Moderate hypoglycemia impairs multiple memory functions in healthy adults.

The effects of acute insulin-induced hypoglycemia on short-term, delayed, and working memory were examined in healthy adults. A hyperinsulinemic glucose clamp was used to maintain arterialized blood glucose at either 4.5 (euglycemia) or 2.5 (hypoglycemia) mmol/L on 2 separate occasions in 16 healthy volunteers. Tests of immediate and delayed verbal memory, immediate and delayed visual memory, and working memory were administered during each experimental condition. All memory systems were impaired during acute hypoglycemia, with working memory and delayed memory being particularly susceptible. These findings are informative concerning the metabolic basis of adequate memory function and are of practical importance to people with insulin-treated diabetes, in whom hypoglycemia is common. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Anti-sulphatide antibodies in peripheral neuropathy

A study was carried out on 135 patients with chronic idiopathic neuropathy (63), neuropathy associated with monoclonal gammopathy (51, including eight with anti-MAG antibody activity) and the Guillain-Barré syndrome (GBS) (21). Serum IgM, IgG and IgA anti-sulphatide antibody titres were compared with titres in 304 patients with other neurological or immunological diseases and in 50 normal subjects. Titres were presented a) as the highest serum dilution at which reactivity could be detected, and b) in the linear region of the optical density curve. A substantial number of patients with neurological or immunological diseases had higher titres than normal subjects. Compared with normal and disease controls, five patients with neuropathy associated with IgMk monoclonal gammopathy had raised titres of IgM anti-sulphatide antibodies and one patient with GBS had raised IgM, IgG and IgA anti-sulphatide antibodies in the acute phase of the disease. Two patients had a predominantly axonal sensory neuropathy with presenting symptoms of painful paresthesiae and minimal neurological deficit. Three patients had a predominantly demyelinating sensorimotor neuropathy associated with anti-MAG antibody activity. The patient with GBS had extensive sensory loss and antibody titres returned to normal within three weeks. Raised titres of anti-sulphatide antibodies occurred in several types of neuropathy, but all had some degree of sensory impairment and associated immunological abnormality.     

Advances in the genetics of peripheral neuropathy in childhood

Pneumocystis carinii pneumonia (PCP) occurs commonly in immunocompromised patients. Sulfamethoxazole-trimethoprim (SMX-TMP) is effective prophylaxis, although PCP may still occur despite apparently adequate use. We report three cases of PCP which highlight some of the pitfalls of prophylaxis.     

Nociceptor hyper-responsiveness during vincristine-induced painful peripheral neuropathy in the rat

Neuropathic pain accompanies peripheral nerve injury after a wide variety of insults including metabolic disorders, traumatic nerve injury, and neurotoxic drugs. Chemotherapy-induced neuropathic pain, caused by drugs such as vincristine and taxol, occurs in cancer patients who receive these drugs as antineoplastic agents. Although a variety of remediations have been attempted, the absence of knowledge concerning mechanisms of chemotherapy-induced neuropathic pain has hindered the development of treatment strategies. Vincristine, a widely used chemotherapeutic agent, produces painful peripheral neuropathy in humans and mechanical hyperalgesia in rats. To test the hypothesis that alterations in C-fiber nociceptor function occur during vincristine-induced painful peripheral neuropathy, we performed in vivo extracellular recordings of single neurons from the saphenous nerve of vincristine-treated rats. Forty-one percent of C-fiber nociceptors were significantly hyper-responsive to suprathreshold mechanical stimulation. As a population, these mechanically hyper-responsive nociceptors also had significantly greater responses to suprathreshold heat stimulation; however, heat hyper-responsiveness was found only in a subset of these nociceptors and was never detected in the absence of mechanical hyper-responsiveness. In addition, mean conduction velocities of A-fibers and C-fibers in vincristine-treated rats were significantly slowed. Mean heat and mechanical activation thresholds of C-fiber nociceptors, their distribution among subclasses, and the percentage of spontaneously active neurons in vincristine-treated rats were not statistically different from controls. Vincristine does not, therefore, cause generalized impairment of C-fiber nociceptor function but rather specifically interferes with mechanisms underlying responsiveness to suprathreshold stimuli. Furthermore, vincristine-induced nociceptor hyper-responsiveness may involve alterations specifically in mechanotransduction in some nociceptors and alterations in general cellular adaptation mechanisms in others.     

Absence of peripheral neuropathy in long-term lead-exposed subjects

The safety of a blood lead concentration of 70 microgram/100 ml as a hygienic border value with regard to development of lead neuropathy was tested in 95 employees, who had been exposed occupationally to lead for more than 9 years. The blood lead concentration was slightly above the border value in nine subjects, while the erythrocyte-Zn-protoporphyrin concentration was significantly elevated in 81 subjects, indicating an abnormal accumulation of metabolically active lead. None of the group showed clinical evidence of peripheral neuropathy, and the vibratory perception thresholds as well as motor conduction data from the median, radial, and common peroneal nerves were normal, as compared with an age-matched control group of 21 non-exposed normal subjects. The amplitude ratio between proximally and distally evoked muscle action potentials was normal in all lead-exposed subjects. These findings suggest that lead-exposed subjects are well protected against peripheral lead neuropathy, when blood lead levels are kept below the hygienic border value.     

Reliability of clinical balance outcome measures in the elderly

BACKGROUND AND PURPOSE: Simple, practical and reliable clinical balance outcome measures are needed to assess baseline status and response to treatment in older people. The reliability of the clinical measures used in this testing protocol had not been determined for this population. This study assessed the inter-rater reliability of three commonly used clinical measures of balance: one leg standing, tandem gait and functional reach. METHOD: Two samples of older people were used: (1) non-disabled and (2) disabled community dwellers. All testing was performed in a single session by two trained examiners according to a standardized protocol. Intra-class correlations were calculated comparing the means of each clinical balance test for Examiner 1 with Examiner 2. RESULTS: Reliability coefficients were 0.75 for one leg standing, 0.73 for functional reach, and 0.31 for tandem gait for the non-disabled sample. Reliability coefficients were 0.85 for one leg standing, 0.79 for functional reach, and 0.62 for tandem gait for the disabled sample. CONCLUSIONS: These findings for the one leg standing and functional reach testing protocols in disabled and non-disabled older people can be used as outcome measures. Further study should be directed towards improving the reliability of the tandem gait test for use with older people.     

Guidelines for the diagnosis and outpatient management of diabetic peripheral neuropathy

AIMS: This series analyses the results of conservative surgery for large lower pole breast cancers by lumpectomy associated with a bilateral remodelling mammoplasty, in order to avoid residual deformities. METHODS: This retrospective study concerns 50 patients with a lower pole breast cancer treated between 1986 and 1996 by lumpectomy, mammoplasty and irradiation. The contralateral breast was immediately made symmetrical in all cases. The mean tumour size was 32.5 mm. RESULTS: The mean weight of the lumpectomy specimen was 270 g. Resection margins were tumour-free in 90% of cases. The main complication observed was delayed healing, thus postponing post-operative treatment in 6.5% of cases. The median follow-up was 48 months. The 5-year actuarial ipsilateral local recurrence rate was 7% and 5-year actuarial metastasis-free and overall survival rates were 81 and 97%, respectively. Cosmesis was satisfactory in 85% of patients. We observed better results when radiotherapy was performed after rather than prior to surgery (92 vs. 67%: NS). CONCLUSIONS: Performing a bilateral mammoplasty at the time of initial surgery for large breast cancers situated in the lower quadrants of the breast facilitates larger lumpectomies with good cosmetic results.     

Dextromethorphan potentiates the effect of morphine in rats with peripheral neuropathy

Neuropathic pain responds poorly to opioids. We now report that combination of systemic morphine (2 mg/kg) and dextromethorphan (45 mg/kg), a clinically available antitussive with NMDA-antagonist properties, markedly alleviated mechanical and cold allodynia-like behavior in a rat model of peripheral mononeuropathy. Neither drug produced a significant effect on its own at these doses. The anti-allodynic effect of morphine plus dextromethorphan was reversed by naloxone. The present results suggest that a combination of NMDA-antagonist and opiates might be effective in treating neuropathic pain. Furthermore, the effect of this drug combination is mainly mediated via opioid receptors.     

Peripheral neuropathy: an often-overlooked cause of falls in the elderly

Peripheral neuropathy is common in the elderly and results in impairments in distal proprioception and strength that hinder balance and predispose them to falls. The loss of heel reflexes, decreased vibratory sense that improves proximally, impaired position sense at the great toe, and inability to maintain unipedal stance for 10 seconds in three attempts all suggest functionally significant peripheral neuropathy. Physicians can help their patients with peripheral neuropathy to prevent falls by teaching them and their families about peripheral nerve dysfunction and its effects on balance and by advising patients to substitute vision for the lost somatosensory function, correctly use a cane, wear proper shoes and orthotics, and perform balance and upper extremity strengthening exercises.     

Cryoglobulinemic peripheral neuropathy: neurophysiologic evaluation in twenty-two patients

The aim of this study was to evaluate the frequency and degree of peripheral neuropathy in 22 consecutive patients with mixed cryoglobulinemia, whether symptom-free or with subjective neurological symptoms. Electrophysiological investigations were carried out and a biopsy of the sural nerve was performed in six patients. Peripheral neuropathy of the lower limbs was demonstrated, which was mostly sensory and light or moderate in 86% of cases (19 patients). F-Wave and H-reflex recordings were found to be the most reliable methods; in 77% of cases, they were abnormal (17 patients). Using somatosensory evoked potentials, we were able to exclude simultaneous central nervous system involvement in 10 patients.     

Prevalence of central autonomic neuropathy in elderly dialysis patients

BACKGROUND: Autonomic neuropathy is frequently present in dialysis patients. In addition, deterioration of autonomic function occurs with ageing. This study examines the true prevalence of autonomic neuropathy in elderly dialysis patients and questions whether the combination of age and uraemia further increases the chance of dysautonomia being present. METHODS: We compared the results of five different tests (30:15 ratio; Valsalva ratio; heart rate response to deep breathing and the blood pressure responses to sustained hand grip and standing) of parasympathetic and combined parasympathetic and sympathetic dysfunction in older haemodialysis patients (mean age 70.2 years), younger haemodialysis patients (mean age 48.1 years) and two groups of subjects with normal renal function (mean age 73.0 years and 42.5 years respectively). RESULTS: Parasympathetic dysfunction was most prevalent in older patients on dialysis (65.9% (95% confidence intervals 51.4-80.4%), compared with 33.3% (95% confidence intervals 19.0-47.5% in younger dialysis patients), and 11.8 and 0% in the old and young control groups respectively). Combined parasympathetic and sympathetic dysfunction was seen in 41.5% (95% confidence intervals 26.5-56.5%) and 11.9% (95% confidence intervals 2.1-56.5%) of the old and young dialysis patients respectively but not in any of the control subjects. No interaction was seen between age and subject type. CONCLUSIONS: We conclude that although older dialysis patients have severe impairment of cardiovascular autonomic innervation, the prevalence of dysfunction is not higher than would be expected in an ageing population with uraemia.     

Better postural balance in elderly women receiving estrogens

OBJECTIVE: The amount of bone mass and the tendency to fall are main risk factors for hip fractures and both deteriorate with advancing age. The dynamics between estrogen exposure and fracture protection seem too rapid to be explained by an effect on bone mass only. Postural balance function may be another potential mechanism for the fracture-protecting effect of estrogens. STUDY DESIGN: We examined 16 long-term users of 17 beta-estradiol implants (20 mg) (mean age 67.9 years and mean duration of treatment 17.3 years [3.3 to 34 years]) and 16 age-matched (+/-2 years) nonusers (mean age 68.3 years). Postural balance (sway velocity) was measured by static posturography before and after blindfolding and application of vibration stimulus (20 to 100 Hz) to the calf muscles to disturb the proprioception and to induce imbalance. RESULTS: Sway velocities were significantly lower in estrogen users than in nonusers (p = 0.0067) and similar to those in young premenopausal women. The differences were accentuated after provocation by blindfolding and by increasing frequencies of vibration stimulus to the calf muscle. Serum levels of estradiol and estradiol/sex hormone-binding globulin were negatively and follicle-stimulating hormone levels positively associated with sway velocity (p = 0.0194, p = 0.0036, and p = 0.0052, respectively) and independent of age (p = 0.02 to 0.005), supporting causality between estrogen exposure and postural balance. CONCLUSIONS: These data indicate that postural balance function is better preserved in long-term estrogen users than in nonusers. Effects on postural balance function may be one mechanism explaining the rapid increase in distal forearm fractures early after menopause and the rapid dynamics between estrogen exposure and hip fracture protection and may potentially reduce the fracture risk in elderly women starting estrogen replacement therapy in spite of marginal increases in bone mass.     

Food intake, energy balance and body weight control

Obesity is a multifactorial and complex affectation that is characterized by a long-term excess energy intake (EI) above energy expenditure (EE). Since fat oxidation seems to be dependent on SNS activation and also seems to remain acutely unaffected by fat intake, this macronutrient is certainly partly responsible for this situation. In addition, high-fat intake does not induce as potent satiety signals or a compensation effect on subsequent EI as do diets rich in carbohydrates or proteins. Moreover, since alcohol intake acutely inhibits fat oxidation and does not promote subsequent compensation for its energy content, it should consequently be regarded as a substrate which can induce a positive energy balance under free-living conditions. Thus, in a weight reducing context, each energy substrate should be manipulated while taking into account its specific characteristics. Obesity has also often been associated to a decreased sympathetic nervous system (SNS) activity, hence sympathomimetic agents have been proposed as a possible way to partially correct this situation. Two of these agents are the widely consumed caffeine (CAF) and the pungent principle of hot red pepper, capsaicin (CAP), which acutely increase EE and reduce EI under some circumstances. Furthermore, other factors like dietary fibers, that have been shown to increase satiety and fullness, and reduce EI in some cases, should also be considered.     

Evidence of peripheral axonal neuropathy in primary restless legs syndrome

The aim of this study was to assess the risk and prognostic factors of gut perforation after orthotopic liver transplantation in children with biliary, atresia using univariate and stepwise regression analysis. Among 51 pediatric recipients who underwent transplantation because of biliary atresia after failure of portoenterostomy, 10 patients (20%) had 19 episodes of gut perforations after 14 transplantations. The median delay between transplantation and perforation was 13 days. These perforations were treated either by suture (n = 21) or ostomy (n = 11). The study of preoperative and perioperative variables showed that children with gut perforation were in surgery for a significantly longer period of time including a longer period of receiving hepatectomy and undergoing portal venous clamp. These children also needed large amounts of blood transfused during hepatectomy. After transplantation there was no difference regarding total steroid doses and early occurrence of cytomegalovirus disease between the two groups. Stepwise regression analysis identified three factors associated with the occurrence of gut perforation: duration of transplant operation, posttransplant intra-abdominal bleeding requiring reoperation, and early portal vein thrombosis. During the postoperative course, severe fungal infections were significantly more frequent in the gut perforation group. The 3-year patient survival rate was 70% in the group with gut perforation and was not different from the group without perforation (80%). This study shows that children with previous portoenterostomy carry a high risk of developing gut perforation after liver transplantation. This is especially true for those patients with the most difficult hepatectomies, which are responsible for the iatrogenic injury of the bowel. Other risk factors pointed out in this study were splanchnic congestion in case of prolonged portal venous clamp time or early portal vein thrombosis and repeated trauma of the bowel caused by reoperations. On the other hand, other well known risk factors, such as steroid therapy and viral diseases, were not involved in the occurrence of gut perforations in this study. Besides emergent surgical treatment, this type of complication requires aggressive therapy against fungal infections.     

Acute peripheral neuropathy in adults. Guillain-Barré syndrome and related disorders

Wound healing in many tissue types is essentially the same as that which occurs in skin. The repair processes that occur in bone, tendon, the alimentary tract, skin grafts, and bone grafts are substantially different from cutaneous wound repair. Because surgeons frequently encounter these tissues, it is essential to understand how they heal.