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.

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.

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.

Drug concentration in saliva.

It is possible to predict plasma concentrations of drugs by measurement in saliva, obviating the need for venipuncture. Using a selection of weakly acidic and basic drugs, we have found this prediction reliable for drugs largely nonionized at normal plasma pH (phenytoin, phenobarbital, antipyrine) but unreliable for ionized drugs (chlorpropramide, tolbutamide, propranolol, meperidine). Deliberate alteration of saliva flow rate and pH using different stimuli have produced twofold changes in saliva drug concentrations. Wide interindividual variability of saliva pH is the likely explanation for the inconstancy of saliva to plasma concentration ratios for ionized drugs.

Biphasic O-deethylation of phenacetin and 7-ethoxycoumarin by human and rat liver microsomal fractions.

Human and rat liver microsomal fractions exhibit non-linear Michaelis-Menten kinetics in the O-deethylation of both phenacetin and 7-ethoxycoumarin. Comparison of various models indicated that the data were best described by a biphasic plot, which could be interpreted in terms of two populations of cytochrome P-450. The K(m)'s of the high affinity phase of 7-ethoxycoumarin O-deethylase activity were 1.8 +/- 0.4 microM and 2.3 +/- 0.4 microM for human and rat respectively while the K(m)'s of the low affinity phase were 205 +/- 20 microM and 237 +/- 59 microM in the two species respectively. V(max) of the high affinity phase of human 7-ethoxycoumarin O-deethylase activity was 96.9 +/- 19.0 pmol mg(-1) min(-1) and the activity of the corresponding phase in the rat was 2.7 times greater. The activities of the low affinity phase were 10-15 times greater than the respective activity of the high affinity phase. Rat and human also had similar values for the K(m)'s of the two phases of phenacetin O-deethylase activity, around 5 microM for the high affinity phase and 300 microM for the low affinity phase. Total activity was very similar in the two species, 1500-1750 pmol mg(-1) min(-1) and the difference between the two phases of activity was only 2.5-fold in man and 10-fold in rat. Studies on the effects of the in vitro modifiers of monooxygenase activity alpha-naphthoflavone and metyrapone further supported the hypothesis that the two phases of O-deethylase activity represent two different forms or populations of cytochrome P-450.

Acropustulosis of infancy.

Acropustulosis of infancy (Al) is a syndrome consisting of pruritic pustules that are found primarily on the extremities of infants. It is uncommon, but not rare, and persists about two years. In two infants in whom Al began at birth, there was a striking response to sulfones. There was no response to other therapy. Laboratory findings are not diagnostic for Al. Similar histopathologic changes (subcorneal pustules) can be found in other eruptions of infancy.

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.

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.

Strategies for knowledge acquisition.

This paper describes knowledge acquisition strategies developed in the course of handcrafting a diagnostic system and reports on their consequent implementation in MORE, an automated knowledge acquisition system. We describe MORE in some detail, focusing on its representation of domain knowledge, rule generation capabilities, and interviewing techniques. MORE's approach is shown to embody methods which may prove fruitful to the development of knowledge acquisition systems in other domains.

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.

Teaching interpersonal skills in family practice: results of a national survey.

The increasing recognition of the importance of a well-developed set of interpersonal skills to the competent family physician has resulted in a rapid growth in the formal teaching of interpersonal skills within family practice residencies. Of the 168 programs responding to a national survey of family practice residencies, 88 percent indicated that they have formal programs in interpersonal skills. It is estimated that there are well over 500 family practice faculty members who have special responsibilities in teaching interpersonal skills. While most programs address the component skills of the interpersonal process (eg, demonstrating empathy, information gathering, information giving, and psychological intervention), it is of concern that only about half offer explicit training in patient education (53 percent), specific types of counseling (eg, family counseling, 55 percent), or some of the specific interpersonal skills important in team practice and practice management (eg, supervisory skills). One of the most striking findings was that 88 percent of the reporting programs use videotechnology, with 77 percent of these planning to increase their use. Although most programs evaluate their interpersonal skills training using both indirect and direct assessment methods, only 25 percent attempt to use patient outcome as a measure of teaching effectiveness.

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.