Muscle weakness: a progressive late complication in diabetic distal symmetric polyneuropathy.

The aim of the study was to determine the progression of muscle weakness in long-term diabetes and its relation to the neuropathic condition. Thirty patients were recruited from a cohort of 92 diabetic patients who participated in a study on muscular function 6-8 years earlier. Nine subjects were nonneuropathic, 9 had asymptomatic neuropathy, and 12 had symptomatic neuropathy. Thirty matched control subjects who participated in the initial studies were also included. At follow-up, isokinetic dynamometry at the ankle, electrophysiological studies, vibratory perception thresholds, and clinical examination (neuropathy symptom score and neurological disability score [NDS]) were repeated. The annual decline of strength at the ankle was 0.7 +/- 1.7% in control subjects, 0.9 +/- 1.9% in nonneuropathic patients, 0.7 +/- 3.1% in asymptomatic neuropathic patients, and 3.2 +/- 2.3% in symptomatic neuropathic patients. In the symptomatic patients, the decline of muscle strength at the ankle was significant when compared with matched control subjects (P = 0.002) and with the other diabetic groups (P = 0.023). Also, the annual decline of muscle strength at the ankle was related to the combined score of all measures of neuropathy (r = -0.42, P = 0.03) and to the NDS (r = -0.52, P = 0.01). In patients with symptomatic diabetic neuropathy, weakness of ankle plantar and dorsal flexors is progressive and related to the severity of neuropathy.

A Piglet Model of Neonatal Hypoxic-Ischemic Encephalopathy.

Birth asphyxia, which causes hypoxic-ischemic encephalopathy (HIE), accounts for 0.66 million deaths worldwide each year, about a quarter of the world's 2.9 million neonatal deaths. Animal models of HIE have contributed to the understanding of the pathophysiology in HIE, and have highlighted the dynamic process that occur in brain injury due to perinatal asphyxia. Thus, animal studies have suggested a time-window for post-insult treatment strategies. Hypothermia has been tested as a treatment for HIE in pdiglet models and subsequently proven effective in clinical trials. Variations of the model have been applied in the study of adjunctive neuroprotective methods and piglet studies of xenon and melatonin have led to clinical phase I and II trials(1,2). The piglet HIE model is further used for neonatal resuscitation- and hemodynamic studies as well as in investigations of cerebral hypoxia on a cellular level. However, it is a technically challenging model and variations in the protocol may result in either too mild or too severe brain injury. In this article, we demonstrate the technical procedures necessary for establishing a stable piglet model of neonatal HIE. First, the newborn piglet (< 24 hr old, median weight 1500 g) is anesthetized, intubated, and monitored in a setup comparable to that found in a neonatal intensive care unit. Global hypoxia-ischemia is induced by lowering the inspiratory oxygen fraction to achieve global hypoxia, ischemia through hypotension and a flat trace amplitude integrated EEG (aEEG) indicative of cerebral hypoxia. Survival is promoted by adjusting oxygenation according to the aEEG response and blood pressure. Brain injury is quantified by histopathology and magnetic resonance imaging after 72 hr.

Mechanisms of disease: role of neurotrophins in diabetes and diabetic neuropathy.

Neuropathy is an insidious and devastating consequence of diabetes. Early studies provided a strong rationale for deficient neurotrophin support in the pathogenesis of diabetic neuropathy in a number of critical tissues and organs. It has now been over a decade since the first failed human neurotrophin supplementation clinical trials, but mounting evidence still implicates these trophic factors in diabetic neuropathy. Since then, tremendous advances have been made in our understanding of the complexities of neurotrophin signaling and processing and how the diabetic milieu might impact this. This in turn changes both our perception of how the altered trophic environment contributes to the etiology of diabetic neuropathy and the design of future neurotrophin therapeutic interventions. This chapter summarizes some of these findings and attempts to integrate neurotrophin actions on the nervous system with an increasing appreciation of their role in the regulation of metabolic processes in diabetes that impact the diabetic neuropathic state.