Alpha 2-macroglobulin and tissue inhibitor of metalloproteinases: collagenase inhibitors in human preovulatory ovaries.

Extensive remodeling of the follicular extracellular matrix occurs during the process of ovulation. This remodeling involves the breakdown of collagen, which is regulated, in part, by the action of the metalloproteinase collagenase and its associated inhibitors. In the present study, follicular metalloproteinase inhibitors were characterized to determine whether they were serum-borne or of ovarian origin, possibly a tissue-derived inhibitor known as tissue inhibitor of metalloproteinase (TIMP). Human follicular fluid and granulosa cells were obtained from preovulatory follicles of patients in an in vitro fertilization program. Chromatographic separation of follicular fluid on Sepharose 6B resulted in two peaks of inhibitory activity. The large molecular radius (Mr) inhibitor was similar in size to the serum-borne metalloproteinase inhibitor alpha 2-macroglobulin (i.e. Mr 700,000) whereas the small Mr inhibitor approximated the size of TIMP (i.e. Mr 29,000). Incubation of aliquots from either of the two peaks of inhibitor activity or an alpha 2-macroglobulin standard with an antibody to alpha 2-macroglobulin decreased the inhibitory activity in both the large Mr peak and the alpha 2-macroglobulin standard by 86.6 +/- 1.7% and 71.5 +/- 7.7% (n = 4, P less than 0.005), respectively, implying cross-reactivity with the alpha 2-macroglobulin antibody. The inhibitory activity in the small Mr peak, however, was unchanged. Northern analysis of total granulosa cell RNA demonstrated TIMP messenger RNA (mRNA) in all eight granulosa cell samples examined whereas alpha 2-macroglobulin mRNA was virtually undetectable. A positive correlation (r = 0.85, P less than 0.01) was observed between the levels of TIMP mRNA and the ratio of the follicular estradiol-progesterone concentration. However, inhibitor activity in the follicular fluid was not correlated with the levels of TIMP mRNA (r = 0.05). These findings confirm the presence of alpha 2-macroglobulin in follicular fluid and demonstrate that human preovulatory granulosa cells contain mRNA for TIMP, an inhibitor that regulates metalloproteinases such as collagenase, gelatinase, and proteoglycanase. Additionally, the expression of TIMP mRNA is steroid related and may be hormonally regulated. It is proposed that TIMP produced in the granulosa cell compartment in conjunction with alpha 2-macroglobulin from the serum may act to control the site and extent of ovarian connective tissue remodeling.     

Restrained drinking: risk factor for problems with alcohol?

A seven-item Drinking Restraint Scale (DRS) has been developed which indicates that a style of alcohol consumption, equivalent in a number of ways to the style of food consumption termed eating restraint, may exist. Several hypothesized relationships between DRS scores and other drinking-related measures were confirmed. A restrained drinking style was associated with: more extreme patterns of alcohol consumption; a higher proportion of drinking occasions that result in intoxication; more external styles of alcohol consumption control; and more alcohol-related negative consequences. The latter three relationships were found even when heavy drinkers were excluded from the analysis, which suggests that these relationships are not dependent on a heavy drinking pattern. These findings encourage continued investigation of drinking restraint as a risk factor for developing problems with alcohol.     

Improving patient care outcomes by teaching quality improvement to medical students in community-based practices.

PURPOSE: As part of the Undergraduate Medical Education for the 21st Century (UME-21) project, the University of Connecticut School of Medicine developed and implemented a quality improvement curriculum. This study examined its impact on educational outcomes and the effect of the students' continuous quality improvement (CQI) projects on the quality of care delivered at community practice sites. METHOD: Seventy-seven second-year students working in groups of two to four conducted CQI projects on diabetes mellitus at 24 community-based primary care practices. They collected baseline data, implemented a results-specific intervention, and re-assessed quality indicators six months later. Students' knowledge, attitudes, and beliefs were evaluated using Likert-scale rated items as well as open-ended questions. RESULTS: A total of 513 charts were abstracted for the baseline sample, with 380 charts abstracted post-intervention. Attitudinal data revealed students acknowledged the benefit of outcomes measurement in clinical practice despite their frustration with the tedium of the chart-abstraction process. The rate of documentation of performances of foot and eye exams increased significantly from baseline to remeasurement (51.3% to 70.2%; p <.001 and 26.9% to 37.8%; p <.001, respectively). The mean value for glycohemoglobin dropped from 7.71% at baseline to 7.22% at remeasurement (p <.001). CONCLUSIONS: Medical student-driven CQI projects can improve the quality of care for diabetes at practices in which the students participate while introducing them and their preceptors to the process of quality measurement and improvement. Formative input from students should be used to optimize CQI experiences. Using medical students to lead CQI efforts in private practices may represent an underutilized resource to improve the care of patients in community-based practices.     

Randomized, controlled, blinded trial of doxapram for extubation of the very low birthweight infant

The objective of the study was to determine whether administering doxapram by infusion to the very low birthweight infant, prior to extubation during the first 3 weeks of life, would increase the incidence of successful extubation. The study patients, 56 infants of less than 1251 g birthweight and less than 30 weeks' gestation, were entered in the first 3 weeks of life when lung disease had started to improve. A randomized blinded trial was performed, with infants receiving 3.5 mg kg⁻¹ doxapram bolus, followed by an infusion at 1 mg kg⁻¹ h⁻¹, or placebo. Weaning from positive pressure ventilation was standardized and extubation occurred after a 12 h trial of an intermittent mandatory ventilation (IMV) rate of 6 breaths min⁻¹, if PCO₂ < 55 mmHg, pH > 7.26, and FiO₂ < 0.45. Study drug was continued for 48 h postextubation, and the infants were placed on nasopharyngeal continuous positive airway pressure (CPAP) for 72 h postextubation. Extubation failure within the first 72 h after extubation was objectively defined in terms of acidosis (pH < 7.26), hypercarbia (PCO₂ > 55 mmHg), excessive oxygen requirement (FiO₂ > 0.8) or frequent apnoea (more than three in 12 h, or more than two requiring face mask IMV in 24 h). No difference was noted in the frequency of successful extubation between the groups. Fifteen infants in each group were successfully extubated before the 10th day of the study. In conclusion, when given in accordance with this protocol doxapram does not increase the likelihood of successful extubation in the very low birthweight infant. Increasing successful extubations in this group of infants will require other strategies.     

Congenital hip dislocation: the importance of early detection and comprehensive treatment.

Hip dislocation is the musculoskeletal condition most commonly missed during neonatal examinations. Failure to diagnose the condition can lead to long-term disability and is a common target in pediatric legal suits concerning damage to the musculoskeletal system. Early neonatal assessment for hip dislocation includes an examination using the Barlow and Ortolani tests. Later examinations include assessment of gluteal folds, knee height and the degree of hip abduction. The preferred treatment is use of the Pavlik harness, an outpatient treatment regime that provides effective reduction in 90 percent of the cases. The harness uses flexion and free abduction to direct the femoral head into the acetabulum; it uses time, gravity and motion to position the hip in a reduced position. The harness requires three to six months of continuous wear for the hip to become radiographically stable. Health care providers are instrumental in diagnosing congenital hip dislocation and teaching families how to promote the infant's physical and psychosocial well-being. If this condition is not detected until after the infant is 6 weeks old, or the harness is ineffective after three weeks, skin traction, closed reduction and spica-cast application may be needed. Open reduction and recasting are also options. In rare cases, total hip replacement is necessary in later life.     

Rural-urban differences in access to Iowa child health services.

Indicators of access, utilization, and quality of available child health services as well as health status were obtained through a telephone survey of Iowa households with children under age six. These indicators were compared for rural-urban subsamples within an AFDC sample drawn from Iowa Department of Human Service files (N = 637), and within poverty (N = 129) and nonpoverty groups (N = 631) drawn from the population of all households in the state with children under age six. About 55 percent of all households studied were rural. Rural households were generally larger than urban households, more likely to be intact maritally, white, and earning a living from farming. The findings support the hypothesis that place of residence has an impact on access, utilization, and quality of child health services over and above family income, although not always to the disadvantage of rural children. Typical problems for rural children, irrespective of income, were access to pediatric care, greater travel time to providers, and discontinuity of well care and sick care. Rural children in all income groups had lower seat belt use than urban children; they were also less likely to have well visits and their providers showed less attentiveness to behavioral and developmental issues at these visits. Rural residency exacerbated problems in access to care for low income children, who were less likely to be eligible for AFDC/Medicaid than their urban counterparts. Medicaid coverage, however, did not eliminate rural-urban differences in receiving desired medical care.     

Community patterns of transdermal nicotine use and provider counseling

OBJECTIVES: To examine bow transdermal nicotine is prescribed and used in the general population, and to identity variables associated with successful smoking cessation in patch users. DESIGN: Retrospective cohort survey.