Fixation of a trabecular metal knee arthroplasty component. A prospective randomized study.

BACKGROUND: Uncemented tibial components of total knee replacements have lower survival rates than cemented components. Radiostereometric analysis is a highly accurate, effective tool for investigating new implant designs. The purpose of this study was to compare an uncemented Trabecular Metal tibial component with a conventional cemented stemmed tibial component of the same design. METHODS: Seventy subjects undergoing total knee replacement were randomized to receive either the Trabecular Metal or the cemented tibial component. Radiostereometric analysis of micromotion of the tibial components was performed postoperatively at six, twelve, and twenty-four months, and the maximum total point motion of the implant and three-dimensional translations and rotations were recorded. RESULTS: Follow-up was complete for twenty-eight subjects in the Trabecular Metal group and twenty-one subjects in the cemented group. A subset of the Trabecular Metal components migrated extensively in the postoperative period, but all stabilized by one year and the proportion considered to be at risk for early aseptic loosening was 0.0 (95% confidence interval, 0.0 to 0.12) in the group as a whole. Four cemented components were considered to be at risk for early aseptic loosening (proportion at risk, 0.19; 95% confidence interval, 0.08 to 0.4). CONCLUSIONS: This study suggests that the Trabecular Metal component may be an effective alternative to the standard cemented tibial component.

Patient persistency with pharmacotherapy in the management of glaucoma.

PURPOSE: To evaluate persistency with monotherapy in the treatment of glaucoma in patients new to pharmacological management. METHODS: This population-based, retrospective cohort study, using managed care administrative claims data, included patients who were 20 years of age and older and who initiated monotherapy with betaxolol, brimonidine, dorzolamide, latanoprost, or timolol between May 1999 and January 2001. Follow-up continued through January 31, 2001, and prescription refill records for all ocular hypotensive medications were extracted for the full 21-month study period. The primary outcome measures were discontinuation and change (switching/adding on) of the index ocular hypotensive medication. Rates of discontinuation and discontinuation/change were compared using Cox regression methods; survival curves were generated. RESULTS: In all, 14,539 patients were prescribed any ocular hypotensive drug during the study period, and 2850 patients met all inclusion criteria. Patients treated with betaxolol, brimonidine, dorzolamide, or timolol were significantly (p < 0.05) more likely to discontinue and to discontinue/change the index therapy than were those treated with latanoprost. Results were confirmed in analyses adjusted for age and sex. CONCLUSIONS: Patients initially treated with latanoprost monotherapy are more persistent than those who begin treatment with beta-blockers, brimonidine, or the carbonic anhydrase inhibitor dorzolamide. Greater persistency with an initial ocular hypotensive therapy may improve health outcomes and reduce long-term costs to patients and health plans by limiting the increased resource use associated with discontinuations or changes in therapy.

Women's labor in Bangladesh and Sri Lanka: the trade-off with technology.

PIP: This article assesses the impact of technological changes on women's employment in Bangladesh and Sri Lanka. The findings of the research initiated by UN University Institute for New Technologies were used to determine how globalization and technological change alter women's role in the society and the economy in two comparable yet contrasting economies. In Bangladesh and Sri Lanka, the manufacturing and service sectors have grown as a result of the globalization strategies of the two governments. The use of new technologies in work processes has been a function of the countries' participation in global trade, and high levels of foreign direct investment have been the source of much job creation. In both countries, a large proportion of the new industrial workforce consists of women. However, while creating new employment opportunities and improving pay and conditions for some women, jobs tend to be based on flexible, short-term forms of employment with serious health and safety risks. Furthermore, technological advancement like automation increases the number of unemployed "unskilled" workers. Lastly, these two countries seem unaware of the implications of new technology, which makes them vulnerable and weak participants in the global market. Therefore, awareness can be enhanced by a greater exposure to technology through work experience and good quality training.^ieng

Dexamethasone therapy for isosexual precocious pseudopuberty caused by generalized glucocorticoid resistance.

Generalized glucocorticoid resistance presents with clinical features secondary to excess production of mineralocorticoids and adrenal androgens. It is our hypothesis that these clinical and biochemical features will respond to glucocorticoid therapy. We tested this hypothesis in a boy with generalized glucocorticoid resistance and increased adrenal androgens. Dexamethasone was administered from age 7 6/12 yr until the onset of true puberty at 11 0/12 yr. Serum concentrations of cortisol and adrenal androgens decreased to the normal or near normal range. The accelerated precocity improved. Secondary sex characteristics did not progress; the difference between bone age and chronological age decreased from 3 1/2 yr to 2 yr, and the difference between height age and bone age decreased from 2 yr to 1/2 yr. We conclude that dexamethasone is effective and safe therapy for the sexual precocity of generalized glucocorticoid resistance.

An unusual presentation of McCune-Albright syndrome confirmed by an activating mutation of the Gs alpha-subunit from a bone lesion.

The McCune-Albright syndrome (MAS) is characterized clinically by polyostotic fibrous dysplasia, café-au-lait skin lesions, sexual precocity, and various other endocrinopathies. Recent investigations suggest an etiological role for embryonic somatic missense mutations that predict the substitution of a His or Cys for Arg at amino acid 201 of the Gs alpha-subunit (Gs alpha). Identification of these mutations in affected tissues is a sensitive assay that may help define a more complete clinical spectrum of the MAS. We investigated a woman who developed fibrous dysplasia 24 yr after premature menstruation. To determine if this was an unusual MAS variant, DNA and RNA were analyzed from affected and unaffected tissues. From samples of affected rib and normal rib DNA was extracted, amplified by polymerase chain reaction, subcloned, and sequenced. RNA was extracted from affected bone, reverse transcribed, amplified by polymerase chain reaction, subcloned, and sequenced. DNA sequence predicting a His for Arg substitution at Gs alpha amino acid 201 was found in 47% of the recombinant plasmids from DNA of affected bone and 17% of the plasmids from DNA of unaffected bone; a significant (P < 0.05) difference in frequency. The His201 substitution was found in 42% of the recombinant plasmids from RNA of affected bone. We conclude that this clinical variant is qualitatively indistinguishable from presentations of the complete MAS.

A mutation of the glucocorticoid receptor in primary cortisol resistance.

The precise molecular abnormalities that cause primary cortisol resistance have not been completely described. In a subject with primary cortisol resistance we have observed glucocorticoid receptors (hGR) with a decreased affinity for dexamethasone. We hypothesize that a mutation of the hGR glucocorticoid-binding domain is the cause of cortisol resistance. Total RNA isolated from the index subject's mononuclear leukocytes was used to produce first strand hGR cDNAs, and the entire hGR cDNA was amplified in segments and sequenced. At nucleotide 2,317 we identified a homozygous A for G point mutation that predicts an isoleucine (ATT) for valine (GTT) substitution at amino acid 729. When the wild-type hGR and hGR-Ile 729 were expressed in COS-1 cells and assayed for [3H]-Dexamethasone binding, the dissociation constants were 0.799 +/- 0.068 and 1.54 +/- 0.06 nM (mean +/- SEM) (P < 0.01), respectively. When the wild-type hGR and hGR-Ile 729 were expressed in CV-1 cells that were cotransfected with the mouse mammary tumor virus long terminal repeat fused to the chloramphenicol acetyl transferase (CAT) gene, the hGR-Ile 729 conferred a fourfold decrease in apparent potency on dexamethasone stimulation of CAT activity. The isoleucine for valine substitution at amino acid 729 impairs the function of the hGR and is the likely cause of primary cortisol resistance in this subject.

Editorial.

PIP: The focus on gender and the environment highlighted important features of articles included in this issue. The general concern was that women are not considered in the thinking about economic development and environmental issues. The Joan Davison article noted the close relationship of women to their surroundings and degradation, which was affected by debt and structural adjustment, trade, aid, war, and the social structure. Women's access to land and their marginal role in society, law, and economic life needs to be addressed by the environmentally aware. The Judy Adoko article reported on the outrageous criticism by development workers in Uganda of women using wood for fuel, when little attention is focused on the commercialization of firewood. The important communication was that women are limited in their choices and make the most of what they have out of necessity, and not out of a short-term solution compromising their children's future. Environmental stability can be achieved in part through removal of the causes of women's poverty. Women's time and energy are tightly constrained; Irene Guijt's views reflected the concern about assumptions that women's participation in environmental protection can be secured without direct benefit to them. The problem of women's health was considered by Joanne Harnmeijer and Ann Waters-Bayer, who focused on increased agricultural productivity projects which have not taken into account the increased burden of work in time or effort or in terms of the impact of children, both as producers and as a demand on time, energy, and health. Population control has been justified because of its impact on consumption of natural resources in developing countries, without due consideration of developed countries consumption patterns. Hazards in the environment and work place have increased with increasing international trade and industrialization. Industry attracting women workers has been established without concern for sanitation, disease, pollution, or social services. Women plantation workers have often been given the most hazardous jobs with agrochemicals. Rasheda Begum detailed the impact of natural disasters on women. Environmental solutions must be tailored to specific conditions, rather than at the expense of global unification and self-evident assumptions. Acceptability and sustainability for women must be a feature of environmental protection.^ieng

Survey of ACCP members regarding use of computers and information processing.

A questionnaire was sent to a random sample of 480 members of the American College of Clinical Pharmacy to determine their opinions on various issues relating to computer technology and the future role of computers in information processing in pharmacy. Results from the 335 evaluable responses revealed nearly universal use of computers. Word processing was the most common application and IBM or compatible computers were the dominant machines. Respondents used a wide variety of generalized and specialized programs, especially electronic communication products. Computer technology is expected to have a major impact on routine aspects of pharmacy practice, although, respondents were split on its impact on more cognitively intensive functions.

Segmenting the antihistamine market: an investigation of consumer preferences.

The authors combine conjoint analysis and contingent valuation into a single model to estimate the value of product attributes for antihistamine drugs. One hundred forty-three allergic rhinitis suffers were examined. The results show evidence of validity in the data. Cluster analysis reveals five segments of patients with various patterns of preference for product attributes.

Primary cortisol resistance presenting as isosexual precocity.

Primary cortisol resistance (PCR) is a rare cause of hypercortisolism and usually does not produce clinical manifestations. This report describes primary cortisol resistance in a boy with isosexual precocity. A 6 7/12-yr-old boy had Tanner stage 3 pubic hair, accelerated linear growth, and advanced bone age (10 yr), but normal (for age) tests. There were no features of glucocorticoid excess. Serum androstenedione and dehydroepiandrosterone concentrations were 4.7 +/- 0.3 nmol/L (mean +/- SEM of four measurements; normal less than 1.2) and 13.5 nmol/L (single measurement; normal, 1.0-2.2), respectively. The serum testosterone concentration was 0.9 nmol/L (normal, less than 0.7), and FSH and LH were normal. Serum cortisol concentrations were 1590 +/- 110 nmol/L (normal, 190-630) and 580 +/- 60 nmol/L (normal, 50-410) at 0800 and 2000 h, respectively. Serum cortisol responded normally to insulin-induced hypoglycemia. Glucocorticoids and adrenal androgens were resistant to suppression by dexamethasone. The Kd of [3H]dexamethasone binding to the glucocorticoid receptors of mononuclear leukocytes was increased (6.4 +/- 0.8 nM; mean +/- SEM of four determinations; normal, 1.4-3.4; P less than 0.001), but the binding capacity was normal. This patient with isosexual precocity has PCR, as indicated by functionally abnormal glucocorticoid receptors and hypercortisolism without other clinical or biochemical manifestations of Cushing's syndrome. Excessive adrenal stimulation by ACTH caused increased secretion of both cortisol and adrenal androgens, and the latter caused the clinical manifestations. PCR should be considered in other male children with isosexual precocity or female children with heterosexual precocity.

Changing patterns of neuroleptic dosage over a decade.

A study of patterns of neuroleptic dosage for 206 schizophrenic inpatients showed significant differences over time and among three centers--a general hospital psychiatric unit, a community mental health center, and a state hospital. In 1982 patients' mean dose at discharge was higher than the peak mean daily dose in 1973, and high-potency neuroleptics were being used almost exclusively. The mean length of stay decreased from 49 days in 1973 to 34 days in 1982. The possible relationship, if any, between increasing dosage, decreased length of stay, and the switch from low-potency to high-potency neuroleptics remains undetermined.

Family attitudes and patient social adjustment in a longitudinal study of outpatient schizophrenics receiving low-dose neuroleptics: the family's view.

Adverse effects of neuroleptic medication have led to the attempt to develop alternative strategies for the treatment of schizophrenia, but it is generally conceded that these strategies may have their own negative outcomes in the form of symptom exacerbation, reduced social performance and worsened family interactions. This paper examines the effect of one such strategy, low doses of medication, on the social adjustment of and family response to chronic schizophrenic outpatients. Patients who were randomly assigned to either a low-dose or standard-dose condition were rated by their families on various aspects of social adjustment. Despite a considerably higher relapse rate in the low-dose condition, families reported patients in the low-dose condition to be no poorer in their social adjustment than standard-dose patients. In addition, families of low-dose patients were more satisfied with their patients' overall level of adjustment and were no more rejecting at endpoint than families of standard-dose patients. Low-dose patients were viewed even more favorably when patients who relapsed were excluded from the analysis. Negative family attitudes, particularly rejection, measured at study entry, were found to predict time to relapse in the low-dose group. Implications for treatment and family intervention are discussed.