Descaling Injury Impairs the Osmoregulatory Ability of Atlantic Salmon Smolts Entering Seawater

The effect of descaling injury on the osmoregulatory ability of hatchery Atlantic salmon Salmo salar smolts in seawater was investigated. Experimental series were initiated during early, middle, and late periods of the spring smolt migration (April 25, May 11, and May 31, respectively). For each time series, descaled smolts (subjected to descaling on 10% of the body surface area) and control smolts (held out of water for 15 s) were transferred to seawater at 0, 1, 3, or 7 d posttreatment. After fish were held in 35% seawater for 24 h, gill and blood samples were collected and analyzed for Na(+),K(+)-ATPase activity and plasma osmolyte levels. Based on gill Na(+),K(+)-ATPase activity, the three series spanned the period from early smolting (increasing activity) to de-smolting (decreasing activity). In each series, descaled fish transferred to seawater at 0 and 1 d posttreatment had greater plasma osmolality than control fish; descaled fish transferred to seawater at 3 d posttreatment did not differ from controls. The greatest perturbation in osmolality (70 milliosmoles) was observed at the peak of smolting (middle series), whereas lesser increases were seen for early and late-series smolts. The observed osmotic perturbations in descaled fish would probably reduce performance and decrease survival during smolt migration.

An outbreak of Multi-Drug Resistant Acinetobacter in the burn intensive care unit of a large tertiary care center

Risk factors for Multi-Drug Resistant Acinetobacter (MDRA) acquisition were studied in patients in a burn intensive care unit (ICU) where there was an outbreak of MDRA. Forty cases were matched with eighty controls based on length of stay in the Burn ICU and statistical analysis was performed on data for several different variables. Matched analysis showed that mechanical ventilation, transport ventilation, number of intubations, number of bronchoscopy procedures, total body surface area burn, and prior Methicillin Resistant Staphylococcus aureus colonization were all significant risk factors for MDRA acquisition. ^ MDRA remains a significant threat to the burn population. Treatment for burn patients with MDRA is challenging as resistance to antibiotics continues to increase. This study underlined the need to closely monitor the most critically ill ventilated patients during an outbreak of MDRA as they are the most at risk for MDRA acquisition.^

Glomerular number and size in autopsy kidneys: The relationship to birth weight

Background. In the Southeast United States, African Americans have an estimated incidence of hypertension and end-stage renal disease (ESRD) that is five times greater than Caucasians. Higher rates of low birth weight (LBW) among African Americans is suggested to predispose African Americans to the higher risk, possibly by reducing the number of glomeruli that develop in the kidney. This study investigates the relationships between age, race, gender, total glomerular number (N-glom), mean glomerular volume (V-glom), body surface area (BSA), and birth weight. Methods. Stereologic estimates of N-glom and V-glom were obtained using the physical disector/fractionator combination for autopsy kidneys from 37 African Americans and 19 Caucasians. Results. N-glom was normally distributed and ranged from 227,327 to 1,825,380, an 8.0-fold difference. A direct linear relationship was observed between N-glom and birth weight (r=0.423, P=0.0012) with a regression coefficient that predicted an increase of 257,426 glomeruli per kilogram increase in birth weight (alpha=0.050:0.908). Among adults there was a 4.9-fold range in V-glom , and in adults, V-glom was strongly and inversely correlated with N-glom (r=-0.640, P=0.000002). Adult V-glom showed no significant correlation with BSA for males (r=-0.0150, P=0.936), although it did for females (r=0.606, P=0.022). No racial differences in average N-glom or V-glom were observed. Conclusion. Birth weight is a strong determinant of N-glom and thereby of glomerular size in the postnatal kidney. The findings support the hypothesis that LBW by impairing nephron development is a risk factor for hypertension and ESRD in adulthood.

Flammable liquid burns in children

Objectives: To document and describe the effects of flammable liquid burns in children. To identify the at risk population in order to tailor a burns prevention programme. Design, patients and setting: Retrospective study with information obtained from the departmental database of children treated at the burns centre at The Royal Children's Hospital, Brisbane between August 1997 and October 2002. Main outcome measures: Number and ages of children burned, risk factors contributing to the accident, injuries sustained, treatment required and long-term sequelae. Results: Fifty-nine children sustained flammable liquid burns (median age 10.5 years), with a clear preponderance of males (95%). The median total body surface area burned was 8% (range 0.5-70%). Twenty-seven (46%) of the patients required debridement and grafting. Hypertrophic scars occurred in 56% of the children and contractures in 14%, of which all of the latter required surgical release. Petrol was the causative liquid in the majority (83%) of cases. Conclusions: The study identified the population most at risk of sustaining flammable liquid burns were young adolescent males. In the majority of cases these injuries were deemed preventable. (C) 2003 Elsevier Science Ltd and ISBI. All rights reserved.

Electrical burns in children

Electrical burns are an important preventable cause of injury in children. The objective of this study was to document pediatric electrical burns treated in our center. Twenty−three children with electrical burns were treated between 1997 and 2001. Prospective data collection of demographics, nature of contact with electricity, site, total body surface area involved (TBSA), medical and surgical interventions and complications were examined. The median age was six. The majority of burns were caused by direct contact with electrical cords, followed by direct contact with faulty electrical appliances and insertion of foreign metal objects into the electric wall outlet. An adult supervised most of the children when the injury occurred and most sustained hand burns. Although the burns areas were relatively small in size, 61% required skin grafting. Twenty−one percent of the children required secondary surgery to release contractures. In conclusion, electrical burns cause significant morbidity to children and there is clearly a wide scope for prevention.

Kidney volume, blood pressure, and albuminuria: Findings in an Australian Aboriginal community

Background. Australian Aborigines are experiencing epidemic proportions of renal disease, marked by albuminuria and, variably, hematuria. They also have high rates of low birth weight, which have been associated with lower kidney volumes and higher blood pressures. The authors evaluated relationships between kidney volume, blood pressure, albuminuria, and hematuria in 1 homogeneous group. Methods Forty-three percent (672 of 1,560) of the population in a remote coastal Australian Aboriginal community aged 4.4 to 72.1 years participated in the study. Results: Kidney size correlated closely with body size. Systolic blood pressure (SBP) was correlated inversely with kidney length and kidney volume, after adjusting for age, sex, and body surface area (BSA); a 1-cm increase in mean kidney length was associated with a 2.2-mm Hg decrease in SBP, and a 10-mL increase in mean kidney volume was associated with a 0.6-mm Hg decrease in SBP (P = 0.001). Mean kidney volume explained 10% of the variance in SBP in a multivariate model containing age, sex, and BSA. In addition to higher SBP, adults who had the lowest quartiles of kidney volume also had the highest levels of overt albuminuria (P = 0.044). Conclusion: Smaller kidneys predispose to higher blood pressures and albuminuria in this population. The lower volumes possibly represent kidneys with reduced nephron numbers, which might be related to an adverse intrauterine environment. Susceptibility to renal disease could be a direct consequence of reduced nephron numbers; the higher blood pressures with which they are associated could also contribute to, as well as derive from, this association.

What is the best size descriptor to use for pharmacokinetic studies in the obese?

The prevalence of obesity in the western world is dramatically rising, with many of these individuals requiring therapeutic intervention for a variety of disease states. Despite the growing prevalence of obesity there is a paucity of information describing how doses should be adjusted, or indeed whether they need to be adjusted, in the clinical setting. This review is aimed at identifying which descriptors of body size provide the most information about the relationship between dose and concentration in the obese. The size descriptors, weight, lean body weight, ideal body weight, body surface area, body mass index, fat-free mass, percent ideal body weight, adjusted body weight and predicted normal body weight were considered as potential size descriptors. We conducted an extensive review of the literature to identify studies that have assessed the quantitative relationship between the parameters clearance (CL) and volume of distribution (V) and these descriptors of body size. Surprisingly few studies have addressed the relationship between obesity and CL or V in a quantitative manner. Despite the lack of studies there were consistent findings: (i) most studies found total body weight to be the best descriptor of V. A further analysis of the studies that have addressed V found that total body weight or another descriptor that incorporated fat mass was the preferred descriptor for drugs that have high lipophilicity; (ii) in contrast, CL was best described by lean body mass and no apparent relationship between lipophilicity or clearance mechanism and preference for body size descriptor was found. In conclusion, no single descriptor described the influence of body size on both CL and V equally well. For drugs that are dosed chronically, and therefore CL is of primary concern, dosing for obese patients should not be based on their total weight. If a weight-based dose individualization is required then we would suggest that chronic drug dosing in the obese subject should be based on lean body weight, at least until a more robust size descriptor becomes available.

A standard weight descriptor for dose adjustment in the obese patient

Objective: To develop a standard weight descriptor that can be used for estimation of patient size for obese patients. Patients and methods: Data were available from 3849 patients: 2839 from oncology patients (index data set) and 1010 from general medical patients (validation data set). The patients had a wide range of age (16-100 years), weight (25-165kg) and body mass index (BMI) [12-52 kg/m(2)] in both data sets. From the normal-weight patients in the oncology data set, an equation for male and female patients was developed to predict their normal weight as the sum of the lean body mass and normal fat body mass. The equations were evaluated by predicting the weight of patients in the general medical data set who had a normal BMI (30 kg/m(2)).

Hot beverage scalds in Australian children

Our objective was to compile data on the mechanism and severity of injuries associated with hot beverage burns in children. We identified 152 children over a 3-year period who attended a tertiary level burns center, representing 18% of all children treated. Their median age was 17.5 months and median body surface area burned was 4% (range, 0.25% to 32%). Significantly, 52% of children required admission, 18% received a split skin graft, and 26% required long-term scar management. In 70% of all cases, the mechanism of injury was the child pulling the hot beverage over himself or herself. In 80% of incidents, a primary care giver witnessed the injury. These findings indicate that scalding from hot beverages carries significant morbidity and is an important pediatric public health issue. It is clear that further research towards effective education programs for primary caregivers is warranted.

Effect of pravastatin on cardiovascular events in people with chronic kidney disease

Background - Limited data describe the cardiovascular benefit of HMG-CoA reductase inhibitors (statins) in people with moderate chronic kidney disease (CKD). The objective of this analysis was to determine whether pravastatin reduced the incidence of cardiovascular events in people with or at high risk for coronary disease and with concomitant moderate CKD. Methods and Results - We analyzed data from the Pravastatin Pooling Project (PPP), a subject-level database combining results from 3 randomized trials of pravastatin ( 40 mg daily) versus placebo. Of 19 700 subjects, 4491 ( 22.8%) had moderate CKD, defined by an estimated glomerular filtration rate of 30 to 59.99 mL/min per 1.73 m(2) body surface area. The primary outcome was time to myocardial infarction, coronary death, or percutaneous/surgical coronary revascularization. Moderate CKD was independently associated with an increased risk of the primary outcome ( adjusted HR 1.26, 95% CI 1.07 to 1.49) compared with those with normal renal function. Among the 4491 subjects with moderate CKD, pravastatin significantly reduced the incidence of the primary outcome ( HR 0.77, 95% CI 0.68 to 0.86), similar to the effect of pravastatin on the primary outcome in subjects with normal kidney function ( HR 0.78, 95% CI 0.65 to 0.94). Pravastatin also appeared to reduce the total mortality rate in those with moderate CKD ( adjusted HR 0.86, 95% CI 0.74 to 1.00, P = 0.045). Conclusions - Pravastatin reduces cardiovascular event rates in people with or at risk for coronary disease and concomitant moderate CKD, many of whom have serum creatinine levels within the normal range. Given the high risk associated with CKD, the absolute benefit that resulted from use of pravastatin was greater than in those with normal renal function.

Determinants of glomerular volume in different cortical zones of the human kidney

Enlarged glomerular size is a feature of focal segmental glomerulosclerosis, obesity-related glomerulopathy, diabetic nephropathy, and hypertension. The distribution of glomerular volumes within different cortical zones and glomerular volume alterations with age and obesity may contribute to understanding the evolution of these diseases. We analyzed the distributions of volumes of individual glomeruli in the superficial, middle, and juxtamedullary cortex of normal human kidneys using the disector/Cavalieri method. Volumes (V-glom) of 720 nonsclerotic glomeruli (30 per kidney, 10 per zone) were estimated in autopsy kidneys of 24 American men, 12 aged 20 to 30 yr and 12 aged 51 to 69 yr. Black and white individuals were represented equally. The range of individual V-glom within subjects varied from two- to eight-fold. There were no significant zonal differences in V-glom in the young or those with body surface area (BSA) <= 2.11 m(2). In contrast, superficial glomeruli in the older age group, in those with BSA > 2.11 m(2), and in white subjects were significantly larger than juxtamedullary glomeruli. Black subjects tended toward larger V-glom than white subjects, and this difference was significant and most marked in the juxtamedullary zone and independent of age, BSA, and glomerular number. There is a wide range in individual V-glom in adults. BSA, race, and age independently influence V-glom different zones of the renal cortex. These findings might reflect processes of aging and susceptibility factors to renal disease.

Population pharmacokinetic and pharmacogenetic analysis of 6-mercaptopurine in paediatric patients with acute lymphoblastic leukaemia

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The cytotoxic effects of 6-mercaptopurine (6-MP) were found to be due to drug-derived intracellular metabolites (mainly 6-thioguanine nucleotides and to some extent 6-methylmercaptopurine nucleotides) rather than the drug itself. • Current empirical dosing methods for oral 6-MP result in highly variable drug and metabolite concentrations and hence variability in treatment outcome. WHAT THIS STUDY ADDS • The first population pharmacokinetic model has been developed for 6-MP active metabolites in paediatric patients with acute lymphoblastic leukaemia and the potential demographic and genetically controlled factors that could lead to interpatient pharmacokinetic variability among this population have been assessed. • The model shows a large reduction in interindividual variability of pharmacokinetic parameters when body surface area and thiopurine methyltransferase polymorphism are incorporated into the model as covariates. • The developed model offers a more rational dosing approach for 6-MP than the traditional empirical method (based on body surface area) through combining it with pharmacogenetically guided dosing based on thiopurine methyltransferase genotype. AIMS - To investigate the population pharmacokinetics of 6-mercaptopurine (6-MP) active metabolites in paediatric patients with acute lymphoblastic leukaemia (ALL) and examine the effects of various genetic polymorphisms on the disposition of these metabolites. METHODS - Data were collected prospectively from 19 paediatric patients with ALL (n = 75 samples, 150 concentrations) who received 6-MP maintenance chemotherapy (titrated to a target dose of 75 mg m−2 day−1). All patients were genotyped for polymorphisms in three enzymes involved in 6-MP metabolism. Population pharmacokinetic analysis was performed with the nonlinear mixed effects modelling program (nonmem) to determine the population mean parameter estimate of clearance for the active metabolites. RESULTS - The developed model revealed considerable interindividual variability (IIV) in the clearance of 6-MP active metabolites [6-thioguanine nucleotides (6-TGNs) and 6-methylmercaptopurine nucleotides (6-mMPNs)]. Body surface area explained a significant part of 6-TGNs clearance IIV when incorporated in the model (IIV reduced from 69.9 to 29.3%). The most influential covariate examined, however, was thiopurine methyltransferase (TPMT) genotype, which resulted in the greatest reduction in the model's objective function (P < 0.005) when incorporated as a covariate affecting the fractional metabolic transformation of 6-MP into 6-TGNs. The other genetic covariates tested were not statistically significant and therefore were not included in the final model. CONCLUSIONS - The developed pharmacokinetic model (if successful at external validation) would offer a more rational dosing approach for 6-MP than the traditional empirical method since it combines the current practice of using body surface area in 6-MP dosing with a pharmacogenetically guided dosing based on TPMT genotype.

Using multivariate sequential patterns to improve survival prediction in intensive care burn unit

Resuscitation and stabilization are key issues in Intensive Care Burn Units and early survival predictions help to decide the best clinical action during these phases. Current survival scores of burns focus on clinical variables such as age or the body surface area. However, the evolution of other parameters (e.g. diuresis or fluid balance) during the first days is also valuable knowledge. In this work we suggest a methodology and we propose a Temporal Data Mining algorithm to estimate the survival condition from the patient’s evolution. Experiments conducted on 480 patients show the improvement of survival prediction.

Índice del perfil del donante renal (KDPI) como factor pronóstico del trasplante

La enfermedad renal crónica ha aumentado a nivel mundial y nacional, mientras que el número de donantes viene en descenso, y los pacientes en lista de espera aumentan. Los donantes cadavéricos son una opción para estos pacientes, y han sido utilizados en últimos años para aumentar los órganos disponibles. La evaluación de la calidad de estos es importante para optimizar su uso. Estudio analítico tipo cohorte retrospectiva, cálculo de KDPI en donantes cadavéricos, seguimiento función renal creatinina sérica 1 mes, 3 meses, 6 meses y un año. Correlación supervivencia del injerto, función renal, KDPI y EPTS. Análisis de supervivencia y regresión logística con variables del donante, receptor y acto quirúrgico.

Parasite distribution and histopathological studies on certain commercially important fishes of cochin area

In order to check the damage caused by the parasites, even though it is difficult in open waters, a proper understanding of the seasonal variation in the distribution of the parasite and other factors like age of the host, sex of the host, which affect distribution of parasite is a must. Although several workers have carried out investigations on the taxonomy of metazoan parasites of marine and brackish water Fishes of India, very little attempt is made to correlate such investigations with the host and the environment. In this thesis such an attempt is made by the researcher. In chapter one the literature related to the prevalence, mean intensity of infection, and histopathological changes caused by the metazoan parasites, in particular by helminths, copepods and isopods, was reviewed. Chapter two contains observations on the distribution pattern of parasites in relation to the season, sex, and size of the host. It was found that the prevalence rate of radiorynchus_indicus infecting the alimentary canal of Tachysurugs mgacuglatus, Ergasilus sp. infecting the gills of T maculatus, and Lernaeeniicus ramosus found on the body surface of Qeimgipteirfugs jagonicus was higher during monsoon season. But agarna malayi found in the opercular chamber and Ehilometra cephalus infecting the gonads of valamugil speiglari showed a higher prevalence rate during the postmonsoon season. This was discussed on the basis of the hydrographical characteristics prevailing in the study area during the three different seasons. It was also observed that the sex of the host did not influence significantly the distribution pattern of the parasites. The reasons for this were also discussed. Invariably, the size of the host was found to influence the parasite distribution pattern. It was observed that the prevalence rate showed an increase with increase in size of the fish. This was discussed on the basis of food habits of the host, along with other aspects An attempt was made in chapter three to study the histopathological effects of‘ the various parasites on their respective sites of attachments on host Fishes. It was found that except Rhadinorhyhchugs indicus, all other parasites produced damages of varying intensity, in the form of hypertrophy, rhyperplasia, haemorrhage, tissue disruption and ulcers. Interestingly, E. indicus, an acantho— cephalid with a powerful proboscis for attachment was found not to cause any serious damage to the intestine of the host Fish. All these aspects are included in the third and final chapter of the thesis.