Marked increase in severe neurological disorders after nitrous oxide abuse: a retrospective study in the Greater Paris area.

BACKGROUND: Recreational nitrous oxide (N2O) use has become more widespread worldwide, leading to an increase in myelopathies and peripheral neuropathies. The aim of this study was to describe clinical and socioeconomical characteristics of severe N2O-induced (NI) neurological disorders (NI-NDs), to determine its incidence in the Greater Paris area and to compare it with that of similar inflammatory neurological disorders. METHODS: We performed a retrospective multicentric cohort study of all adult patients with severe NI-NDs in the neurology and general internal medicine departments of the Greater Paris area from 2018 to 2021. The incidence was compared with that of non-NI-myelitis and Guillain-Barré syndrome (GBS) using a sample of 91,000 hospitalized patients sourced from health insurance data. RESULTS: Among 181 patients, 25% had myelopathy, 37% had peripheral neuropathy and 38% had mixed disease. Most were aged between 20 and 25 years, lived in socially disadvantaged urban areas, and exhibited high rates of unemployment (37%). The incidence of NI-NDs increased during 2020 and reached a peak mid-2021. The 2021 incidence in 20-25-year-olds was 6.15 [4.72; 8.24] per 100,000 persons for NI-myelopathy and 7.48 [5.59; 9.37] for NI-peripheral neuropathy. This was significantly higher than for non-NI-myelitis (0.35 [0.02; 2.00]) and GBS (2.47 [0.64; 4.30]). The incidence of NI-NDs was two to three times higher in the most socially disadvantaged areas. CONCLUSION: The recent increase in recreational N2O use has led to a rise in the incidence of severe NI-NDs, particularly in young adults with low socioeconomic status for whom NI-NDs strongly outweigh similar neurological disorders.

The use of low-glycaemic index diets in diabetes control.

The aim of diabetes management is to normalise blood glucose levels since improved blood glucose control is associated with fewer complications. Food affects blood glucose levels; however, there is no universal approach to the optimal diabetic diet and there is controversy about the usefulness of the low-glycaemic index (GI) diet. To assess the effects of low-GI diets on glycaemic control in diabetes, we conducted electronic searches of the Cochrane Library, MEDLINE, EMBASE and CINAHL. We assessed randomised controlled trials (RCT) with interventions >4 weeks that compared a low-GI diet with a higher-GI diet for type 1 or type 2 diabetes. Twelve RCT (n 612) were identified. There was a significant decrease in glycated Hb (HbA1c) with low-GI diet than with the control diet, indicating improved glycaemic control (seven trials, n 457, weighted mean difference (WMD) - 0.4 % HbA1c, 95% CI - 0.7, - 0.20, P = 0.001). In four studies reporting the results for glycaemic control as fructosamine, three of which were 6 weeks or less in duration, pooled data showed a decrease in fructosamine (WMD - 0.23 mmol/l, 95% CI - 0.47, 0.00, P = 0.05), n 141, with low-GI diet than with high-GI diet. Glycosylated albumin levels decreased significantly with low-GI diet, but not with high-GI diet, in one study that reported this outcome. Lowering the GI of the diet may contribute to improved glycaemic control in diabetes.

Commentary on "Prognostic effect of carcinoma in situ in muscle-invasive urothelial carcinoma patients receiving neoadjuvant chemotherapy."

BACKGROUND: Carcinoma in situ (CIS) is a poor prognostic finding in urothelial carcinoma. However, its significance in muscle-invasive urothelial carcinoma (MIUC) treated with neoadjuvant chemotherapy (NAC) is uncertain. We assessed the effect of CIS found in pretreatment transurethral resection of bladder tumor (TURBT) biopsies on the pathologic and clinical outcomes. MATERIALS AND METHODS: Subjects with MIUC treated with NAC before cystectomy were identified. The pathologic complete response (pCR) rates stratified by TURBT CIS status were compared. The secondary analyses included tumor response, progression-free survival (PFS), overall survival (OS), and an exploratory post hoc analysis of patients with pathologic CIS only (pTisN0) at cystectomy. RESULTS: A total of 137 patients with MIUC were identified. TURBT CIS was noted in 30.7% of the patients. The absence of TURBT CIS was associated with a significantly increased pCR rate (23.2% vs. 9.5%; odds ratio = 4.08; 95% CI: 1.19-13.98; P = 0.025). Stage pTisN0 disease was observed in 19.0% of the TURBT CIS patients. TURBT CIS status did not significantly affect the PFS or OS outcomes. Post hoc analysis of the pTisN0 patients revealed prolonged median PFS (104.5 vs. 139.9 months; P = 0.055) and OS (104.5 vs. 152.3 months; P = 0.091) outcomes similar to those for the pCR patients. CONCLUSION: The absence of CIS on pretreatment TURBT in patients with MIUC undergoing NAC was associated with increased pCR rates, with no observed differences in PFS or OS. Isolated CIS at cystectomy was frequently observed, with lengthy PFS and OS durations similar to those for pCR patients. Further studies aimed at understanding the biology and clinical effect of CIS in MIUC are warranted.

Low glycaemic index or low glycaemic load diets for overweight and obesity.

BACKGROUND: Obesity is increasingly prevalent, yet the nutritional management remains contentious. It has been suggested that low glycaemic index or load diets may stimulate greater weight loss than higher glycaemic index or load diets or other weight reduction diets. OBJECTIVES: To assess the effects of low glycaemic index or load diets for weight loss in overweight or obese people. SEARCH STRATEGY: Trials were identified through The Cochrane Library, MEDLINE, EMBASE, CINAHL and manual searches of bibliographies. SELECTION CRITERIA: Randomised controlled trials comparing a low glycaemic index or load diet (LGI) with a higher glycaemic index or load diet or other diet (Cdiet) in overweight or obese people. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials, assessed quality and extracted data, including any information provided on adverse effects. MAIN RESULTS: We identified six eligible randomised controlled trials (total of 202 participants). Interventions ranged from five weeks to six months duration with up to six months follow-up after the intervention ceased. The decrease in body mass (WMD -1.1 kg, 95% confidence interval (CI) -2.0 to -0.2, P < 0.05) (n = 163), total fat mass (WMD -1.1 kg, 95% CI -1.9 to -0.4, P < 0.05) (n =147) and body mass index (WMD -1.3, 95% CI -2.0 to -0.5, P < 0.05) (n = 48) was significantly greater in participants receiving LGI compared to Cdiets. The decrease in total cholesterol was significantly greater with LGI compared to Cdiets (WMD -0.22 mmol/L, 95% CI -0.43 to -0.02, P < 0.05), as was the change in LDL-cholesterol (WMD -0.24 mmol/L, 95% CI -0.44 to -0.05, P < 0.05). No study reported adverse effects, mortality or quality of life data. AUTHORS' CONCLUSIONS: Overweight or obese people on LGI lost more weight and had more improvement in lipid profiles than those receiving Cdiets. Body mass, total fat mass, body mass index, total cholesterol and LDL-cholesterol all decreased significantly more in the LGI group. In studies comparing ad libitum LGI diets to conventional restricted energy low-fat diets, participants fared as well or better on th LGI diet, even though they could eat as much as desired. Lowering the glycaemic load of the diet appears to be an effective method of promoting weight loss and improving lipid profiles and can be simply incorporated into a person's lifestyle. Further research with longer term follow-up will determine whether improvement continues long-term and improves quality of life.

Exercise for type 2 diabetes mellitus.

BACKGROUND: Exercise is generally recommended for people with type 2 diabetes mellitus. However, some studies evaluate an exercise intervention including diet or behaviour modification or both, and the effects of diet and exercise are not differentiated. Some exercise studies involve low participant numbers, lacking power to show significant differences which may appear in larger trials. OBJECTIVES: To assess the effects of exercise in type 2 diabetes mellitus. SEARCH STRATEGY: Trials were identified through the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and manual searches of bibliographies. Date of last search was March 3, 2005. SELECTION CRITERIA: All randomised controlled trials comparing any type of well-documented aerobic, fitness or progressive resistance training exercise with no exercise in people with type 2 diabetes mellitus. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials, assessed trial quality and extracted data. Study authors were contacted for additional information. Any information on adverse effects was collected from the trials. MAIN RESULTS: Fourteen randomised controlled trials comparing exercise against no exercise in type 2 diabetes were identified involving 377 participants. Trials ranged from eight weeks to twelve months duration. Compared with the control, the exercise intervention significantly improved glycaemic control as indicated by a decrease in glycated haemoglobin levels of 0.6% (-0.6 % HbA(1c), 95% confidence interval (CI) -0.9 to -0.3; P < 0.05). This result is both statistically and clinically significant. There was no significant difference between groups in whole body mass, probably due to an increase in fat free mass (muscle) with exercise, as reported in one trial (6.3 kg, 95% CI 0.0 to 12.6). There was a reduction in visceral adipose tissue with exercise (-45.5 cm(2), 95% CI -63.8 to -27.3), and subcutaneous adipose tissue also decreased. No study reported adverse effects in the exercise group or diabetic complications. The exercise intervention significantly increased insulin response (131 AUC, 95% CI 20 to 242) (one trial), and decreased plasma triglycerides (-0.25 mmol/L, 95% CI -0.48 to -0.02). No significant difference was found between groups in quality of life (one trial), plasma cholesterol or blood pressure. AUTHORS' CONCLUSIONS: The meta-analysis shows that exercise significantly improves glycaemic control and reduces visceral adipose tissue and plasma triglycerides, but not plasma cholesterol, in people with type 2 diabetes, even without weight loss.

Solid-state 13C-NMR studies of the effects of sodium ions on the gramicidin A ion channel.

End-to-end helical dimers of gramicidin A form transmembrane pores in lipid bilayers, through which monovalent ions may pass. The groups within the peptide that interact with these ions have been studied by application of solid-state spectroscopic methods to a series of gramicidin A analogues synthesized with 13C in selected peptide carbonyl groups. The resonances of D-Leu10, D-Leu12 and D-Leu14 analogues were perturbed in the presence of 0.16 M sodium ions, whereas the resonances of the carbonyls of Gly2, Ala3, D-Leu4 and Val7, which are closer to the formylated N-terminal end of the peptide, were unaffected. The observed changes in chemical shift anisotropy are indicative of a change in orientation of the abovementioned leucine carbonyls.

Effect of acyl chain length on the structure and motion of gramicidin A in lipid bilayers.

The transmembrane ion transport properties of gramicidin A have previously been shown to dependent on the nature of its lipid environment. Solid-state NMR spectroscopic studies of 13C-labelled analogues of gramicidin in oriented multilayers of phosphatidylcholine have shown that variation of the lipid hydrocarbon chain length has no effect on the structure or orientation of the peptide backbone.

How many beds should a hospital department serve?

Departmental cost functions are constructed for selected hospital departments, using total number of beds in the hospital served as a proxy output measure. Calculation of maxima or minima for the resulting cost functions reveals that, on average, different departments have extremes in their cost functions of different levels of output. A relative cost index is constructed, using parameters of the departmental cost functions, and departmental costs are compared across regions. The significance of departmental differences in optimum output is discussed with regard to sharing of services and modified system design.

Elevated in vivo expression of the costimulatory molecule B7-BB1 (CD80) on antigen presenting cells from a patient with SLE.

The CD28/CTLA4-B7-family plays an important role in T-cell costimulation and is crucial for IL-2 production and tolerance induction. The costimulatory molecule B7-BB1 (CD80) is expressed on activated antigen presenting cells, but its expression on peripheral blood mononuclear cells is very low. Here we report a patient with untreated SLE whose peripheral blood antigen presenting cells expressed increased amounts of B7-BB1.

Referrals to a hospital-based child abuse committee: a comparison of the 1960s and 1990s.

OBJECTIVE: Although reports of child maltreatment have increased yearly since national data were first collected in 1976, little information is available about changes in the characteristics of children reported. Therefore, to examine changes over time in recognition and reporting in a medical setting, we compared referrals to a hospital-based child abuse committee in the late 1960s and early 1990s. DESIGN: Retrospective, cross-sectional review of medical records and logs of the hospital's child abuse committee. SETTINGS: Ambulatory, emergency, and inpatient services at Yale-New Haven Hospital. PATIENTS: Medical records were reviewed for 101 of the 165 children referred to the child abuse committee in 1968-1969 (early group) and 107 of the 843 children referred in 1990-1991 (late group). Cases of sexual abuse were excluded. RESULTS: Referrals for nonsexual abuse cases increased from 80 children per year in the early group to 181.5 per year in the late group; the late group was characterized by a larger number of newborn referrals (1% vs. 52%, p < .001). When non-newborns were compared, the two groups were similar with respect to gender and race, but the late group had fewer patients with private insurance (31% vs. 12%, p < .05). The late group also had more female-headed households (32% vs. 67%, p < .05) and more parents with a history of substance abuse (4% vs. 49%, p < .001). Excluding newborns, who were all classified as "at-risk," the types of problems were classified as abuse (41% early vs. 29% late), neglect (41% vs. 35%), and "at-risk" (16% vs. 35%). Although the types of injuries were similar: superficial injuries (20% vs. 16%), burns (9% vs. 8%), and fractures (6% vs. 4%), fewer maltreated children suffered physical injuries in the late group (71% vs. 49%, p < .05). CONCLUSIONS: A substantial change has occurred in referrals to the hospital's child abuse committee for abuse or neglect. Most referrals have become socially high-risk newborns and children or children with minimal injuries. This shift is likely due to broader definitions of maltreatment and earlier recognition of troubled families.

Evaluation of the iScreen digital screening system for amblyogenic factors.

BACKGROUND: A digital photoscreener, the iScreen screening system, is now available to detect amblyogenic factors. We carried out a prospective study to evaluate the accuracy of the device in detecting anisometropia, significant refractive error, strabismus and opacities of the ocular media. METHODS: A total of 449 consecutive patients (median age 7 years) from a private pediatric ophthalmology practice underwent screening with the iScreen photoscreener operated by a minimally trained technician. The results were compared to the masked clinical examination of a pediatric ophthalmologist. RESULTS: The iScreen device had a sensitivity of 92.4%, specificity of 89.1%, positive predictive value of 94.1% and false-negative rate of 13.8%. Of the 21 patients with a false-negative result, 12 had myopia of less than -1.50 dioptres. High hyperopia was missed in two patients, high astigmatism in one, unequal cylindrical error in one and strabismus in five. INTERPRETATION: The iScreen digital photoscreener produced accurate and timely screening for potentially amblyogenic defects in the study population.

Effects of phenobarbital treatment on 3-methylindole toxicosis in ponies.

To study the role of cytochrome P-450-dependent mixed function oxidase reactions in equine 3-methylindole (3MI) toxicosis, ponies were given 20 mg of phenobarbital/kg of body weight at 72, 60, 48, 36, and 24 hours before 100 mg of oral 3MI/kg to induce cytochrome P-450 or no treatment (controls). Maximal 3MI plasma concentration was decreased and clearance was faster in phenobarbital-treated ponies. Plasma 3MI was still detectable 12 and 36 hours after dosing in phenobarbital-treated and control ponies, respectively. Phenobarbital treatment induced a distribution phase with transition from a 1-compartment to a 2-compartment extravascular model. Bronchiolitis occurred in all ponies 72 hours after 3MI, but was more severe in those treated with phenobarbital. Appearance of a distribution phase, increased total body clearance, and more severe bronchiolitis in phenobarbital-treated ponies indicated that mixed function oxidases are involved in metabolism and conversion of 3MI to a toxic metabolite.

Pharmacokinetics of small doses of 3-methylindole given to horses.

The pharmacokinetics of 3-methylindole (3MI) given orally in 2 doses (10 mg/kg and 20 mg/kg) to horses were determined. The pharmacokinetic plasma-concentration profiles for 3MI (10- and 20-mg/kg dosages) in horses were represented by a 2-compartment open model with first-order absorption, as determined by nonlinear least-squares regression analysis. Absorption of 3MI at both dosages was rapid. Comparisons of the peak plasma concentrations, the postdistribution half lives, total clearances, and areas under the curve of the plasma-concentration profiles between the 10- and the 20-mg/kg dosages may indicate the presence of nonlinear or dose-dependent kinetics for 3MI in horses.

Comparison of single-dose and conventional trimethoprim-sulfadiazine therapy in experimental Staphylococcus intermedius cystitis in the female dog.

Cystitis was produced in 4 groups of 6 female dogs each, using salicylic acid, ethanol, and Staphylococcus intermedius. Group-I dogs served as nontreated controls. Starting 2 days after infection was induced, group-II dogs were treated with trimethoprim-sulfadiazine at a dosage of 15 mg/kg given orally 2 times a day for 21 days; groups-III and -IV dogs were treated with single oral dosages of the antibiotic at 60 mg/kg and 90 mg/kg, respectively. Group-I dogs (controls) remained infected for the 26-day duration of the study. The response to therapy seen in group-II dogs was better than the therapeutic responses in groups-III and -IV dogs (P less than 0.05). Results of the present study do not support the efficacy of single-dose therapy for this model of cystitis.

Reuse of single-use medical devices: informed consent and physician liability.

This overview addresses the controversial practice of reuse and reprocessing of single-use medical devices and the issues this practice raises for physician liability. Specifically, we describe the health risks associated with medical device reprocessing, analyze the market costs arising from the reuse and reprocessing of single-use medical devices, and discuss physician liability for failure to obtain informed consent of the patient for the use of reprocessed single-use medical devices.

Composition of the subsistence foods of the Wopkaimin people of Papua New Guinea.

Forty-four samples of food, representing 35 species of animals and plants consumed by the Wopkaimin people of highland Papua New Guinea, were analyzed for their nutrient composition, many for the first time. Moisture, protein, fat and minerals (Na, K, Mg, Ca, Fe, Zn, Cu) were assayed directly. Energy and total carbohydrate content were calculated. The animal foods were high in protein, Fe and Zn. Ca was very high (greater than 1000mg/100g) in birds, frogs and fish containing soft edible bones. Leafy vegetables were relatively high in protein, iron and calcium. The five samples of taro (Colocasia esculenta) showed wide variation in composition. The results provide further information on the nutritional value of Papua New Guinean foods.

Novel Pharmacological Interventions to Maintain Sinus Rhythm after DC Cardioversion.

Despite the availability of potentially curative interventions for atrial fibrillation, there remains an important role for conventional anti-arrhythmic therapy and anti-coagulation combined with direct current cardioversion. Unfortunately, the latter approach is disturbed by high recurrence rates of atrial fibrillation. In recent years, several adjunctive therapies have emerged which may facilitate the maintenance of sinus rhythm. These novel therapies and their potential mechanisms of action are reviewed in this article.

Heart rate deceleration after exercise predicts patients most likely to respond to cardiac resynchronisation therapy.

OBJECTIVE: This study examines the relationship between heart rate recovery following exercise and subsequent response to cardiac resynchronisation therapy (CRT). BACKGROUND: Blunted heart rate recovery is an adverse prognostic marker in heart failure and has been shown to correlate with disease severity. METHODS: 37 patients receiving biventricular pacemakers for conventional indications underwent functional assessments; cardiopulmonary exercise test, 6-min walk test and quality-of-life assessment, together with echo analyses, before and at 3 months following implant. Heart rate deceleration (HRD) gradients were calculated at 30-, 60-, 90- and 120-s intervals following cessation of the baseline exercise test and compared with subsequent markers of response to CRT. Functional response was defined as > or =20% improvement in any two of the three functional assessments, and echo response defined as > or =5% increase in ejection fraction. RESULTS: Functional responders demonstrated steeper HRD gradients than non-responders at 30, 60 and 90 s. Echo responders also demonstrated steeper HRD at 30 and 60 s from the cessation of exercise. Receiver-operating curve analysis demonstrates area under the curve of 0.87 and 0.82, respectively, for HRD30 to predict functional and echo response to CRT. A cut-off value of 3 for HRD30, equating to a 5% reduction in HR between peak exercise and 30 s into recovery, demonstrates the optimal sensitivity/specificity profile to perform this function. CONCLUSIONS: HRD following exercise correlates with functional and echocardiographic response to CRT. Application of this parameter in addition to standard criteria may provide valuable supplementary information in the evaluation of prospective CRT candidates.