Biomedical subjects

A Stevenson

Publications and source records attributed to A Stevenson.

At least 19 recordsLinked to original sources

PubMed2006

Exercise responses following heart transplantation: 5 year follow-up.

Heart transplantation is an established treatment for end stage heart failure. In addition to increased life expectancy, heart transplant recipients report a remarkable improvement in symptoms and functional capacity. Exercise performance following heart transplantation, however, remains impaired even in the absence of exertional symptoms. We have assessed the response to exercise in 47 patients with cardiac failure prior to and then at yearly intervals to five years post transplantation. All patients performed incremental symptom limited exercise tests during which minute ventilation (V'E), oxygen consumption (V'O2) and carbon dioxide production (V'CO2) and heart rate (HR) were measured. Ventilatory response (V'E/V'CO2), anaerobic threshold (V'O2 AT %predicted) and heart rate response (HR/VO2) were calculated. The dead space to tidal volume ratio (VD/VT) and alveolar-arterial oxygen gradient (A-aO2) were computed from transcutaneous monitoring. Despite substantial improvement in subjective functional capacity, heart transplant recipients continue to have limited exercise performance [Maximal V'O2% predicted pre-transplant 41.3 (2.2); 1 year 48.6 (1.7), p <0.001: V'O2 AT% 31.5 (1.1); 1 year 35.6 (1.0); respectively p<0.05]. The maximal oxygen uptake continued to improve at two years post-transplant but, thereafter, there was no further significant change at up to 5 years post transplant [50.9 (1.5)]. At one year post-transplantation peak HR [65.2 (0.9) vs 79.1(1.4)] and the HR/VO2 response [24.0(1.8) vs 79.6(4.2)] were significantly reduced compared to pre-transplant values. The heart rate response remained lower compared to predicted at 5 years post-transplant although there was a significant increase compared to one year post-transplant (32.9 vs 24.0mls/bt). There was a weak but significant relationship between maximal VO2 and peak HR (0.39, p<0.05) and HR/VO2 (r= 0.37, p<0.05) at one year post-transplant. Prior to transplantation the ventilatory response to exercise was elevated [V'E/V'CO2 45.6 (2.5)] and decreased significantly following transplantation [1 yr 34.1 (1.3), respectively p<0.001]. In addition, despite significant improvement in VD/VT after transplantation, it remained higher than normal [Pre VD/VT at maximum exercise 0.35 (0.02); 1 yr 0.31 (0.02); p<0.05]. There was a further fall in the VE/VCO2 and VD/VT at two years post-transplantation with no further change at up to 5 years post transplantation [VE/VCO2 32.0 (1.0); VD/VT 0.29 (0.01)]. Although cardiac output is markedly improved after transplantation, due to chronotropic incompetence associated with denervation, its response remains subnormal and this may explain the residual abnormalities of ventilatory and gas exchange responses to exercise following transplantation.

Adult↗

PubMed2005

Emergency department organisation of critical care transfers in the UK.

OBJECTIVES: Transport of the critically ill patient to or from the emergency department (ED) is a frequent occurrence. This study was designed to determine whether UK EDs currently have appropriate equipment, monitoring, staff training systems, and processes of care for transportation of the critically ill patient. METHODS: A postal questionnaire regarding ED transfer patients was sent to 247 UK EDs, followed by repeat mailing and telephone follow up of non-responders. RESULTS: In total, 139 EDs (56%) responded. An estimated 20-30 critically ill patients are transferred from and <20 are received by each ED annually. Processes of care are poorly developed; only 79 EDs (56%) have transfer guidelines available. Audit of transfers is ongoing in 59 EDs (42%), and critical incident reporting is ongoing in 122 (88%). There is a lack of immediately available transport equipment; for example, 17 EDs (12%) have no transport ventilator, 9 (6%) have no transport monitor, and 9 (6%) have no syringe pump. Transport equipment is invariably not standardised. Anaesthetic staff of specialist registrar (74 doctors; 53%) or senior house officer (36 doctors; 26%) grades carry out the majority of ED transfers accompanied by a D or E grade nurse. Both invariably have no formal transfer training. CONCLUSIONS: This study highlights inadequacies in provision of equipment and monitoring during interhospital transfer from the ED. Training and processes of care for transport of the critically ill are also suboptimum. Many departments are currently reviewing these processes to formalize and improve transfer training procedures and protocols.

Ambulances↗

PubMed2001

Absolute band intensities of acetone ((CH3)2CO) in the infrared region of 830-3200 cm(-1) at low and room temperatures.

Absolute integrated band intensities of acetone (CH3)2CO in the region of 830-3200 cm(-1) have been measured near the temperatures of 233, 260 and 293 K. The spectra were recorded with a Fourier transform infrared (FTIR) spectrometer. The investigated region encompasses a total of 15 fundamental bands. At 293 K, for example, the band intensities range from 16.8 to 554.3 cm(-2) atm(-1) (at 300 K). The intensities have uncertainties of about 5%. All the band intensities increase with decreasing temperature. An empirical formulation was introduced which fit this temperature dependence well and which can be used to predict other unmeasured band intensities in the temperature region of approximately 200-300 K. The 295 K intensities reported here agree to within approximately 10% of previously published values, with lower estimated uncertainties. Low temperature intensity measurements are not available in the literature.

Acetone↗

PubMed2001

Phase I clinical evaluation of a neutralizing monoclonal antibody against epidermal growth factor receptor in advanced brain tumor patients: preliminary study.

High levels of growth factors and their receptors have been demonstrated in human tumors. Gliomas and meningiomas are characterized by overexpression of epidermal growth factor receptor (EGF-R). Ior egf/r3, is a neutralizing murine monoclonal antibody (MAb) against EGF-R, and was generated at the Cuban Institute of Oncology. The antibody recognizes EGF-R with high affinity, inhibiting tyrosine kinase activation. A clinical trial was conducted in brain tumor patients to evaluate toxicity, immunogenicity, and clinical benefit of escalating doses of the antibody. Nine patients with histologically confirmed gliomas or meningiomas, who had active or recurrent disease after receiving conventional treatment, received four intravenous doses of ior egf/r3. Total dosages ranged from 160 to 480 mg. As inclusion criteria, radioimmunoscintigraphy with the same MAb labeled with 99mTechnetium (99mTc) was performed. Immune response against the murine antibody was also evaluated. After four doses of ior egf/r3 MAb, no significant toxicity was found, except in one patient who developed a grade 4 allergic adverse event. This reaction was probably related with previous sensitization to the same MAb and the development of human anti-mouse antibodies (HAMA) response. Despite no major objective antitumor responses, eight patients had stable disease on the 6-month evaluation, and two patients remain alive after four years of MAb therapy.

Adult↗

PubMed2001

Down-regulation of cell adhesion molecules LFA-1 and ICAM-1 after in vitro treatment with the anti-TNF-alpha agent thalidomide.

The tumor necrosis factor-alpha (TNF-alpha) inhibitor thalidomide is known to be a potent modulator of host immunity, a potential treatment for autoimmune disorders such as rheumatoid arthritis (RA) and a treatment for complications of HIV-1 infection. RA is an autoimmune disease of the joints that has been associated with hyperactivity of lymphocytes and other leukocytes, over-expression of pro-inflammatory cytokines (TNF-alpha and IL-1) and chronic debilitating inflammation. Thalidomide may play a role in RA treatment by altering leukocyte function through down-modulation of cell adhesion molecules necessary for leukocyte migration to inflammatory sites. The present study investigates down-regulation of cell adhesion molecules (ICAM-1 and LFA-1) and decreases in cell-cell contacts between human T leukemic (CEM) cells and human umbilical vein endothelial cells (HUVEC) after thalidomide exposure. CEM cells were cultured in RPMI 1640 medium with 0, 10 or 50 microg/ml thalidomide, stained with fluorescent monoclonal antibodies specific to ICAM-1 and LFA-1 and expression was measured with flow cytometry. For cell-cell adhesion measurements, monolayers of HUVEC cultured in Kaign's F-12 medium were incubated with thalidomide treated CEM cells stained with calcein AM. Specific cell adhesion between the two cell types was visualized with fluorescence microscopy. Thalidomide treatment significantly reduced cell adhesion molecule expression in a dose-dependent fashion and inhibited HUVEC/CEM cell adhesion. These data support the hypothesis that thalidomide has modulatory actions on leukocyte functions through expression of cell adhesion molecules.

Cell Adhesion↗

PubMed2000

Absolute band intensities in the nu19/nu23 (530 cm(-1)) and nu7 (777 cm(-1)) bands of acetone ((CH3)2CO) from 232 to 295 K.

Absolute band intensities of acetone ((CH3)2CO) in the nu19/nu23 and nu7 band systems near 530 and 777 cm(-1), respectively, were measured at temperatures of 232, 262 and 295 K, using a Fourier transform infrared (FTIR) spectrometer. No evident temperature dependence for the band intensities was observed. The dipole moments and the fundamental band intensities were derived in the harmonic oscillator approximation. The results are useful for the spectroscopic retrieval of acetone concentrations in the upper atmosphere.

Acetone↗

PubMed1999

Extraskeletal osteochondroma of the foot.

A case of pathologically proven extraskeletal osteochondroma is presented with magnetic resonance imaging (MRI), computed tomography (CT), bone scan and radiographic findings. The diagnosis of extraskeletal osteochondroma should be considered when a discrete, ossified mass is localized in the soft tissues of the distal extremities. Nomenclature surrounding this entity is controversial and is discussed.

Adolescent↗

PubMed1999

The alternative sigma factor, sigmaE, is critically important for the virulence of Salmonella typhimurium.

In Escherichia coli, extracytoplasmic stress is partially controlled by the alternative sigma factor, RpoE (sigmaE). In response to environmental stress or alteration in the protein content of the cell envelope, sigmaE upregulates the expression of a number of genes, including htrA. It has been shown that htrA is required for intramacrophage survival and virulence in Salmonella typhimurium. To investigate whether sigmaE-regulated genes other than htrA are involved in salmonella virulence, we inactivated the rpoE gene of S. typhimurium SL1344 by allelic exchange and compared the phenotype of the mutant (GVB311) in vitro and in vivo with its parent and an isogenic htrA mutant (BRD915). Unlike E. coli, sigmaE is not required for the growth and survival of S. typhimurium at high temperatures. However, GVB311 did display a defect in its ability to utilize carbon sources other than glucose. GVB311 was more sensitive to hydrogen peroxide, superoxide, and antimicrobial peptides than SL1344 and BRD915. Although able to invade both macrophage and epithelial cell lines normally, the rpoE mutant was defective in its ability to survive and proliferate in both cell lines. The effect of the rpoE mutation on the intracellular behavior of S. typhimurium was greater than that of the htrA mutation. Both GVB311 and BRD915 were highly attenuated in mice. Neither strain was able to kill mice via the oral route, and the 50% lethal dose (LD50) for both strains via the intravenous (i.v.) route was very high. The i.v. LD50s for SL1344, BRD915, and GVB311 were <10, 5.5 x 10(5), and 1.24 x 10(7) CFU, respectively. Growth in murine tissues after oral and i.v. inoculation was impaired for both the htrA and rpoE mutant, with the latter mutant being more severely affected. Neither mutant was able to translocate successfully from the Peyer's patches to other organs after oral infection or to proliferate in the liver and spleen after i.v. inoculation. However, the htrA mutant efficiently colonized the livers and spleens of mice infected i.v., but the rpoE mutant did not. Previous studies have shown that salmonella htrA mutants are excellent live vaccines. In contrast, oral immunization of mice with GVB311 was unable to protect any of the mice from oral challenge with SL1344. Furthermore, i.v. immunization with a large dose ( approximately 10(6) CFU) of GVB311 protected less than half of the orally challenged mice. Thus, our results indicate that genes in the sigmaE regulon other than htrA play a critical role in the virulence and immunogenicity of S. typhimurium.

Animals↗

PubMed1998

Monoclonal antibody NB84 in the differential diagnosis of neuroblastoma and other small round cell tumors.

Two hundred fifty-five well-characterized formaldehyde-fixed and paraffin-embedded small round cell tumors mainly from children and young adults including 105 neuroblastomas were immunohistochemically analyzed with the NB84 monoclonal antibody raised to neuroblastoma cells. Most of the undifferentiated neuroblastomas (21 of 22) and all 83 differentiated neuroblastomas reacted with NB84, but none of these tumors were CD99 positive. Compared with synaptophysin, NB84 was more sensitive, although less specific, in the identification of neuroblastoma in formaldehyde-fixed tissue. In addition to neuroblastoma, skeletal and extraskeletal Ewing's sarcoma and medulloblastoma showed NB84 reactivity in approximately 20% of cases, and 50% of desmoplastic small round cell tumors showed positive cells, usually in smaller numbers than the neuroblastomas. The NB84 reactivity was seen slightly more commonly in morphologically defined (rosette-positive) cases of peripheral primitive neuroectodermal tumors than in Ewing's sarcoma. However, the NB84 positivity did not correlate with the expression of other neural markers (neurofilament proteins, CD57, and synaptophysin) in these tumors. All other small round cell tumors including rhabdomyosarcomas, Wilms' tumors, and lymphomas were NB84 negative. In the case of NB84-positive tumors other than neuroblastoma, their specific reactivity for other markers was useful (Ewing's sarcoma CD99 positive, desmoplastic small round cell tumor desmin and keratin positive). The NB84 monoclonal antibody is a useful reagent to separate neuroblastoma from other small round cell tumors. In problem cases it is best used in a panel together with other markers that address the significant differential diagnostic alternatives.

Adolescent↗

PubMed1998

A volumetric study of guided bone regeneration around titanium implants in the New Zealand white rabbit.

Previous studies have shown the ability for bone to grow under occlusive membranes. This study was undertaken to determine the time required for bone to form in the space created under the membrane and to determine the amount of bone that may be grown under the membrane. Thirty-two New Zealand white rabbits were divided into three groups. A Brånemark implant, having a diameter of 3.75 mm with a length of 7 mm, was placed in each tibia and Gore-Tex membrane was draped over the implant on the experimental side and tethered to the wound margin. Sixteen rabbits were sacrificed at six weeks, eight at twelve weeks, and eight at eighteen weeks. At six weeks the available space under the membrane was filled to 68 per cent, at twelve weeks it was 45 per cent, and at eighteen weeks 54 per cent. A comparison of bone height measurements on test and control sides showed a significant difference (p = 0.0001) at the three time intervals. A comparison of grown bone volumes (test vs control) was also statistically significant (p = 0.0001). The ability to grow bone under an occlusive membrane was confirmed but the long-term survival rate and ability to support load needs to be investigated.

Analysis of Variance↗

PubMed1998

Occupational hydrocarbon exposure and nephrotoxicity: a cohort study and literature review.

Hydrocarbon exposure has been shown to play an important role in the development of renal dysfunction in several occupational settings. In this study, renal screening was performed in a group of paint sprayers with exposure to hydrocarbon-based paints, recruited from a car manufacturing plant where personal protective equipment was widely used. The hydrocarbon exposure scores and various markers of renal injury were compared between these subjects and a group of paint sprayers from a previous study who did not use personal protective equipment regularly. Cumulative hydrocarbon exposure scores were calculated from a validated questionnaire. Serum creatinine, urinary total protein, albumin, transferrin, retinol-binding protein, and N-acetylglucosaminidase were evaluated, Both groups experienced heavy hydrocarbon exposure but sprayers who regularly used personal protective equipment had significantly reduced exposure scores due to improved skin and respiratory protection. A significant number of sprayers from both groups had elevated levels of serum creatinine. Interestingly, urinary N-acetylglucosaminidase activity, a marker of proximal tubular damage, was abnormal in a significant proportion of sprayers in the unprotected group but normal in those with improved protection. Our results are in keeping with the hypothesis that hydrocarbon exposure through paint spraying may result in active proximal tubular damage which may be reduced by improvement of protection at the worksite. However, renal impairment independent of tubular injury may result from chronic paint exposure, even with improved protection.

Adult↗

PubMed1997

Genetic variants of microsomal metabolism and susceptibility to hydrocarbon-associated glomerulonephritis.

Hydrocarbon (HC) exposure can play a role in the development of chronic glomerulonephritis (GN). Interindividual variations in various metabolizing enzymes may influence HC biotransformation, and hence susceptibility to HC-associated GN. We evaluated the role of human genotypic polymorphism in HC-associated GN, in 41 patients (30 male, 11 female) with primary GN (17 diffuse mesangial proliferative GN, 12 focal segmental GN, 11 membranous GN, one membranoproliferative GN) and 60 (46 male, 14 female) healthy controls. Genotypic polymorphisms of (CYP) P450 2D6 (CYP2D6), glutathione S-transferases mu (GSTM1) and theta (GSTT1) and N-acetyltransferase (NAT-2) were determined using polymerase chain reaction analysis of white-blood-cell DNA. HC exposure scores were determined using a validated questionnaire, and were significantly elevated in GN patients compared to controls. While no significant differences in the various genotypic frequencies were observed in the GN group overall, compared to controls, there was a significant increase in GSTM1 null (n = 10) to GSTM1 wild type (n = 1), and NAT fast (n = 10) to slow (n = 1) acetylators, in the membranous GN group compared to controls (p < 0.05). These results suggest a possible role for GSTM1 null and NAT fast acetylator in the development of HC-associated membranous GN.

Acetyltransferases↗

PubMed1997

Microvascular anastomotic thrombosis in experimental diabetes mellitus.

An experimental model was developed to investigate the effects of glycemic control and pentoxifylline administration on microvascular anastomotic patency rates in streptozotocin-induced diabetic rats. Diabetes was confirmed by blood glucose levels of more than 300 mg/dl prior to administering insulin and/or pentoxifylline. Microvascular anastomoses of the femoral artery and vein were performed 4 weeks after induction of diabetes. Subsequently, the comparative rates of anastomotic thrombosis in diabetic and nondiabetic groups with or without insulin or pentoxifylline administration were assessed by direct visualization of the anastomotic sites after 4 days. The results suggest that hyperglycemia impairs the post-operative patency of microvascular venous anastomoses. The diabetic animals maintained under insulin regimens that tightly controlled their serum glucose levels (100 to 200 mg/dl) experienced patency rates similar to those of nondiabetic controls (p < 0.05). Pentoxifylline improved microvenous patency at all levels of hyperglycemia studied, suggesting a possible hemorrheologic mechanism for microvascular venous anastomotic thrombus formation in diabetic animals.

Anastomosis, Surgical↗

PubMed1996

5-amino salicylic acid absorption and metabolism in ulcerative colitis patients receiving maintenance sulphasalazine, olsalazine or mesalazine.

BACKGROUND: All 5-aminosalicylic acid (5-ASA) preparations are potentially nephrotoxic, but there has been concern that newer delivery systems may increase this risk, either because of altered absorption or altered metabolism. Previous studies of 5-ASA absorption and excretion have usually either been performed in healthy controls or have only examined short-term therapy. 5-ASA and N-acetyl-5-ASA have therefore been measured in blood samples, and N-acetyl-5-ASA in urine samples, from patients with ulcerative colitis on long-term maintenance with different 5-ASA preparations and compared with sensitive markers of renal damage. METHODS: Patients receiving mesalazine (Asacol) (n = 13), sulphasalazine (n = 12) or olsalazine (Dipentum) (n = 8), all at doses within the recommended range were studied. Six-hour and trough serum concentrations of 5-ASA and N-acetyl-5-ASA and 24-h urinary excretion of N-acetyl-5-ASA were measured by high-performance liquid chromatography. RESULTS: Absorption of 5-ASA, assessed as 24-h excretion of N-acetyl-5-ASA expressed as molar % of ingested dose, was greater in patients receiving mesalazine, 23.25 +/- 10.65% (mean +/- s.d.; n = 13), than those receiving sulphasalazine (11.16 +/- 10.52%, n = 12; P = 0.003) or olsalazine (9.70 +/- 3.89%, n = 8; P < 0.002). The ratio of 5-ASA: N-acetyl-5-ASA in the serum 6 h after dose was also greater with mesalazine (1.02 +/- 0.44, mean +/- s.d.) than sulphasalazine (0.54 +/- 0.44, P < 0.02) or olsalazine (0.38 +/- 0.44, P < 0.005). Urinary markers of tubular damage were increased in four of 33 patients, but showed no correlation with concentration of 5-ASA or N-acetyl-5-ASA in serum and N-acetyl-5-ASA in urine, nor with lifetime dose or average daily dose of 5-ASA. CONCLUSIONS: In patients with ulcerative colitis receiving maintenance 5-ASA therapy there was greater absorption and less acetylation of 5-ASA from mesalazine (Asacol) compared with sulphasalazine or olsalazine, but no evidence from this study that this resulted in increased nephrotoxicity.

Absorption↗

PubMed1995

Tubular damage in microalbuminuric patients with primary glomerulonephritis and diabetic nephropathy.

Tubular damage as suggested by enzymuria and tubular proteinuria is a recognized feature of glomerulonephritis (GN) with clinical proteinuria and both incipient and overt diabetic nephropathy (DN). However, little is known about the presence of tubulopathy in patients with primary GN, microalbuminuria [albumin excretion (AER) 30-300 mg/d] and microhematuria. Three groups were studied. The GN group comprised 17 (2 F) patients with biopsy-proven GN with microalbuminuria. The DN group comprised 35 (14 F) patients with incipient diabetic nephropathy with AER 30-300 mg/d, and controls comprised 38 (15 F) normal subjects with normal AER < 30 mg/d. Serum creatinine, albuminurinuria, transferrinuria, and markers of tubular damage such as urinary excretion of N-acetyl-glucosaminidase (NAG), leucine aminopeptidase (LAP), gamma-glutamyl transferase (gGT), and retinol binding protein (RBP) were measured. GN and DN had comparable degrees of albuminuria, transferrinuria, and LAP excretion, and these were significantly higher than controls. Serum creatinine was significantly higher in GN than DN and controls. DN had significantly higher NAG and RBP, and lower gGT than GN and controls. In both GN and DN groups, both glomerular proteins correlated with each other and NAG correlated significantly to LAP and gGT. Albuminuria correlated to tubular enzymuria in GN group but not in patients with DN. The results suggest that tubular damage is less marked in microalbuminuric patients with GN than those with DN despite similar degree of glomerular proteinuria. The pattern of tubulopathy is also different in the two groups, indicating differences in the pathogenesis of tubular damage in these two clinical settings.

Acetylglucosaminidase↗

PubMed1995

Biochemical markers of basement membrane disturbances and occupational exposure to hydrocarbons and mixed solvents.

To investigate possible mechanisms of hydrocarbon or solvent-induced renal damage, we studied three groups of healthy men employed in a UK manufacturing plant. Group 1 (n = 111) were occupationally exposed to hydrocarbon-based paints, Group 2 (n = 100) were occupationally exposed to petroleum-based mineral oils, and Group 3 (n = 92) had low background occupational exposure to hydrocarbons. Occupational atmospheric exposure levels for toluene, xylene, butanol and oil mist around the time of this study were within UK permissible limits. Group 4 (controls) were males with no known occupational hydrocarbon or solvent exposure (n = 108). Circulating laminin antibodies and the auto-antibody implicated in Goodpasture's syndrome (anti-GBM) were measured, as were serum laminin, a basement membrane turnover marker, and soluble E-selectin, an endothelial activation marker. Group 1 had a significantly greater proportion of subjects with high levels of both anti-laminin antibodies and soluble E-selectin; Group 2 had significantly more subjects with raised anti-GBM antibodies, laminin and soluble E-selectin. Mean levels of soluble E-selectin were increased in Groups 1 and 2. In a small but significant proportion of these workers exposed to hydrocarbons/mixed solvents there are alterations both to basement membranes, resulting in auto-antibody production, and to overlying vascular endothelial cells.

Adult↗

PubMed1995

beta-Carboline gamma-aminobutyric acidA receptor inverse agonists modulate gamma-aminobutyric acid via the loreclezole binding site as well as the benzodiazepine site.

The benzodiazepine site on the gamma-aminobutyric acid(A) (GABAA) receptor is the principle site of action for a number of structurally diverse compounds, including the beta-carbolines, many of which bind with high affinity. The apparent reversal of inhibition and potentiation by high concentrations of methyl-6,7-dimethoxy-4-ethyl-beta-carboline (DMCM) and other beta-carbolines has been reported by several groups and is insensitive to the benzodiazepine antagonist Ro 15-1788. By using alpha 6-containing receptors, which have low affinity for benzodiazepines, we observed robust potentiation of GABAA responses by micromolar concentrations of DMCM and other beta-carbolines that is dependent on the beta subunit variant. The beta subunit-dependent potentiation by the anticonvulsant loreclezole is dependent on a single amino acid in the putative transmembrane 2 region. By using single point mutations that discriminate the loreclezole site, we show that potentiation by DMCM is also dependent on the presence of the same amino acid, Asn290, in beta 2 or beta 3 (serine in beta 1), providing evidence that the low affinity site for beta-carboline potentiation is the loreclezole site. The potentiation is independent of the alpha subunit and is more pronounced on alpha 6-containing receptors due to the lack of DMCM inhibition via the benzodiazepine site. In addition, the potentiation observed is competitive with that of loreclezole, and other beta-carbolines, such as ethyl-beta-carboline-3-carboxylate and propyl-beta-carboline-3-carboxylate, act in a similar manner. The finding that beta-carbolines can act via the loreclezole site as well as the benzodiazepine site suggests that a wider variety of compounds may act via this site and shows that compounds can interact with more than one modulatory site on the GABAA receptor.

Animals↗

PubMed1994

Occupational hydrocarbon exposure and diabetic nephropathy.

Exposure to hydrocarbons has been implicated in the pathogenesis of glomerulonephritis but its role in the development of diabetic nephropathy remains unknown. Three groups of patients with Type 1 diabetes of over 10 years duration were studied. Group 1 comprised 45 patients (23 F) with no diabetic nephropathy (urinary albumin excretion (AER) < 30 mg 24 h-1), group 2 comprised 37 patients (17 F) with incipient diabetic nephropathy (AER between 30-300 mg 24 h-1), and group 3 comprised 31 patients (15 F) with overt diabetic nephropathy (AER > 300 mg 24 h-1). The groups were comparable for age, sex, duration of diabetes, recent glycaemic control, social class, and residential area. Patients were assessed blindly by a validated questionnaire and interview for hydrocarbon exposure, consumption of tobacco, analgesic agents, and alcohol. Exposure scores to hydrocarbons derived from the questionnaire were significantly higher in patients with incipient and overt diabetic nephropathy with smoking adjusted odds ratios of 3.6 and 5.2, respectively. The consumption of alcohol, analgesic agents, tobacco, and smoking habits were similar in the three groups. In conclusion, hydrocarbon exposure may be a key environmental factor in the development of diabetic nephropathy in patients with Type 1 diabetes.

Adult↗