Maternal estradiol and progesterone concentrations among singleton spontaneous pregnancies during the first trimester.

BACKGROUND: Pregnancy hormonal milieu represents a crucial determinant of fetal outcome. We aim to determine 17ß-estradiol (E2) and progesterone (PGT) concentrations in spontaneous pregnancies during the first trimester. In addition, we aim to determine E2 concentrations as a function of gestational age (GA) and PGT. METHODS: Between November 2015 and March 2017, 104 healthy women of at least 18 years undergoing medical consultation for voluntary interruption of pregnancy were enrolled in an observational study at University Hospital ASST Fatebenefratelli Sacco, Milan, Italy. Only singleton pregnancies between 5+0 and 13+6 weeks of gestation were eligible. First trimester ultrasound scans were performed for dating and one fasting venous blood sample was collected for E2 and PGT determinations. RESULTS: E2 and PGT concentrations steadily increased according to GA. The correlation between E2 on a logarithmic scale and PGT concentrations was expressed by the following equation, explaining 12.6% of E2 variance: logE2 = 2.57 + 0.1 × PGT, (r = 0.34, p < 0.001). By performing a multivariable linear regression analysis adjusted for variables significantly correlated with E2 concentrations, we obtained a model explaining the 53.5% of E2 variance. The final equation to determine E2 concentrations among Caucasian women was: logE2 = 1.96 + 0.01 × GA + 0.004 × PGT. CONCLUSIONS: Gestational week-specific reference intervals are reported for maternal E2 and PGT concentrations during early pregnancy, further providing a model for E2 assessment in this period. This will represent a starting point for further evaluations between twin and ART pregnancies, as well as to potentially improve pregnancy outcome and future health of the offspring.

Improving adherence to and persistence with oral therapy of osteoporosis.

UNLABELLED: Osteoporosis treatment has low adherence and persistence. This study evaluated if greater patient involvement could improve them. At 12 months, only 114 out of 344 participants were "fully adherent and persistent" (all drug doses taken throughout the study). Only frequency of drug administration had a significant influence on adherence. INTRODUCTION: Osteoporosis affects millions of individuals worldwide. There are now several effective drugs, but adherence to and persistence with treatment are low. This 12-month multicenter, prospective, randomized study evaluated the efficacy of two different methods aimed at improving adherence and persistence through greater patient involvement, compared with standard clinical practice. METHODS: Three hundred thirty-four post-menopausal women, receiving an oral prescription for osteoporosis for the first time, were recruited and randomized into three groups: group 1 (controls, managed according to standard clinical practice) and groups 2 and 3 (managed with greater patient and caregiver involvement and special reinforcements: group 2, instructed to use several different "reminders"; group 3, same "reminders" as group 2, plus regular phone calls from and meetings at the referring Center). All enrolled women had two visits (baseline and 12 months). RESULTS: Of 334 enrolled women, 247 (74%) started the prescribed therapy. Of those who started, 219 (88.7%) persisted in therapy for at least 10 months. At final evaluation, only 114 women were considered as "fully adherent and persistent" (all doses taken throughout the 12 months). There were no significant differences regarding "full adherence" among the three randomized groups. The frequency of drug administration had a significant influence: weekly administration had a >5-fold higher adherence and monthly administration an 8-fold higher adherence (p < 0.0001) than daily administration. CONCLUSIONS: The special effort of devising and providing additional reminders did not prove effective. Additional interventions during the follow-up, including costly interventions such as phone calls and educational meetings, did not provide significant advantages.

Decreasing incidence of CNS AIDS-defining events associated with antiretroviral therapy.

The authors enrolled 1,029 patients with CD4 counts

Improved survival after coronary bypass surgery in patients with poor left ventricular function: role of intraaortic balloon counterpulsation.

The operative mortality rate of aortocoronary bypass surgery in 23 patients with poor left ventricular function (ejection fraction 0.30 or less) operated on in 1973-74 was 34.7 percent. The incidence rate of operative myocardial infarction was 30.4 percent. In an attempt to improve survival, intraaortic balloon counterpulsation was used therafter in 25 similar patients. Counterpulsation was instituted preoperatively and continued intra- and postoperatively for 2 to 5 days. Preoperative studies revealed an "unloading" effect of the left ventricle, with significant reductions of systolic arterial blood pressure, end-diastolic pulmonary arterial pressure and end-diastolic left ventricular volume and pressure. Metabolic improvement was demonstrated by the lesser production of myocardial lactate after pacing-induced tachycardia when the ventricle was balloon-assisted. Intraoperatively, blood flow through the vein graft was found to increase with counterpulsation. The rate of operative myocardial infarction was reduced to 4 percent and the mortality rate to 8 percent. In patients who have sustained a significant loss of functioning myocardium, the beneficial hemodynamic and metabolic effects of intraaortic balloon counterpulsation appear to prevent furhter, possibly critical, myocardial damage in the perioperative period.

Spectrum of coronary arterial spasm. Clinical, angiographic and myocardial metabolic experience in 29 cases.

A relationship of coronary arterial spasm to variant angina pectoris, subendocardial ischemia, major ventricular arrhythmias and myocardial infarction has been demonstrated. In 29 patients, spasm was angiographically observed in normal-appearing coronary arteries (7 patients) as well as superimposed on various degrees of coronary atherosclerotic obstruction (22 patients). All patients experienced an atypical anginal syndrome;16 patients also experienced typical exertional angina. Coronary spasm appeared to be a major contributory factor in eight occurrences of myocardial infarction and in 11 incidents of ventricular tachycardia, ventricular fibrillation and heart block. Coronary spasm in the 29 cases was distributed in the following fashion: left main trunk, 6 cases; right main trunk, 12 cases; proximal left anterior descending artery, 13 cases; proximal circumflex artery, 1 case; distal left anterior descending artery, 1 case; and distal circumflex artery, 2 cases. In 5 cases coronary spasm was noted at multiple sites.

Amplified in situ hybridization with peptide nucleic acid probes for differentiation of Mycobacterium tuberculosis complex and nontuberculous Mycobacterium species on formalin-fixed, paraffin-embedded archival biopsy and autopsy samples.

The aim of this study was to evaluate sensitivity and specificity of in situ hybridization (ISH) using peptide nucleic acid (PNA) probes and tyramide-based amplification for the differentiation between Mycobacterium tuberculosis (MTB) and mycobacteria other than tuberculosis (MOTT) on formalin-fixed, paraffin-embedded tissue samples. We performed ISH simultaneously with both probes on 86 specimens from different organs: 70 obtained at autopsy and 16 by biopsy, all with a histologic evidence of mycobacterial infection confirmed by Ziehl-Neelsen-positive staining. Taking culture as the "gold standard," the sensitivity and the specificity of the MTB probe were 100% (41/41) and 95% (38/40), respectively. In only 2 cases ISH failed to identify mycobacteria. Culture results were not available in 3 cases. We propose ISH as a relatively simple and rapid method to differentiate mycobacteria on formalin-fixed, paraffin-embedded specimens (it is more specific than usual histologic stains) and as an alternative to polymerase chain reaction, allowing the morphologic evaluation of positive bacilli.

Changes in receptor status after treatment with tamoxifen in endometrial cancer.

Estrogen (ER) and progesterone receptor (PgR) status was determined in 41 women with operable endometrial cancer before and after administration of tamoxifen (TAM). The first sample was obtained by hysteroscopy to ensure a precise biopsy of neoplastic tissue; the second was done on the surgical specimen. PgR content was significantly increased after TAM treatment and this data was compared with the degree of tumor differentiation.

Erythrocyte uroporphyrinogen decarboxylase activity: diagnostic value and relationship with clinical features in hereditary porphyria cutanea tarda.

A marked discrepancy between mild and late clinical features and a nearly complete absence of erythrocyte uroporphyrinogen decarboxylase activity (Ery-UROD activity) was observed in a case of inherited porphyria cutanea tarda. The entity and time of appearance of clinical features, the onset of clinical symptoms after exposure to contributing factors, the effectiveness of phlebotomies and heterozygosity of the mother alone for uroporphyrinogen decarboxylase (UROD) deficiency were typical for familial porphyria cutanea tarda (F-PCT), whereas the extremely low UROD activity was peculiar to hepatoerythropoietic porphyria (HEP). These observations indicate that: 1) Ery-UROD activity may not always be useful to discriminate between F-PCT and HEP; 2) Ery-UROD activity does not always correlate with clinical symptoms; 3) in inherited UROD deficiency, the genetic defect may be heterogeneous. Finally, the observed discrepancy may provide additional evidence for the existence of tissue-specific isozymes.

Lactate metabolism as a prognostic index in unstable angina.

Fifty patients evaluated because of unstable angina were followed up for a mean period of 63.7 months. Analysis of transmyocardial lactate metabolism was performed in all patients in addition to coronary angiography and ventriculography. All patients had at least one coronary lesion of great than 75%. Although technically feasible, aortocoronary bypass surgery was not performed on initial hospitalization and all patients were treated medically. Patients were divided into two groups on the basis of lactate metabolism; group A lactate production great than 15%, group B lactate production less than 15% or lactate extraction. There was no difference in left ventricular end-diastolic pressure or ejection fraction between the two groups. A coronary score index was higher in group A than group B (5.45 +/- 2.2 vs 3.13 +/- 1.2) (p less than 0.05). The incidence of myocardial infarction was higher in group A than group B in hospital (44.4% vs. 4.3%, p less than 0.05), and long term (70.3% vs. 17.3%, p less than 0.05). Mortality was higher in group A than group B in hospital (25.9% vs. 0%, p less than 0.05) and long term (66.7% vs. 13%, p less than 0.05). Analysis of lactate metabolism thus provides a prognostic index in unstable angina which complements information obtained by coronary angiography and ventriculography.

The synergistic effect of simultaneous addition of retinoic acid and vitamin D3 on the in-vitro differentiation of human promyelocytic leukemia cell lines could be efficiently transposed in vivo.

Both human cell lines HL-60 and AML-193 exhibit a myeloblastic and promyelocytic morphology, respectively, but may be regarded as bipotent leukemic precursors. They can be triggered to differentiate to either granulocytes or monocytes upon retinoic acid (RA) or 1,25-dihydroxyvitamin D (D3) addition, respectively. We have investigated the effect of combined addition of these chemical inducers on the in-vitro differentiation of both cell lines. RA and D3 added together exert synergistic effects on the in-vitro maturation of these myeloid cell lines. Interestingly, the additive effects were lost if the cells were incubated with the inducers added at sequential times. The synergistic effect could be transposed in vivo and could be clinically significant in the treatment of the promyelocytic leukemia. This clinical strategy may help to prevent retinoic acid resistance or to overcome it in patients relapsed after RA therapy and usually unresponsive to a reinduction therapy with RA alone.

Statistical aspects of the estimation of reference limits.

This paper deals with some basic statistical issues arising from biological monitoring. Data description, Gaussianity tests, outlier identification, parametric and non-parametric estimates of fractiles and their standard errors, and parametric estimate of the one tail upper side tolerance interval are treated and exemplified using two data sets. Sample size and power determination are considered in terms of the cut-off point of the diagnostic quantitative test.

Estimation of pooled reference values for cadmium in blood using meta-analysis and TRACY criteria.

Reference values for blood-cadmium levels (B-Cd) are available for only a limited number of geographical areas and for particular population strata (sex, age, smoking habits). This paper, in agreement with the TRACY guidelines, describes and discusses the criteria used to rank published papers on reference values for cadmium retrieved by Medline and Toxline between 1976 and 1991. The TRACY criteria deal with the grading of published papers in terms of their suitability for calculating provisional reference values. Only four out of 18 papers were considered suitable for the TRACY project. The four articles were finally used via meta-analysis to provide provisional reference values for smokers and non-smokers. The comparison of results obtained using published statistics and individual data is used to discuss the appropriateness of meta-analysis in the case of cadmium. Due to the availability of large enough studies and to the clear differences across countries, the suitability of a compound upper reference limit to B-Cd levels seems limited.

Discovering asymptomatic non-precancerous lesions with cervical cytologic mass-screening campaigns: is it a benefit or a cost?

A total of 3357 women (88.1% married, 82.0% parous) were examined at least once in the mass-screening program carried out by the Legnano Hospital Screening Center in Nerviano (a small town near Milan with 15,600 inhabitants) in 1974, 1977 and 1980. Married women with visible portio and adequate smear were 2758: a visibly healthy cervix was found only in 1143 subjects (41.4%). A total of 1516 married women were examined at least in 2 consecutive campaigns: 1279 (84.4%) reported "no gynecologic treatment in the previous 5 years" at the first campaign, and 899 (59.3%) reported "no gynecologic treatment in the previous 3 years" at their second one. Of 350 women with "medical lesions" and 525 with "surgical lesions" recorded at the first visit, 111 (31.7%) and 232 (44.2%) reported, respectively, a "medical treatment" or a "surgical treatment" at the second visit. In women with "medical lesions" at the first visit, at the second visit a healthy cervix was found in 66.2% of the treated women and in 72.6% of the untreated patients. In those with "surgical lesions" a healthy cervix was successively found in 91.6% of treated and in 40.7% of the untreated patients.

Intralaboratory reproducibility of interpretation of Pap smears: results of an experiment.

One hundred and twenty Pap-smears were examined by 3 cytotechnologists on two occasions in the Legnano Hospital Cytologic Center. A 10-category classification system was used. Chance-adjusted overall and category-specific agreement was estimated (Cohen's unweighted kappa-statistics) within and between cytotechnologists. Mean K for the Center, weighted for precision, was 0.432, S.E. 0.029 (between cytotechnologists). The most reproducible categories (between cytotechnologists) were "9: malignant cells" (K = 0.683) and "1: normal" (K = 0.533); the least reproducible categories were "4: endocervical metaplastic cells" (K = 0.024) and "8: severe squamous dysplasia CIN III" (K = 0.227).

Reliability and accuracy in reporting CIN in 14 laboratories. Developing new indices of diagnostic variability in an interlaboratory study. The Working Group for External Quality Control in Cervical Cytopathology.

OBJECTIVE: To report the results of the second phase of a pilot study of an Italian national external quality evaluation program (EQA) aimed at assessing whether participation in the first phase had increased the reliability and accuracy of diagnoses and to what extent. STUDY DESIGN: In the second phase, two sets of cervical smears (similar to the ones examined in the first phase) were circulated among the 14 participating cytologic laboratories throughout Italy. Responses were recorded on a standardized form. Participants were asked to judge the adequacy of each smear and to formulate a diagnosis. They were also asked to recommend management of the patient on the basis of the smear report and to evaluate the degree of diagnostic difficulty of each slide. The results were discussed in workshops, and it was possible to reach a consensus diagnosis on 37 of 40 smears. In the statistical analysis, new indices of diagnostic variability were developed and calculated; a gross index of agreement, unweighted and weighted kappas, analysis of exchangeability, sensitivity and specificity were also estimated. RESULTS: The results of the second phase are similar to those of the first phase and no substantial improvement in accuracy and little reduction in variability were observed. The interventions carried out in this study (discussion between representatives of laboratories of diagnostic differences and reassessment of the most controversial slides) were aimed at increasing consensus among the participating pathologists but were insufficient to change the diagnostic routines in their laboratories. CONCLUSION: It may be advisable to promote two kinds of interlaboratory quality programs with two separate but integrated components: (1) a core component with slides having clear-cut diagnoses, and (2) a continuing education component.

[Duodenal ulcer and Helicobacter pylori]. / Ulcera duodenale in epoca Helicobacter pylori.

BACKGROUND: The purpose of this study was to evaluate the relationship between duodenal ulcer (DU), Helicobacter pylori (Hp) infection and genetic and enviromental factors, and its influence on treatment and long-term RESULTS. METHOD: In the course of an epidemiological study on the prevalence of esophagogastroduodenal diseases, 1,169 volunteers underwent an endoscopy of the upper part of the gastrointestinal tract. The relationship of incidence rate and size of duodenal ulcers and several risks factors was investigated. RESULTS: A DU was observed in 240 subjects (20.5%), mostly of male gender (64.4% - p<0.0001). The Histological presence of a gastric Hp infection was confirmed in 179 cases (74.6%); it did not influenced the mean size of the ulcers and the presence of gastric intestinal metaplasia, compared to subjects without Hp infection. However, a superficial chronic gastritis was observed in 95.9% of Hp+ subjects and in 83.3% of Hp- (p<0.003), whereas a familiar history of DU was noted in 33.3% of Hp+ subjects and in 50.8% of Hp- (p<0.02). The main risk factor for DU was represented by Hp infection in 119 cases (49.6%), by infective and genetic factors in 60 cases (25%) and only by the genetic factor in 31 cases (12.9%), and was not detected in 30 cases (12.5%). Ulcer recurrence rates, after medical therapy, were 0,5% and 6.5% (p<0.03) at a 2-month follow-up, and 2.2% and 49.1% (p<0.00001) at a 12-month follow-up, among Hp+ and Hp- patients, respectively. CONCLUSIONS: The most common risk factor for DU was a gastric Hp infection, alone or associated to the genetic factor. Since the high incidence of recurrences at a 12-month follow-up, patients affected with a DU but Hp- represented an important therapeutic concern.

[Reflux oesophagitis and risk factors. Results of a population study]. / Esofagite da reflusso e fattori di rischio. Risultati di uno studio di popolazione.

BACKGROUND: To evaluate the prevalence and endoscopic grade of reflux oesophagitis (RO) and to correlate them to symptoms and to a list of risk factors including age, sex, weight, smoking, alcohol, work, hiatus hernia. METHODS: This study was carried out in Roccacorga (LT), a little town of 3435 inhabitants in central Italy. The sample totalled 1084 volunteers, aged over 18 years old and enlisted in opened cohort. After filling in the questionnaire, all the patients were subjected to esophagogastroduodenoscopy without eating for at least six hours and diazepam pretreated (10 mg ev). Three biopsies were routine performed on the 3 biopsies on distal esophagous wall. The RO range was evaluated according to the Savary-Miller classification. RESULTS: The RO was found in 443 patients (188 M, 42%; 255 F, 58%) (p<0.0002), a large number of asymptomatic patients (39%). The prevalence of hiatus hernia was 7.2%, RO associated in 60.3% (p<0005). The prevalence of associated gastroduodenal injuries was pointed out (p<0.03). Patients affected only by RO were mostly female (p<0.02). Precancerous esophagous were 0,37%. CONCLUSIONS: According to this study the RO diagnosed through endoscopy is much more prevalent than supposed, especially among females and it affects a younger age than reported (31-50 years). Smoking and alcohol are among male risk factors, while, in female, agricultural works, weight and hormonal state could have a leading role (p=NS).

Interpreting cardiac catheterization data. Part 2.

Data obtained by cardiac catheterization, properly interpreted, are an extremely useful supplement to information obtained from the medical history, physical examination, electrocardiography, chest x-ray examination, and other noninvasive diagnostic techniques. Elevations of pressure in the cardiac chambers and great vessels and corresponding patterns of pressure curves are discerned in the presence of various pathologic conditions affecting the heart. Blood samples are taken during cardiac catheterization for measurement of cardiac output and to detect intracardiac shunting. Attempts have been made to estimate the magnitude of shunts from abnormal dye-dilution curves. Exercise stress is often used during cardiac catheterization to evaluate overall cardiovascular performance. Angiocardiography gives a permanent graphic record of structural abnormalities. Myocardial lactate metabolism provides a means of evaluating the adequacy of coronary blood flow.

Medical facilities environmental concerns and the role of the hospital sanitarian.

The hospital setting is an environmental microcosm with many characteristics similar to the general environment with some unique characteristics. Yet trained environmental experts are in short supply within medical facilities, resulting in other disciplines trying to meet the need. A Hospital Sanitarian is the most likely candidate to assume the responsibility for environmental health in a hospital setting. The author examines the common environmental concerns in hospitals: Food Service, Central Sterile Supply, Laundry, Housekeeping, Infection Control, Infectious Waste, Toxic Substances, and Pest Control. The Sanitarian's proficiencies are described in relation to these areas as well as major obstacles to the Sanitarian entering this specialty area. Discussed are education, internal resistance, and the Sanitarian's own sense of professionalism. The ability of this environmental health professional to make the transition may be dictated by the strength of the profession. Recommendations include specialized certification for the Hospital Sanitarian which would offer a potent force in working with other hospital specialists to ensure a safe and sanitary environment.

[Several risk indicators in industrial accidents]. / Considerazioni su alcuni indicatori di rischio di infortunio sul lavoro.

Since the 1986, the National Institute for Occupational Accident Insurance (INAIL) provides each single Region with the occupational accident data on magnetic support. This strengthens the need to critically evaluate the most commonly used risk indicators. In this paper we discuss advantages and limits of the usual frequency and severity measures; the formulae for the standard errors are also given. A method proposed by I. Bross (1958), the RIDIT Analysis, is considered and exemplified. The appealing properties of this method ask for a more extensive application in this field.