Long-term neurocognitive outcomes after pediatric intensive care: exploring the role of drug exposure.

BACKGROUND: Concerns exist regarding the impact of widely used clinical drugs on brain development. This study investigates long-term neurocognitive functioning in relation to frequently used drug exposure at the Pediatric Intensive Care Unit (PICU). METHODS: This study compared children aged 6-12 years with previous PICU admission (age ≤1 year) for bronchiolitis requiring mechanical ventilation (patient group, n = 65) to a demographically comparable control group (n = 76) on a broad range of neurocognitive outcomes. The patient group was selected because bronchiolitis seldom manifests neurologically and is therefore not expected to affect neurocognitive functioning in itself. The relation between exposure to sedatives, analgesics and anesthetics and neurocognitive outcomes was assessed by regression analyses. RESULTS: The patient group had lower intelligence than the control group (p < 0.001, d = -0.59) and poorer performance in neurocognitive functions; i.e., speed and attention (p = 0.03, d = -0.41) and verbal memory (p < 0.001, d = -0.60). Exposure to sedatives, analgesics and anesthetics was not related to neurocognitive outcomes. CONCLUSIONS: Children with PICU admission for bronchiolitis requiring mechanical ventilation are at risk of adverse neurocognitive outcomes. This study found no evidence for a role of exposure to sedatives, analgesics or anesthetics. Findings underline the importance of long-term follow-up after PICU admission, even in the absence of disease with neurological manifestation. IMPACT: Animal studies have indicated that exposing the maturing brain to clinical drugs may cause neurodegeneration. Clinical studies show mixed evidence regarding the association between clinical drugs and neurocognitive outcomes. This study provides evidence for considerably lower neurocognitive functioning among children with a history of PICU admission for bronchiolitis compared to healthy peers. Bronchiolitis seldom manifests neurologically and is therefore not expected to affect neurocognitive functioning in itself. We found no evidence supporting a relation between drug exposure (i.e., sedatives, analgesics and anesthetics) and long-term neurocognitive outcomes. Findings underline the importance of structured follow-up after PICU admission.

INSULIN AUTOIMMUNE SYNDROME IN A YOUNG CAUCASIAN WOMAN.

A young Caucasian woman presents several episodes of severe fasting hypoglycemia. Fasting lab tests revealed: glycemia 28 mg/dL, insulinemia 143.3 µU/mL, insulin antibodies above 100 U/mL, leading to the diagnosis of insulin autoimmune syndrome. Due to lack of clinical improvement after 2 months, prednisone was started at 0.5 mg/kg/day, and then tapered by 5 mg every 5 days. Three weeks after discontinuing corticotherapy, the patient had no more severe fasting hypoglycemia, but occasionally postprandial mild hypoglycemia. Fasting lab tests showed: glycemia 83 mg/dL, insulinemia 58.6 µU/mL. At 5 hours during oral glucose tolerance test glycemia was 33 mg/dL, insulinemia 152.9 µU/mL.

Bone and non-contractile soft tissue changes following open kinetic chain resistance training and testosterone treatment in spinal cord injury: an exploratory study.

Twenty men with spinal cord injury (SCI) were randomized into two 16-week intervention groups receiving testosterone treatment (TT) or TT combined with resistance training (TT + RT). TT + RT appears to hold the potential to reverse or slow down bone loss following SCI if provided over a longer period. INTRODUCTION: Persons with SCI experience bone loss below the level of injury. The combined effects of resistance training and TT on bone quality following SCI remain unknown. METHODS: Men with SCI were randomized into 16-week treatments receiving TT or TT + RT. Magnetic resonance imaging (MRI) of the right lower extremity before participation and post-intervention was used to visualize the proximal, middle, and distal femoral shaft, the quadriceps tendon, and the intermuscular fascia of the quadriceps. For the TT + RT group, MRI microarchitecture techniques were utilized to elucidate trabecular changes around the knee. Individual mixed models were used to estimate effect sizes. RESULTS: Twenty participants completed the pilot trial. A small effect for yellow marrow in the distal femur was indicated as increases following TT and decreases following TT + RT were observed. Another small effect was observed as the TT + RT group displayed greater increases in intermuscular fascia length than the TT arm. Distal femur trabecular changes for the TT + RT group were generally small in effect (decreased trabecular thickness variability, spacing, and spacing variability; increased network area). Medium effects were generally observed in the proximal tibia (increased plate width, trabecular thickness, and network area; decreased trabecular spacing and spacing variability). CONCLUSIONS: This pilot suggests longer TT + RT interventions may be a viable rehabilitation technique to combat bone loss following SCI. CLINICAL TRIAL REGISTRATION: Registered with clinicaltrials.gov : NCT01652040 (07/27/2012).

Intérêt du masque laryngé en anesthésie pédiatrique: expérience d'une mission humanitaire

Introduction: L'optimisation du réveil anesthésique repose en grande partie sur la gestion des voies aériennes. Notre travail avait pour objectif d'évaluer l'impact du masque laryngé lors d'une mission ponctuelle de chirurgie pédiatrique.Patients et méthodes : Il s'agit d'une étude prospective, descriptive, observationnelle et comparative portant sur les patients de 0-16 ans ayant bénéficié d'une chirurgie sous anesthésie générale. Deux groupes ont été constitués, un groupe masque laryngé (ML) et un groupe intubation trachéale (IT). Les paramètres étudiés étaient : âge, risque anesthésique (ASA), type de chirurgie, protocole anesthésique, temps opératoire et délai de réveil anesthésique.Résultats: Trente-cinq patients ont été inclus, 12 ML et 23 IT. Les enfants de 1 à 8 ans étaient majoritaires dans les deux groupes. La classe ASA 1 constituait 83% de ML et 95,7% d'IT. Les chirurgies viscérales, urologiques et orthopédiques étaient les plus réalisées. Le recours à la curarisation a été noté uniquement chez 56,5% d'IT. La majorité des patients des deux groupes a présenté un temps opératoire de 1 et 2 heures, soit 83,3% (ML) et 60,9% (IT).Presque la moitié des patients ML (41,7%) a eu un réveil rapide en moins de 10 minutes après la fin de la chirurgie, aucun dans le groupe IT mais par contre 26,1% de patients avec un réveil plus retardé. Conclusion : Notre étude montre que le masque laryngé a contribué à atteindre l'objectif de cette mission de chirurgie pédiatrique dans laréalisation d'un grand nombre d'actes dans les temps requis

Intérêt de l'association bupivacaïne-fentanyl-morphine intrathécale pour l'analgésie post-césarienne au centre hospitalier universitaire de Libreville

Introduction. La césarienne est un acte chirurgical le plus souvent réalisé sous rachianesthésie. Le but de ce travail était d'évaluer la qualité de l'analgésie chez des parturientes ayant bénéficié d'une césarienne pratiquée sous rachianesthésie associant bupivacaïne, fentanyl et morphine. Patientes et méthodes. Il s'agit d'une étude prospective, descriptive, d'une durée de deux ans (1er mai 2016 au 30 avril 2018). Les critères d'inclusion étaient: être opérée pour césarienne en chirurgie programmée ou en urgence relative, être sous rachianesthésie réalisée avec l'association bupivacaïne, fentanyl et morphine. Les variables étudiées étaient les données sociodémographiques, les paramètres hémodynamiques et respiratoires, l'apparition de la douleur, la durée des blocs sensitif et moteur, les effets indésirables et la satisfaction de la patiente. Résultats. 1645 césariennes ont été pratiquées soit 18,5% des naissances. 250 patientes ont été retenues, 160 (64%) en urgence relative et 90 (36%) en chirurgie programmée. L'âge moyen des patientes était de 27,5 ± 6,1 ans. L'extension des blocs était au niveau de T6 dans 64% des cas. Les besoins en analgésiques intraveineux étaient observés à H4, H8 et H12 pour 15 patientes (6%), 25 patientes (10%) et 80 (32%) respectivement. Les effets secondaires les plus rencontrés étaient les nausées-vomissements (12%) et le prurit (18%). Le taux de satisfaction des parturientes concernant les informations sur la technique et le protocole anesthésique était de 92%. Conclusion. Le protocole bupivacaïne-fentanyl-morphine en intrathécal procure une analgésie efficace et durable. Il devrait s'intégrer dans notre stratégie d'analgésie multimodale postopératoire

Dose-Response Effects of Tai Chi and Physical Therapy Exercise Interventions in Symptomatic Knee Osteoarthritis.

BACKGROUND: Therapeutic exercise is a currently recommended nonpharmacological treatment for knee osteoarthritis (KOA). The optimal treatment dose (frequency or duration) has not been determined. OBJECTIVE: To examine dose-response relationships, minimal effective dose, and baseline factors associated with the timing of response from 2 exercise interventions in KOA. DESIGN: Secondary analysis of a single-blind, randomized trial comparing 12-week Tai Chi and physical therapy exercise programs (Trial Registry #NCT01258985). SETTING: Urban tertiary care academic hospital PARTICIPANTS: A total of 182 participants with symptomatic KOA (mean age 61 years; BMI 32 kg/m2, 70% female; 55% white). METHODS: We defined dose as cumulative attendance-weeks of intervention, and treatment response as ≥20% and ≥50% improvement in pain and function. Using log-rank tests, we compared time-to-response between interventions, and used Cox regression to examine baseline factors associated with timing of response, including physical and psychosocial health, physical performance, outcome expectations, self-efficacy, and biomechanical factors. MAIN OUTCOME MEASURES: Weekly Western Ontario and McMasters Osteoarthritis Index (WOMAC) pain (0-500) and function (0-1700) scores. RESULTS: Both interventions had an approximately linear dose-response effect resulting in a 9- to 11-point reduction in WOMAC pain and a 32- to 41-point improvement in function per attendance-week. There was no significant difference in overall time-to-response for pain and function between treatment groups. Median time-to-response for ≥20% improvement in pain and function was 2 attendance-weeks and for ≥50% improvement was 4-5 attendance-weeks. On multivariable models, outcome expectations were independently associated with incident function response (hazard ratio = 1.47, 95% confidence interval 1.004-2.14). CONCLUSIONS: Both interventions have approximately linear dose-dependent effects on pain and function; their minimum effective doses range from 2-5 weeks; and patient perceived benefits of exercise influence the timing of response in KOA. These results may help clinicians to optimize patient-centered exercise treatments and better manage patient expectations. LEVEL OF EVIDENCE: II.

NON-INVASIVE ASSESSMENT OF LIVER STEATOSIS AND FIBROSIS USING TRANSIENT ELASTOGRAPHY AND CONTROLLED ATTENUATION PARAMETER IN TYPE 2 DIABETES PATIENTS.

CONTEXT: Nonalcoholic fatty liver disease is common in type 2 diabetes mellitus patients, being difficult to diagnose. OBJECTIVE: To find a correlation between elastographic parameters and lab results, for facilitating the diagnosis of nonalcoholic fatty liver disease. DESIGN: This is a cross sectional study, conducted at the Departments of Diabetes, Nutrition and Metabolic Diseases, and Gastroenterology and Hepatology, of the Clinical Emergency Hospital "Pius Brinzeu" Timisoara. SUBJECTS AND METHODS: We included 190 type 2 diabetes mellitus patients, collected data regarding medical history, clinical and biological features and applied the Alcohol Use Disorders Identification Test. We excluded patients with other causes of liver disease. Liver steatosis and fibrosis were evaluated through transient elastography, yielding two parameters: liver stiffness as an indicator of liver fibrosis stage, expressed in kPa, and liver steatosis stage, assessed by controlled attenuation parameter, expressed in dB/m. Data were analyzed using SPSS 15. RESULTS: The analyzed group comprised 113 patients. Elastographic measurements showed that 93.8% of the patients had steatosis (controlled attenuation parameter ≥232.5 dB/m) and 70.8% severe steatosis (controlled attenuation parameter ≥290 dB/m). Severe steatosis was more common in women (75.7%) than in men (68.1%) (p<0.0001). From the patients with steatosis, 47.2% had liver stiffness values suggestive for fibrosis and 19.8% for cirrhosis. Most patients with steatosis and severe fibrosis were obese (66.7%). Triglycerides/HDLc ratio >4 correlated with hepatic steatosis (p=0.04), being more common in patients with severe fibrosis/cirrhosis (58.3%) than in those with absent or mild fibrosis (36.2%). CONCLUSIONS: Our study found a clear correlation between type 2 diabetes mellitus and the presence of liver steatosis. It correlates with body mass index, waist circumference (in men) and triglycerides/HDLc ratio. Controlled attenuation parameter is a useful noninvasive method for detection and quantification of liver steatosis.

Evaluation of a biosimilar recombinant alpha epoetin in the management of anemia in hemodialysis patients.

BACKGROUND: The efficacy of human recombinant erythropoietins (rHuEPOs) in the treatment of anemia with different etiologies is proven. Development of biosimilar rHuEPO products with lower cost and wider availability is important for the care of anemic patients. OBJECTIVE: The aim of the present study was to determine the bioequivalence and safety of a biosimilar rHuEPO (Pastopoitin(®)) and compare it with the innovator product Eprex(®), as a standard rHuEPO. METHODS: One hundred and seven anemic patients on stable hemodialysis were recruited to this randomized double-blind comparative trial and assigned to either subcutaneous Pastopoitin (n = 50) or Eprex (n = 57). Each study group received rHuEPO at a dose of 80-120 IU/kg/week in 2-3 divided doses for a period of 3 months. Hematologic parameters including Hemoglobin, hematocrit, RBC, EBC, platelet, MCV, MCH and MCHC were checked every 2 weeks. Blood iron, ferritin, TIBC, creatinine, BUN and electrolytes (Na, K, Ca and P) were evaluated monthly over the 3 months. RESULTS: A significant increase in hemoglobin, hematocrit and RBC was observed by the end of study in both Pastopoitin and Eprex groups (p < 0.001). However, these factors were not significantly different between the groups, neither at baseline nor at the end of study (p > 0.05). Likewise, the groups were comparable regarding MCV, MCH, MCHC, iron, ferritin, TIBC, creatinine, BUN and electrolytes at baseline as well as at the end of trial. Adverse events were not serious and occurred with the same frequency in the study groups. CONCLUSION: Pastopoitin showed comparable efficacy and safety profile with Eprex in anemic patients on hemodialysis. Hence, Pastopoitin may be considered as a rHuEPO with a lower cost and wider availability compared with the innovator product Eprex.

Prevalence of mental health conditions after military blast exposure, their co-occurrence, and their relation to mild traumatic brain injury.

PRIMARY OBJECTIVES: To measure common psychiatric conditions after military deployment with blast exposure and test relationships to post-concussion syndrome (PCS) symptoms and mild traumatic brain injury (mTBI) history. RESEARCH DESIGN: Cross-sectional. METHODS AND PROCEDURES: Service members or Veterans (n = 107) within 2 years of blast exposure underwent structured interviews for mTBI, post-traumatic stress disorder (PTSD) and multiple mood and anxiety diagnoses. MAIN OUTCOMES AND RESULTS: MTBI history and active PTSD were both common, additionally 61% had at least one post-deployment mood or anxiety disorder episode. Psychiatric diagnoses had a high degree of comorbidity. Most dramatically, depression was 43-times (95% CI = 11-165) more likely if an individual had PTSD. PCS symptoms were greater in those with post-deployment PTSD or mood diagnosis. However, neither mTBI nor blast exposure history had an effect on the odds of having PTSD, mood or anxiety condition. CONCLUSIONS: These findings support that psychiatric conditions beyond PTSD are common after military combat deployment with blast exposure. They also highlight the non-specificity of post-concussion type symptoms. While some researchers have implicated mTBI history as a contributor to post-deployment mental health conditions, no clear association was found. This may partly be due to the more rigorous method of retrospective mTBI diagnosis determination.

Association of MDR1 C3435T and RFC1 G80A polymorphisms with methotrexate toxicity and response in Jordanian rheumatoid arthritis patients.

OBJECTIVES: Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug for the treatment of rheumatoid arthritis (RA). Genetic polymorphisms of reduced folate carrier (RFC1 G80A) and multi-drug resistance-1 (MDR1 C3435T) might affect MTX response and/or toxicity. The aim of this study was to find out if there is an association between those polymorphisms and MTX toxicity and/or response in Jordanian RA patients. METHOD: A genotyping approach was used to determine the studied polymorphisms in 159 RA patients. RESULTS: There was an association between RFC1 G80A and MDR1 C3435T polymorphisms with MTX toxicity. Patients with RFC1 80GG genotype were at higher risk for gastrointestinal toxicity (p = 0.036). Patients carrying at least one MDR1 3435T variant allele were at higher risk for MTX overall toxicity (p = 0.04), especially hepatotoxicity (p = 0.028). Furthermore, the distribution of RFC1 G80A polymorphism between males and females was significantly different. The variant genotype 80AA was found to be more in males than in females (60% vs. 31%) (p = 0.011). CONCLUSIONS: Our results suggest that genetic polymorphisms in methotrexate transporters affect the toxicity but not the response of MTX treatment. Further studies should be performed to have more conclusive results.

Phenotyping animal models of diabetic neuropathy: a consensus statement of the diabetic neuropathy study group of the EASD (Neurodiab).

NIDDK, JDRF, and the Diabetic Neuropathy Study Group of EASD sponsored a meeting to explore the current status of animal models of diabetic peripheral neuropathy. The goal of the workshop was to develop a set of consensus criteria for the phenotyping of rodent models of diabetic neuropathy. The discussion was divided into five areas: (1) status of commonly used rodent models of diabetes, (2) nerve structure, (3) electrophysiological assessments of nerve function, (4) behavioral assessments of nerve function, and (5) the role of biomarkers in disease phenotyping. Participants discussed the current understanding of each area, gold standards (if applicable) for assessments of function, improvements of existing techniques, and utility of known and exploratory biomarkers. The research opportunities in each area were outlined, providing a possible roadmap for future studies. The meeting concluded with a discussion on the merits and limitations of a unified approach to phenotyping rodent models of diabetic neuropathy and a consensus formed on the definition of the minimum criteria required for establishing the presence of the disease. A neuropathy phenotype in rodents was defined as the presence of statistically different values between diabetic and control animals in 2 of 3 assessments (nocifensive behavior, nerve conduction velocities, or nerve structure). The participants propose that this framework would allow different research groups to compare and share data, with an emphasis on data targeted toward the therapeutic efficacy of drug interventions.

Complications of Roux-en-Y gastric bypass.

INTRODUCTION: Bariatric surgery is a method of treating morbid obesity, which has been raising more and more interest in the past years. Among all types of intervention, the most frequently used is Roux-en-Y gastric bypass, an intervention both restrictive and malabsorptive, which leads to best results in weight loss. In Romania, bariatric surgery, and especially Roux-en-Y gastric bypass, is not widely practiced due to poor addressability of patients, both due to lack of information, and to poor recommendation from general practitioners and specialists in metabolic diseases. MATERIAL AND METHOD: The study group includes 14 patients aged between 18 and 65 years old, with BMI above 40 kg m2. The study aims to present the complications that occurred in this group of patients in which we performed Roux-en-Y gastric bypass in the Surgery Department of the Emergency City Hospital Timisoara. The surgery was performed by xifo-umbilical laparotomy technique. Subsequently, patients were followed postoperatively at 1 month, and then every 3 months, up to 2 years. RESULTS: The only complications we found were wound infections (7/14 - 50%) and incisional hernias (5/14 - 35.71%). CONCLUSIONS: We only found in our group only complications related to the postoperative wound that can be minimized by modifying the suturing technique of the abdominal wall. Gastric bypass should be performed despite all incriminated risks, providing a better lifestyle to obese patients.

The elimination of the onchocerciasis vector from the island of Bioko as a result of larviciding by the WHO African Programme for Onchocerciasis Control.

The island of Bioko is part of the Republic of Equatorial Guinea and is the only island in the World to have endemic onchocerciasis. The disease is hyperendemic and shows a forest-type epidemiology with low levels of blindness and high levels of skin disease, and the whole population of 68,000 is estimated to be at risk. Control of onchocerciasis began in 1990 using ivermectin and this yielded significant clinical benefits but transmission was not interrupted. Feasibility and preparatory studies carried out between 1995 and 2002 confirmed the probable isolation of the vector on the island, the high vectorial efficiency of the Bioko form of Simulium yahense, the seasonality of river flow, blackfly breeding and biting densities, and the distribution of the vector breeding sites. It was proposed that larviciding should be carried out from January to April, when most of the island's rivers were dry or too low to support Simulium damnosum s.l., and that most rivers would not need to be treated above 500 m altitude because they were too small to support the breeding of S. damnosum s.l. Larviciding (with temephos) would need to be carried out by helicopter (because of problems of access by land), supplemented by ground-based delivery. Insecticide susceptibility trials showed that the Bioko form was highly susceptible to temephos, and insecticide carry was tested in the rivers by assessing the length of river in which S. damnosum s.l. larvae were killed below a temephos dosing point. Regular fly catching points were established in 1999 to provide pre-control biting densities, and to act as monitoring points for control efforts. An environmental impact assessment concluded that the proposed control programme could be expected to do little damage, and a large-scale larviciding trial using ground-based applications of temephos (Abate 20EC) throughout the northern (accessible) part of the island was carried out for five weeks from 12 February 2001. Following this, a first attempt to eliminate the vectors was conducted using helicopter and ground-based applications of temephos from February to May 2003, but this was not successful because some vector populations persisted and subsequently spread throughout the island. A second attempt from January to May 2005 aimed to treat all flowing watercourses and greatly increased the number of treatment points. This led to the successful elimination of the vector. The last biting S. damnosum s.l. was caught in March 2005 and none have been found since then for more than 3 years.

Degeneration of the Golgi and neuronal loss in dorsal root ganglia in diabetic BioBreeding/Worcester rats.

AIMS/HYPOTHESIS: The aim of this study was to evaluate the nature and extent of neuronal loss in dorsal root ganglia (DRG) in diabetic polyneuropathy. MATERIALS AND METHODS: We examined 10-month diabetic BioBreeding/Worcester (BB/Wor) rats with respect to DRG ultrastructure and morphometry, sural nerve morphometry, pro- and anti-apoptotic proteins, the expression of neurotrophic factors and their receptors, and sensory nerve functions. RESULTS: In diabetic rats, DRG neurons decreased to 73% of normal, owing to loss of substance P and calcitonin gene-related peptide-positive neurons. Levels of pro-apoptotic active caspase-3, Bax and low-affinity nerve growth factor (NGF) were increased in DRG. The concentration of anti-apoptotic heat shock protein (HSP) 70 in DRG was decreased, whereas concentrations of Bcl-xl and HSP27 were unaltered. Levels of poly(ADP-ribose) polymerase (PARP) and cleaved PARP were unaltered. Levels of NGF in sciatic nerve and concentrations of the high-affinity NGF receptor, insulin receptor and IGF-I receptor in DRG were significantly decreased. Sensory nerve conduction velocity decreased to 78% of normal. Hyperalgesia increased up to 6 months. Myelinated and unmyelinated fibre numbers of the sural nerve were significantly decreased in diabetic rats. DRG examinations revealed no evidence of apoptosis, mitochondrial changes or abnormalities of the endoplasmic reticulum. Instead, neurons demonstrated progressive vacuolar degenerative changes of the Golgi apparatus, with fragmentation and formation of large cytoplasmic vacuoles. These data show that sustained apoptotic stress is present in DRG of chronically diabetic BB/Wor rats, but fails to proceed to apoptotic cell death. CONCLUSIONS/INTERPRETATION: Progressive DRG neuronal loss, particularly of small neurons, occurs in the type 1 diabetic BB/Wor rat. This is associated with neurotrophic withdrawal and progressive degeneration of the Golgi apparatus.

Reduction in the prevalence and intensity of infection in Onchocerca volvulus microfilariae according to ethnicity and community after 8 years of ivermectin treatment on the island of Bioko, Equatorial Guinea.

Bioko is the only island known in the world with endemic onchocerciasis. The island's rural communities consist of villages and cocoa plantations inhabited by Bubi and Fang ethnic groups. The aim of this study was to evaluate the impact of 8 years of vertical ivermectin distribution on the prevalence and intensity of Onchocerca volvulus infection in the rural population by means of pre- (1989) and post-long term treatment (1998) epidemiological surveys. In both surveys, the entire population of 12 randomly selected communities (1723 and 1082 individuals) was examined. The mean ivermectin therapeutic coverage for the 8 years was 53.2%. Iliac crest skin snips were used for differential diagnosis between O. volvulus and Mansonella streptocerca. The crude O. volvulus infection prevalence before ivermectin intervention was 74.5% (1284/1723); after the intervention it was 38.4% (415/1082). The Community Microfilarial Load (CMFL) before and after ivermectin intervention was 28.29 microfilariae/snip vs. 2.32 microfilariae/snip. The reduction in prevalence and CMFL after eight annual rounds of ivermectin treatment corroborates the drug microfilaricidal activity and good tolerability. In the pre-treatment survey, the prevalence was higher in the Bubi group (77.1%, 1126/1461); post-treatment it was higher among the Fang (51.1%, 92/180). The reduction in prevalence and intensity of O. volvulus infection differed between ethnic groups and communities.

The preventive and therapeutic effects of GCPII (NAALADase) inhibition on painful and sensory diabetic neuropathy.

Excitotoxic glutamate release occurs in several neurological disorders. One source is derived from the hydrolysis of the neuropeptide N-acetyl aspartyl glutamate (NAAG) by glutamate carboxypeptidase II (GCPII, also known as NAALADase). Drugs that attenuate glutamate transmission have been shown to relieve neuropathic pain, however side effects have limited their clinical use. It appears that GCPII is exclusively recruited to provide a glutamate source in hyperglutamatergic, excitotoxic conditions and therefore would be devoid of such side effects. Here we report on the therapeutic effects of an orally bio-available GCP II inhibitor on established painful and sensory neuropathy in the spontaneously diabetic BB/Wor rat. It significantly improved hyperalgesia, nerve conduction velocity and underlying myelinated fiber atrophy. The data suggest that GCP II inhibition may provide a meaningful and effective approach to the treatment of painful diabetic neuropathy.

[Immunoregulatory cytokines and chronization of type C hepatitis: matching of clinical and immunological manifestations].

The study demonstrates significant changes of cytokine-producing ability of mononuclear blood leucocytes in type 'hepatitis, correlating with the degree of hepatic lesion. The results showed that various morphologic types of chronic virus type C hepatitis were associated with disbalance in production of pro- and antiinflammatory cytokines, i.e. decrease of tumor necrosis factor (TNF)-alpha concentration and a significant rise of interleukin (IL)-4 and IL-10 concentations, which were the most prominent in cases of severe hepatic fibrosis and high histologic activity of hepatitis. The study established a direct correlation between increase of the ability of mononuclear blood leucocytes to synthesize IL-4, and the progress of the pathologic process.

New insights into the metabolic and molecular basis for diabetic neuropathy.

Diabetic polyneuropathy is the most common complication of diabetes mellitus. Several interactive pathogenetic mechanisms have been identified mainly in streptozotocin-induced diabetes in rats and have been ascribed to hyperglycemia. Over the last number of years it is becoming increasingly clear that diabetic neuropathy differs in type 1 and type 2 diabetes in humans and in murine models that more accurately mimic the human disorders. Beside hyperglycemia, attention is increasingly being paid to the pathogenetic roles of insulin and C-peptide deficiencies, particularly in type 1 diabetic neuropathy. There is now evidence to suggest that insulin and C-peptide deficiencies are mainly responsible for perturbations of neurotrophic factors and contribute to oxidative stress in diabetic nerve. This may also be true for apoptotic phenomena afflicting both the peripheral and central nervous systems in diabetes. The new data have lead to re-evaluations of pathogenetic components in this complex disorder, and their further exploration is likely to form a more refined basis for future therapeutic and preventive measures.