Risk of cardiovascular events in patients with polycystic ovary syndrome.

Women with polycystic ovary syndrome (PCOS) have increased prevalence of cardiovascular (CV) risk factors. However, data on the incidence of CV events are lacking in this population. Using Rochester Epidemiology Project resources, we conducted a retrospective cohort study comparing CV events in women with PCOS with those of women without PCOS in Olmsted County, Minnesota. Between 1966 and 1988, 309 women with PCOS and 343 without PCOS were identified. Mean (SD) age at PCOS diagnosis was 25.0 (5.3) years; mean age at last follow-up was 46.7 years. Mean (SD) follow-up was 23.7 (13.7) years. Women with PCOS had a higher body mass index (29.4 kg÷m2 vs 28.3 kg÷m2; p=.01). Prevalence of type 2 diabetes mellitus and hypertension and levels of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglycerides were similar in the two groups. We observed no increase in CV events, including myocardial infarction (adjusted hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.32 to 1.72; p=.48); coronary artery bypass graft surgery (adjusted HR 1.52; 95% CI 0.42 to 5.48; p=.52); death (adjusted HR 1.03; 95% CI, 0.29 to 3.71; p=.96); death due to CV disease (adjusted HR 5.67; 95% CI 0.51 to 63.7; p=.16); or stroke (adjusted HR 1.05; 95% CI 0.28 to 3.92; p=.94). Although women with PCOS weighed more than controls, there was no increased prevalence of other CV risk factors. Furthermore, we found no increase in CV events. While prospective studies are needed to confirm these findings, women with PCOS do not appear to have adverse CV outcomes in midlife.

Feasibility of quantitative pain assessment in outpatient oncology practice.

PURPOSE: Although physicians view failure to assess pain systematically as the most important barrier to outpatient cancer pain management, little is known about pain assessment in this setting. We sought to determine whether pain is routinely assessed and whether routine quantitative pain assessment is feasible in a busy outpatient oncology practice. PATIENTS AND METHODS: We conducted a pre- and postintervention chart review of 520 randomly selected medical and radiation oncology patient visits at a community hospital-based private outpatient practice. The intervention consisted of training health assistants (HAs) to measure and document patient pain scores by using a visual analog scale. The main outcome measures included HA documentation of patient pain scores, quantitative and qualitative mention of pain in the physician note, and analgesic treatment before and after the intervention. RESULTS: After the intervention, HA documentation of pain scores increased from 1% to 75.6% (P < .0001). Physician documentation increased from 0% to 4.8% for quantitative documentation (P < .01), and from 60.0% to 68.3% for qualitative documentation (not significant). Of all the patients, 23.1% reported significant pain. Subgroups with greater pain included patients actively receiving radiation treatments and patients with lung cancer. Of patients with significant pain, 28.2% had no mention of pain in the physician note and 47.9% had no documented analgesic treatment. CONCLUSION: Quantitative pain assessment was virtually absent before our intervention but easily implemented and sustained in a busy outpatient oncology practice. Pain score collection identified a high prevalence of pain, patient subgroups at risk for pain, and a significant proportion of patients with pain that was neither evaluated nor treated by their oncologists.

Breast cancer prevention trials.

A new option for women at increased risk for breast cancer is chemoprevention--namely, an attempt to decrease breast cancer incidence by means of drug therapy. The efficacy of tamoxifen as a chemopreventive agent has been studied to date in three randomized, controlled trials, with varying results. Investigators with the National Surgical Adjuvant Breast and Bowel Project (NSABP) Breast Cancer Prevention Trial found that tamoxifen reduced the incidence of breast cancer by almost half, whereas British and Italian researchers found no significant benefit. This disparity is due, in part, to differences in the baseline breast cancer risk characteristics among the study populations, differing cohort sizes, variable use of hormone replacement therapy, and other factors. In this article, we review the eligibility criteria, treatment plans, and results from the three published randomized trials of tamoxifen versus placebo. We also review the data on raloxifene and breast cancer incidence. Chemoprevention with tamoxifen, in a non-study setting, is one option for women at increased risk for breast cancer. The ongoing Study of Tamoxifen and Raloxifene (STAR) is a randomized, double-blinded trial comparing the effectiveness of raloxifene with that of tamoxifen in postmenopausal women at increased risk for developing breast cancer. Until the results of this trial are available, it is premature to use raloxifene for primary breast cancer prevention.

Chromosomal insertion of phenazine-1-carboxylic acid biosynthetic pathway enhances efficacy of damping-off disease control by Pseudomonas fluorescens.

A disarmed Tn5 vector (pUT::Ptac-phzABCDEFG) was used to introduce a single copy of the genes responsible for phenazine-1-carboxylic acid (PCA) biosynthesis into the chromosome of a plant-growth-promoting rhizobacterium Pseudomonas fluorescens. The PCA gene cluster was modified for expression under a constitutive Ptac promoter and lacked the phzIR regulators. PCA-producing variants significantly improved the ability of the wild-type P. fluorescens to reduce damping-off disease of pea seedlings caused by Pythium ultimum, even under conditions of heavy soil infestation. Under conditions of oxygen limitation that are typical of the rhizosphere, PCA production per cell in vitro was greater than that recorded in fast-growing, nutrient-rich cultures. Similarly, when the in vitro nutrient supply was limited, P fluorescens::phz variants that produced the most PCA effectively competed against P. ultimum by suppressing mycelial development. Soil-based bioassays confirmed that the level of PCA biosynthesis correlated directly with the efficacy of biological control and the persistence of inocula in soil microcosms. They also showed that soil pretreatment with bacteria provides a suitable method for plant protection by reducing infection, effectively decontaminating the soil. These data demonstrate that the insertion of a single chromosomal copy of the genes for a novel antifungal compound, PCA, enhances the ecological fitness of a natural isolate already adapted to the rhizosphere and capable of suppressing fungal disease.

CLCN5 mutation Ser244Leu is associated with X-linked renal failure without X-linked recessive hypophosphatemic rickets.

This study demonstrates that a missense mutation in the voltage gated chloride channel, CLCN5, can cause X-linked renal failure without X-linked recessive hypophosphatemic rickets. A large kindred (Family A), initially evaluated in 1974 with an inherited syndrome characterized by hypercalciuria, nephrocalcinosis, low molecular weight proteinuria, renal tubular acidosis, and renal failure, was clinically re-evaluated and genetically characterized. Medical histories, physical examinations, blood chemistries, and 24-hour urine collections were obtained from 48 family members. Both female and male family members exhibited hypercalciuria, nephrolithiasis, and low molecular weight proteinuria. However, only men developed renal insufficiency, consistent with an X-linked recessive gene defect. Genetic linkage located the disease locus on the proximal short arm of the X chromosome (Xp11) where a voltage gated chloride channel gene, CLCN5, had previously been mapped. DNA sequence of the CLCN5 gene demonstrated a missense mutation (Ser244Leu) in affected family members. The same missense mutation has previously been shown to cause X-linked recessive hypophosphatemic rickets. No affected member of Family A had evidence of chronic hypophosphatemia, clinically significant rickets, or osteomalacia. We hypothesize that genetic background, environment, diet, or an unidentified modifying gene may account for the differing phenotypes resulting from this shared gene defect.

The management of cancer pain.

The majority of patients with cancer experience significant pain during their illness. Most cancer pain can be readily managed with oral analgesic therapy. However, cancer pain is often under-treated because of poor communication between physicians and patients and inadequate training of physicians in pain management. A systematic pain-oriented history, pain intensity assessment physical exam, and diagnostic evaluation are needed to delineate the cause of pain. A therapeutic plan can then be tailored to the patient's needs, preferences, and severity of pain. This paper reviews the evaluation and treatment of cancer pain, with guidelines for initiating and monitoring non-opioid and opioid analgesic therapy.

Hydromorphone polymer implant. A potential alternative to methadone maintenance.

Although methadone maintenance remains the best available treatment for opioid addiction, the need for daily oral dosing limits the effectiveness of methadone as opioid substitution therapy. Limitations of methadone maintenance include the administrative costs and burdensome time commitment associated with daily clinic visits, the danger of illicit diversion and accidental overdose associated with oral dosing, the low rate of treatment retention, and inadequate treatment capacity. A new opioid delivery device awaiting approval for clinical use may overcome some of these limitations. The device, a button-size polymer containing hydromorphone, releases near constant levels of opioid when implanted subcutaneously. Because of its location and duration of effect, the polymer may eliminate the need for daily clinic visits, reduce the costs and time constraints of treatment, reduce the risk of illicit diversion, provide an incentive for compliance with initial methadone maintenance treatment, and increase treatment capacity and retention.

Economics of baculovirus-insect cell production systems.

CONCLUSIONS: Commercial production of pharmaceutical proteins in baculovirus - insect cell systems is already a reality, and has therefore not been discussed in detail here. Cost-efficacy will depend on the productivity of the protein in culture, the dose, and the quantities required. According to the model described here, cost-effective production of baculoviruses for use in agriculture should also be feasible, assuming the commercial availability of a low-cost medium, together with a baculovirus with high productivity in cell culture, which is effective at a field application rate of 10(12) PIB ha(-1) or lower. All of these criteria appear to be achievable, given fairly modest advances over currently available technology. Given the relatively high fixed costs associated with production of baculoviruses on an agricultural scale in bioreactors however, profitability will depend on the scale of production. A substantial market opportunity (perhaps in the order of 1 million hectares) would be necessary in order to exploit the economies of scale achievable with baculovirus -insect cell production systems.

Acne induced by inhaled corticosteroids.

Four cases of acne apparently induced by inhalation of potent corticosteroids prescribed for the treatment of asthma are described. In one case there appeared to be a dose-dependent relationship. While acne induced by topical or systemic administration of corticosteroids is well recognized, acne following inhaled corticosteroids has not previously been reported.

The impact of DRGs on the cost and quality of health care in the United States.

The prospective Payment System (PPS) represents a fundamental change in the way the United States government reimburses hospitals for medical services covered under Medicare, a federal health care insurance program for the elderly and disabled. PPS replaced the retrospective cost-based system of payment for Medicare services with a prospective payment system. Under PPS, a predetermined specific rate for each discharge dictates payment according to the diagnosis related group (DRG) in which the discharge is classified. The PPS was intended to create financial incentives that encourage hospitals to restrain the use of resources while providing high-quality inpatient care. Both objectives appear to have been met under PPS. Hospital utilization has declined, average length of stay has fallen, and the locus of care has shifted from the inpatient setting to less costly outpatient settings. The growth in inpatient hospital benefits has slowed and the impending insolvency of the Medicare trust fund has been forestalled. Studies have found no deterioration in the quality of care rendered to Medicare beneficiaries. Neither the mortality rate nor the rate of re-admission (presumably related to premature discharge) increased under PPS. Indeed, PPS appears to have enhanced the quality of inpatient care by discouraging unnecessary and potentially harmful procedures, and by encouraging the concentration of complex procedures in facilities in which the high frequency of these procedures promotes efficiency. Incentive-based reimbursement also appears to have contributed to the growth in alternative delivery systems, such as HMOs and PPOs, which contain costs by maintaining a high volume of a limited range of services. The success of the PPS/DRG system in controlling costs and promoting quality in this country suggests its application in other countries, either as a method of reimbursement or as a product line management tool.

Drop-size measurement techniques for sprays: comparison of Malvern laser-diffraction and Aerometrics phase/Doppler.

The purpose of this paper is to compare the drop sizing results of an Aerometrics phase/Doppler particle analyzer with those of a Malvern laser-diffraction instrument. Measurements were performed on a small pressure-swirl atomizer. Since the laser-diffraction instrument measures a line-of-sight average through different regions of the spray while the phase/Doppler instrument characterizes the spray in a small volume, a conversion procedure was necessary prior to comparison. After conversion to equivalent forms, the point-measured average drop sizes exhibited similar trends throughout the spray, but the phase/Doppler values were generally larger. The total volume flow rate measured by the phase/Doppler instrument was inconsistent at different axial locations but significantly larger than the actual value at most locations.

A calibration protocol for serum-based secondary standards.

In this procedure, tentative calibration values are assigned to secondary standards by analysis of that material with the routinely used instrument calibrated by use of the former lot of material. Aliquots of serum from patients are then analyzed by the routine method and an appropriate calibration method in which primary standards are used. If the patient-sera results by both methods are the same, the assigned calibration value is assumed to be correct; if not, the calibration value of the secondary-standard material is adjusted to produce agreement in patient-sera results between the two methods. Thus, calibration of the routine method is linked via the calibration method to primary standards as the criterion of accuracy. This approach corrects for matrix interference of serum-based secondary standards. All that is expected for the secondary standard to obtain an accurate result for patient sera is to produce an analytical signal (irrespective of the origin of the signal) that is equivalent to the calibration value. Differences were significant between the secondary-standard calibration value we determined by this procedure and that assigned by the manufacturer for bilirubin, calcium, phosphorus, chloride, CO2, creatinine, glucose, sodium, uric acid, and commonly measured enzymes.

Giant cell arteritis in general practice.

The clinical syndrome of polymyalgia rheumatica is reviewed. The relationship of this disease with temporal arteritis is discussed, and I consider both syndromes have a pathological basis of generalised giant cell arteritis.Seven cases of polymyalgia and four cases of temporal arteritis were recorded during the six-year period (1969-1975) in one general practice.The outlines of management are discussed, with a plea for earlier recognition of the syndromes of polymyalgia rheumatica and temporal arteritis in general practice.