The effect of aromatase inhibition on sex steroids, gonadotropins, and markers of bone turnover in older men.

There is evidence that estrogen decreases bone turnover in men as well as women. We therefore hypothesized that older men would show increased bone resorption in response to inhibition of the aromatase enzyme, which converts androgens to estrogen. Fifteen eugonadal men over 65 yr were treated for 9 weeks with 2.0 mg/day of anastrozole, an aromatase inhibitor. After 9 weeks of treatment, there were significant decreases in estradiol, estrone, and sex hormone-binding globulin levels by 29%, 73%, and 16%, respectively, and total testosterone increased significantly by 56%. Despite the limited decrease of estrogen and the increase in testosterone, C-telopeptide of type 1 collagen showed a progressive significant increase of 11%, 24%, and 33% (P for trend = 0.033) above baseline at 3, 6, and 9 weeks, respectively. N-telopeptide of type 1 collagen values were highly correlated with C-telopeptide of type 1 collagen, but the change in N-telopeptide of type 1 collagen was not statistically significant. Bone-specific alkaline phosphatase and N-terminal type I procollagen peptides showed significant decreases of 8% and 11% of baseline at 9 weeks. Osteocalcin decreased significantly by 30% at 18 weeks. We conclude that aromatase inhibition can reduce estrogen levels in older men, but this effect is limited, perhaps because of feedback stimulation of testosterone production, and that endogenous estrogen derived from aromatization of testosterone plays a role in bone metabolism of older men by limiting the rate of bone resorption.

Evidence for senescent convergence during human aging.

'Senescent convergence' is the observation that, with advancing age, multiple measurements of organ/body size, chemistry or function, reveal values for the higher percentiles which decrease faster than those of the lower percentiles. That is, values of the extremes appear to be converging with advanced age. In some cases, the equations for describing this can be modified to include a term that accounts for the percentile of the observation. Examples were given of calculating the age at which values of 2 different percentiles, of the property being measured, become identical ('age at convergence'). Exceptions to senescent convergence, such as related to diseases like osteoporotic vertebral fractures, were mentioned. It was noted that the curves of senescent convergence resembled the inverse of those of postnatal growth.

Analysis of mortality rate from carcinoma of prostate.

Age-specific mortality from carcinoma of the prostate was analyzed by drawing a line between the value at age 52 years and that at age 87. Slope of the line was relatively constant for the pooled years 1962-1966, 1967-1971 and 1972-1976 (maximum variation from the mean of 4.5%). However, the slope was 17.7% greater for the period 1977-1981 and 29.8% over the prior mean in 1987-1992. This was explored by two models. Mortality versus age was well described by a power function, with an increase in slope noted in the mid-1970s. An exponential growth model was also utilized and revealed the existence of a 'change point' around the year 1975. Hence, two models are available for further exploring the increase in age-specific mortality from carcinoma of the prostate which occurred in the mid-1970 period.

Elevated second-trimester maternal serum hCG alone or in combination with elevated alpha-fetoprotein.

OBJECTIVE: To evaluate the clinical significance of a second-trimester elevated maternal serum hCG in women carrying singleton, chromosomally normal fetuses. METHODS: The results of second-trimester maternal serum screening (alpha-fetoprotein [MSAFP], hCG, and unconjugated estriol) for 25,438 women were reviewed, and those with hCG values exceeding 3.0 multiples of the median (MoM) were identified. A control population was selected only on the basis of samples accessioned by the laboratory at the same time as the study group. Follow-up information was collected from physicians' offices for both groups. Incidence of fetal or neonatal loss (spontaneous abortion, fetal death, and neonatal death combined), preterm birth (before 37 weeks' gestation), small for gestational age, and preeclampsia were compared. RESULTS: Three hundred twenty-two women (1.3%) had hCG levels exceeding 3.0 MoM. In addition to chromosomal abnormalities and fetal death at the time of testing, this group showed a significantly higher incidence of fetal or neonatal death, preterm birth, low birth weight, and preeclampsia than did controls. For patients with elevated second-trimester hCG, many of the preterm deliveries occurred before 34 weeks' gestation. Logistic regression analysis indicated that hCG, MSAFP, and race were significant independent factors in predicting risk for adverse outcome. CONCLUSIONS: Similar to elevated AFP, elevated hCG is associated with poor pregnancy outcome. By combining the results of the two tests, it may be possible to improve substantially the identification of patients at very high risk for adverse outcomes.

Meta-analyses of surfactant replacement therapy of infants with birth weights less than 2000 grams.

OBJECTIVES: We conducted a meta-analysis of surfactant replacement therapy to determine (1) the efficacy of surfactant therapy in the reduction of short-term morbidity and long-term outcome in terms of bronchopulmonary dysplasia (BPD) and mortality; (2) whether there are differences in efficacy between modified natural surfactant and synthetic surfactant; (3) the effectiveness of prophylactic surfactant therapy; and (4) whether there are differences in efficacy between the prophylactic approach and the rescue strategy. STUDY DESIGN: We included studies in which infants with birth weights between 500 and 1500 gm were eligible. Studies were grouped into the following categories: (1) rescue therapy with modified natural surfactant; (2) rescue therapy with synthetic surfactant; (3) prophylaxis with modified natural surfactant; (4) prophylaxis with synthetic surfactant; (5) prophylaxis versus rescue studies; (6) modified natural surfactant versus Exosurf (Burroughs-Wellcome Co., Research Triangle Park, NC) studies. The relative risk ratios, corrected for study size, were calculated for the outcome variables (pneumothorax, incidence of BPD, survival, survival without BPD, prevention of hyaline membrane disease [HMD], and intraventricular hemorrhage [IVH]). RESULTS AND CONCLUSION: Surfactant therapy is efficacious in reducing the risk for pneumothorax and increasing the chance for survival without BPD. Synthetic surfactant is not efficacious in the prevention of HMD. Modified natural surfactant is more effective in reducing the risk of pneumothorax and increasing the chance for survival without BPD than is synthetic surfactant. These data do not support the use of either synthetic or modified natural surfactant for routine prophylaxis.

A prognostic model for assessment of the outcome of endodontic treatment: Effect of biologic and diagnostic variables.

OBJECTIVE: Many biological variables, endodontic treatment factors, and restorative considerations have been suggested in the literature to affect the outcome of endodontic treatment. However, few attempts have been made recently to study these variables further. The purpose of this study was to identify the biologic and endodontic treatment-associated variables that are most predictive of treatment outcome for conventional endodontic therapy and to determine the magnitude of risk these variables pose on the outcome. STUDY DESIGN: The population of this historical prospective cohort study comprised a total of 200 teeth with 441 root canals. Diagnostic and treatment information was abstracted from the original patient records. An endodontic follow-up examination was conducted 4 +/- 0.5 years after obturation. Each tooth/root was analyzed according to 3 indices of periradicular status at 2 time points. The main outcome measure was the presence of apical periodontitis. The criteria used for evaluation of the outcome were modified from Strindberg. Data were subjected to univariate and multivariate analysis. Logistic regression models were fit by using various clinical measures to determine which combination of biologic and treatment-associated factors best predicted treatment outcome. RESULTS: The preoperative pulp diagnosis, the periapical diagnosis, the preoperative periapical radiolucency size, and the sex of the patients were revealed, by means of univariate analysis, to exert a significant influence on endodontic treatment outcome (P <.05). In the logistic regression model, the strongest effect on postoperative healing was the presence and magnitude of preoperative apical periodontitis. In the presence of this variable, no other factor contributed value to the prediction. The correct prediction of this model was 74.7% (P <.05). CONCLUSION: The major biologic factors influencing the outcome of endodontic treatment appear to be the extent of microbiological insult to the pulp and periapical tissue, as reflected by the periapical diagnosis and the magnitude of periapical pathosis.

Comparison of number and mean charge between dental sealants and one-surface restorations.

An important concern of the insurer is how sealants, if a covered benefit, will affect the premium. Important factors that may have an influence on determining the premium include the decline in caries rate coupled with the long-term cost to an insurer for sealants vs one-surface restorations. In this study of more than 1 million dentally insured children (aged 5-15), the mean charge ($) for sealants and one-surface restorations was determined, along with the frequency of these procedures, by patient age. For this group of children, 43 percent of one-surface restorations occurred between ages 12-14, whereas 32 percent of the patients received sealants at either 7 or 8 years of age. States varied substantially in the number of sealants as a percentage of the number of restorations. Only three states had more sealants placed than one-surface, posterior restorations. Three states had an annual increase in the ratio of sealant to restoration charge, while 13 states had an annual decrease. With the exclusion of a few states with a minimum number of sealants and restorations in 1988, the highest ratio of the cost of sealants to the cost of one-surface restorations was observed in New York (.60) and New Jersey (.56) and the lowest observed in Kansas and Utah (.37). The ratios for both New York and New Jersey were lower in 1988 than in the previous two years. The ratio of the number of one-surface, posterior restorations to the population served was approximately the same for each NIDR region in the contiguous United States. Alaska and Hawaii had a higher proportion.

Extractions prior to comprehensive orthodontic treatment in the mixed dentition.

Studies concerning the prevalence of extractions prior to orthodontic treatment have been limited in scope. This quasi-experimental analysis from secondary data explores patient and provider variables as they relate to extractions prior to comprehensive orthodontic therapy in the mixed dentition. This national database contains 38,529 children who had at least one comprehensive orthodontic (mixed dentition) visit within a 27-month period (January 1987-March 1989). Because of the relatively small number of Class III malocclusion cases, an equal allocation, random sample method was used in choosing children from the three Angle malocclusion classifications and the seven NIDR regions. Of those selected 24.7% had one or more extractions prior to orthodontic treatment, with 56% occurring at either 11 or 12 years of age. There were slightly more extraction cases for the Class I malocclusion children (26.7%) than either Class II (23.1%) or Class III (24.1%). Those children who had an orthodontic extraction were slightly older (P < 0.05). There were no statistically significant differences relating to orthodontic extractions for the following patient and provider variables: gender, malocclusion classification, years since dental graduation, and type of dental practice. There were regional differences among extraction rates for pediatric dentists, with those from the NIDR Midwest region more likely to have children receiving one or more extractions.

Impact of CK-MB testing policies on hospital length of stay and laboratory costs for patients with myocardial infarction or chest pain.

We obtained data on hospital length of stay (LOS) and total laboratory charges for Medicare patients admitted to 82 hospitals in Massachusetts during 1994. Five Diagnosis Related Groups (DRGs) were selected: surviving acute myocardial infarction (AMI) with, and without, complications; AMI with death; angina pectoris; and chest pain. The hospitals were grouped according to their laboratory policies for testing CK-MB (e.g., frequency of assay runs; information obtained by telephone survey). The study was conducted to determine whether there was an association between turnaround times for results and LOS for cardiac DRGs. The mean LOS for AMIs with complication for 1513 patients admitted to 22 hospitals whose laboratories perform CK-MB testing once or twice daily was 8.4 days [95% confidence interval (CI): 8.2-8.7]. In contrast, the mean LOS for hospitals with CK-MB test policies of at least 3 runs daily or random-access stat was significantly (P <0.05) lower, 7.7 days (CI: 7.4-8.0 and 7.5-7.9, respectively). Overall laboratory charges were lower in the hospitals with shorter LOS. With one exception, there was no significant difference in LOS between patients with DRGs of angina pectoris or chest pain or other AMI DRGs. For AMI, a CK-MB testing policy that produces shorter turnaround times may be justified because of an association with reductions in LOS and overall laboratory costs.

Medians for second-trimester maternal serum alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol; differences between races or ethnic groups.

Second-trimester maternal serum alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated estriol (uE3) are routinely measured in screening fetuses at high risk for Down syndrome or open neural tube defects (ONTD). For test interpretation, individual patient values of these three analytes are related to population-derived median values. We evaluated data from >21000 pregnancies to determine the extent of race-specific differences in median concentrations. For samples at most gestational ages, median AFP, hCG, and uE3 values for white, black, Hispanic, and other patients were all significantly different. Differences remained significant even when data were corrected for patient weights. For each analyte, the extent of the variation was not the same at different gestational ages. Differences in median values across race/ethnicity groups appear to have only a small impact in Down syndrome screening but it may be appropriate to use alternative sets of AFP medians or adjustment factors to AFP medians for some Asian populations receiving ONTD screening.

Allergic rhinitis and olfactory loss.

BACKGROUND: Allergic rhinitis is associated with reports of olfactory loss, but there are few formal investigations. Patients with diminished smell function frequently have nasal polyps or sinusitis, making it difficult to separate the impact of allergic rhinitis from the effects of these other problems. OBJECTIVE: The goals of this descriptive study were to establish the prevalence of positive skin tests in patients reporting rhinitis and olfactory deficiency, and to assess olfactory function and the results of skin testing in a patient group with chronic rhinitis but without concomitant sinusitis or nasal polyps. METHODS: Sixty-two patients reporting olfactory loss and chronic rhinitis were examined by history, physical examination, olfactory testing, skin testing with perennial and seasonal allergens, endoscopic rhinoscopy, and CT scan of the paranasal sinuses. RESULTS: Seventy-one percent of all the subjects had at least one positive skin test, 69% to a perennial allergen, and 58% to mite. Eighty-two percent of the 28 subjects with chronic rhinitis but no evidence of polyps or sinusitis had positive tests. The mean olfactory score for this rhinitis group was 4.35, consistent with moderate hyposmia. The mean olfactory score of 34 subjects with polyps and/or chronic sinusitis was 0.61, consistent with anosmia, and significantly lower (P < .001). Sixty-two percent of this group had positive skin tests. CONCLUSION: These subjects who experienced olfactory loss and rhinitis appeared to have a high prevalence of allergic rhinitis as suggested by the number of positive skin tests. Olfactory loss was observed in patients without polyps or sinusitis, which suggests that allergic processes may have affected olfactory function.

Zinc transport in pregnancy.

Although the importance of zinc nutrition during pregnancy has been well recognized, there have been few studies of zinc transport in maternal or fetal sera. We examined total serum zinc levels as well as zinc associated with its major transport proteins, albumin and alpha 2-macroglobulin, prospectively in 46 women during gestation and in 27 of their infants at term. In five women who developed preeclampsia during the third trimester, the mean total serum zinc level at 6 to 14 weeks was decreased by 14% compared to control values (p less than 0.05). Fetomaternal differences between the zinc transport proteins support the concept that each may have a specific role(s) in zinc homeostasis which is regulated to a greater extent by metabolic factors than by dietary zinc intake alone.

Idiopathic pneumonia syndrome following myeloablative chemotherapy and autologous transplantation.

OBJECTIVE: To report the outcome as well as the clinical, radiographic, and pathologic features of idiopathic pneumonia syndrome (IPS) following autologous peripheral blood stem cell transplantation (aPBSCT). CLINICAL FINDINGS: A total of 271 patients with a variety of underlying malignancies received busulfan-containing myeloablative chemotherapy prior to aPBSCT; none of these patients received total body irradiation. Ten individuals developed IPS, with a median time of onset of 102 days after stem cell infusion. The major clinical and radiographic findings included an acute or subacute onset of dyspnea, cough, hypoxemia, and bilateral or unilateral infiltrates with or without pleural effusion. Pathologic findings consisted mainly of diffuse interstitial pneumonitis, organizing alveolitis, and cellular atypia. Nine patients diagnosed with IPS were treated with high doses of glucocorticoids parenterally. Despite heroic measures, eight patients died of IPS. The two remaining individuals recovered without experiencing significant long-term pulmonary sequelae. DISCUSSION: Chronic low-dose busulfan therapy results in lung injury in 4-6% of patients after several years of treatment and once the cumulative dosage begins to approach 3g. High-dose, short-course busulfan (16 mg/kg)-containing conditioning chemotherapy prior to aPBSCT can also be complicated by IPS. IPS differs from lung damage due to chronic busulfan therapy by its earlier onset, an acute or subacute rather than indolent presentation, characteristic clinical and radiographic features, and lack of multinucleated giant cells on pathologic review. The pathophysiology of IPS secondary to high-dose busulfan-containing myeloablative regimens is not known, but cell-mediated immune reactions and release of cytokines may contribute to the lung injury. Mortality is high (80%) despite the use of heroic measures, including mechanical ventilation. Some patients, however, can respond to high doses of parenteral corticosteroid therapy. CONCLUSIONS: IPS following high-dose, short-course busulfan-containing regimens exhibits unique clinical, radiographic, and pathologic features that differ from lung damage characteristic of chronic, low-dose busulfan therapy. Mortality from this complication is 80%, but some patients survive without long-term pulmonary sequelae following early treatment with glucocorticoids.