A two year observational study of nicotinamide and intensive insulin therapy in patients with recent onset type 1 diabetes mellitus

BACKGROUND AND AIMS: A number of trials have evaluated residual beta-cell function in patients with recent onset type 1 diabetes mellitus (DM1) treated with nicotinamide in addition to intensive insulin therapy (IIT). In most studies, only a slight decline of C-peptide secretion was observed 12 months after diagnosis; however, no data is available on C-peptide secretion and metabolic control in patients continuing nicotinamide and IIT for up to 2 years after diagnosis. PATIENTS AND METHODS: We retrospectively analysed data from 25 patients (mean age 14.7 years +/- 5 SD) with DM1 in whom nicotinamide at a dose of 25 mg/kg b. wt. was added from diagnosis (< 4 weeks) to IIT (three injections of regular insulin at meals + one NPH at bed time) and continued for up to 2 years after diagnosis. Data were also analysed from patients (n = 27) in whom IIT was introduced at diagnosis and who were similarly followed for 2 years. Baseline C-peptide as well as insulin dose and HbA1c levels were evaluated at 12 and 24 months after diagnosis. RESULTS: In the course of the follow-up, patients on nicotinamide + IIT or IIT alone did not significantly differ in terms of C-peptide secretion (values at 24 months in the two groups were 0.19 +/- 0.24 nM vs 0.19 +/- 0.13 nM, respectively). Insulin requirement (0.6 +/- 0.3 U/kg/day vs 0.7 +/- 0.2 U/kg/day at 24 months, respectively) did not differ between the two groups. However, HbA1c was significantly lower 2 years after diagnosis in patients treated with nicotinamide + IIT (6.09 +/- 0.9% vs 6.98 +/- 0.9%, respectively, p < 0.01). No adverse effects were observed in patients receiving nicotinamide for 2 years. CONCLUSION: Implementation of IIT with the addition of nicotinamide at diagnosis continued for 2 years improves metabolic control as assessed by HbA1c. In both nicotinamide and control patients, no decline in C-peptide was detected 2 years after diagnosis, indicating that IIT preserves C-peptide secretion. We conclude that nicotinamide + IIT at diagnosis of DM1 prolonged for up to 2 years can be recommended, but longer follow-up is required to determine whether nicotinamide should be continued beyond this period.     

A case of CPT deficiency, homoplasmic mtDNA mutation and ragged red fibers at muscle biopsy

A 45-year-old male patient had an episode of acute renal failure with myoglobinuria, myalgias, weakness, and markedly increased serum CK levels. Similar episodes had occurred in the past. Carnitine palmitoyl-transferase II (CPT II) deficiency was documented both biochemically and genetically. Interestingly, muscle biopsy also showed some ragged red fibers (RRF) and complete mitochondrial DNA (mtDNA) sequence disclosed a homoplasmic T3394C point mutation. This mutation is described in Leber's hereditary optic neuropathy (LHON) or in patients with diabetes mellitus.     

Prophylactic gene therapy with human tissue kallikrein ameliorates limb ischemia recovery in type 1 diabetic mice

Diabetes macro- and microvascular disease causes tissue hypoperfusion. This deficit, together with a failure to mount an adequate angiogenic response, might explain why vascular occlusion evolves more severely among diabetic patients. The present study investigated whether prophylactic gene therapy with human tissue kallikrein (hTK) may protect diabetic limbs from the consequences of supervening ischemia. Vehicle (saline) or an adenovirus carrying the gene for either hTK (Ad.hTK) or luciferase (Ad.Luc) was injected into left adductor muscles of streptozotocin-induced type 1 diabetic mice 2 weeks before operative occlusion of the ipsilateral femoral artery. Saline-injected nondiabetic mice served as controls. Hindlimb blood flow recovery was analyzed sequentially over the 2 weeks after ischemia induction. At necroscopy, microvessel density and endothelial cell proliferation and apoptosis were quantified in skeletal muscles. We found that limb perfusion recovery of saline-injected type 1 diabetic mice is delayed because of insufficient reparative neovascularization and excessive activation of endothelial cell apoptosis. By contrast, prophylactic Ad.hTK renewed the ability to mount an appropriate neovascularization response to ischemia, suppressed apoptosis, and upregulated endothelial nitric oxide synthase expression. Ultimately, correction of diabetic endotheliopathy by Ad.hTK allowed proper perfusion recovery as seen in nondiabetic mice. These discoveries disclose new therapeutic options for the treatment of diabetic complications.     

Second-line treatment with carboplatin for recurrent or progressive oligodendroglial tumors after PCV (procarbazine, lomustine, and vincristine) chemotherapy: a phase II study

BACKGROUND: The efficacy of second-line chemotherapy for patients with recurrent or progressive oligodendroglial tumors is limited. In the current study, the authors investigated the use of carboplatin as a second-line chemotherapeutic agent against these types of tumors. METHODS: Twenty-three patients with recurrent or progressive oligodendrogliomas or oligoastrocytomas after first-line PCV (procarbazine, lomustine, and vincristine) chemotherapy were enrolled in a single-institution Phase II study of second-line carboplatin chemotherapy. All patients had undergone surgery, and most also had undergone conventional radiotherapy. Carboplatin was administered at a dose of 560 mg/m2 intravenously every 4 weeks. Responses were evaluated according to conventional criteria, based on magnetic resonance imaging (MRI) findings. RESULTS: Three of 23 patients (13%) had partial responses, with neurologic improvement. Twelve patients (52%) had stable disease; in 2 of these 12 patients, a minor response was seen on MRI. Eight patients (35%) had progressive disease. The median time to tumor progression was 3 months for all patients and 9 months for patients who experienced responses to treatment. Progression-free survival rates at 6 and 12 months were 34.8% and 8.7%, respectively. Among the salvage treatment plans followed after carboplatin chemotherapy were supportive care alone, radiotherapy, third-line chemotherapy, and reoperation. The median survival duration from the start of carboplatin administration was 16 months. Myelotoxicity was severe, with Grade 3 or 4 thrombocytopenia in 60% of patients and Grade 3 or 4 neutropenia in 48% of patients. CONCLUSIONS: When administered according to a monthly schedule, carboplatin exhibited modest activity in adult patients with recurrent or progressive oligodendroglioma or oligoastrocytoma who experienced treatment failure after PCV chemotherapy; the current treatment regimen also was associated with severe toxicity. Further improvement of second-line chemotherapy for the patient group examined in the current study is necessary.     

Endovascular repair of a penetrating thoracic aortic ulcer by way of the carotid artery

INTRODUCTION: Endovascular repair of thoracic aortic lesions offers an attractive alternative to traditional open repair. Access to the thoracic aorta can occasionally be challenging because of large device size and vessel tortuosity. Traditional access by way of the femoroiliac vessels might not be possible in the setting of synchronous iliac occlusive disease. MATERIALS AND METHODS: A 63-year-old woman presented with a 7.1-cm symptomatic, penetrating ulcer of the descending thoracic aorta. The patient's severe pulmonary disease prohibited an open repair. A Talent endoprosthesis was placed under compassionate use with approval of the institutional review board. The graft was placed by way of the left common carotid artery because of severe iliac occlusive disease. RESULTS: The thoracic endograft was successfully placed with exclusion of the pseudoaneurysm. The patient's chest pain resolved immediately. She developed mild left-sided weakness from a postoperative right anterior cerebral artery stroke that quickly resolved. The patient was discharged on postoperative day 5. No aortic endoleak was noted on follow-up computerized tomography scan at 1 month. CONCLUSIONS: Endovascular repair should be considered in patients with thoracic aortic aneurysms, particularly those with severe medical comorbidities. Placement by way of the common carotid artery is technically feasible in the setting of synchronous aortoiliac disease.     

American Cancer Society guidelines for breast cancer screening: update 2003

In 2003, the American Cancer Society updated its guidelines for early detection of breast cancer based on recommendations from a formal review of evidence and a recent workshop. The new screening recommendations address screening mammography, physical examination, screening older women and women with comorbid conditions, screening women at high risk, and new screening technologies.     

Trends in risk factors for the major "lifestyle-related diseases" in Geneva,Switzerland, 1993-2000

PURPOSE: Continuous monitoring of health determinants in populations is necessary to predict future disease burdens. The objective of this study was to assess the prevalences of major risk factors for lifestyle diseases for 8 years (1993 to 2000) in representative samples of the general population. METHODS: Independent cross-sectional surveys representative of adults aged 35 to 74 years (4228 men and 4190 women) in Geneva, Switzerland, conducted continuously between 1993 and 2000. RESULTS: Prevalence of hypertension decreased 15% in men and 10% in women (trend p's<.0001), while overweight/obesity prevalences increased 10% in men and 8% in women (trend p's<.05). The prevalences of smoking (men: 29%; women: 24%) and physical inactivity (men: 44%; women: 50%) remained high and unchanged, and the dietary unsaturated/saturated fat ratio did not change (men: 0.40; women: 0.48). CONCLUSIONS: Because of the persistent high prevalence of risk factors, the global burden of chronic diseases is likely to grow in the next decade and beyond. Continuous monitoring provides reliable trends, beyond seasonal and sampling variations.