aorta and endograft without leak of contrast into the AAA sac or the false lumen of the dissection. Contrast computed tomography 6 months after operation demonstrated that the false lumen was no longer evident.

Aortic Dissection↗
PubMed1995

Detailed mapping and loss of heterozygosity analysis suggests a suppressor locus involved in sporadic breast cancer within a distal region of chromosome band 17p13.3.

The chromosome region 17p13.3 is thought to encode a tumour suppressor gene involved in sporadic breast cancer and other malignancies. Physical ordering of markers has been carried out by a series of multicolour fluorescent in situ hybridisation (FISH) experiments, using isolated yeast artificial chromosomes (YACs) and cosmids. Eight polymorphic markers ordered within this new physical map and one external marker were used to investigate the pattern of loss of heterozygosity in a panel of 40 sporadic breast tumour patients. The data revealed a region of high loss (60%) within distal 17p13.3, defined by markers D17S926, D17S695 and D17S849 which mapped close together. A contig of YACs was constructed physically linking these three markers.

Base Sequence↗
PubMed1995

Efficacy of photodynamic therapy on original and recurrent rat mammary tumors.

Photodynamic therapy has demonstrated efficacy toward primary, metastatic and recurrent human tumors. Here, we investigated the ability of photodynamic therapy, using Photofrin, to inhibit growth of R3230AC mammary adenocarcinomas when tumors were treated as original implants and again as lesions recurring at the initial treatment site. The results demonstrate that both initial implants and lesions recurring after the first photodynamic treatment respond similarly to the same photodynamic therapy protocol, with mean tumor volume doubling times of approximately 11 days in both cases. Cells cultured from original tumor implants or tumors that recurred after photodynamic treatment accumulate equivalent amounts of [14C]polyhematoporphyrin. Single cell suspensions prepared from either original or recurrent tumors from animals administered 5 mg/kg Photofrin and exposed to light in vitro displayed comparable phototoxicity. Additionally, examination of tumors by light microscopy revealed no morphological differences between the original tumor implants and the recurrent lesions. Taken together, these data indicate that lesions which recurred at the site of the initial photodynamic treatment were not resistant to a second identical course of photodynamic therapy.

Animals↗
PubMed1995

An audit of the accuracy of upper gastrointestinal diagnoses in Scottish Morbidity Record 1 data in Tayside.

INTRODUCTION: Scottish Morbidity Record (SMR1) data are coded by trained clerical staff from case records and discharge summaries. They form the basis of many strategic NHS decisions. Their accuracy for upper gastrointestinal (UGI) diagnosis is unknown and the study was undertaken to assess this accuracy in Tayside. METHOD: Patients who fulfilled the following criteria were identified using a record-linkage pharmacoepidemiological database, and their case records retrieved: over 50 years of age, had encashed at least one prescription for a non-steroidal anti-inflammatory drug at a Tayside pharmacy and who had SMR1 records containing one or more symptom/diagnosis codes between January 1989 and December 1991. Medically qualified staff were trained to examine case records and to code UGI diagnoses. They searched the case records for every UGI SMR1 entry for these patients from 1980-1992 and produced re-coded diagnoses (RCD) for each hospital event (admission and discharge), using all the data available in the case records. They also abstracted data on the clinical presentation, investigations and management of patients. Each event was then examined by a single medically qualified researcher who compared the original SMR1 codes with the RCDs. RESULTS: 2,101 patients had a total of 3,764 events in 1989-1991. 317 events were either day case procedures or elective surgery or the case records were not found. They were therefore excluded. Of the remainder, the SMR1 and RCD codes were judged equivalent in 1,608 events (46.6%). However, 1,005 SMR1 events (29.2%) contained a symptom code but no diagnosis code and the remaining 834 (24.2%) were judged suboptimal for other reasons. Of those with a symptom code only, 406 could not be improved upon and were transformed into RCD symptom codes only, 435 were assigned symptom and diagnostic RCDs and 164 were assigned diagnostic RCDs only. In the other 834 events, 279 had one or more diagnoses missing, 425 had one or more diagnoses inaccurate, 23 had both missing and inaccurate diagnoses and 107 were not UGI. Thus 1,433 (41.6%) of UGI SMR1 events could be more accurately coded. Examination of investigation data revealed that coding inaccuracy was not due to diagnostic procedures being carried out after admission. CONCLUSION: UGI SMR1 data were satisfactory in about half of all events. In about a quarter there were symptom codes but no satisfactory diagnosis codes, whilst in another quarter the data were inaccurate. These findings have implications for health care activities and research that use these data.

Aged↗
PubMed1995

Non-steroidal anti-inflammatory drugs and hospitalization for acute renal failure.

Non-steroidal anti-inflammatory drugs (NSAIDs) have been implicated in the aetiology of acute renal failure (ARF), but epidemiological studies examining this association have produced disparate results. We conducted a case-control study using a purpose-built record-linkage database for a population of 420,600 patients, resident in Tayside since May 1990. Patients (n = 207) hospitalized with a diagnostic code for ARF between 1990 and 1992 had their diagnosis validated by a renal physician. Six community controls and two hospital controls, matched for age and sex, were generated for each of these cases. Exposure to dispensed oral NSAIDs, topical NSAIDs and aspirin during the 90 days prior to the index date were investigated (recent exposure), as was exposure at any time since January 1989 (previous exposure). The most significant associations were modelled using conditional logistic regression. When community controls were used, recent exposure to NSAIDs and previous exposure to aspirin were independently associated with hospitalization for ARF, with adjusted odds ratios of 2.20 (1.49-3.25) and 2.19 (1.46-3.30), respectively. Only recent exposure to oral NSAIDs was associated when hospital controls were used: 1.84 (1.14-2.93). No significant interactions were present with previous chronic renal failure, other possible causes of ARF or whether the diagnosis was primary or secondary. There is an approximate doubling of the risk of hospitalization for ARF with use of oral NSAIDs.

Acute Kidney Injury↗
PubMed1995

Human alpha and beta subunits contribute to the EC50 for GABA at the GABAA receptor expressed in Xenopus oocytes.

The GABAA receptor/ionophore complex (GABAAR) may be composed of at least alpha, beta, and gamma subunits. Alpha subunits can influence the concentration of GABA at which a half maximal current response is elicited (EC50). There are no data to suggest that beta subunits can also influence this pharmacological property of the GABAAR. We examined the influence of human derived beta and alpha subunits on the EC50 for GABA. Nine different subunit combinations were evaluated: alpha 1, alpha 2, alpha 3 in combination with beta 1 gamma 2, beta 2 gamma 2, and beta 3 gamma 2. cRNA coding for these subunit combinations was injected into Xenopus oocytes that were subsequently recorded from using the two electrode voltage-clamp technique. A two-way analysis of variance showed that both alpha and beta subunits interact to influence the EC50 of GABAARs. The EC50 for alpha 3 changed significantly with beta subunits. The EC50 for alpha 2 was significantly different in beta 3 compared to beta 1 and beta 2 subunits, while the EC50 for alpha 1 was not significantly different between beta subunits. These findings suggests that other pharmacological and physiological properties may also be determined by interactions between alpha and beta subunits.

Animals↗