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An evaluation of the nitric oxide/cGMP/cGMP-dependent protein kinase cascade in the induction of cerebellar long-term depression in culture.

Cerebellar long-term depression (LTD) is a model system of information storage in which a persistent attenuation of the parallel fiber-Purkinje neuron (PN) synapse is induced by conjunctive stimulation of parallel fiber and climbing fiber inputs at low frequency. As some studies have suggested that release of the gaseous second messenger, nitric oxide (NO), in the molecular layer and the consequent activation of soluble guanylate cyclase and cGMP-dependent protein kinase (PKG) in the PN, is necessary for LTD induction, we have further examined this hypothesis using a cell culture protocol. In cerebellar cultures made from transgenic mice in which the gene for neuronal nitric oxide synthase (nNOS) has been rendered null, LTD induced by glutamate/depolarization conjunctive stimulation was indistinguishable from that in cultures from wild-type mice in terms of amplitude, rate of onset, and duration. Bath application of cGMP analogs produced a large (80%), transient attenuation of glutamate-gated inward currents. However, application of an activator of soluble guanylate cyclase or an inhibitor of type V cGMP-phosphodiesterase did not mimic the effect of cGMP analogs, and inclusion of cGMP analogs in the patch pipette did not give rise to a slowly developing attenuation, suggesting that these compounds exert their effects at the cell surface. Free Ca was measured in the distal dendritic arbor of single PNs by fura-2 microfluorimetry.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate Ribose↗

Transgenic mice expressing the human C99 terminal fragment of betaAPP: effects on cytochrome oxidase activity in skeletal muscle and brain.

In order to furnish a combined model of relevance to human inclusion-body myopathy and Alzheimer's disease, transgenic mice expressing human betaAPP-C99 in skeletal muscle and brain under the control of the cytomegalovirus/beta-actin promoter were produced (Tg13592). These transgenic mice develop Abeta deposits in muscles but not in brain. Cell metabolic activity was analyzed in brain regions and muscle by cytochrome oxidase (CO) histochemistry, the terminal enzyme of the electron transport chain. By comparison to age-matched controls of the C57BL/6 strain, CO activity was selectively increased in dark skeletal muscle fibers of Tg13592 mice. In addition, only increases in CO activity were obtained in those brain regions where a significant difference appeared. The CO activity of Tg13592 mice was elevated in several thalamic nuclei, including laterodorsal, ventromedial, and midline as well as submedial, intralaminar, and reticular. In contrast, the groups did not differ in most cortical regions, except for prefrontal, secondary motor, and auditory cortices, and in most brainstem regions, except for cerebellar (fastigial and interpositus) nuclei and related areas (red and lateral vestibular nuclei). No variation in cell density and surface area appeared in conjunction with these enzymatic alterations. The overproduction of betaAPP-C99 fragments in brain without (amyloidosis did not appear to affect the metabolic activity of structures particularly vulnerable in Alzheimer's disease.

Alzheimer Disease↗

Orthotic devices for treating patellofemoral pain syndrome.

BACKGROUND: Patellofemoral pain syndrome is a frequently reported condition in active adults. A wide variety of conservative treatment strategies have been described. As yet, no optimal strategy has been identified. Application of orthotic devices e.g. knee braces, knee straps, forms of taping of the knee, active training devices, knee sleeves and in-shoe orthotics to support the foot have been advocated to treat this condition. OBJECTIVES: To assess the effectiveness of foot and knee orthotics for treatment of patellofemoral pain syndrome. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group specialised register (December 2001), the Cochrane Controlled Trials register (Issue 2, 2000), MEDLINE (January 1966 to March 2000; EMBASE (January 1988 to March 2000); CINAHL (January 1982 to March 2000) and PEDro (up to March 2000). Relevant orthotic companies were contacted. SELECTION CRITERIA: All randomised and quasi-randomised trials comparing the effectiveness of knee or foot orthotics for treatment of patellofemoral pain syndrome were selected. Trials describing the use of orthotic devices in conjunction with operative treatment were excluded. DATA COLLECTION AND ANALYSIS: Three reviewers independently assessed methodological quality of the identified trials by use of a modified version of the Cochrane Musculoskeletal Injuries Group assessment tool, consisting 11 items. Two reviewers extracted data without blinding. Trialists were contacted to obtain missing data. MAIN RESULTS: Five trials involving 362 participants were included in this review. Five other trials await possible inclusion if further information can be obtained and one awaits further assessment. Due to clinical heterogeneity, we refrained from statistical pooling and conducted analysis by grading the strength of scientific evidence. The level of obtained research-based evidence was graded as limited as all trials were of low methodological quality. This limited research-based evidence showed the Protonics orthosis at six week follow-up was significantly more effective for decrease in pain (weighted mean difference (WMD) between groups 3.2; 95% confidence interval (CI) 2.8 to 3.6), functional improvement on the Kujala score (WMD 45.6; 95% CI 43.4 to 47.7) and change in patellofemoral congruence angle (WMD 17.2; 95% CI 14.1 to 20.3) when compared to no treatment. A comprehensive programme including tape application was significantly superior to a monitored exercise programme without tape application for decrease in worst pain (WMD 1.6; 95% CI 0.4 to 2.8) and usual pain (WMD 1.2; 95% CI 0.2 to 2.1), and clinical change and functional improvement questionnaire scores (WMD 10, 95% CI 2.07 to 17.93) at four weeks follow-up. The trials reported statistically significant differences in patient satisfaction after applied therapy (WMD 3.3; 95% CI 0.5 to 6.1) in favour of the McConnell regimen compared with the Coumans bandage at six weeks follow-up. REVIEWER'S CONCLUSIONS: The evidence from randomised controlled trials is currently too limited to draw definitive conclusions about the use of knee and foot orthotics for the treatment of patellofemoral pain. Future high quality trials in this field are warranted.

Arthralgia↗

Use of scintillometric quantitation of unscheduled DNA synthesis in isolated rat hepatocytes for the screening of genotoxic agents.

The induction of unscheduled DNA synthesis has been considered as a suitable endpoint for the screening of genotoxic agents. Experimentally, unscheduled DNA synthesis is most frequently measured by autoradiography. The purpose of this report was to examine the usefulness of the liquid scintillation counting technique in measuring unscheduled DNA synthesis response in isolated rat hepatocytes. The various liquid scintillation counting-based unscheduled DNA synthesis assay procedures were examined according to the following groupings: (1) procedures based on the acid precipitation of cellular macromolecules, (2) procedures based on isopycnic gradient centrifugation of solubilized cells, (3) procedures based on nuclei isolation in conjunction with other DNA purification methods, and (4) procedures based on the selective retention of hepatocellular DNA. Limited cases in which test chemicals gave positive unscheduled DNA synthesis response in liquid scintillation counting-based assays and negative unscheduled DNA synthesis response in autoradiography-based assays are presented. It is concluded that liquid scintillation counting-based unscheduled DNA synthesis assays represent an appropriate system for inclusion in carcinogenicity and mutagenicity testing programs.

Animals↗

Refractive and visual outcome of hyperopic cataract cases operated on before and after implementation of the Holladay II formula.

OBJECTIVE: The primary objective was to evaluate the refractive and visual outcomes in a series of hyperopic cataract cases in which the Holladay II intraocular lens (IOL) power formula was used in conjunction with added eye measurements (measured anterior chamber depth [ACD], lens thickness, and corneal diameter) to improve predictability of refractive outcome. In addition, the impact of use of a double ("piggyback") IOL on refractive outcome was evaluated. DESIGN: Prospective, nonrandomized comparative clinical trial. PARTICIPANTS: A total of 136 consecutive hyperopic primary cataract-IOL cases operated on at in an outpatient eye surgery center were evaluated. The main inclusion criterion was the requirement of at least 30 D of emmetropia power. INTERVENTION: Implantation of a total implanted power calculated using a newly developed (Holladay II) formula, which uses additional eye measurements (measured ACD, lens thickness, corneal diameter) in addition to the axial length and keratometry normally used, was performed. In the first series, IOL powers were chosen using the Lloyd-Gills formula with modifiers; in the second series, powers were chosen using the Holladay II formula option in the Holladay IOL Consultant software. Selection criteria for both series were the same (requiring at least 30 diopters [D] of power for emmetropia). Keratometry and axial length measurements (by immersion) were taken using the same instrumentation and methodology in both series. Predicted postoperative refraction based on the IOL implanted and the method of power calculation used were computed for each case in both groups and compared to the actual achieved refraction. MAIN OUTCOMES MEASUREMENTS: Main clinical outcome parameters evaluated were the postoperative spherical equivalent (compared with the predicted spherical equivalent) and the best-corrected vision. These outcome parameters were evaluated within each surgical series, in the total group of cases (regardless of power calculation method). Further stratification according to the use of single or double implants also was done. RESULTS: In the group using an older formula system, mean preoperative spherical equivalent of 4.79 D was reduced to -0.67 D. Similarly, in the Holladay II group, the preoperative mean of 5.60 D was reduced to -0.58 D. However, there were fewer large deviations between predicted and achieved spherical equivalent in the Holladay II group as indicated by a smaller standard deviation of the absolute deviation (0.47 vs. 0.59), and the range of postoperative refractions was smaller with fewer large overcorrections or undercorrections. However, almost 90% of both groups were within a diopter of the predicted refraction. Visual results were comparable in the two groups. CONCLUSION: Both IOL calculation systems showed good predictability in these extremely short eyes. The Holladay II formula was simpler because it is incorporated into a user-friendly software package (Holladay IOL Consultant) and required only the input of IOL constants and preoperative measurements with no "fudge factor" modifiers. Results within the series using this formula had a tendency toward a smaller standard deviation with fewer outliers.

Cataract Extraction↗

Presence of vascular anomalies with congenital hemihypertrophy and Wilms tumor: an evidence-based evaluation.

Congenital hemihypertrophy is an uncommon condition of unknown etiology characterized by unilateral overgrowth of part or all of one side of the body. Hemihypertrophy is known to be associated with certain childhood tumors, most notably Wilms tumor (or nephroblastoma), and for this reason infants with hemihypertrophy are often followed with serial abdominal ultrasounds. Klippel-Trénaunay syndrome (KTS) is the triad of port-wine stain, venous varicosities, and soft tissue and/or bony hypertrophy. Children with KTS typically have localized rather than generalized hemihypertrophy, but occasionally the hypertrophy is more extensive than the vascular anomaly itself. Information is lacking about whether hemihypertrophy in this setting can also be a risk factor for Wilms tumor. We systematically reviewed the medical literature to determine whether well-documented cases of Wilms tumor in the setting of both hemihypertrophy and vascular anomalies have been described, and if found, whether the association was sufficiently frequent that routine screening for Wilms tumor in this setting should be recommended. A review of case reports and case series in the pediatric population was undertaken using specific inclusion and exclusion criteria. We found 4 of 58 subjects with hemihypertrophy and Wilms tumor had a reported vascular anomaly, but in only one case was a clear-cut diagnosis of KTS confirmed. The relationship of the other three vascular anomalies reported was of uncertain significance. In conclusion, our review suggests that the risk of Wilms tumor in the setting of localized soft-tissue hypertrophy in conjunction with a vascular malformation is quite low. More extensive hemihypertrophy extending to body sites remote from the vascular malformation itself could have a higher risk of Wilms tumor, although the magnitude of this risk is uncertain. Our findings suggest that routine serial abdominal ultrasounds in patients with vascular malformations in association with localized soft-tissue hypertrophy are unwarranted.

Abnormalities, Multiple↗

Synthesis and conformational analysis by 1H NMR and restrained molecular dynamics simulations of the cyclic decapeptide [Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly].

The design of enzyme mimics with therapeutic and industrial applications has interested both experimental and computational chemists for several decades. Recent advances in the computational methodology of restrained molecular dynamics, used in conjunction with data obtained from two-dimensional 1H NMR spectroscopy, make it a promising method to study peptide and protein structure and function. Several issues, however, need to be addressed in order to assess the validity of this method for its explanatory and predictive value. Among the issues addressed in this study are: the accuracy and generizability of the GROMOS peptide molecular mechanics force field; the effect of inclusion of solvent on the simulations; and the effect of different types of restraining algorithms on the computational results. The decapeptide Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly, which corresponds to the sequence of ACTH1-10, has been synthesized, cyclized, and studied by two-dimensional 1H NMR spectroscopy. Restrained molecular dynamics (RMD) and time-averaged restrained molecular dynamics (TARMD) simulations were carried out on four different distance-geometry starting structures in order to determine and contrast the behavior of cyclic ACTH1-10 in vacuum and in solution. For the RMD simulations, the structures did not fit the NOE data well, even at high values of the restraining potential. The TARMD simulation method, however, was able to give structures that fit the NOE data at high values of the restraining potential. In both cases, inclusion of explicit solvent molecules in the simulation had little effect on the quality of the fit, although it was found to dampen the motion of the cyclic peptide. For both simulation techniques, the number and size of the NOE violations increased as the restraining potential approached zero. This is due, presumably, to inadequacies in the force field. Additional TARMD vacuum-phase simulations, run with a larger memory length or with a larger sampling size (16 additional distance-geometry structures), yielded no significantly different results. The computed data were then analyzed to help explain the sparse NOE data and poor chymotryptic activity of the cyclic peptide. Cyclic ACTH1-10, which contains the functional moieties of the catalytic triad of chymotrypsin, was evaluated as a potential mimic of chymotrypsin by measurement of the rate of hydrolysis of esters of L- and D-phenylalanine. The poor rate of hydrolysis is attributed to the flexibility of the decapeptide, the motion of the side chains, which result in the absence of long-range NOEs, the small size of the macrocycle relative to that of the substrate, and the inappropriate orientation of the Gly, His, and Ser residues. The results demonstrate the utility of this method in computer-aided molecular design of cyclic peptides and suggest structural modifications for future work based on a larger and more rigid peptide framework.

Adrenocorticotropic Hormone↗

Effect of food enzymes on AME and composition of digesta from broiler chickens fed on diets containing non-starch polysaccharides isolated from lupin kernel.

1. The effects of lupin non-starch polysaccharides (NSPs) on apparent metabolisable energy (AME) and composition of digesta from broiler chickens were examined in a dose-response experiment in conjunction with a single combination of 2 commercial enzyme products known from previous studies to partially depolymerise NSPs in diets containing sorghum, casein and lupin kernel. The 7-d experiment was conducted on broiler chickens (24 to 31 d of age) in metabolism cages. 2. The basal diet used in this study contained (in g/kg) sorghum (low tannin) 800, casein 134, celite 20 and vitamins and minerals 46. The inclusion rate for each enzyme product was 0.2 g/kg. Lupin kernel isolate (containing 560 g/kg total NSPs) replaced some of the sorghum and casein. The dose rates of lupin kernel isolate (50, 100 and 150 g/kg) were equivalent to dietary inclusion rates of 80, 160 and 240 g/kg, approximately, of untreated lupin kernel from Lupinus angustifolius cultivar Gungurru. 3. Inclusion of lupin kernel isolate in the diet depressed AME and bird performance, and raised ileal viscosity and excreta moisture, in a dose-dependent manner. 4. A combination of 2 proprietary enzyme products improved dietary AME by 0.3 MJ/kg dry matter. Enzymes reduced excreta moisture when inclusion of lupin kernel isolate was 50 g/kg (equivalent to lupin kernel at 80 g/kg, approximately) but not at higher inclusions. 5. Food enzymes partially depolymerised some insoluble NSPs in lupin kernel isolate, which increased ileal viscosity and soluble NSP content of digesta. 6. It was concluded that development of appropriate exogenous enzyme products could lead to lupin NSPs being used as an energy source for poultry.

Animal Feed↗

Evaluation of spleen in children with heterotaxia and congenital heart disease.

Congenital heart disease (CHD) affects 8 to 10 children out of every 1,000 live births. Of these, 2.2% have an abnormality associated with the spleen. Many previous studies have associated CHD and asplenia or polysplenia syndrome. We report a case of a 12-year-old girl with complex CHD who was noted to have Howell-Jolly bodies on her peripheral blood smear at birth, but disappeared at 2 months of age and radiographic evidence of splenic tissue with situs inversus. Unfortunately, she presented with overwhelming sepsis at 20 months of age. In this paper, we discuss multiple tests available for evaluating splenic function in children with CHD and heterotaxia. Hepatoiminodiacetic acid (HIDA) scan in conjunction with radiocolloid scan is the best available choice today to document the presence or absence of a functional spleen in children with heterotaxia and CHD.

Child↗

Diagnosis and testing in bronchiolitis: a systematic review.

BACKGROUND: The diagnosis of bronchiolitis is based on typical history and results of a physical examination. The indications for and utility of diagnostic and supportive laboratory testing (eg, chest x-ray films, complete blood cell counts, and respiratory syncytial virus testing) are unclear. OBJECTIVES: To review systematically the data on diagnostic and supportive testing in the management of bronchiolitis and to assess the utility of such testing. DESIGN: In conjunction with an expert panel, we generated admissibility criteria and derived relevant terms to search the literature published from 1980 to November 2002 in MEDLINE and the Cochrane Collaboration Database of Controlled Clinical Trials. Trained abstractors completed detailed data collection forms for each article. We summarized the data in tables after performing data integrity checks. RESULTS: Of the 797 abstracts identified, we present evidence from 82 trials that met our inclusion criteria (17 are primary articles on diagnosis of bronchiolitis and 65are reports of treatment or prevention trials). Numerous studies demonstrate that rapid respiratory syncytial virus tests have acceptable sensitivity and specificity, but no data show that respiratory syncytial virus testing affects clinical outcomes in typical cases of the disease. Seventeen studies presented chest x-ray film data. Abnormalities on chest x-ray films ranged from 20% to 96%. Insufficient data exist to show that chest x-ray films reliably distinguish between viral and bacterial disease or predict severity of disease. Ten studies included complete blood cell counts, but most did not present specific results. In one study, white blood cell counts correlated with radiologically defined disease categories of bronchiolitis. CONCLUSIONS: A large number of studies include diagnostic and supportive testing data. However, these studies do not define clear indications for such testing or the impact of testing on relevant patient outcomes. Given the high prevalence of this disease, prospective studies of the utility of such testing are needed and feasible.

Bronchiolitis↗

The effect of trachoma virus vaccine on the course of experimental trachoma infection in blind human volunteers.

The TRIC-Taiwan-1-1958 strain of elementary body virus isolated from a trachoma patient on Taiwan has been proven capable of reproducing trachoma by experimental inoculation of six human volunteers. Virus material derived from the seventh passage in embryonated hen eggs caused the clinical picture of trachoma in every inoculation, even at the dilution of 10(-4) of infected yolk sacs (approximately 1 EID(50)). There was a similar clinical picture with each inoculation beginning with an acute follicular conjunctivitis which progressed for 4 months and then persisted with chronic changes until 9 months when treatment was begun. The illness was generally more acute than would be expected in natural trachoma. That trachoma was reproduced was shown by the involvement of the cornea with epithelial keratitis and pannus, and by the occurrence of gelatinous follicles and eventual cicatrization of the conjunctiva. These clinical findings were supported by repeated demonstrations of typical inclusion bodies of Halberstaedter-Prowazek from conjunctival and even corneal cells, by repeated reisolation of elementary body virus in egg yolk sacs, and by the development of complement-fixing antibody with a "specific" trachoma antigen in each volunteer. Control inoculations with adenovirus type 4 and normal yolk sac showed different clinical and laboratory findings. Experimental trachoma vaccine was given to three of the volunteers to study its effect on the course of illness. An antibody response to the vaccine was demonstrated and there was a modification of disease in the volunteers receiving vaccine. While the three volunteers who received placebo each developed cross-infection of their uninoculated eye and had an acute reactivation of the bilateral disease after 1 to 2 months of antibiotic eye ointment therapy, the vaccinated volunteers remained free of infection in uninoculated eyes and showed no relapse after ointment therapy. Treatment with sulfamethoxypyridazine, a sulfa drug with prolonged action, proved to be an effective and relatively simple method of therapy for experimental trachoma.

Antibody Formation↗

High density- and beta-lipoprotein screening for risk of coronary artery disease in the context of new findings on reverse cholesterol transport.

This article considers how high density lipoproteins (HDL) act as anti-arteriosclerotic agents, examines the usefulness of HDL indexes alone and in conjunction with other markers of coronary artery disease (CAD), and discusses how HDL markers compare with what one might expect from known metabolic mechanisms. This is accomplished by: (i) an overview of mechanisms associated with CAD, especially new findings regarding reverse cholesterol transport; (ii) a brief review of the clinical literature on biochemical markers for automated use; and (iii) analysis of data for persons with or without angiographically documented CAD. Based on these considerations, the ratio of optimized apo A-I/apo B appears superior to lipoprotein lipid markers for predicting the risk of CAD. Yet the ratio shows poor diagnostic accuracy by itself; it yields poorer diagnostic accuracy than would be expected from assessing the metabolic pathways. Discrimination is improved by using the ratio in conjunction with risk factors defined by the National Cholesterol Education Program (NCEP). Based on receiver-operator characteristic (ROC) curve data, this approach increases the accuracy by 13-14% above that obtained with current lipid markers; it improves discrimination more than the use of inflammatory markers. Apolipoprotein testing is better related to the mechanisms of cholesterol transport, is widely available, and requires only two tests, compared to three, to improve discrimination. However, inclusion of inflammatory markers may need to be considered in the future, when more information is available about their functions and clinical value.

Adult↗

Solute exclusion by polymer and protein-dominated water: correlation with results of nuclear magnetic resonance (NMR) and calorimetric studies and their significance for the understanding of the physical state of water in living cells.

According to the polarized multilayer (PM) theory of cell water proteins with their backbones fully extended and their NHCO groups directly exposed to bulk water, polarize water in multilayers. Experimental testing of the theory led to a new understanding of the uniqueness of gelatin, due to its permanently maintained fully extended conformation and its ability to polarize the bulk phase water in multilayers with reduced solubilities for solutes in a size dependent manner ("size rule"). Other models which behave like gelatin are urea-denatured proteins, synthetic polymers like polyethylene oxide (PEO), and polyvinylpyrrolidine (PVP), but not native proteins. NMR studies showed that the majority of water molecules dominated by these polymers does indeed suffer rotational (and translational) motional restriction as predicted by the PM theory. In conjunction with ultra-high frequency dielectric studies but particularly quasielastic neutron scattering of both model systems (e.g., PEO) and living cells (i.e., brine shrimp cysts and frog muscle), this finding offers confirmation of the PM theory of living cell water and model systems. Studies of the freezing point depression showed that the presence of as much as 50% of native proteins had no effect on the freezing point of water while inclusion of gelatin, PEO, etc., caused concentration-dependent lowering of the freezing temperature. These findings demonstrate the key role of polarized water in the phenomena of freezing point depression and the unusual ice forms seen in living cells.

Biopolymers↗

Mousepox outbreak in a laboratory mouse colony.

Mousepox was diagnosed in and eradicated from a laboratory mouse colony at the Naval Medical Research Institute. The outbreak began with increased mortality in a single room; subsequently, small numbers of animals in separate cages in other rooms were involved. Signs of disease were often mild, and overall mortality was low; BALB/cByJ mice were more severely affected, and many of them died spontaneously. Conjunctivitis was the most common clinical sign of disease in addition to occasional small, crusty scabs on sparsely haired or hairless areas of skin. Necropsy findings included conjunctivitis, enlarged spleen, and pale liver. Hemorrhage into the pyloric region of the stomach and proximal portion of the small intestine was observed in experimentally infected animals. In immune competent and immune deficient mice, the most common histologic finding was multifocal to coalescing splenic necrosis; necrosis was seen less frequently in liver, lymph nodes, and Peyer's patches. Necrosis was rarely observed in ovary, vagina, uterus, colon, or lung. Splenic necrosis often involved over 50% of the examined tissue, including white and red pulp. Hepatic necrosis was evident as either large, well-demarcated areas of coagulative necrosis or as multiple, random, interlacing bands of necrosis. Intracytoplasmic eosinophilic inclusion bodies were seen in conjunctival mucosae and haired palpebra. Ectromelia virus was confirmed as the causative agent of the epizootic by electron microscopy, immunohistochemistry, animal inoculations, serologic testing, virus isolation, and polymerase chain reaction. Serologic testing was of little value in the initial stages of the outbreak, although 6 weeks later, orthopoxvirus-specific antibody was detected in colony mice by indirect fluorescent antibody and enzyme-linked immunosorbent assay procedures. The outbreak originated from injection of mice with a contaminated, commercially produced, pooled mouse serum. The most relevant concern may be the unknown location of the source of the virus and the presence of a reservoir for this virus within the United States.

Animals↗

Habit retraining for the management of urinary incontinence in adults.

BACKGROUND: Habit retraining is toileting assistance given by a caregiver to adults with urinary incontinence. It involves the identification of an incontinent person's natural voiding pattern and the development of an individualised toileting schedule which pre-empts involuntary bladder emptying. OBJECTIVES: To assess the effects of habit retraining for the management of urinary incontinence in adults. SEARCH STRATEGY: We searched the Cochrane Incontinence Group specialised register (9 May 2002), MEDLINE (January 1966 to December 2002), EMBASE (January 1980 to Week 18 2002), CINAHL (January 1982 to February 2001), PsycINFO (January 1972 to current), Biological Abstracts (January 1980 to December 2000), Current Contents (January 1993 to December 2001) and the reference lists of relevant articles. We also contacted experts in the field, searched relevant websites and hand searched journals and conference proceedings. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials comparing habit retraining delivered either alone or in conjunction with another intervention for urinary incontinence in adults. DATA COLLECTION AND ANALYSIS: Data extraction and quality assessment were undertaken by at least two people working independently of each other. Any differences were resolved by discussion. The relative risks for dichotomous data were calculated with 95% confidence intervals. Where data were insufficient for a quantitative analysis, a narrative overview was undertaken. MAIN RESULTS: Three trials with a total of 337 participants met the inclusion criteria, describing habit retraining combined with other approaches compared with usual care. Participants were primarily care-dependent elderly women with concurrent cognitive and/or physical impairment, residing in either a residential aged-care facility or in their own home. Outcomes included incidence and/or severity of urinary incontinence, the prevalences of urinary tract infection, skin rash and skin breakdown, cost and caregiver preparedness, role strain and burden. Caregivers found it difficult to maintain voiding records and to implement the toileting program. A 61% compliance rate was reported in one trial. There were no statistically significant differences in the incidence and in the volume of incontinence between groups. Within group analyses did however show improvements on these measures. Reductions were also reported for the intervention group in one study for skin rash, skin breakdown and in caregivers' perceptions of their level of stress. Descriptive data on the intervention suggests that habit retraining is a labour-intense activity. Electronic loggers, used as an adjunct to caregiver-delivered wet/dry checks, were reported as providing more accurate data than that from caregiver conducted wet/dry checks. To date, no analysis of the time and resources associated with these comparisons is available. REVIEWERS' CONCLUSIONS: Data on habit retraining are few and of insufficient quality to provide a firm basis for practice.

Habits↗

Nutritional treatment for acquired immunodeficiency virus infection using an enterotropic peptide-based formula enriched with n-3 fatty acids: a randomized prospective trial.

OBJECTIVE: Dietary counseling and intervention based on application of conventional criteria have been ineffective in preventing the progressive weight loss associated with HIV infection. The aim of the study was to compare the progression of clinical and nutritional indicators during nutritional supplementation with or without an enterotropic peptide-based formula enriched with n-3 fatty acids. DESIGN: Randomized trial. SETTING: Tertiary care. SUBJECTS: Ninety-one patients were screened for the study. Twenty-three did not meet the inclusion criteria, therefore 74 patients were randomized. Of these, 38 were randomized to group I (standard formula) and 36 were randomized to group II supplementation (enterotropic peptide-based formula enriched with n-3 fatty acids). INTERVENTIONS: Group I received standard enteral formula and group II received a enterotropic peptide-based enteral formula. The volume was the same (3 cans/day, 236 ml per can). In both groups enteral supplementation were recommended in conjunction with a registered dietitian under a dietary counseling program based on standard nutrition principles. Patients received a prospective serial assessment of nutrition status, nutritional intake with 24 h written food records, GI symptoms, immune function, anthropometric status and intercurrent health events including infections and hospitalization. These determinations were performed at baseline and at 3 months. RESULTS: Treatment with both supplements resulted in a significant and sustained increase in weight (3.2% in group I and 3.1% in group II); this increase was mostly due to fat mass (12.8% in group I) and (7.5% in group II). Total body water and fat free-mass remained unchanged. CD4 counts remained stable in group I, while a significant increase was detected in group II (576+/-403 vs 642+/-394 cells/mm(3); P<0.05). After the 3 month period CD4 counts remained higher in group II. Hospitalization events (infections) were also followed during the 3 month period. Group II had fewer hospitalizations than group I, but no statistical differences were found. CONCLUSIONS: Oral nutritional supplements for a 3 month period were well tolerated and resulted in body weight gain in HIV-infected patients. Supplement-enriched formula, with peptides and n-3 fatty acids, increased CD4 count.

Adolescent↗

Postoperative irradiation for pterygium: retrospective analysis of 1,253 patients from the Osaka University Hospital.

BACKGROUND AND PURPOSE: Irradiation of ocular pterygium is considered a valuable treatment supplementation after surgical therapy. Since prospective randomized trials are scare and only limited patient data are available, the aim of this study was to evaluate the patient population treated with fractioned 90Sr irradiation after surgical pterygium resection. PATIENTS AND METHODS: Between September 1993 and March 2001, 1,147 patients with pterygium lesions (1,320 lesions) were treated surgically and with 90Sr postoperative beta-irradiation. A total dose of 30 Gy was used for patients treated within 48 h after surgery, while those treated>48 h postoperatively received a total dose of 35 Gy. A minimum follow-up period of 3 months was required for inclusion in the analysis, and 1,253 lesions were ultimately analyzed. RESULTS: Recurrence of the pterygium after postoperative 90Sr irradiation was observed in 97 of 1,253 cases (7.7%). Statistical analysis (uni- and multivariate) revealed, that male gender, younger age (<40 years), prior treatment (surgery and radiotherapy) and immediate irradiation (<2 h after surgery) were negative predictors for local recurrence. Temporary radiotherapy-induced side effects were observed in 15.2% of patients, including moderate conjunctivitis, local pain, visual disturbance and photophobia or an increase in tear flow. However, no long-term serious side effects were documented. CONCLUSION: 90Sr irradiation of pterygium after surgery represents a safe and effective treatment option to prevent disease recurrence. The data obtained in this study indicate that a certain interval after surgery might improve therapy outcome.

Adult↗

Premenstrual syndromes.

The recent inclusion of research criteria for premenstrual dysphoric disorder in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders should help physicians recognize women with symptoms of irritability, tension, dysphoria, and lability of mood that seriously interfere with their lifestyle. Premenstrual dysphoric disorder can be differentiated from premenstrual syndrome, which is primarily reserved for milder physical symptoms and minor mood changes. The use of criteria from the Diagnostic and Statistical Manual in conjunction with prospective daily charting for at least two menstrual cycles is now accepted as common practice in confirming the diagnosis. Treatment options range from the conservative (lifestyle and stress management) to treatment with psychotropic medications and hormonal or surgical interventions to eliminate ovulation for the more extreme cases. Results from several randomized, placebo-controlled trials have clearly demonstrated that selective serotonin reuptake inhibitors, as well as medical or surgical oophorectomy, are effective in treating premenstrual dysphoric disorder. Taken together, these data indicate that treatment may be accomplished by either eliminating the hormonal trigger or by reversing the sensitivity of the serotonergic system.

Diagnosis, Differential↗