ABSTRACT
Kaposi's sarcoma (KS) is a vascular neoplasm typically observed in the immunocompromised patient populations, such as acquired immunodeficiency syndrome or transplant patients. KS can appear simultaneously at multiple sites as red to purple, maculo-papular or nodular cutaneous lesions sometimes showing a visceral extension. Sirolimus, an immunosuppressive agent with potent antitumor activity, has been effective in combating post-transplant KS. However, an aggressive regimen of immunosuppression for therapy of severe acute rejection episodes may abolish the antitumor effects of sirolimus. The following is a description of KS development under immunosuppressive therapy with sirolimus, and the successful treatment of KS lesions utilizing the topical application of imiquimod 5% cream, an immune response modifier.
Subject(s)
Aminoquinolines/therapeutic use , Antineoplastic Agents/therapeutic use , Immunosuppressive Agents/adverse effects , Kidney Transplantation/adverse effects , Sarcoma, Kaposi , Sirolimus/adverse effects , Aged , Aminoquinolines/administration & dosage , Antineoplastic Agents/administration & dosage , Graft Rejection/drug therapy , Herpesvirus 8, Human/isolation & purification , Humans , Imiquimod , Immunosuppression Therapy , Sarcoma, Kaposi/chemically induced , Sarcoma, Kaposi/drug therapy , Sarcoma, Kaposi/virologyABSTRACT
BACKGROUND: Cardiovascular disease is associated with platelet dysfunction in patients with diabetes. Hyperglycaemia is known as an independent risk factor for micro- and macrovascular complications, and improvement of metabolic control has shown beneficial effects on diabetic late complications. Our study attempts to clarify the effect of improved metabolic control on platelet activation markers in patients with type-2 diabetes. MATERIALS AND METHODS: Thirty patients were studied at baseline and 3 months after improvement of metabolic control and compared with an age-matched nondiabetic control group. Platelet activation markers (CD31, CD36, CD49b, CD62P and CD63) were assessed by flow cytometry analysis. RESULTS: Significantly more activated platelets were detected in patients with diabetes compared with controls. After 3 months' improvement of metabolic control, a significant decline of all platelet activation markers except CD36 was noted. Furthermore a significant correlation between CD62P, CD63 and HbA(1c) levels was observed. CONCLUSIONS: We conclude therefore that improvement of metabolic control has a beneficial effect on platelet activation. This may have an implication in the pathogenesis of vascular disease in patients with type-2 diabetes.
Subject(s)
Diabetes Mellitus, Type 2/blood , Platelet Activation , Adult , Aged , Antigens, CD/blood , Biomarkers/blood , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/drug therapy , Female , Glycated Hemoglobin/metabolism , Humans , Hypoglycemic Agents/therapeutic use , Male , Middle Aged , Platelet Activation/drug effects , Prospective StudiesABSTRACT
Interferon (IFN)-alpha is used for the treatment of chronic viral hepatitis. It has been associated with various forms of autoimmune disease, e.g. autoimmune hepatitis, Hashimoto thyroiditis and insulin-dependent diabetes mellitus. Further, an increase of insulin resistance and development of non-insulin-dependent diabetes mellitus has been described after treatment with IFN-alpha. Several studies have investigated the induction of different autoimmune markers by IFN-alpha, but only few specified patients who developed insulin-dependent diabetes mellitus. We report the case of a 37-year-old man with chronic hepatitis C who was treated with IFN-alpha plus ribavirin. Thirty weeks after the start of treatment, the patient developed insulin-dependent diabetes mellitus and therapy was withdrawn. HLA typing showed an HLA-DR1,3 phenotype. At manifestation of diabetes mellitus, the C-peptide level was 0.37 ng/ml (normal range 0.5-3 ng/ml). The patient had a positive family history for type 2 diabetes. Several autoimmune markers were investigated before, during and 6 months after withdrawal of antiviral treatment. High titres of glutamic acid decarboxylase (GAD) antibodies were present before therapy. A significant increase in titres of islet cell antibodies, parietal cell antibodies and sperm antibodies was present after 14 weeks of IFN-alpha treatment. Six months after withdrawal of IFN-alpha therapy, these antibodies had significantly decreased whereas GAD antibodies remained unchanged. There was no clinical sign of any other autoimmune disease. Our data show that, in patients with a predisposition to insulin-dependent diabetes mellitus, the disease may become manifest as a side-effect during therapy with IFN-alpha. Several pathogenetic factors may be involved in this process, and, in addition to IFN-alpha, hepatitis C itself may induce autoimmune mechanisms. We conclude that screening for autoantibodies specific for type 1 diabetes should be performed before the start of IFN-alpha treatment. In patients found to be at increased risk of developing diabetes mellitus type 1, monitoring of titres of these antibodies during therapy could help to assess the individual risk-benefit ratio of IFN-alpha treatment.
Subject(s)
Antiviral Agents/adverse effects , Autoimmunity , Diabetes Mellitus, Type 1/etiology , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/immunology , Interferon-alpha/adverse effects , Adult , Antibodies/blood , Antiviral Agents/therapeutic use , Diabetes Mellitus, Type 1/immunology , Glutamate Decarboxylase/immunology , Hepatitis C, Chronic/complications , Humans , Interferon alpha-2 , Interferon-alpha/therapeutic use , Male , Recombinant Proteins , Ribavirin/therapeutic use , RiskABSTRACT
Persistent increased urinary albumin excretion rate (UAER) is associated with increased cardiovascular mortality in type-2 diabetes, however, there are no conclusive data about the progression of advanced UAER in these patients. The present study has investigated the effect of metabolic intervention on the progression in UAER in relation to initial UAER levels. A total of 20 patients with type-2 diabetes and secondary failure to sulfonylurea were observed during 1 year (age, 60 +/- 8 years; HbA1c, 10.8 +/- 1.4%; and duration of diabetes, 17 +/- 10 years) and divided into two groups: group 1 (n = 10; UAER: 51 +/- 35 mg/24 h); and group 2 (n = 10; UAER: 191 +/- 175 mg/24 h). Despite a significant improvement of metabolic control by insulin treatment in both groups (HbA1c: group 1: 11 +/- 1.5 vs. 7.9 +/- 1.2%; group 2: 10.6 +/- 0.9 vs. 9.1 +/- 1.3%, P < 0.001), a progression of UAER was observed in group 2 (191 +/- 175 vs. 331 +/- 237 mg/24 h, P < 0.02), but not in group 1 (51 +/- 35 vs. 41 +/- 24 mg/24 h). Still serum creatinine levels remained normal in all patients during the observation period. The 24 h blood pressure (RR) values in the two groups remained normal under antihypertensive therapy throughout the study (group 1: RR syst: 130 vs. 136 mmHg; RR diast: 80 vs. 81 mmHg, mean arterial pressure (MAD): 89 vs. 93 mmHg; group 2: RR syst: 139 vs. 134 mmHg; RR diast: 78 vs. 75 mmHg, MAD: 97 vs. 90 mmHg). The data shows that in type-2 diabetic patients with normotensive blood pressure values the initial urinary albumin excretion levels determine the progression of UAER. When metabolic control is improved incipient UAER remains constant, but advanced UAER shows progression.
Subject(s)
Albuminuria/urine , Blood Pressure/physiology , Diabetes Mellitus, Type 2/physiopathology , Diabetes Mellitus, Type 2/urine , Aged , Cholesterol, HDL/blood , Diabetes Mellitus, Type 2/drug therapy , Disease Progression , Female , Humans , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Lipids/blood , Male , Middle Aged , Reference ValuesABSTRACT
OBJECTIVE: To investigate whether autonomic neuropathy or hyperglycemia plays a crucial etiological role in gastric retention of ingesta frequently found in type I diabetic patients. RESEARCH DESIGN AND METHODS: We investigated the gastric emptying of a radiolabeled semisolid 1,168 kJ meal in 38 female and 45 male patients (age 18-75 years; illness duration 3-46 years). None took drugs affecting gastrointestinal motility. Fasted patients underwent tests of cardiovascular autonomic and peripheral nerve function. Blood glucose levels were determined before and after the scintigraphic recording of gastric emptying. RESULTS: The percentage of meal remaining in the stomach at the end of the 50-min recording time was related significantly to the patients' degree of cardiovascular autonomic neuropathy [r (81) = 0.235, P < 0.028] but not to their degree of peripheral neuropathy, preprandial blood glucose level, HbA1c indicative of glycemic control, diabetes duration, and age. The patients' mean residual percentage of meal was significantly greater than that of 48 healthy subjects, that is, 71.1 +/- 15.1 vs. 53.5 +/- 13.1% [means +/- SD; t (129) = 6.48, P < 0.0001]. The healthy individuals' mean residual percentage + 2 SD was exceeded in 22 patients. CONCLUSIONS: Slow gastric emptying in patients with type I diabetes seems related to the degree of autonomic neuropathy but not to peripheral neuropathy, actual blood glucose, and glycemic control.
Subject(s)
Autonomic Nervous System Diseases/physiopathology , Blood Glucose/analysis , Diabetes Mellitus, Type 1/physiopathology , Diabetic Neuropathies/physiopathology , Gastric Emptying/physiology , Hyperglycemia/prevention & control , Peripheral Nervous System Diseases/physiopathology , Adult , Aged , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/complications , Female , Food, Formulated/analysis , Humans , Hyperglycemia/physiopathology , Linear Models , Male , Middle Aged , Reference Values , Technetium Tc 99m Sulfur Colloid/metabolismABSTRACT
Since January 1997 the first insulin analogue, lispro has been approved for clinical use in Austria. Insulin lispro has a more rapid onset of action than regular insulin and can therefore be injected immediately before the meal, providing increased therapeutic flexibility for the patients. In many studies a slight decrease in frequency of hypoglycaemic attacks was reported. Insulin lispro did not alter the glycosylated haemoglobin values in the largest multicentre study, although the postprandial glucose concentrations were significantly lower. There was no increased incidence of allergic or other adverse events. No data have been published as yet on the use of insulin lispro in children under 10 years of age and during pregnancy. Potential advantages and disadvantages of insulin lispro therapy, as well as individual factors pertaining to the patient must be taken into consideration on planing treatment with this new insulin analogue. Patients should be well informed about the different action profile of insulin lispro, especially with regard to exercise.
Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Insulin/analogs & derivatives , Adult , Blood Glucose/metabolism , Child , Diabetes Mellitus, Type 1/blood , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Glycated Hemoglobin/metabolism , Humans , Infant, Newborn , Insulin/adverse effects , Insulin/therapeutic use , Insulin Lispro , Male , Pregnancy , Treatment OutcomeABSTRACT
OBJECTIVE: To investigate the effects of long-term high-dose oral magnesium (Mg) therapy (30 mmol/day) in patients with type II diabetes. Low plasma magnesium levels have been reported in type II diabetes and are associated with insulin resistance and diabetic late complications. RESEARCH DESIGN AND METHODS: Forty patients with type II diabetes and hypomagnesemia were observed in a randomized double-blind placebo-controlled trial for 3 months (body mass index: 28 +/- 4 kg/m2; HbA1c: 7.4 +/- 0.8%). Plasma and urine magnesium and metabolic control parameters were determined, and side effects were considered, especially with regard to patients' compliance. RESULTS: A significant increase in plasma magnesium levels was observed after 3 months of treatment (Mg: 0.73 +/- 0.8 vs. 0.81 +/- 0.1 mmol/l), reaching magnesium levels of the control group (0.88 +/- 0.8 mmol/l; NS); metabolic control, however, was not altered (HbA1c: 7.2 +/- 0.7 vs. 7.4 +/- 0.9%). Six months after the end of the trial, plasma magnesium declined to pretreatment levels (Mg: 0.73 +/- 0.07 mmol/l). The prevalence of side effects was high at the beginning and was reduced significantly during treatment. CONCLUSIONS: We conclude that oral magnesium replacement therapy corrects hypomagnesemia after a minimum treatment period of 3 months. These observations might be important for the prevention of diabetic late complications.