Knee osteoarthritis, degenerative meniscal lesion and osteonecrosis of the knee: Can a simple gait test direct us to a better clinical diagnosis.

INTRODUCTION: The purpose of the current study was to compare the gait patterns in patients with three differing knee pathologies - knee osteoarthritis (OA), degenerative meniscal lesion (DML) and spontaneous osteonecrosis of the knee (SONK) and a group of healthy controls. HYPOTHESIS: A simple gait test will detect differences between different knee pathologies. MATERIAL AND METHODS: Forty-seven patients with bilateral knee OA, 47 patients with DML, 28 patients with SONK and 27 healthy controls were included in this analysis. Patients underwent a spatiotemporal gait assessment and were asked to complete the Western Ontario and McMaster University (WOMAC) Index and the Short-Form (SF)-36 Health Survey. ANOVA tests, followed by Bonferroni multiple comparison tests and the Chi2 tests were performed for continuous and categorical variables, respectively. RESULTS: Significant differences were found for all gait measures and clinical questionnaires between healthy controls and all knee conditions. Patients with SONK differed from patients with bilateral knee OA and DML in all gait measures and clinical questionnaires, except for WOMAC subscales. There were no significant differences between patients with bilateral knee OA and patients with DML. Symmetry was also examined and revealed asymmetry in some gait parameters in patients with SONK and DML. DISCUSSION: Based on the differences in gait parameters that were found in the current study, adding an objective functional spatiotemporal gait test may assist in the diagnostic process of knee pathologies. TYPE OF STUDY: Case Control study Level III.

Epidemiology and prospects for prevention of rotavirus disease in India.

CONTEXT: With rotavirus vaccines now available globally, it will be useful to assemble the available evidence on the epidemiology and burden of rotavirus gastroenteritis in India, in order to weigh the urgency of introducing a vaccine to help control rotavirus disease. EVIDENCE ACQUISITION: We reviewed published studies on rotavirus infection and genotype distribution in India, as well as safety and immunogenicity studies of currently available vaccines. PubMed was searched for papers published after 1990, and several authors who are experts in the field recommended papers of known significance. RESULTS: Rotavirus accounts for close to 40% of hospitalizations for diarrhea in India, with more recent studies showing an increased proportion compared with older studies. There is substantial serotype diversity in India, although there is less intra-country variation than previously thought. Two genotypes, G1P[8] and G2P[4], account for roughly 50% of symptomatic infections in non-neonates. Currently licensed vaccines are safe, and although the efficacy appears lower in developing countries, given the extremely high incidence of diarrhea these could still be cost-effective interventions. CONCLUSIONS: The epidemiology and burden of rotavirus diarrhea is fairly well characterized in India. Introducing rotavirus vaccine into the UIP, along with adequate surveillance, should be an important part of efforts to reduce diarrhea mortality, the third leading cause of death among Indian children, and achieve the country's MDG goals.

Spondylolysis as a cause of low back pain in swimmers.

Low back pain (LBP) has recently become a common complaint in swimmers. The differential diagnosis of LBP in swimmers includes muscle and ligament sprains, Scheuerman disease, herniated disc, facet joint injury, tumors, infections, and spondylolysis. Although spondylolysis or listhesis is a frequent injury in the athlete, mainly in weightlifters, wrestlers, gymnasts, divers and ballet dancers, it is infrequently reported in swimmers. We have recently encountered four adolescent elite swimmers who complained of low back pain and were diagnosed as having spondylolysis. Three of the patients were either breast-strokers or butterfly swimmers. Plain radiography demonstrated the lesion in two patients. Increased uptake in bone scan was noted in all patients. CT was performed only in two patients and revealed the lesion in both. One patient was diagnosed within two weeks, and the diagnosis in the others was deferred for 2-7 months. The patients were treated successfully by reducing the intensity of their training program and the use of a corset for at least three months. Repeated hyperextension is one of the mechanisms for spondylolysis in athletes as is the case in breast-strokers and butterfly style swimmers. LBP in swimmers should raise the suspicion of spondylolysis. Plain radiography and bone scan should be performed followed by SPEC views, CT, or MRI as indicated. If the case is of acute onset as verified by bone scan, a Boston or similar brace should be used for 3 to 6 months in conjunction with activity modification and optional physical therapy. Multidisciplinary awareness of low back pain in swimmers, which includes trainers, sport medicine physicians, and physical therapists, should lead to early diagnosis and appropriate treatment.

An evaluation of the effectiveness of oral iron therapy in hemodialysis patients receiving recombinant human erythropoietin.

Iron balance is critical for adequate erythropoiesis in hemodialysis patients treated with recombinant human erythropoietin (EPO). The role of oral iron therapy in maintaining or replenishing iron stores has not yet been well defined in such patients. We undertook a double-blind, placebo-controlled study to evaluate the efficacy of oral iron in 49 hemodialysis patients, divided into two groups, based on adequate or deficient iron stores. These groups were treated for 3 months with 150 mg elemental iron (Polysaccharide complex, Central Pharmaceuticals) or placebo, twice daily. Laboratory parameters were followed for five months. These parameters included: hematocrit (Hct), ferritin, transferrin saturation (Tsat), and zinc protoporphyrin (ZPP). A side-effects questionnaire was recorded monthly. Our results indicate that iron replete patients show evidence of falling iron stores during the study period; this observation was identical in both oral iron and placebo subgroups. Iron deficient patients had a significantly greater drop-out rate due to side effects when compared to iron replete patients (33% vs. 8%), despite equivalent responses to the side-effect questionnaire. We conclude: 1) Oral iron fails to maintain iron stores in iron replete patients; 2) Iron deficiency observed in this study may be due to poor medication compliance rather than side-effects.

Dr. Welford's chart notes.

We examined a robust and highly customizable menu-based charting program created and maintained by a practicing physician. The program offers a number of well-conceived and often elegantly executed features, integrating clinically related administrative and decision-support functions at a reasonable price. The drawbacks are lack of a graphic interface with mouse support, limited importing and exporting abilities, and dependence on a single individual for maintenance of the program.

Computer-based patient education: a progress report.

Computer-based teaching can help patients make informed decisions and protect both patients and physicians from the serious consequences of poor communication. This article discusses the benefits of computer-based patient education and its role in the emerging field of "patient informatics."

Munchausen syndrome by proxy: mother fabricates infant's hearing impairment.

Munchausen syndrome by proxy is a form of child abuse in which a mother causes or simulates her child's symptoms and presents the child for diagnosis and treatment. All previously reported cases have involved acute illnesses. This case study describes the ways in which a mother obtained a diagnosis of sensorineural hearing loss as well as amplification for her normally hearing infant.

Hypolipidemic effect of beta, beta'-tetramethyl hexadecanedioic acid (MEDICA 16) in hyperlipidemic JCR:LA-corpulent rats.

Short-term treatment of male and female obese JCR:LA-corpulent rats with beta,beta'-tetramethyl hexadecanedioic acid (MEDICA 16) resulted in a marked decrease (as much as 80%) in plasma triglyceride values, with a concomitant decrease in the highly elevated very low density lipoprotein (VLDL) levels of the corpulent rat. There were modest decreases in cholesterol levels and increases in low density lipoprotein and high density lipoprotein lipids. The concentrations of apolipoproteins C-II and C-III were decreased in both the whole-serum and the VLDL fractions. Food consumption, rate of weight gain, fasting insulin levels, and the integrated insulin response to an intravenous glucose load remained unaffected. The decrease in plasma VLDL may be accounted for by inhibition of liver long-chain fatty acid synthesis at the level of ATP citrate lyase, with a concomitant reduction of VLDL triglyceride production by the liver. This decrease in plasma VLDL production was accompanied by a twofold to threefold increase in the triglyceride and cholesterol components of the low density lipoprotein and high density lipoprotein fractions, together with a twofold to fourfold decrease in plasma apolipoprotein, indicating that activation of plasma VLDL catabolism may further account for the overall hypolipidemic effect induced by MEDICA 16. The overall hypolipidemic effect of MEDICA 16 may be expected to inhibit the spontaneous atherogenic sequelae induced in the corpulent rat by severe VLDL hyperlipidemia.

Inhibition of rat liver acetyl-CoA carboxylase by beta, beta'-tetramethyl-substituted hexadecanedioic acid (MEDICA 16).

Rat liver acetyl-CoA carboxylase activity was inhibited by the free as well as the CoA monothioester of beta, beta'-methyl-substituted hexadecanedioic acid (MEDICA 16) (Bar-Tana, J., Rose-Kahn, G. and Srebnik, M. (1985) J. Biol. Chem. 260, 8404-8410 (1985). (1) The CoA monothioester of MEDICA 16 served as a dead-end inhibitor with an apparent Ki of 2 microM and 58 microM for the biotin-carboxylated and noncarboxylated enzyme forms, respectively. MEDICA 16-CoA binding was not mutually exclusive with that of citrate and did not affect the avidin-resistance of rat liver acetyl-CoA carboxylase. (2) The free dioic acid of MEDICA 16 was competitive to citrate, having an apparent Ki of about 70 microM, as compared to a Ka of 2-8 mM for the citrate activator. Inhibition of the carboxylase by the free dioic acid of MEDICA 16 was accompanied by an increase in its avidin resistance. The resultant inhibition of acetyl-CoA carboxylase by MEDICA 16 and its CoA thioester, together with the previously reported citrate-competitive inhibition of ATP-citrate lyase by MEDICA 16, may account for the observed hypolipidemic effect of MEDICA 16 under dietary conditions where liver lipogenesis constitutes a major flux of liver lipid synthesis.

High-performance liquid chromatographic method for the simultaneous determination of the enantiomers of carvedilol and its O-desmethyl metabolite in human plasma after chiral derivatization.

Quantitative methodology for the simultaneous high-performance liquid chromatographic (HPLC) resolution and determination of the enantiomers of carvedilol, a new multiple-action antihypertensive agent exhibiting both vasodilator and beta-blocking activity, and its active metabolite, O-desmethylcarvedilol, in human plasma is described. The method involves reversed-phase solid-phase extraction of the analytes, followed by derivatization of the extract with the chiral reagent, 2,3,4,6,-tetra-O-acetyl-beta-D-glucopyranosyl isothiocyanate and injection of the resultant diastereoisomers onto a reversed-phase HPLC column coupled to a fluorescence detector. Both pairs of diastereoisomers formed are completely resolved within 12 min (resolution for the respective pairs is 2.26 and 3.32) and the baseline is clean and free from extraneous peaks. The assay is linear over the range 0.6-80 ng/ml of human plasma with a lower limit of detection of approximately 100 pg on-column for each of the enantiomers. The method can be adapted for a number of structural analogues of carvedilol and is currently applied in support of preclinical and clinical studies of the drug.

Hypolipidemic, antiobesity, and hypoglycemic-hypoinsulinemic effects of beta,beta'-methyl-substituted hexadecanedioic acid in sand rats.

Treatment of male sand rats kept on a balanced laboratory chow diet ad libitum with beta,beta'-tetramethyl-substituted hexadecanedioic acid (MEDICA 16) resulted in a hypolipidemic effect accompanied by an extensive reduction in adiposity, with a concomitant hypoglycemic-hypoinsulinemic effect. The overall effect was sustained as long as the drug was administered. The hypolipidemic effect of MEDICA 16 consisted of a 70 and 40% decrease in plasma triacylglycerols and cholesterol, respectively, and resulted from inhibition of liver lipogenesis and cholesterogenesis. Adipose reduction by MEDICA 16 treatment or calorie restriction consisted of a 75-90% decrease in the perirenal, omental, epididymal, and subcutaneous fat, with a 50% decrease in liver neutral lipids. The reduction in adiposity was accounted for by a respective decrease in the lipid content of individual adipocytes, with a concomitant decrease in the number of adipocytes of selected adipose tissues. The decrease induced in adiposity by MEDICA 16 treatment could not be accounted for by anorectic or cathartic effects of the drug. The hypoglycemic-hypoinsulinemic effect of MEDICA 16 consisted of amelioration of the tolerance of glucose with normalization of plasma insulin. It was accompanied by an eightfold increase in the number of insulin receptors in epididymal adipocytes, which was, however, counteracted by a decrease in their affinity for insulin. The receptor and postreceptor effects exerted by MEDICA 16 were similar to those of calorie restriction. The overall effect of MEDICA 16 in sand rats may reflect the pharmacological potential of MEDICA compounds in pathological hyperlipidemic-obesity-diabetic syndromes.

Hypolipidemic effect of beta, beta'-methyl-substituted hexadecanedioic acid (MEDICA 16) in normal and nephrotic rats.

Treatment of normal or puromycin aminonucleoside-nephrotic rats, kept on a balanced Purina chow diet, with beta, beta'-tetramethyl-substituted hexadecanedioic acid (MEDICA 16) (Bar-Tana, J., G. Rose-Kahn, and M. Srebnik. 1985. J. Biol. Chem. 260: 8404-8410) resulted in an acute reversible inhibition of liver lipogenesis and cholesterogenesis with a concomitant hypolipidemic effect which was sustained as long as the drug was administered. The hypolipidemic effect in normal and nephrotic rats consisted of 70-80% and 40-60% reduction in plasma VLDL-triacylglycerols and cholesterol, respectively, with a respective increase in the HDL-cholesterol/(VLDL + LDL)-cholesterol ratio. The observed hypolipidemic effect was accompanied by a 10-fold decrease in VLDL-apoC-III content with a concomitant enrichment of the VLDL fraction by VLDL remnants having an increased apoB-100/apoB-48 ratio. The pharmacological reduction of VLDL by MEDICA 16 may offer a treatment mode of choice for selected hyperlipidemic states.

Phenacetin O-deethylase activity of the rat: strain differences and the effects of enzyme-inducing compounds.

Phenacetin O-deethylase activity in microsomal fractions from liver of DA and Fischer rats has been determined. No major sex or strain differences were found. Kinetic analysis revealed two major components of O-deethylase activity in the liver of both strains of rats. Michaelis-Menten analysis revealed no major difference between the strains. Phenacetin O-deethylase activity is inducible by both 3-methylcholanthrene and phenobarbitone in DA and Fischer rats. 3-Methylcholanthrene selectively increases the high-affinity component of activity, by 20- to 25-fold, whereas phenobarbitone selectively increases the low-affinity component, by two- to three-fold. It is concluded that there is no major difference between the DA and Fischer strains in their ability to O-deethylate phenacetin. Thus, unlike poor metabolizers of debrisoquine in the human population, who appear also to have impaired phenacetin O-deethylase activity, the DA rat is deficient in only the former activity.

Routine monitoring of cyclosporine in whole blood and in kidney tissue using high performance liquid chromatography.

A simple isocratic reversed-phase high pressure liquid chromatographic procedure for the specific estimation of cyclosporine in 1 mL of whole blood using cyclosproin D as internal standard is described. The chromatographic conditions chosen afford a high degree of resolution and sensitivity, a prolonged analytical column life (four months), and complete analysis of ether extracts within 8 min. The limit of detection is 10 micrograms/L. Thirty-five patient samples can be analyzed in a single batch with a turnaround time of 7 hr. This method has been in use in the authors' therapeutic drug monitoring laboratory for nearly two years. It can be simply adapted for the analysis of cyclosporine in kidney samples as a possible aid in the diagnosis of therapeutic failure or toxicity in renal allograft recipients. Examples are given to illustrate the usefulness of frequent monitoring of cyclosporine in stabilizing graft function after organ transplantation.

Photosensitivity and photodermatitis in childhood.

Photosensitivity disorders of children are uncommon, except for banal overexposure reactions to sunlight. Although the long-term sequelae of chronic or intense sun exposure are not often seen in children, physicians should advise patients of the harmful effects and irreversible skin damage that results from unduly prolonged sun exposure. Damage accumulates over the years to cause premature aging, senile elastosis, actinic keratoses, and squamous- and basal-cell carcinomas. Besides the pigmentary changes, wrinkles, and skin cancers--genuine sources of altered appearance and morbidity--we now know that sunburned children develop a higher incidence of melanoma, which is not a rare cause of death in young adults. In Australia, where the incidence of melanoma is highest, a strong correlation exists for melanoma in children who get sunburn before the age of 10. Also, the incidence of melanoma is 50 times as great in bikini wearers who get sunburn as in girls who wear one-piece bathing suits.