Premenopausal metrorrhagia as a symptom of sarcoidosis

Objective: The aim of this study was to examine the social conditions of women who never attended prenatal care and to evaluate the perinatal outcome of their newborns. Study Design: A retrospective analysis of uncared pregnancies of women who delivered at the Department of Obstetrics and Gynaecology, University of Szeged, Hungary between 1 January 1996 and 31 December 1998. There were 5262 deliveries during this period, of which 54 (1%) had no prenatal care. Matched controls (108 cases) were selected on the basis of maternal age, educational level, the number of gravidity and parity, and marital status. Results: The mean age of women with out-of-care pregnancies was 27 years±3.9; 5 women were under 18, 23 (43%) were unmarried, 5 (9.3%) did not finish elementary school and 35 (65%) had only elementary school education. Compared to the controls there were more in preterm labors (33 versus 14% (OR 3.1, 95% CI 1.4–6.8)), lower birth weight (P<0.001) and more given up for adoption (17 versus 0.9% (OR 21.4, 95% CI 2.63–173.9)). Conclusion: These data underline the importance of regular prenatal care in the prevention of preterm delivery.     

A framework for clinical general practice and for research and teaching in the discipline

This paper uses three typical case stories from general practice to demonstrate that a GP simultaneously considers four dimensions when making a diagnosis and planning subsequent treatment of a patient in the consultation: (i). a biomedical dimension; (ii). a culture and context dimension; (iii). a medico-psychological dimension; and (iv). a network and social dimension. By taking this diagnostic and therapeutic approach, the GP adds value to the total performance of the health care system. It is demonstrated that a GP needs theoretical, research-based knowledge and skills within all four dimensions, and that it is necessary for a GP to work together with both medical and non-medical disciplines when defining the research and teaching agenda. It is stressed that consultation and communication skills are important tools for any doctor, and the value of continuity of care is discussed. Finally, the implications of the diagnostic approach with respect to planning research and teaching programmes are discussed, and the need for a better balance is stressed.     

Magnetic resonance imaging and transvaginal ultrasonography for the diagnosis of adenomyosis

OBJECTIVE: To compare the diagnostic potential of magnetic resonance imaging (MRI) and transvaginal ultrasonography (TVS) in the diagnosis of adenomyosis. DESIGN: Double blind set-up. SETTING: University medical school. PATIENT(S): We studied 106 consecutive premenopausal women who underwent hysterectomy for benign reasons. INTERVENTION(S): Transvaginal ultrasonography and MRI were compared with histopathologic examination as the golden standard. MAIN OUTCOME MEASURE(S): Adenomyosis. RESULT(S): Twenty-two (21%) patients had adenomyosis. The sensitivity and specificity were as follows: sensitivity: MRI 0.70 (0.46-0.87) and TVS 0.68 (0.44-0.86) (P=.66); specificity: MRI 0.86 (0.76-0.93) and TVS 0.65 (0.50-0.77) (P=.03). The combination of MRI and TVS was most sensitive (0.89 [0.64-0.98]), but produced the lowest specificity (0.60 [0.44-0.73]). Adenomyosis was not detected by either MRI or TVS at uterine volumes >400 mL. Exclusion of uteri >400 mL from the analysis improved the diagnostic precision of MRI, but not that of TVS. The diagnostic accuracy at MRI was improved by calculating the maximum difference between the thinnest and thickest junctional zone (JZdif) (i.e., > or =5-7 mm). CONCLUSION(S): Magnetic resonance imaging was superior to TVS for the diagnosis of adenomyosis. Magnetic resonance imaging had a higher specificity than TVS, but their sensitivities were in line. The diagnostic accuracy of MRI, as that of TVS, was at an intermediate level, but the diagnostic accuracy of the former improved by exclusion of uteri >400 mL. The combination of MRI and TVS produced the highest level of accuracy for exclusion of adenomyosis, but the low specificity may necessitate further investigation of positive findings. Measurement of the difference in junctional zone thickness may optimize the diagnosis of adenomyosis at MRI.     

Combined analysis of DTI and fMRI data reveals a joint maturation of white and grey matter in a fronto-parietal network

The aim of this study was to explore whether there are networks of regions where maturation of white matter and changes in brain activity show similar developmental trends during childhood. In a previous study, we showed that during childhood, grey matter activity increases in frontal and parietal regions. We hypothesized that this would be mediated by maturation of white matter. Twenty-three healthy children aged 8-18 years were investigated. Brain activity was measured using the blood oxygen level-dependent (BOLD) contrast with functional magnetic resonance imaging (fMRI) during performance of a working memory (WM) task. White matter microstructure was investigated using diffusion tensor imaging (DTI). Based on the DTI data, we calculated fractional anisotropy (FA), an indicator of myelination and axon thickness. Prior to scanning, WM score was evaluated. WM score correlated independently with FA values and BOLD response in several regions. FA values and BOLD response were extracted for each subject from the peak voxels of these regions. The FA values were used as covariates in an additional BOLD analysis to find brain regions where FA values and BOLD response correlated. Conversely, the BOLD response values were used as covariates in an additional FA analysis. In several cortical and sub-cortical regions, there were positive correlations between maturation of white matter and increased brain activity. Specifically, and consistent with our hypothesis, we found that FA values in fronto-parietal white matter correlated with BOLD response in closely located grey matter in the superior frontal sulcus and inferior parietal lobe, areas that could form a functional network underlying working memory function.     

Fluvoxamine-Clozapine drug interaction: inhibition in vitro of five cytochrome P450 isoforms involved in clozapine metabolism

Administration of fluvoxamine to patients receiving clozapine therapy may increase the steady-state serum concentrations of clozapine by a factor of 5 to 10. The authors undertook in vitro studies to disclose the mechanism behind this clinically important interaction. In a human liver microsome preparation, fluvoxamine showed a concentration-dependent inhibition of clozapine N-demethylation. Fluvoxamine was much less effective as an inhibitor of clozapine N-oxidation. Fluvoxamine also inhibited in a concentration-dependent manner the activity of all five cytochrome P450 (CYP) isoforms previously determined to be capable of catalyzing the demethylation of clozapine. Fluvoxamine inhibited CYP1A2 and 2C19 with the highest affinities (Ki values of 0.041 and 0.087 microM, respectively). The Ki values for CYP2C9 and 2D6 were 2.2 and 4.9 microM, respectively, whereas the Ki for CY3A4 was 24 microM. Assuming a hepatic tissue concentration of fluvoxamine in the range of 4 to 7 microM under therapeutic conditions, a clinically significant inhibition of all but CYP3A4 is expected in relation to clozapine N-demethylation. No significant effect of fluvoxamine on clozapine N-oxidation is to be expected under therapeutic conditions. Because of the large interindividual variability of the quantity of the various CYP isoforms in liver tissue, it is not possible to predict the fluvoxamine-induced increase in the plasma concentration of clozapine of an individual patient.     

Cardiovascular effects of pregnanolone emulsion: an experimental study in artificially ventilated dogs

The acute cardiovascular effects of pregnanolone emulsion, a new steroid preparation for intravenous anaesthesia, were investigated in artificially ventilated dogs. The anaesthetic was administered as repeated intravenous bolus injections, doubling the dosage with each injection. The plasma concentration of pregnanolone, and the haemodynamic, respiratory and metabolic variables were determined after each injection. Cardiac output and heart rate increased from the first bolus dose of the anaesthetic (0.5 mg/kg), which produced anaesthesia lasting 10 to 15 min. Both continued to increase after administration of 1.0, 2.0 and 4 mg/kg, whereas reductions of systemic arterial pressure and estimated myocardial contractility were observed only at the two highest dosages. A decrease in vascular resistance was calculated in the systemic circulation, whereas vascular resistance increased in the pulmonary circulation. A state of circulatory shock followed administration 8, 16 and 32 mg/kg of the anaesthetic.     

Clomipramine and mianserin in chronic idiopathic pain syndrome

The reduction of pain by two antidepressants, clomipramine and mianserin, was, in this study on 253 patients with chronic idiopathic pain syndrome, found to be not better than a placebo when all patients were compared independently of the classification of pain. The improvement rate was around 40% after 6 weeks of treatment when using a 50% or better reduction in pain level. However, in patients who fulfilled a checklist definition of minor to major depression (30% of the total patient material) clomipramine was superior to mianserin and placebo with an improvement rate of 75% after 6 weeks. Using pain curves over time as outcome measure in the various clinical pain categories it was found that both mianserin and clomipramine seemed superior to placebo in patients with tension headache, but in patients with low back pain syndrome placebo was superior to the two antidepressants. No difference among the three treatments was found in patients with burning mouth syndrome or in patients with abdominal pain. These differences underline the importance of studying specific pain syndromes rather than composite groups of patients with idiopathic pain. The clinical significance of these pain curves needs further placebo controlled investigations.     

Quantitative features of goblet cells in the rat tracheobronchial tree

The whole-mount quantitative method was used to study the density and distribution of goblet cells in the male rat lung. The airway of the left lung in 10 lung specimens were dissected downwards in the axial pathway and the airway generation levels were determined by an exact numbering system. The entire bronchial mucous membrane was separated and stained according to the PAS-alcian blue whole-mount method. There was a significant decrease in goblet cell density from the proximal to the distal airways (6 to 0 cells/field). The overall median density was 1 cell/field, corresponding to 56 cells per mm2. The goblet cells were irregularly distributed throughout the airways. When using the rat airway epithelium as an animal model system the whole-mount method is recommended and this study provides an exact quantitative mapping of the rat airway epithelial system to be used for baseline comparison.     

Localized in vivo proton spectroscopy in the brain of patients with multiple sclerosis.

Localized proton spectroscopy was performed in 15 patients with acute or chronic multiple sclerosis (MS). Some of the patients were investigated serially, being given a total of 22 spectroscopic investigations. Resonances corresponding to free lipids were observed in six plaques. This was distinctly seen in two plaques at Days 70 and 85 after the occurrence of the plaques. A lesser content of lipids in plaques was observed as early as Day 10 and as late as nearly 1 year after occurrence. The relative concentration of N-acetyl asparate (NAA) was significantly lower in patients than in controls, and the relative concentration of choline (Cho) was significantly higher in patients than in controls. These differences were most pronounced in older plaques. MR spectroscopic demonstration of lipids in a MS plaque probably reflects disintegration of myelin, and a decreased NAA/Cho ratio may be related either to gliosis or to axonal degeneration, which sometimes occurs in longstanding MS.