ISSN:0002-9629    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Our current understanding of Na+transport defects has been greatly expanded over the last several years and has provided new insights into unusual clinical syndromes resulting from mutations of specific ion transporters. These genetic disorders affect Na+balance, with both Na+retaining and Na+wasting conditions being the consequence. A major focus of these studies has been the epithelial sodium channel (ENaC), which can be directly affected by mutations (eg, Liddle syndrome, autosomal recessive pseudohypoaldosteronism, type I) or by changes in the response to (autosomal recessive pseudohypoaldosteronism, type I), or production of mineralocorticoids (apparent mineralocorticoid excess syndrome, glucocorticoid-remediable aldosteronism). As a result, we now have clearly defined syndromes in which ENaC activity is “dysregulated” with subsequent development of disorders of systemic blood pressure that can be attributed to a primary renal mechanisms. The focus of the current review is on Liddle syndrome (“pseudoaldosteronism”).

ISSN:0002-9629    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Aldosterone, the most important mineralocorticoid, regulates electrolyte excretion and intravascular volume mainly through its effects on renal cortical collecting ducts, where it acts to increase sodium resorption from and potassium excretion into the urine. Excess secretion of aldosterone or other mineralocorticoids, or abnormal sensitivity to mineralocorticoids, may result in hypokalemia, suppressed plasma renin activity, and hypertension. The syndrome of apparent mineralocorticoid excess (AME) is an inherited form of hypertension in which 11&bgr;-hydroxysteroid dehydrogenase (11-HSD) is defective. This enzyme converts cortisol to its inactive metabolite, cortisone. Because mineralocorticoid receptors themselves have similar affinities for cortisol and aldosterone, it is hypothesized that the deficiency allows these receptors to be occupied by cortisol, which normally circulates at levels far higher than those of aldosterone. We cloned cDNA and genes encoding two isozymes of 11-HSD. The liver or 11-HSD1 isozyme has relatively low affinity for steroids, is expressed at high levels in the liver but poorly in the kidney, and is not defective in AME. The kidney or 11-HSD2 isozyme has high steroid affinity and is expressed at high levels in the kidney and placenta. Mutations in the gene for the latter isozyme have been detected in all kindreds with AME. Moreover, the in vitro enzymatic activity conferred by each mutation is strongly correlated with the ratio of cortisone to cortisol metabolites in the urine, with age of diagnosis, and with birth weight. This suggests that the biochemical and clinical phenotype of AME is largely determined by genotype.

ISSN:0002-9629    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Inherited hypokalemic metabolic alkalosis, or Bartter syndrome, comprises several closely related disorders of renal tubular electrolyte transport. Recent advances in the field of molecular genetics have demonstrated that there are four genetically distinct abnormalities, which result from mutations in renal electrolyte transporters and channels. Neonatal Bartter syndrome affects neonates and is characterized by polyhydramnios, premature delivery, severe electrolyte derangements, growth retardation, and hypercalciuria leading to nephrocalcinosis. It may be caused by a mutation in the gene encoding the Na-K-2Cl cotransporter (NKCC2) or the outwardly rectifying potassium channel (ROMK), a regulator of NKCC2. Classic Bartter syndrome is due to a mutation in the gene encoding the chloride channel (CLCNKB), also a regulator of NKCC2, and typically presents in infancy or early childhood with failure to thrive. Nephrocalcinosis is typically absent despite hypercalciuria. The hypocalciuric, hypomagnesemic variant of Bartter syndrome (Gitelman syndrome), presents in early adulthood with predominantly musculoskeletal symptoms and is due to mutations in the gene encoding the Na-Cl cotransporter (NCCT). Even though our understanding of these disorders has been greatly advanced by these discoveries, the pathophysiology remains to be completely defined. Genotype-phenotype correlations among the four disorders are quite variable and continue to be studied. A comprehensive review of Bartter and Gitelman syndromes will be provided here.

ISSN:0002-9629    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Background:We have shown previously that the calciuric response to salt does not differ in Dahl salt-sensitive (S) and salt-resistant (R) male rats. Clinical studies with women, however, suggest an effect of salt sensitivity on the calciuric response to salt. The objective of this study was to determine whether there is an effect of salt sensitivity on the calciuric response to salt of female S and R rats.Method:Dahl S and R female rats were fed high- (8%) or low- (0.3%) salt diets for 3 weeks. The rats were placed in metabolic cages for 24-hour urine collection at baseline and weekly (for sodium and calcium determination).Results:Blood pressure of female S rats was 177 ± 3.0 mm Hg at week 3 of high salt intake compared with 96 ± 1 mm Hg for female R rats. Female S rats excreted significantly more calcium than female R rats at baseline (P< 0.001), when fed a nonpurified diet, and during high salt intake (P= 0.004). Salt sensitivity significantly increased calcium excretion, water intake, and urine output when rats were fed a high-salt diet. Calcium excretion, water intake, and urine output of female S rats were time-dependent during high salt intake. Plasma 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D concentrations were markedly lower in female S rats fed a high-salt diet, but not in female R rats. Plasma parathyroid hormone and 1,25-dihydroxyvitamin D concentrations did not significantly differ between female S and R rats, but plasma concentrations of these two hormones at week 3 were significantly higher in S rats fed a high-salt diet compared with S rats fed a low-salt diet.Conclusions:Our data indicate that the calciuric response to salt is greater in female S compared with female R rats, thus supporting findings on the effect of salt sensitivity reported in several clinical studies with women. The greater calciuric response to salt of female S rats compared with female R rats, which was not seen in a previous study when male S rats were compared to male R rats, suggest a gender difference in the calciuric response to salt.

ISSN:0002-9629    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Background:Prevailing hospital practice dictates a protracted phase of observation for patients with chest pain to establish or exclude the diagnosis of myocardial infarction. Early diagnosis of acute myocardial infarction may improve patient care and reduce both complications and hospital costs. A study was performed to investigate the feasibility of early diagnosis of myocardial infarction within the first 9 hours of the hospital stay.Methods:The records of all patients admitted with chest pain within one calendar year were analyzed. The timing of creatine kinase-MB (CK-MB) quantification was determined with reference to the initial phlebotomy (time 0). An enzymatic diagnosis of myocardial infarction was assigned if any determination of CK-MB exceeded the upper limit of normal, and the diagnosis of each patient at or before 9 hours (early diagnosis) was compared to the ultimate diagnosis at 14 to 24 hours (final diagnosis) beyond initial assessment.Results:Of the 528 included patients, 523 patients (99.1%) had identical early and final diagnostic outcomes; 5 patients (0.9%) had conflicting results. An early diagnosis of myocardial infarction was assigned to 195 of the 528 patients (36.9%). Of these, 190 achieved the diagnosis within 9 hours (sensitivity 97.4%). The negative predictive value was 98.5%.Conclusion:Standard CK-MB mass measurements within 9 hours of arrival provided an accurate clinical assessment in > 99% of the cases. The high sensitivity and negative predictive values suggest that early diagnosis of myocardial infarction is feasible and reliable.

ISSN:0002-9629    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Background:When carbon monoxide binds to hemoglobin, it increases the affinity of hemoglobin for oxygen and shifts the oxygen dissociation curve to the left. The resulting decrease in sickling tendency could have clinical benefit, and carbon monoxide has been suggested as a treatment for sickle-cell disease. Furthermore, in sickle-cell disease, as in other hemolytic diseases, endogenous carbon monoxide production is increased because of increased heme catabolism.Methods:In the present study, we measured carboxyhemoglobin levels in sickle-cell patients and compared them with estimates of the hemolytic and the vaso-occlusive severity of the disease.Results:Significant correlation was found between carboxyhemoglobin (HbCO) levels and hematocrit, reticulocyte count, unconjugated bilirubin level, and percentage of irreversibly sickled cells. However, there was no significant correlation between carboxyhemoglobin levels and measures of the vaso-occlusive severity of the disease.Conclusions:The correlations between HbCO levels and measures of hemolytic severity are best explained by the known relationship between hemoglobin catabolism and CO production. The lack of correlation with vaso-occlusive severity may be due to the complex changes involved and the difficulty of quantifying vaso-occlusive severity.

ISSN:0002-9629    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Background and Objective:We describe an approach for the resolution of difficulties that some preclinical medical students appeared to have when acquiring patient interviewing skills.Setting:Two medical schools in Israel.Type of Study:Descriptive.Observations:Students’ difficulties were related to the inconsistency between the patient-centered approach that was emphasized in the preclinical teaching programs and the disease-centered (biomedical) approach that was practiced on the wards. Others were confused by ambiguous vocabulary and by the multiplicity of rules that they had to remember. Still others appeared to resent attempts to teach them what they thought was elementary courtesy, to reject counterintuitive interviewing rules, and to be bored by the repetitive nature of the practice sessions.Teaching Intervention:We used an integrated learner- and teacher-centered approach, which is based on the premise that students learn more effectively when autonomous and self-motivated than when responding to instructions from others. Rather than the students being lectured, they were asked to identify the problems in doctor-patient communication and to propose solutions. We conducted live demonstrations of patient- and disease-centered interviews and encouraged students to discuss the advantages and disadvantages of each of them. Lastly, we supervised students as they interviewed patients with increasingly difficult communication problems.Conclusions:The described approach is consistent with current theories of adult learning. It permits the instructor’s input and also supports students’ autonomy in identifying and resolving problems in patient interviewing and in choosing the balance between patient- and disease-centered interviewing styles according to the patient’s needs. The feasibility of our approach is conditional on the availability of instructors who feel comfortable conducting group discussions, are familiar with the literature on doctor-patient relations, and are experienced enough to demonstrate different interviewing techniques using live patients.

ISSN:0002-9629    

出版商:OVID    

年代:2001

数据来源: OVID

ISSN:0002-9629    

出版商:OVID    

年代:2001

数据来源: OVID

ISSN:0002-9629    

出版商:OVID    

年代:2001

数据来源: OVID