GLUT1 and GLUT8 in endometrium and endometrial adenocarcinoma.

Glucose is provided to cells by a family of glucose transport facilitators known as GLUTs. These transporters are expressed in a tissue specific manner and are overexpressed in many primary tumors of these tissues. Regulation of glucose transport facilitator expression has been demonstrated in endometrial tissue and endometrial adenocarcinoma. The following experiments were conducted to quantify and localize the expression of GLUT1 and GLUT8 in benign endometrium and compare this expression to endometrial cancer. Endometrial tissue samples were obtained from random hysterectomy specimens of patients with benign indications for surgery and endometrial cancer. Immunoblot and immunolocatization studies were performed using GLUT1 and GLUT8 specific antisera. Endometrial samples from 65 women who had undergone hysterectomy were examined (n=38 benign, n=27 malignant). A 44 and a 35.4 kDa immunoreacive species was demonstrated in endometrium and endometrial cancer for GLUT1 and GLUT8, respectively. Upregulation of GLUT1 expression was demonstrated with increasing grade of tumors (P<0.002). GLUT8 expression was increased in all tumor subtypes compared to atrophic endometrium (P<0.001). Apical localization by GLUT1 and GLUT8 was demonstrated in endometrial glands. GLUT1 and GLUT8 demonstrated diffuse intracellular localization in the cancer subtypes. GLUT1 and GLUT8 are expressed in both human endometrium and endometrial cancer. There appears to be a step-wise progression in GLUT1 and GLUT8 expression as tumor histopathology worsens. GLUT1 and GLUT8 may be important markers in tumor differentiation, as well as providing energy to rapidly dividing tumor cells.     

Hepatic UDP-glucose 13C isotopomers from [U-13C]glucose: a simple analysis by 13C NMR of urinary menthol glucuronide.

Menthol glucuronide was isolated from the urine of a healthy 70-kg female subject following ingestion of 400 mg of peppermint oil and 6 g of 99% [U-(13)C]glucose. Glucuronide (13)C-excess enrichment levels were 4-6% and thus provided high signal-to-noise ratios (SNRs) for confident assignment of (13)C-(13)C spin-coupled multiplet components within each (13)C resonance by (13)C NMR. The [U-(13)C]glucuronide isotopomer derived via direct pathway conversion of [U-(13)C]glucose to [U-(13)C]UDP-glucose was resolved from [1,2,3-(13)C(3)]- and [1,2-(13)C(2)]glucuronide isotopomers derived via Cori cycle or indirect pathway metabolism of [U-(13)C]glucose. In a second study, a group of four overnight-fasted patients (63 +/- 10 kg) with severe heart failure were given peppermint oil and infused with [U-(13)C]glucose for 4 hr (14 mg/kg prime, 0.12 mg/kg/min constant infusion) resulting in a steady-state plasma [U-(13)C]glucose enrichment of 4.6% +/- 0.6%. Menthol glucuronide was harvested and glucuronide (13)C-isotopomers were analyzed by (13)C NMR. [U-(13)C]glucuronide enrichment was 0.6% +/- 0.1%, and the sum of [1,2,3-(13)C(3)] and [1,2-(13)C(2)]glucuronide enrichments was 0.9% +/- 0.2%. From these data, flux of plasma glucose to hepatic UDPG was estimated to be 15% +/- 4% that of endogenous glucose production (EGP), and the Cori cycle accounted for at least 32% +/- 10% of GP.     

DLCO/Q and diffusion limitation at rest and on exercise in patients with interstitial fibrosis

Pulmonary diffusing capacity for carbon monoxide (DLCO) and pulmonary capillary blood flow (Qp) were measured on exercise in patients with a low DLCO with the aim of predicting, from the overall DL/Qp ratio, diffusion limitation for oxygen and relating it to the fall in arterial oxygen saturation actually observed. Five patients with cryptogenic fibrosing alveolitis (DLCO ranging from 20-54% predicted normal) exercised for 5 min at a work load equal to 60% of their maximum (45 to 90 watts). At 5 min (and previously at rest) they rebreathed rapidly for 15 sec from a 1.0 L bag containing helium (He), sulphur hexafluoride (SF6) and freon-22, 30% oxygen in argon and less than 1 ppm 11C-labelled carbon monoxide. Pulmonary capillary blood flow (Qp) and diffusing capacity (DLCO) were measured from flow-weighted breath-by-breath concentrations of freon-22 and 11CO, after correction for gas mixing delays (using He and SF6). Oxygen saturation (SaO2) (ear oximetry), MO2 and MCO2 and cardiac frequency were measured. PAO2 (ideal) was derived and mixed venous O2 saturation and content were calculated (Fick); PaO2 and PVO2 were derived from standard dissociation curves. For comparison, DLCO and Qp were measured in a similar fashion in five normal subjects exercising at 60 watts. Mean DLCO in patients with fibrosis was 9.62 (SD 2.88) ml.min-1, mm Hg-1 on exercise and mean Qp was 10.48 (SD 1.79) L.min-1 giving mean DLCO/Q ratios of 0.92 (SD 0.28). At 60 watts mean DLCO/Qp in normal subjects was 2.54 (SD 0.3), 2.76-times greater than in patients. SaO2% fell in patients by 3-15% on exercise. Predictions of alveolar-end capillary PO2 gradients from these overall DL/Q gradients showed that diffusion limitation accounted for 99% of the alveolar-arterial PO2 gradient on exercise in fibrosing alveolitis. Hughes (1991 Respir. Physiol. 83:167-178) [corrected] suggests that this simple approach overestimates the contribution of diffusion limitation by about 30%.     

Anaesthesia for endovascular treatment of cerebral aneurysms.

Endovascular treatment of cerebral aneuryms is now widely used and has important implications for the neuroanaesthetist. Significant issues include the decision to use general anaesthesia, factors associated with anaesthesia in the interventional radiology suite and treatment of complications. As endovascular treatment is now supported by evidence and established in practice, neuroanaesthetists should be involved in planning these procedures from a process, and individual patient, perspective.     

Photometrics: a new method of measuring the cross-sectional area of the subglottis.

A new endoscopic method of measuring the cross-sectional area of a subglottic stenosis is presented. The method was tested against existing techniques using a model. By standardizing the distance from the objective of the endoscope to the stenotic area we were able to measure the cross-sectional area using a graduated grid held against the video screen. This technique was then compared with the standard one of estimating the diameter of a stenosis from the external diameter of the bronchoscope which can be passed through the stenosis. The methods were found to be equally accurate in measuring the lumen diameter. However, when measuring the minimum cross-sectional area, three of five observers were significantly better (P less than 0.01) using the photometric method rather than the standard method (Wilcoxon's rank sum test for paired data). The photometric technique of measuring the cross-sectional area of the subglottis is easily performed, non-traumatic, and allows a visual record to be kept.     

Autologous graft-versus-host disease: a novel approach for antitumor immunotherapy.

Autologous bone marrow transplantation (BMT) is a therapeutic option for the treatment of lymphohematopoietic malignancies and solid tumors. Despite the intensive cytoreductive therapy, however, the rates of tumor recurrence after autologous BMT remain unacceptably high. Current studies suggest that the administration of cyclosporine (CsA) disrupts the reconstitution of self-tolerance following autologous BMT leading to the induction of an autoimmune graft-versus-host disease (GVHD). Studies in a rat tumor model and preliminary clinical trials suggest that this autoimmune or autologous GVHD provides a significant antitumor effect. Moreover, the antitumor effect of autologous GVHD can be enhanced by administration of gamma-interferon, which upregulates the antigen recognized by the autoreactive effector cells of autologous GVHD. These studies indicate that the induction of an autoimmune GVHD after autologous BMT may be a promising immunotherapeutic approach for treatment of certain neoplastic diseases.     

Marathon medicine.: Dan Tunstall-Pedoe (ed.). (348 pages, {pound}19.95.) Royal Society of Medicine Press Ltd, 2000. ISBN 1-85315-460-1.

If there was to be an award for the most readable digest ofall medical matters relating to running marathons, then DanTunstall-Pedoe’s latest volume must surely stand a winningchance. The contents are based on discussions     

Sexual Risk Intervention In Multiethnic Drug And Alcohol Users

An estimated 38.6 million persons globally are living with HIV, of whom over 1.1 million reside in Zambia. Of the 2 million cases in the US, 64% of new cases among women are among African Americans. Alcohol and drug use represents a significant risk factor for HIV transmission among both Zambians and African Americans. In addition, gender dynamics in both the US and Zambia promote transmission. This study examines two interventions targeting HIV risk behavior among HIV positive substance users, women in Miami, USA (the New Opportunities for Women (NOW) Project) and men in Lusaka, Zambia (the Partner Project). The study compares the efficacy of these two culturally tailored sexual behavior interventions provided in group and individual session formats. US and Zambian participants increased sexual barrier use and reduced substance-related sexual risk. Comparatively greater gains were made by higher risk Zambian males than US females in both group and individual conditions. Among lower risk participants, women in the group condition achieved and sustained the greatest comparative risk reductions. Results suggest that cost effective group HIV transmission risk reduction interventions for multiethnic individuals can be successfully implemented among both female and male drug and alcohol users in multinational settings.     

Vulvar leiomyomatosis in a patient with esophagogastric leiomyomatosis: review of the syndrome

A case of vulvar leiomyomatosis in a young adult with a history of esophagogastrectomy as a child for esophagogastric leiomyomatosis is presented. The steroid receptor profile of the tumor is described. Therapy with a combination of gonadotropin suppression and surgery was undertaken. The literature pertaining to this rare combination is discussed.