Wernicke's encephalopathy following gastroplasty for morbid obesity.

BACKGROUND: The syndrome of Wernicke's encephalopathy consists of two of four features of (1) dietary deficiency; (2) oculomotor abnormality; (3) cerebellar dysfunction; and (4) confusion or mild memory impairment. Predisposing risk factors include alcoholism, hyperemesis gravidarum and prolonged intravenous feeding. METHODS: A 35-year-old female developed refractory emesis, severe weight loss, and hypokalemia following banded gastroplasty for morbid obesity. Reversal of gastroplasty was performed four months following initial surgery. Following reversal, the patient developed confusion, ataxia, leg weakness and nystagmus. RESULTS: Examination of the patient demonstrated disorientation with confusion, vertical nystagmus worse on downgaze, diffuse weakness of the lower extremities, and bilateral dysmetria. Magnetic resonance imaging of the brain demonstrated symmetrical areas of increased T2 signal present bilaterally in the medial thalamic nuclei. The patient did not demonstrate any initial improvement with intravenous thiamine but improved over two months of follow-up. CONCLUSION: Wernicke's encephalopathy has been reported in the European literature as a complication of gastroplasty, with rare recognition of this clinical entity in the North American literature. This potential complication of gastroplasty may be preventable by nutritional intervention in subjects experiencing severe weight loss and emesis following surgery.

Testing specificity and guidance hypotheses by manipulating relative frequency of KR scheduling in motor skill acquisition.

This investigation tested predictions of specificity and guidance hypotheses by manipulating relative frequency of knowledge of results scheduling using a shuffleboard task. Participants were assigned to either a 100%-KR, three 50%-KR conditions (Constant, Fade, Reverse), or 00%-KR condition. Based on predictions of the specificity hypothesis, it was expected the 00%-KR condition would perform the best on a no-KR retention test. It was also expected the 100%-KR condition would perform poorly on a no-KR retention test based on predictions of the guidance hypothesis. Analysis for 55 men's and 55 women's retention did not support predictions of the specificity hypothesis and provided partial support for the guidance hypothesis.

Cardiovascular risk, renal hypertensive damage, and effects of amlodipine treatment in transgenic TGR(mREN2)27 rats.

Transgenic rats (TGRs) TGR(mREN2)27 are characterized by fulminant hypertension, an inverse circadian blood pressure rhythm, and severe hypertensive target organ damage. In the present study, we evaluated cardiovascular risk factors, renal function, and urinary protein loss in transgenic rats before and after treatment with the calcium channel blocker amlodipine. Amlodipine was injected intraperitoneally in a dose of 5 mg/kg/day, either once daily at 8.00 h or twice daily in divided doses at 8.00 and 20.00 h. Untreated TGRs and Sprague-Dawley rats served as hypertensive and normotensive controls, respectively. Before and after 5 weeks of treatment, rats were placed in metabolic cages for sampling of urine. Prior to treatment, urinary excretion rates of protein, albumin, and Ca2+ were significantly higher in TGRs than in Sprague-Dawley controls. Urinary excretion of protein and albumin was reduced by 5 weeks of amlodipine treatment, whereas the excretion of Ca2+ was not affected. The reductions in renal proteinuria and albuminuria by amlodipine treatment were significantly correlated with the treatment-induced decrease in blood pressure. These findings indicate that blood pressure itself is an important contributor to albumin loss by the kidney in renin-dependent hypertension of TGRs.

Athletic training education programs: to rank or not to rank?

OBJECTIVE: To discuss the literature regarding educational program ranking and to provide insights concerning undergraduate and graduate athletic training education ranking systems. BACKGROUND: The demand for accountability and the need to evaluate the quality of educational programs have led to program ranking in many academic disciplines. As athletic training becomes more recognized within the medical community, determining a program's quality will become increasingly important. DESCRIPTION: We describe program rankings used in other disciplines for determining quality and providing measures of accountability. We discuss the strengths and weaknesses of both subjective and objective ranking systems, as well as the arguments for using program rankings in athletic training. Future directions for program ranking and potential research questions are suggested. APPLICATIONS: Ranking systems on the basis of levels of perceived quality and academic productivity of programs that prepare future professionals will help potential undergraduate and graduate students make informed decisions when selecting an educational program.

Effects of amlodipine once or twice daily on circadian blood pressure profile, myocardial hypertrophy, and beta-adrenergic signaling in transgenic hypertensive TGR(mREN2)27 rats.

The effects of amlodipine on blood pressure profiles, cardiac hypertrophy, and beta-adrenergic signal transduction were studied in transgenic hypertensive TGR(mREN2)27 rats (TGRs), which are characterized by an inverse circadian blood pressure rhythm. Cardiovascular parameters were monitored by radiotelemetry; beta-adrenoceptor density and function were measured by radioligand binding and by determination of beta-adrenergic stimulation of adenylyl cyclase. Ventricular weight and the activity of cardiac sarcolemmal 5-nucleotidase were used as measures of hypertrophy. Acute i.p. injection of amlodipine (1, 3, 10 mg/kg body weight) either at 8:00 or at 20:00 h dose-dependently reduced blood pressure irrespective of the dosing time. For long-term treatment, TGRs were divided into three groups: untreated; amlodipine, once-daily, 5 mg/kg; and amlodipine, twice daily, 2.5 mg/kg. Both treatment schedules resulted in decreased 24 h means in systolic and diastolic blood pressure and a reduction in ventricular hypertrophy but had no effects on cardiac beta-adrenergic signaling. Once-daily dose of amlodipine at 8:00 h decreased blood pressure predominantly during the daily resting period of the rats, whereas twice-daily dosing induced a bimodal blood pressure pattern. However, even after 5 weeks of treatment, typical circadian profiles could not be observed with either treatment, indicating a short duration of action of amlodipine in rats. Thus it remains an open question whether pharmacologic normalization of the circadian blood pressure pattern in TGRs will more effectively reduce myocardial hypertrophy and restore beta-adrenergic signaling than a reduction in 24-h blood pressure per se.

(-)Deprenyl reduces delayed neuronal death of hippocampal pyramidal cells.

Ischemia-induced delayed neuronal death can be mediated by apoptosis, and (-)deprenyl has been shown to block apoptosis in dopaminergic and cholinergic neurons. This study has investigated whether (-)deprenyl can prevent delayed neuronal death of hippocampal pyramidal cells. Rats were subjected to unilateral hypoxia-ischemia and treated with (-)deprenyl (0.25 mg/kg, s.c.) or saline daily. After sacrifice the left and right hippocampi were examined histologically. Unilateral delayed neuronal death was seen in the CA1, CA3 and CA4 fields up to 14 days after the ischemia. After 14 days' treatment with (-)deprenyl there was 66%, 91% and 96% reduction in delayed neuronal death in the CA1, CA3 and CA4 fields, respectively. (-)Deprenyl was effective when given at the onset or after ischemia, but not when given 2 h before ischemia. The reduction in ischemia-induced delayed neuronal death is consistent with an anti-apoptotic mechanism of (-)deprenyl.

Insulin elevates hippocampal GABA levels during ischemia. This is independent of its hypoglycemic effect.

There are reports that insulin may protect neurons from the effects of ischemia. The mechanisms for this protection are not fully understood. We studied the extracellular levels of glutamate and GABA in insulin-treated animals exposed to transient forebrain ischemia under normoglycemic and hypoglycemic conditions. In vivo microdialysis technique was used to collect extracellular fluid from the CA1 region of the hippocampus. There was a significant increase in GABA levels in the two insulin-treated sub-groups compared with the controls. GABA levels were < 1 pmol/10 microliters in three 10 min collections prior to ischemia in all the groups. It increased from 11.1 +/- 3.5 pmol/10 microliters in the conrol group to 47 +/- 5 (P < 0.001) in the insulin-treated hypoglycemic group and up to 47.2 +/- 9.3+ (P < 0.005) in the insulin-treated normoglycemic group (two-way ANOVA with repeated measures). Ischemia resulted in an increase in the glutamate levels. The glutamate levels returned to baseline within 30 min of the insult. There were no significant differences in the glutamate levels in three groups. The increase in GABA concentrations in the extracellular space may result in the inhibition of CA1 pyramidal neurons. This may be a possible mechanism of neuronal protection in animals treated with insulin (with or without being hypoglycemic) during ischemia.

Polymyositis with plasma cell infiltrate in essential mixed cryoglobulinaemia.

A patient with essential cryoglobulinaemia who presented with polymyositis is described. Muscle biopsy showed intense plasma cell infiltration of muscle. Plasmapheresis produced a rapid resolution of the cutaneous manifestations of the disease, but little improvement in muscle strength. Oral steroids resulted in moderate improvement in muscle strength. There have been no previously reported cases of polymyositis in association with essential cryoglobulinaemia.

Insulin attenuates ischemic brain damage independent of its hypoglycemic effect.

Insulin, an endogenously produced circulating peptide that enters the brain, has been shown to reduce ischemic brain and spinal cord damage in several animal models. Because of its potential clinical use in humans, the present study was undertaken to test the hypotheses that (a) survival and regional ischemic brain necrosis are improved by insulin; (b) insulin requires concomitant hypoglycemia to exert its neuroprotective effect; (c) insulin is still neuroprotective with delayed administration after an episode of postischemic hypotension; and (d) insulin is beneficial after normoglycemic, as well as hyperglycemic ischemia. Rats were subjected to 10.5 min two-vessel occlusion forebrain ischemia followed by 30 min of hypotension to increase the infarction rate. Insulin administered concomitantly with glucose significantly reduced the seizure rate, as well as cortical and striatal neuronal necrosis below that seen in untreated animals. Neuroprotection was seen whether insulin was given before or after a 30-min episode of postischemic hypotension. Insulin reduced pan-necrosis in addition to selective neuronal necrosis: The infarction rate was reduced in the cerebral cortex, thalamus, and substantia nigra pars reticulata. Normoglycemic ischemia produced only selective neuronal necrosis, but a beneficial effect on structural damage was also seen. The results indicate that insulin acts directly on the brain, independent of hypoglycemia, to reduce ischemic brain necrosis. Possible direct CNS mechanisms of action include an effect on central insulin receptors mediating inhibitory neuromodulation, an effect on central neurotransmitters, or a growth factor effect of insulin.

Transesophageal echocardiography in the detection of potential cardiac source of embolism in stroke patients.

To compare the diagnostic yields of transesophageal and transthoracic echocardiography in the detection of potential cardiac sources of embolism, 63 patients (mean +/- SD age 63 +/- 15 [range 18-87] years) with transient ischemic attacks or stroke underwent both procedures. Transthoracic echocardiography revealed a potential cardiac source of embolism in 14% (nine) of the patients, all of whom had clinical evidence of heart disease. Transesophageal echocardiography revealed a potential cardiac source of embolism in 41% (26) of the patients; 27% (seven) of these patients had no clinical cardiovascular abnormalities. Abnormalities detected only by transesophageal echocardiography in the patients with unsuspected cardiac disease included atrial septal aneurysm in two, patent foramen ovale in two, left atrial appendage thrombus in one, and myxomatous mitral valve in two. The 26 patients with an identified cardiac source of embolism were older (67.5 versus 59.4 years, p = 0.04), more frequently in atrial fibrillation (62% [16] versus 8% [3], p less than 0.0001), had a larger left atrium (43 versus 37 mm, p = 0.01) and more commonly had left ventricular hypertrophy (62% [16] versus 32% [12], p less than 0.02) than the 37 patients in whom no cardiac source of embolism was identified. Thus, transesophageal echocardiography is more sensitive than transthoracic echocardiography in the detection of potential cardiac sources of embolism in patients with cerebral ischemic events.

Postischemic seizures and necrotizing ischemic brain damage: neuroprotective effect of postischemic diazepam and insulin.

Insulin has recently been shown experimentally to modify ischemic brain damage when administered either before or after the episode of ischemia. In controlled studies in the rat, high doses of insulin (greater than or equal to 8 IU/kg) result in seizures and early death. The present study was undertaken to determine whether diazepam, a potent, centrally penetrating GABAmimetic, alone or in combination with insulin, could mitigate postischemic seizures or regional selective neuronal necrosis and infarction. Forebrain ischemia was induced in rats for 10 1/2 minutes by carotid clamping and hypotension. The animals were observed clinically until elective perfusion-fixation and quantitative pathologic examination at 1-week recovery. Diazepam, either alone or with insulin, reduced regional brain necrosis and reduced the seizure rate. Insulin alone also led to reduced regional necrosis. However, the combination of diazepam plus insulin yielded the greatest proportion of undamaged brains in the hippocampus, thalamus, and midbrain. In the neocortex, the diazepam-only group showed the greatest number of normal hemispheres. Hypothalamic infarction was eliminated by all three treatments. Seizures per se were associated with increased damage in the cerebral cortex, thalamus, and brainstem, irrespective of treatment group. The findings indicate that ischemic brain necrosis can be mitigated by diazepam and insulin treatment begun in the immediate postischemic period.

Postischemic insulin reduces spatial learning deficit following transient forebrain ischemia in rats.

We investigated the ability of postischemic insulin administration to modify the structural and neurobehavioral consequences of cerebral ischemia in rats. Forebrain ischemia was induced in fed rats by combining controlled systemic hypotension with bilateral carotid artery clamping for 10 1/2 minutes. Following clamp release, one group of six rats [corrected] was given insulin (2 IU/kg s.c. b.i.d.) for 1 week. An ischemic-control group of five rats [corrected] received no postischemic treatment. A sham-ischemia group of rats was used as a behavioral control. Throughout the recovery period until sacrifice, the drinking water of all rats was supplemented with 25% glucose. Rats were trained on two water maze place navigation tasks 1-2 months after ischemia. Escape latencies and swim patterns were recorded. Performance in the insulin-treated group was better than that in the ischemic-control group (p less than 0.05) on both tasks and did not differ significantly from that of the sham-ischemia group. Improvement in behavior correlated with a significant reduction in CA1 hippocampal necrosis in the insulin-treated group (p less than 0.05). Our findings demonstrate that postischemic treatment with insulin improves neurobehavioral performance in addition to lessening ischemic neuronal necrosis.

Platelet aggregability in sleep-related stroke.

We examined platelet aggregability during nocturnal sleep and daytime wakefulness in patients with a history of sleep-related stroke onset (SOS) and compared it to that of matched awake-onset stroke (AOS) patients and controls without evidence of vascular disease. Aggregability was evaluated in-vitro at least seven weeks following stroke onset. Platelets were more aggregable to ADP, collagen and arachidonic acid (AA) during both sleep and wakefulness in patients with AOS (p less than 0.01). No significant difference in the mean aggregation thresholds during sleeping or waking periods were found between SOS and control groups. However, platelets were significantly more responsive to AA during sleep than during wakefulness in the SOS patients (p less than 0.01). This difference was confined to the subgroup of SOS patients who had experienced nocturnal as opposed to daytime sleep-related stroke onset, suggesting that the observed difference in platelet responsiveness to AA may be related to a circadian fluctuation in platelet aggregability rather than to a sleep-related fluctuation. Significant sleep-related changes in platelet aggregability were not identified in the other two groups.

The effect of postischemic blood glucose levels on ischemic brain damage in the rat.

The effect of insulin-induced hypoglycemia following 10.5 minutes of forebrain ischemia was studied in the rat. All groups received preischemic glucose loading (2 gm/kg) to promote brain infarction. Following completion of ischemia, rats received either 2 to 3 IU/kg (low-dose group) or 8 to 20 IU/kg (high-dose group) insulin. During the survival period, blood glucose concentrations were maintained in the ranges of 1.2 to 2.9 mM and 2.9 to 4.9 mM, respectively, for the low-dose and high-dose insulin groups. Control rats were given 2 gm/kg glucose immediately following ischemia. During the recovery period, until perfusion at 7 days, they were given glucose, 2 gm/kg, twice daily by intraperitoneal injection, and their drinking water was supplemented with 25% glucose. Mortality (p less than 0.05) and postischemic seizure incidence (p less than 0.01) were significantly reduced in the low-dose insulin group compared to the control group. Mortality was increased in the high-dose insulin group compared to the control group and was associated with an increased incidence of postischemic seizures. Neuropathological examination revealed no cortical infarction in the low-dose or high-dose insulin-treated rats compared to a 60% incidence of cortical infarction in the control group. In addition, the high-dose insulin-treated group showed a significant reduction in striatal and hippocampal CA1 selective neuronal necrosis compared to control rats with comparable survivals (p less than 0.05). The findings suggest that postischemic blood glucose concentrations play an important role in modulating both ischemic infarction and selective neuronal necrosis.

Internal ophthalmoplegia and cranial neuropathy without external ophthalmoplegia. A report of 2 cases.

Two patients presented with an acute syndrome of internal ophthalmoplegia in the absence of external ophthalmoplegia, bilateral involvement of other cranial nerves, and minimal evidence of peripheral neuropathy. Cerebrospinal fluid protein was slightly raised, and moderate slowing of nerve conduction velocity was observed peripherally. It is suggested that these cases may represent a variant of acute post-infectious polyneuritis.

The value of noninvasive investigation in the diagnosis of total occlusion of the internal carotid artery.

A battery of simple noninvasive tests consisting of directional Doppler ultrasound and carotid phonoangiography has been used to detect carotid stenosis in 700 patients Forty four carotid occlusions in 42 patients were confirmed on angiography, and this study examines the accuracy of this noninvasive battery in predicting the presence of an occluded internal carotid artery. Although the sensitivity of the battery described has been 70% for occlusion, with a specificity of 98% (only five false positives), this relatively low sensitivity and the uniform requirement for surgery in the false positive group have led us to conclude that this battery should not be used as a substitute for angiography when the diagnosis of internal carotid occlusion requires to be confirmed. Nevertheless, these noninvasive tests do have a role in alerting the physician to the presence of carotid occlusion and contralateral carotid artery stenosis, allowing more specific planning of any subsequent arteriography required.