Systemic venous drainage of pancreas allografts as independent cause of hyperinsulinemia in type I diabetic recipients

To evaluate the metabolic consequences of pancreas transplantation with systemic venous drainage on beta-cell function, we examined insulin and C-peptide responses to glucose and arginine in type I (insulin-dependent) diabetic pancreas recipients (n = 30), nondiabetic kidney recipients (n = 8), and nondiabetic control subjects (n = 28). Basal insulin levels were 66 +/- 5 pM in control subjects, 204 +/- 18 pM in pancreas recipients (P less than 0.0001 vs. control), and 77 +/- 17 pM in kidney recipients. Acute insulin responses to glucose were 416 +/- 44 pM in control subjects, 763 +/- 91 pM in pancreas recipients (P less than 0.01 vs. control), and 589 +/- 113 pM in kidney recipients (NS vs. control). Basal and stimulated insulin levels in two pancreas recipients with portal venous drainage were normal. Integrated acute C-peptide responses were not statistically different (25.3 +/- 4.3 nM/min in pancreas recipients, 34.2 +/- 5.5 nM/min in kidney recipients, and 23.7 +/- 2.1 nM/min in control subjects). Similar insulin and C-peptide results were obtained with arginine stimulation, and both basal and glucose-stimulated insulin-C-peptide ratios in pancreas recipients were significantly greater than in control subjects. We conclude that recipients of pancreas allografts with systemic venous drainage have elevated basal and stimulated insulin levels and that these alterations are primarily due to alterations of first-pass hepatic insulin clearance, although insulin resistance secondary to immunosuppressive therapy (including prednisone) probably plays a contributing role. To avoid hyperinsulinemia and its possible long-term adverse consequences, transplantation of pancreas allografts into sites with portal rather than systemic venous drainage should be considered.

Heart failure events, and case fatalities in Switzerland based on hospital statistics and cause of death statistics

In Switzerland there is a shortage of population-based information on heart failure (HF) incidence and case fatalities (CF). The aim of this study was to estimate HF event rates and both in- and out-of-hospital CF rates.

Imaging structural abnormalities in the hip joint: instability and impingement as a cause of osteoarthritis

Osteoarthritis is thought to be caused by a combination of intrinsic vulnerabilities of the joint, such as anatomic shape and alignment, and environmental factors, such as body weight, injury, and overuse. It has been postulated that much of osteoarthritis is due to anatomic deformities. Advances in surgical techniques such as the periacetabular osteotomy, safe surgical dislocation of the hip, and hip arthroscopy have provided us with effective and safe tools to correct these anatomical problems. The limiting factor in treatment outcome in many mechanically compromised hips is the degree of cartilage damage which has occurred prior to treatment. In this regard, the role of imaging, utilizing plain radiographs in conjunction with magnetic resonance imaging, is becoming vitally important for the detection of these anatomic deformities and pre-radiographic arthritis. In this article, we will outline the plain radiographic features of hip deformities that can cause instability or impingement. Additionally, we will illustrate the use of MRI imaging to detect subtle anatomic abnormalities, as well as the use of biochemical imaging techniques such as dGEMRIC to guide clinical decision making.

Polyarteritis Nodosa, a vanishing vasculitis since its main cause has been identified

The polyarteritis nodosa is a vasculitis for which the main cause had been identified as hepatitis B, a chronic infectious disease inducing an overshooting immune reaction. Thanks to this discovery, the treatment of polyarteritis nodosa has changed from a symptomatic immunosuppressive therapy to a treatment strategy focusing on the disease inducing infectious agent. Vaccination against hepatitis B- virus has been instrumental in the reduction of the prevalence of polyarteritis nodosa. In case of the rare entity of polyarteritis nodosa without hepatitis B, only a symptomatic immunosuppressive therapy can be prescribed. The history of polyarteritis nodosa clearly illustrates that future research in the field of so called autoimmune diseases should focus on the causes rather than on the immunologic effector mechanisms and/or the symptomatic immunosuppressive therapy.

Cladophialophora bantiana: a rare cause of fungal brain abscess. Clinical aspects and new therapeutic options

Black molds or dematiaceous fungi are rare etiologic agents of intracerebral abscesses and such infections carry a high mortality of up to 70% despite combined surgical and antifungal therapy. While the growing use of immunosuppressive therapies and organ transplantation have caused an increase in the incidence of rare fungal cerebral infections, occurrence in immunocompetent hosts is also possible. We describe a 60-year-old female patient with a cerebral abscess caused by Cladophialophora bantiana. The case illustrates the clinical and radiological similarities between glioblastomas and brain abscesses and emphasizes the need to perform histological and microbiological studies prior to the initiation of any form of therapy. Long-term survival from cerebral black mold abscesses has been reported only when complete surgical resection was possible. The recommended antifungal treatment involves the use of amphotericin B combined with a triazole and, if possible, flucytosine. Highly-active new generation triazole antifungal compounds (voriconazole or posaconazole) are likely to offer improved survival rates for patients with rare mold infections. In particular, posaconazole could be a new therapeutic option given its better tolerance, lower toxicity and fewer drug-drug interactions. We discuss clinical, microbiological and practical pharmacological aspects and review current and evolving treatment options.

The ventro-medial prefrontal cortex: a major link between the autonomic nervous system, regulation of emotion, and stress reactivity?

ABSTRACT: Recent progress in neuroscience revealed diverse regions of the CNS which moderate autonomic and affective responses. The ventro-medial prefrontal cortex (vmPFC) plays a key role in these regulations. There is evidence that vmPFC activity is associated with cardiovascular changes during a motor task that are mediated by parasympathetic activity. Moreover, vmPFC activity makes important contributions to regulations of affective and stressful situations.This review selectively summarizes literature in which vmPFC activation was studied in healthy subjects as well as in patients with affective disorders. The reviewed literature suggests that vmPFC activity plays a pivotal role in biopsychosocial processes of disease. Activity in the vmPFC might link affective disorders, stressful environmental conditions, and immune function.

Puma indirectly activates Bax to cause apoptosis in the absence of Bid or Bim

Bcl-2 family members regulate apoptosis in response to cytokine withdrawal and a broad range of cytotoxic stimuli. Pro-apoptotic Bcl-2 family members Bax and Bak are essential for apoptosis triggered by interleukin-3 (IL-3) withdrawal in myeloid cells. The BH3-only protein Puma is critical for initiation of IL-3 withdrawal-induced apoptosis, because IL-3-deprived Puma(-/-) cells show increased capacity to form colonies when IL-3 is restored. To investigate the mechanisms of Puma-induced apoptosis and the interactions between Puma and other Bcl-2 family members, we expressed Puma under an inducible promoter in cells lacking one or more Bcl-2 family members. Puma rapidly induced apoptosis in cells lacking the BH3-only proteins, Bid and Bim. Puma expression resulted in activation of Bax, but Puma killing was not dependent on Bax or Bak alone as Puma readily induced apoptosis in cells lacking either of these proteins, but could not kill cells deficient for both. Puma co-immunoprecipitated with the anti-apoptotic Bcl-2 family members Bcl-x(L) and Mcl-1 but not with Bax or Bak. These data indicate that Puma functions, in the context of induced overexpression or IL-3 deprivation, primarily by binding and inactivating anti-apoptotic Bcl-2 family members.