Clinical acid-base pathophysiology: disorders of plasma anion gap

The plasma anion gap is a frequently used parameter in the clinical diagnosis of a variety of conditions. The commonest application of the anion gap is to classify cases of metabolic acidosis into those that do and those that do not leave unmeasured anions in the plasma. While this algorithm is useful in streamlining the diagnostic process, it should not be used solely in this fashion. The anion gap measures the difference between the unmeasured anions and unmeasured cations and thus conveys much more information to the clinician than just quantifying anions of strong acids. In this chapter, the significance of the anion gap is emphasized and several examples are given to illustrate a more analytic approach to using the clinical anion gap; these include disorders of low anion gap, respiratory alkalosis and pyroglutamic acidosis.     

Promoting Healthy Lifestyles: Alternative Models' Effects (PHLAME)

The Promoting Healthy Lifestyles: Alternative Models' Effects (PHLAME) study evaluates the efficacy of two intervention strategies for improving nutrition and physical activity practices in fire fighters: a team-centered program and a one-on-one format targeting the individual. PHLAME compares these two behavior change models (the team-based versus the one-on-one approaches) against a usual-care control group. As a group, fire fighters have a concentration of the same harmful behaviors and health risks commonly afflicting the US population. Fire fighters have a unique work structure which is ideal for a team-centered model of behavior change. This strategy, based on Social Learning Theory, focuses on a team of fire fighters who work together on the same shift. If this team-centered model proves successful, it could provide a cost-effective method to impact behavior, and be disseminated among fire bureaus and in other team settings. The one-on-one intervention incorporates the Transtheoretical Model of behavior change, uses Motivational Interviewing for its counseling strategy and could be used in the more typical provider-client clinic setting. Findings from PHLAME will provide information about the process and outcomes of these models' ability to achieve health behavior change.     

Effect of sorption and desorption resistance on aerobic trichloroethylene biodegradation in soils

Biodegradation of trichloroethylene (TCE) by toluene-degrading bacteria was measured under aerobic conditions in aqueous and soil-slurry batch microcosms. For soil-phase experiments, a freshly contaminated soil and a soil containing only the desorption-resistant fraction of TCE were tested. In both cases, presence of soil resulted in biodegradation rates substantially lower than those determined in the absence of soil. In aqueous-phase experiments, an appreciable increase in the rate and extent of TCE biodegradation was observed in microcosms when toluene was added multiple times. The TCE degradation rates were clearly correlated with toluene dioxygenase (TOD) enzyme activity over time, thus providing an indication of the cometabolic pathway employed by the microbial population. In soil-slurry experiments containing freshly contaminated soil, a TCE degradation rate of approximately 150 microg TCE/kg/h was observed during the first 39-h period, and then the TCE degradation rate slowed considerably to 0.59 and 0.84 microg TCE/kg/h for microcosms receiving one and two additions of toluene, respectively. The TCE degradation rates in soil-slurry microcosms containing the desorption-resistant fraction of TCE-contaminated soil were approximately 0.27 and 0.32 microg TCE/kg/h in microcosms receiving one and two additions of toluene, respectively. It is clear from these results that mass transfer into the aqueous phase limited bioavailability of TCE in the contaminated soil.     

Changing incidence of lobular carcinoma in situ of the breast

Estimating the incidence of lobular carcinoma in situ (LCIS) of the breast is challenging because it lacks both clinical and mammographic signs and is usually an incidental finding in breast biopsies performed for other reasons. In general, population-based studies are believed to provide the most accurate measures, but few documenting changes in LCIS incidence rates over time have been reported. Age-adjusted age-specific LCIS incidence rates among women with no prior history of in situ or invasive breast carcinoma from 1978 to 1998 were obtained from nine population-based cancer registries that participate in the Surveillance, Epidemiology, and End Results (SEER) Program. Linear trends were evaluated using negative binomial regression. Overall, LCIS incidence rates increased fourfold (95% confidence interval, 2.9–5.6) over the study period. Specifically, they rose from 0.90/100,000 person-years in 1978–80 to 2.83/100,000 person-years in 1987–89, but then increased only modestly up to 1996–98 where the incidence rate was 3.19/100,000 person-years. However, among women 50–79 years of age, LCIS incidence rates increased continuously over the study's duration. In 1996–98, 50–59 year-olds had the highest incidence rate (11.47/100,000 person-years) and experienced the greatest absolute increase in incidence over the study period (9.48/100,000 person-years). LCIS incidence rates have steadily increased from 1978 to 1998 only among postmenopausal women. Further research is required to assess what factors are contributing to these trends.     

The adolescents training and learning to avoid steroids program: preventing drug use and promoting health behaviors

BACKGROUND: Use of alcohol and other illicit drugs by adolescent male athletes is a significant problem. Participation in sports may encourage use of drugs that enhance athletic performance, especially anabolic steroids (AS). Because, to our knowledge, no other intervention has successfully altered substance abuse by athletes, we developed and assessed the efficacy of a team-centered, sex-specific education program designed to reduce adolescent athletes' intentions to use and use of AS and alcohol and other illicit drugs. METHODS: We studied 31 high school football teams that comprised 3207 athletes in 3 successive annual cohorts (1994-1996). The intervention included interactive classroom and exercise training sessions given by peer educators and facilitated by coaches and strength trainers. Program content included discussion of sports nutrition, exercise alternatives to AS and sport supplements, and the effects of substance abuse in sports, drug refusal role-playing, and the creation of health promotion messages. Questionnaires assessing AS, the use of sport supplements and alcohol and other illicit drugs, and potential risk and protective factors were administered before and after the intervention (before and after the football season) and up to 1 year after the program. RESULTS: At season's end, intentions to use (P<.05) and actual AS use (P<.04) were significantly lower among students who participated in the study. Although AS reduction did not achieve significance at 1 year (P<.08), intentions to use AS remained lower (P = .02). Illicit drug use (marijuana, amphetamines, and narcotics) was reduced at 1 year, whether alcohol was included (P = .04) or excluded (P = .02) from the index. Other long-term effects included fewer students reporting drinking and driving (P = .004), less sport supplement use (P = .009), and improved nutrition behaviors (P<.02). CONCLUSIONS: Use of alcohol and other illicit drugs and associated harmful activities can be prevented with a sex-specific, team-centered education. School athletic teams provide an optimal environment in which to provide drug prevention and health promotion education.     

Ontogeny of Na+/H+ antiporter activity in rat proximal convoluted tubules

Neonates have a lower serum bicarbonate level than adults, which is caused by a lower renal threshold for bicarbonate. Eighty percent of bicarbonate reabsorption occurs in the proximal tubule, in which proton secretion is predominantly mediated by a luminal Na+/H+ antiporter. Previous studies have demonstrated that there is a maturational increase in apical membrane rabbit proximal convoluted tubule Na+/H+ antiporter activity. However, in rat brush border membrane vesicles, Na+/H+ activity was higher in neonates than that in adult rats. To examine the maturation of Na+/H+ antiporter activity in rat proximal convoluted tubules, we perfused rat proximal convoluted tubules in vitro. Na+/H+ antiporter activity was assayed as the proton secretory rate on luminal sodium removal. Na+/H+ antiporter activity was 121.2 +/- 18.4 pmol/mm x min in neonatal and 451.8 +/- 40.6 pmol/mm x min in adult proximal convoluted tubules (p < 0.001). We next examined whether the increase in Na+/H+ antiporter activity was associated with changes in renal cortical NHE3 mRNA and brush border membrane NHE3 protein abundance. Adult renal cortical NHE3 mRNA abundance was 10-fold greater than that in 1-d-old neonates (p < 0.001). There was a comparable developmental increase in renal brush border membrane vesicle NHE3 protein abundance (p < 0.001). In summary, this study demonstrates that there is a maturational increase in rat apical membrane Na+/H+ antiporter activity, renal cortical NHE3 mRNA, and brush border membrane vesicle NHE3 protein abundance.     

Inositol 1,4,5-trisphosphate turnover enzymes--activities and subcellular distribution in hepatocarcinogenesis

The metabolism of inositol 1,4,5-trisphosphate and inositol 1,3,4,5- tetrakisphosphate in homogenates and sub-fractions from normal rat liver and premalignant liver nodules was investigated. The activities of 5-phosphatase, expressed as pmol converted substrate per minute and mg protein, were equal when using the two substrates, and did not differ between normal and nodular homogenates. Subcellular fractions were purified by sequential steps of differential centrifugation and density gradient fractionation procedures. The total phosphatase activity was found to be distributed between cytosol (15%) and membraneous fractions (75%), with most of the enzyme activity residing in the plasma membranes. A doubling of phosphatase specific activity was seen in the nodular low density membrane fraction, containing Golgi apparatus and endosomes, as compared with normal liver. Inositol 1,4,5- trisphosphate 3-kinase activity was found to be exclusively cytosolic. No difference in this enzyme was seen between the two tissue types studied. Vasopressin (0.2 or 2 microM) had no effect either on phosphatase or kinase activity. The compartmentalization of inositol polyphosphate 5-phosphatase activity presents a possible explanation of earlier findings that premalignant liver tissue was able to respond with inositol 1,4,5-trisphosphate, but not inositol 1,3,4,5- tetrakisphosphate formation after agonist stimulation.      

A BPA survey of recently appointed consultants

A postal survey of recently appointed consultant paediatricians was undertaken to determine whether they perceived their training had adequately equipped them for their current job. The response rate was 69% (207/299). After excluding replies from consultants trained outside the UK the analysis was carried out on 167 replies. Trainees held a mean 5.2 posts during general and higher professional training, necessitating a mean 1.8 house moves. Altogether 82% felt moves were beneficial to training but 46% found moves 'very disruptive' to family life. Only 12% of district general hospital and 22% of teaching hospital senior registrars took two research sessions a week. Supervision and training in research was absent or poor for more than 60%; 24% felt major changes and 55% moderate changes were needed to current training. Training in non-clinical skills was particularly in demand and a curriculum for both trainers and trainees with regular appraisals is required. Research at senior registrar level needs review and educational methods improved to achieve better training in a shorter period.