Increased expression of platelet-derived growth factor receptor alpha and beta and vascular endothelial growth factor in the skin of patients with chronic venous insufficiency

Growth factors produced by a variety of cells act as signalling peptides through specific cell surface receptor pathways. Functions such as cell proliferation, migration and differentiation have been assigned to each of them. Here, we report alterations of platelet-derived growth factor receptor alpha (PDGFR-alpha) and beta (PDGFR-beta) and vascular endothelial growth factor (VEGF) expression patterns in the progressive clinical stages of chronic venous insufficiency (CVI). A total of 30 punch biopsies were taken from patients with CVI, and VEGF and PDGFR were detected by indirect immunofluorescence and immunoperoxidase techniques. PDGFR-alpha and PDGFR-beta expression was strongly increased in endothelial cells of capillaries, pericapillary cells and connective tissue cells in the stroma of the skin of venous eczema and venous leg ulcer patients, and to a smaller extend in the dermis of those with lipodermatosclerosis. VEGF staining showed a similar expression pattern in the progressive CVI stages. However, staining of vessels in particular might simply reflect binding of VEGF, secreted by keratinocytes or fibroblasts, to its receptors. Growth factor and receptor expression in specimens from telangiectases and reticular veins, and from pigmented areas, resembled that of normal skin. We conclude that PDGFR-alpha, PDGFR-beta and VEGF play an important role in mediating inflammation and epithelial hyperproliferation in venous eczema, inducing connective tissue sclerosis in lipodermatosclerosis, and causing the reduced reepithelialization tendency in venous ulcers. We speculate that endothelial proliferation with chronic venous hypertension might be mediated by these growth factors.     

Growth hormone secretion, puberty and adult height after cranial irradiation with 18 Gy for leukaemia

The dose of prophylactic cranial irradiation given to patients for acute lymphoblastic leukaemia has been decreased from 24 to 18 Gy, but the beneficial effect of this decrease on growth is controversial. This study compares the growth hormone (GH) secretion and growth of 35 patients (20 boys) given 18 Gy at 3.7+/-0.3 (SE) years, and routinely evaluated 5.4+/-0.4 years after irradiation to define the indications for GH treatment in these patients. Of these, 63% had a low GH peak (< 10 microg/l) after one (22 cases) or two (17 cases) stimulation tests. The plasma concentrations of insulin-like growth factor I and its GH-dependent binding protein were normal for age in all but two cases. The height changes between irradiation and evaluation were correlated with the GH peaks (P < 0.03) and were concordant, except in patients with early puberty. This occurred in 16 patients including all 12 girls irradiated before 4 years of age. A significant (P < 0.03) reduction in height (SD) between irradiation and adult height occurred in untreated GH-deficient patients (-1+/-0.3, n=6), but not in GH-deficient patients given GH (-0.6+/-0.3, n=8) or in those with normal GH peak (-0.4+/-0.3, n=7). CONCLUSION: In children irradiated for acute lymphoblastic leukaemia, GH deficiency is frequent after 18 Gy but its impact on adult height is smaller than after higher doses. We suggest that the indications for gonadotropin releasing hormone analogue therapy should be broad in patients with early or rapidly progressing puberty and those for GH therapy in those patients with a below average constitutional height before irradiation.     

Abnormalities in plasma and red blood cell fatty acid profiles of patients with colorectal cancer

Intravenous injection of stearoyl vanillylamide (C18-VA), a nonpungent capsaicin (CAP) analog, enhances adrenaline secretion significantly and as effectively as CAP in rats. Because swimming capacity was enhanced by CAP in mice due to CAP-induced adrenal catecholamine secretion, we investigated the effects of oral administration of C18-VA on swimming capacity using an adjustable-current water pool. Male Std ddY 6-wk-old mice were fed a commercial diet for this study and one group was orally administered C18-VA via a stomach tube. Treated mice were able to swim longer before exhaustion than the control mice (62.9 +/- 5.6 vs. 49.6 +/- 7. 0 min, P < 0.05). The swimming capacity of two groups administered C18-VA (0.02 and 0.033 mmol/kg) was significantly greater than that of those administered vehicle alone, (P < 0.05). Substance P concentration in cerebrospinal fluid, which is involved in pain transmission and is the first direct measure of pungency, was not affected by C18-VA administration. In an experiment examining the effects of C18-VA on serum adrenaline concentration, adrenaline was significantly greater in C18-VA treated mice than in controls at 2-h post-dose (C18-VA group, 26.09 +/- 2.82; control group 13.29 +/- 0. 96 microg/L, P < 0.01). In a separate study free fatty acids in serum were elevated in treated mice at 2-h post-dose (P < 0.01). While serum glucose concentration was not affected. These results suggest that C18-VA increased swimming capacity of mice via adrenaline release, independent of pungency. In addition, the present study suggests the usefulness of its application to humans.     

Failure to differentiate Cryptosporidium parvum from C. meleagridis based on PCR amplification of eight DNA sequences

PURPOSE: Little is known about the developmental effects of high urinary diversion and bladder defunctionalization in infancy. Although clinical experience shows that a poorly functional bladder may result from urinary diversion in infancy, the mechanisms of change and specific bladder wall alterations have not been well characterized. We hypothesized that cyclic filling and emptying are necessary for normal bladder development. To investigate this important question we created a new animal model. MATERIALS AND METHODS: We designed a new method of hemibladder urinary diversion in 3-week-old New Zealand white rabbits. After vertical midline bladder division half of the bladder was formed into a functional reservoir, which remained in continuity with the ipsilateral ureter and urethra. The other bladder half was defunctionalized and isolated from the urine flow by ureteral ligation. Diversion was created for 3, 7, 14 and 28 days. Urodynamic evaluation was done in the functionalized hemibladders and age matched normal rabbit bladders to test the validity of the functionalized hemibladder as an internal control. Functional and defunctionalized hemibladders as well as age matched, nonoperated normal rabbit bladders were weighed, sectioned and stained to demonstrate muscle and connective tissue components. RESULTS: In 22 of the 27 healthy rabbits (81%) good quality diverted and functional bladder specimens were obtained after diversion. Defunctionalized hemibladders grew more slowly than functionalized bladders and normal age matched control bladders. Histological staining of the bladder wall demonstrated increased connective tissue between the muscle bundles within the diverted specimens than in functional bladders. CONCLUSIONS: Our successful model of urinary diversion may be used to study the developmental and histological effects of urinary diversion in the young bladder. Bladder growth and histological appearance are altered when the stimulus of cyclic filling and emptying is removed. Further studies using this model are warranted to define fully bladder changes that result from diversion and investigate the mechanism of the observed changes.     

Cell-associated viral RNA expression during acute infection with HIV type 1

The mechanism of decline in viremia following acute infection with HIV is unknown. To characterize this process virologically, the expression of viral RNAs was analyzed in samples of peripheral blood mononuclear cells (PBMCs) from a patient who experienced a 100-fold decline in plasma viremia over a 13-day period prior to the initiation of antiretroviral therapy. Cell-associated viral RNA declined in association with the decline in plasma virus. During the initial 7 days of observation, plasma viremia declined more than 10-fold with no change in the ratio of unspliced to multiply spliced mRNAs. The efficiency of viral gene expression did not decline during the study period and varied from 380 to 2800 unspliced RNA copies per productively infected cell. Together, these data indicate no change in the relative proportion of cells in late- and early-stage gene expression during the initial decline and provide evidence against shortening of the viral replication cycle by immune surveillance. However, the prevalence of productively infected cells declined markedly during the 13 days of observation, from 1 in 250 to 1 in 25,000 PBMCs. These data are compatible with depletion of available target cells during the initial decline in viremia. As the level of plasma virus stabilized after 8 days of observation, the ratio of unspliced to multiply spliced mRNAs rose; this rise was due to a relatively greater decline in multiply spliced mRNA. These data suggest the possible onset of a blockade to new infection events (for example, by neutralizing antibody or chemokines), causing an increase in the relative proportion of cells in late-stage gene expression. They may also be explained, however, by the persistence of cell-associated virions together with the near disappearance of productively infected cells from the circulation.     

Applying nutrition and diabetes recommendations in the nurse practitioner setting

Medical nutrition therapy is essential for successful management in persons with diabetes. This article discusses implementation of the 1994 revised nutrition guidelines for persons with diabetes by the nonregistered dietitian professional, particularly in the nurse practitioner's setting. Major changes in the guidelines are addressed including the liberalization of sucrose, and basic nutrition assessment, referral guidelines, a sample nutrition history, and case studies to assist the nurse practitioner when a registered dietitian is unavailable.     

Poncet's disease and papulonecrotic tuberculid in a patient infected with the human immunodeficiency virus

We report the case of a 27-year-old patient with the human immunodeficiency virus (HIV) infection who presented with a 2-week history of crops of painful, red papules over the trunk and extremities, together with a sterile, symmetric polyarthritis involving the small and large joints. Histologic study of a skin biopsy specimen demonstrated features of papulonecrotic tuberculid. Analytical and microbiologic studies ruled out tuberculous infection. Both the synovial and the skin processes were considered to be an immune response secondary to Mycobacterium tuberculosis infection. Specific treatment was established, and there was marked improvement in both the skin and joint symptoms. This case illustrates the complex relationship between the host and the HIV, suggesting an immune dysregulation cause for both the synovial and the skin lesions.     

The influence of sex hormones on obesity across the female life span

Women have a higher prevalence of obesity than men in most developed countries. Obesity affects many aspects of women's health by increasing risk for heart disease, diabetes, breast cancer, and infertility. One reason for the gender difference in obesity may be that fluctuations in reproductive hormone concentrations throughout women's lives uniquely predispose them to excess weight gain. Studies in experimental animals and women have shown that hormonal changes across the menstrual cycle affect calorie and macronutrient intake and alter 24-hour energy expenditure. Pregnancy is a significant factor in the development of obesity for many women. Various factors are associated with excess weight retention following pregnancy, including weight gain during pregnancy, ethnicity, dietary patterns, and interval between pregnancies. There is a need to tailor recommendations for energy intake during pregnancy to individual women, and recent evidence also suggests that the timing of weight gain during pregnancy is a critical factor. Menopause is also a high-risk time for weight gain in women. Although the average woman gains 2-5 pounds during menopausal transition, some women are at risk for greater weight gains. There is also a hormonally driven shift in body fat distribution from peripheral to abdominal at menopause, which may increase health risks in older women. Hormone therapies have varying impacts on body weight and fat distribution. In summary, hormonal fluctuations across the female life span may explain the increased risk for obesity in women. Awareness of these factors allows development of targets for prevention and early intervention.     

Allelotype analysis of uterine leiomyoma: localization of a potential tumor suppressor gene to a 4-cM region of chromosome 7q

The degree and nature of patient involvement in consultations with health professionals influences problem and needs recognition and management, and public accountability. This paper suggests a framework for understanding the scope for patient involvement in such consultations. Patients are defined as co-producers of formal health services, whose potential for involvement in consultations depends on their personal rights, responsibilities and preferences. Patients' rights in consultations are poorly defined and, in the National Health Service (NHS), not legally enforceable. The responsibilities of patients are also undefined. I suggest that these are not to deny, of their own volition, the rights of others, which in consultations necessitate mutuality of involvement through information-exchange and shared decision-making. Preferences should be met insofar as they do not militate against responsibilities and rights.