NID67, a small putative membrane protein, is preferentially induced by NGF in PC12 pheochromocytoma cells.

In an effort to identify genes involved in neuronal differentiation, we have used representational difference analysis (RDA) to clone cDNAs that are preferentially induced by nerve growth factor (NGF) vs. epidermal growth factor (EGF) in PC12 pheochromocytoma cells. We now report the cloning of a previously unknown primary response gene, NID67. In addition to a robust induction by NGF and FGF, both of which cause PC12 cells to differentiate, NID67 is strongly induced by forskolin, A23187 and ATP. EGF, TPA and KCl induce NID67 only weakly. NID67 mRNA is most abundant in heart, ovary and adrenal. Modest levels are present in most brain regions, testis, thyroid, thymus, pituitary, kidney and intestine; little NID67 is present in skeletal muscle and cerebellum. The NID67 cDNA contains a 180 bp open reading frame (ORF) that encodes a 60 amino acid protein. The central 29 amino acids are very hydrophobic and very likely comprise a transmembrane domain. Mouse and human NID67 cDNAs contain an ORF similar to NID67; the rat and human protein sequences are 85% identical whereas the rat and mouse sequences are 92% identical. In vitro transcription and translation reactions confirmed that the ORF we identified produces a 6000 Da protein product. Several small membrane proteins are similar to NID67; they contain a transmembrane domain and little more. All of these proteins participate in forming or regulating ion channels. NID67 may play a similar role in cellular physiology.

p53 mutations isolated in yeast based on loss of transcription factor activity: similarities and differences from p53 mutations detected in human tumors.

p53 is a transcriptional activator that plays a key role in the integration of signals inducing cell division arrest and programmed cell death. Moreover, p53 is a tumor suppressor gene, mutations of which are the most commonly detected mutations in diverse malignancies. In order to better understand the significance of p53 mutations to human cancer, we isolated mutant alleles of p53 that had lost transcription factor activity in yeast. These mutant alleles were evaluated for their precise changes, their activity against three different p53 responsive enhancers and their ability to act in a transdominant fashion to the wild type allele. While many of the mutations isolated in yeast resembled those found in human tumors, consistent with the importance of transcription factor activity for p53 in mammalian cells, the mutational spectrum obtained was dependent upon the p53 enhancer employed for the selection. Some mutations specifically inactivated p53 in yeast for a single enhancer element. Virtually all missense mutations tested had a dominant inhibitory effect on wild type p53 in yeast. Since some of these transdominant mutations are virtually unknown in human tumors we conclude that transdominance, per se, fails to predict which mutations occur frequently in cancer.

Women who lead.

This essay reviews aspects of historical and cultural changes that now permit women increasing opportunities to lead both women and men. Women assuming leadership responsibilities undergo psychic reorganization, reworking their personal histories and their modes of interaction. The author challenges women who inhibit their leadership potential to scrutinize their attitudes and to consider the implications for the next generation of women.

Inpatient treatment patterns of human immunodeficiency virus-associated Pneumocystis carinii pneumonia in New York State Medicare patients.

Hospital charts were reviewed to ascertain the frequency with which patients with human immunodeficiency virus (HIV)-associated Pneumocystis carinii pneumonia (PCP) were being managed in accordance with current guidelines or recommendations in New York State for the calendar year 1993. Comparisons were made between hospitals that are designated by the New York State Department of Health as comprehensive treatment centers--designated acquired immunodeficiency syndrome (AIDS) centers--and all other hospitals. For patients who had been on PCP prophylaxis before admission, 34% had documentation of positive histologic evidence for PCP infection during the studied hospitalization period. Of all patients not on PCP prophylaxis at the time of admission, 94% had at least one of the diagnostic tests for PCP done during the PCP hospitalization. Eighty-one percent of all patients had either pulse oximetry or an arterial blood gas determination. Seventy-seven percent of all patients with a PO2 equal to or less than 70 mm Hg received steroids. All eligible patients received one of nine possible treatment combinations, which included either single drug therapy, multiple drug therapy, or participation in a clinical trial. Sixteen percent of eligible patients had no documentation of receiving PCP medication at discharge. Proportions receiving diagnostic or treatment interventions were usually higher in designated AIDS centers than in non-designated AIDS centers.

Surgical antibiotic prophylaxis and Clostridium difficile toxin positivity.

OBJECTIVE: To examine a possible relationship between prophylactic antibiotic therapy (PAT) and the development of Clostridium difficile toxin (CDT) positivity. DESIGN: Retrospective case-control study. SETTING: Tertiary care medical center in New York, NY. PATIENTS: A total of 357 patients, admitted from November 1992 to April 1994, with positive. CDT assays. Of these, 23 patients (6%) received only PAT for elective surgical procedures. Thirty-nine patients were matched as controls for age, sex, and surgical procedure. MAIN OUTCOME MEASURES: Both CDT positivity and inappropriate use of PAT. RESULTS: Appropriate PAT was used in 26 (42%) of 62 patients (17% cases, 56% controls). The Mantel-Haenszel estimator for the summary odds ratio for the development of CDT positivity from inappropriate use of PAT was 5.1 (95% confidence interval, 1.10 to 23.64). Main duration between the operation and the final antibiotic dose was significantly longer in the CDT-positive group compared with the control group (3.1 vs 1.7 days, P < .05). The length of hospital stay was significantly longer in the CDT-positive group compared with the control group (16.5 vs 10.2 days, P < .05). CONCLUSIONS: The prolonged use of PAT in elective surgical cases increases the risk of developing CDT positivity. The appropriate use of PAT could significantly reduce health costs by eliminating unnecessary doses of antibiotics, by decreasing the rate of CDT positivity, and by shortening the hospital stay. Restrictive policies may need to be implemented to prevent further antibiotic misuse.

Quality of care problems among Medicare and Medicaid patients.

The purpose of this study was to characterize quality of care problems among Medicare and Medicaid inpatients in New York State. The patients selected for this study comprised 1991 and 1992 Medicare and all 1992 Medicaid inpatients in whom quality of care problems with actual or potential adverse effects were found. The patients in this study were drawn from public, proprietary, voluntary and teaching hospitals. A total of 1000 quality of care problems with either actual or potential adverse effects were found in 706 Medicare patients. Two hundred and seventy-five (275) quality of care problems with actual or potential adverse effects were found in 154 Medicaid patients. Premature death occurred in 53 (7.4%) of the 706 Medicare and in 42 (27.2%) of the 154 Medicaid patients. Treatment problems and monitoring failures accounted for the majority of quality of care problems with actual or potential adverse effects for both Medicare (63.0%) and Medicaid (75.7%) patients. Among Medicare patients, the treatment of infections and antibiotic use, fluid and electrolyte management, and inappropriate drug use were among the leading causes of quality of care problems. Attending physicians were associated with the majority of Medicare quality of care problems while house staff and attending physicians were associated with the majority of those among Medicaid patients. The results of this study indicate that there are several leading causes of quality of care problems among Medicare and Medicaid patients. Treatment problems and monitoring failures together comprise the majority of such problems. Among Medicare patients, it was found that most quality of care problems were associated with the treatment of infections and antibiotic use, fluid and electrolyte management, and inappropriate drug use. Most quality of care problems among Medicaid patients were associated with these categories as well as with labor and delivery problems, and poor discharge planning. The results of this study reflect the peer-review process in which providers are given an opportunity to respond to physician-reviewer decisions about the presence of actual or potential adverse effects. Such a process, which permits the presentation of additional data and information by providers, produces fewer final adverse outcome determinations than a process uniquely based on chart review. The quality of care problems observed in this study are amenable to focused educational interventions. Such remedial interventions could yield significant improvements in the quality of care for all patients.

Intensive psychotherapy of psychosis in a decade of change.

The past decade has brought extraordinarily rapid changes to the treatment of patients with severe mental illnesses. Changes evolved from advances in technologic and pharmacologic understanding as well as from complex fiscal and political pressures. Increasingly, regimented standardization in approach narrows the range of treatment options. Both within and outside of psychiatry, some disparage psychodynamic approaches. Psychiatrists are required to accept as plausible standardized and constricted time frames for evaluation and treatment. Thus we are asked to view the mind's storms as strictly neuronally based and to view our patients as passively compliant. By implication, treatment alliance is to be cemented by a prescription and authority. This paper presents clinical material drawn from hospital-based experience at The Chestnut Lodge Hospital, Rockville, Maryland, meant to place current trends in an historic context. The author offers possible alternatives to resignation in the face of current pressures.

Tuberculin screening: cost-effectiveness analysis of various testing schedules.

Because there is no tuberculin screening schedule currently recommended for adults, we used a Markov process in a cost-effectiveness analysis to determine an optimal strategy. We simulated the prognosis of a cohort of black 20-year-olds to evaluate the effects of various screening schedules with intradermal tuberculin and administration of isoniazid prophylaxis to those with positive results. The schedule with the lowest cost-effectiveness ratio is a single screening at 50 years of age, which costs $41,672 per quality-adjusted life year (QALY) gained. The cost-effectiveness ratio is nearly the same for all schedules involving a single screening between 30 and 70 years of age. Repeated screening strategies are less cost effective. Sensitivity analysis shows that the range of acceptable screening strategies changes significantly under alternate assumptions about the mortality from isoniazid hepatitis. However, screening at 50 years of age remains nearly optimal under the alternatives considered. Altering the values of other parameters generally produced only small changes. Tuberculin screening at 50 years of age should be added to primary care preventive practices because the strategy is as cost effective as standard health interventions and is robust to alternative assumptions. If further research confirms the base case assumptions about isoniazid toxicity, consideration should be given to increasing screening to every 10 years, which would produce a larger health benefit, albeit at substantially higher cost.

Tuberculosis prevention: cost-effectiveness analysis of isoniazid chemoprophylaxis.

Isoniazid chemoprophylaxis is not recommended for all persons infected with tubercle bacilli. Because of the small but significant risk of isoniazid hepatotoxicity, chemoprophylaxis is reserved for only those at the highest risk of tuberculosis activation. To evaluate this policy, we performed a cost-effectiveness analysis of isoniazid chemoprophylaxis for two populations with positive tuberculin skin tests: recent tuberculin converters, who are at high risk for activation, and older tuberculin reactors, who have a low risk for activation and for whom chemoprophylaxis is not now recommended. The cost-effectiveness ratios found were stable, despite wide variations in model assumptions and probability estimates. For high-risk tuberculin reactors, chemoprophylaxis resulted in net medical care monetary savings, extended life expectancy, and fewer fatal illnesses. For low-risk tuberculin reactors, chemoprophylaxis resulted in positive, but small, health effects. Because the cost to gain these positive effects were also small, the resulting cost-effectiveness ratios were reasonable and in the realm of accepted prevention strategies: $12,625 to gain one year of life and $35,011 to avert one death. These findings suggest that the current policy is too restrictive and that many in the large population of low-risk tuberculin reactors should be considered for isoniazid chemoprophylaxis.