[Vitamin intake and pregnancy]. / Apporto vitaminico ed evoluzione della gravidanza.

A suitable intake of vitamins and minerals both during preconceptional period and pregnancy is essential in reducing the incidence of adverse maternal and perinatal outcomes. This is more evident in developing countries, particularly during periods of famine, when women suffer from an inadequate intake of vitamins and minerals. Even in developed countries, however, most women's diet does not meet their increased needs for micronutrients. The association of different micronutrients in a single multivitamin preparation is consequently a useful, easy to take solution and with a good cost/benefit ratio, and can prevent some important obstetrics pathologies, as preterm delivery, fetal growth restriction and preeclampsia.

Pregnancy in a woman with recurrent immunoglobulin a nephropathy: A case report.

Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis and is increasingly encountered in pregnancy. The obstetric and renal outcomes of pregnancy are controversial, however. Women with IgAN are at higher risk of hypertension, preeclampsia and foetal loss; the prognosis is worse for those who have advanced chronic kidney disease and proteinuria. Here we report the case of a 32-year-old nulliparous woman with chronic hypertension who conceived during an active phase of her IgAN, which had been diagnosed 8 years earlier. Antihypertensive therapies and a low-protein diet were key to her reaching 34 weeks' gestation with acceptable kidney function. Rupture of membranes occurred at 34 weeks 3 days' gestation and a healthy boy was delivered the next day. This report aims to provide clinicians with useful information for the management of patients with IgAN during pregnancy.

Changes of dimeric inhibin B levels in maternal serum throughout healthy gestation and in women with gestational diseases.

Human placenta expresses subunit messenger RNAs for synthesizing inhibin A and B. Experimental studies have shown an effect of inhibins on placental hormone secretion, but an endocrine function is suggested by the high levels in maternal circulation. Although information is available on the changes of inhibin A in serum of healthy pregnant women, data on inhibin B levels are limited to early gestation. The aim of the present study was to investigate the changes of inhibin B levels in maternal circulation in healthy pregnant women throughout gestation, and to evaluate whether early pregnancy disturbances or gestational diseases are characterized by abnormal inhibin B levels. The protocol included various groups of pregnant women. A longitudinal evaluation of serum inhibin B levels was done at specific intervals (8-12, 13-18, 19-24, 25-28, 29-33, and 34-40 weeks) in the following groups: 1) healthy pregnant women (n = 13); 2) women at risk of hypertension who did not develop hypertension (n = 8); and 3) women with chronic hypertension (n = 13). In women in group 1, a blood sample was also obtained in the postpartum period (12, 24, and 48 h after delivery). Other pregnant women with abnormal bleeding in the first trimester were studied; they were subdivided into women with ongoing pregnancy (n = 12); and women with miscarriage (n = 22); a control group of healthy pregnant women at the same gestational age was also included (n = 18). A final group of women with gestational diseases (n = 34) was included in the study and included women with: 1) pregnancy-induced hypertension (n = 10); 2) preeclampsia (n = 17); and 3) intrauterine fetal growth retardation (n = 7). A group of healthy nonpregnant women (n = 9) was used as controls, and a blood specimen was collected during both the early- to midfollicular and midluteal phases of the menstrual cycle. Serum dimeric inhibin B levels were measured by using a double-antibody enzyme-linked immunoadsorbent assay. Early gestation inhibin B levels were similar to those of nonpregnant controls and showed a significant rise during the third trimester (P < 0.01). The highest maternal serum inhibin B levels were found at term (P < 0.01). Values significantly returned to control levels within 12-48 h (P < 0.01) after placental delivery. Women at risk of hypertension showed a similar gestational-related increase of inhibin B levels during the third trimester, without any significant difference when compared with healthy women. Women with chronic hypertension showed significantly lower levels at term (P < 0.01). Women with pregnancy-induced hypertension or preeclampsia, or who were carrying a fetus with intrauterine growth retardation showed serum inhibin B levels during the third trimester of gestation consistently lower than in control healthy women at the same gestational age (P < 0.001, mean +/- SEM). Maternal serum inhibin B levels in women with early pregnancy bleeding or miscarriage were similar to those of healthy pregnant women at the same gestational age, independent from the outcome of gestation. The present study showed that maternal serum inhibin B levels increase in the last trimester of normal pregnancy, with low levels in women with hypertensive disturbances or intrauterine growth retardation.

Hypertension in pregnancy: changes in activin A maternal serum concentration.

Human placenta is the major source of activin A in maternal circulation. The aim of the present study was to evaluate maternal activin A serum concentration in pregnant women with chronic hypertension (n = 14), pregnancy-induced hypertension (n = 10) or pre-eclampsia (n = 16). In the group of pregnant women with chronic hypertension and of healthy pregnant women (n = 10) activin A was measured in samples collected longitudinally throughout gestation. Using a specific two-site enzyme-linked immunosorbent assay, it has been possible to measure maternal serum activin A concentration. In addition, the effect of recombinant human activin A administration on mean arterial pressure and heart rate in female rats have been also investigated. Mean +/- SEM of maternal serum activin A concentration in pre-eclamptic women (57.4 +/- 28.3 ng/ml), was significantly higher than in women with pregnancy-induced hypertension (14.8 +/- 10.5 ng/ml), chronic hypertension (10.3 +/- 5.4 ng/ml) or healthy control women (9.2 +/- 9.4 ng/ml) (P < 0.01). Serum activin A levels evaluated 2 weeks after anti-hypertensive treatment were not significantly different in pre-eclamptic women. Moreover, when exogenous recombinant human activin A was administered in female rats arterial pressure or frequency of heart rate did not change. The present study showed that maternal serum activin A concentration is abnormally high in patients with pre-eclampsia. Thus, since the patients with chronic hypertension or pregnancy-induced hypertension have activin A concentration in the normal range of values, activin A may be a prognostic marker of hypertension in pregnancy.

Blood pressure patterns in normal pregnancy and in pregnancy-induced hypertension, preeclampsia, and chronic hypertension.

OBJECTIVE: To compare the 24-hour blood pressure (BP) pattern in physiologic pregnancy, pregnancy-induced hypertension, preeclampsia, and chronic hypertension. METHODS: We investigated four groups of women with singleton pregnancy: 73 controls, 48 patients with pregnancy-induced hypertension, 38 with preeclampsia, and 53 with mild to moderate chronic hypertension. The 24-hour BP monitoring was performed longitudinally in controls and in patients with chronic hypertension, and at the time of diagnosis in those with pregnancy-induced hypertension or preeclampsia. RESULTS: Nineteen thousand eight hundred seventy-two BP measurements were analyzed. In controls, the mean values of BP indices were lower than those first reported in nonpregnant women, and the acrophase was always localized in the first part of the afternoon. In pregnancy-induced hypertension and especially in preeclampsia, besides the obvious quantitative increase in BP, circadian BP oscillations were less pronounced than in controls, and the severity of hypertension seemed to favor the loss of diurnal rhythm. Conversely, in chronic hypertension, circadian oscillations were the same as in controls. CONCLUSION: Standardized 24-hour BP monitoring during pregnancy allows quantitative and qualitative evaluations of the hypertensive status. However, if such a technique is used routinely in every clinical setting, we should establish specific thresholds of normality for pregnancy.

[Pre-menopausal dysfunctional menometrorrhagia: therapeutic approach]. / Menometrorragie disfunzionali in pre-menopausa: approccio terapeutico.

Approximately 10% of premenopausal women suffer from dysfunctional menometrorrhagia. The correct therapeutic approach to this pathology above all requires a precise diagnostic framework. For this purpose the doctor can employ a number of laboratory and instrumental tests, both invasive and non-invasive, in order to differentiate the dysfunctional forms from those supported by organic pathologies or non-gynecological diseases. Once the diagnostic iter has been completed, the choice of therapy can be directed towards surgical or medical treatment; the latter may be symptomatic or causal. This review focuses on the most commonly used treatments for dysfunctional menometrorrhagia in premenopausal women and proposes clinical protocols for a correct diagnostic and therapeutic approach.

Naproxen sodium in short-term prophylaxis of pure menstrual migraine: pathophysiological and clinical considerations.

We investigated the biological and clinical effects of naproxen sodium (NxS) in the short-term prophylaxis of pure menstrual migraine (PMM) in 25 women suffering from migraine without aura, occurring exclusively from 2 days before to 5 days after menstruation onset. Daily oral NxS (550 mg) from 7 days before menstruation to 7 days after menstruation onset was given for 3 menstrual cycles, and 5 days before menstruation to 5 days after menstruation onset over the next 3 menstrual cycles. In the month before initiation of treatment and in the third month of treatment, 6-keto-PGF1(alpha), TXB(2) and PGE(2) were measured in plasma before menstruation (day -2) and on the second day (day +2) after bleeding onset. In the 20 women analysed, 6-keto-PGF1(alpha) was 17% lower (p<0.0001) and TXB(2) was 30% lower (p<0.0001) on day -2 during treatment than the same day pretreatment; TXB(2) was also lower (p<0.02) on day +2 during treatment than day +2 pretreatment. The 6-keto-PGF1(alpha)/TXB(2) ratio was higher (p<0.01) on day -2 treatment than day -2 pretreatment. PGE(2) levels were significantly lower (p<0.002) on day +2 than pre-treatment values on the same day. The number of attacks reduced from 1.7+/-0.11 pretreatment to 1.2+/-0.10 at the 3rd month (p<0.001), to 1.1+/-0.06 at the 6th month (p<0.0001). The duration reduced from 25.6+/-4.42 h pretreatment to 15.5+/-4.43 h in the 3rd month (p<0.02), to 13.35+/-4.26 h in the 6th month (p<0.001). The intensity reduced from 2.4+/-0.11 pretreatment, to 1.2+/-0.10 in the 3rd month of treatment (p<0.0001), and 1.1+/-0.07 in the 6th month (p<0.0001).

Radiographic abnormalities in eosinophilic esophagitis.

Eosinophilic gastroenteritis is an unusual condition of unknown cause in which there is eosinophilic infiltration of the gastrointestinal tract usually accompanied by a peripheral eosinophilia. Rarely, it can also involve the esophagus. Recently, the authors have encountered 3 cases of eosinophilic infiltration of the esophagus. All patients had a strong history of allergies. Two of our patients have had upper esophageal strictures, as have 2 other previously reported cases. This appears to be the most common manifestation. One patient had polypoid lesions of the esophagus as well as of the rest of the gastrointestinal tract. Motility disturbances may also be present. Although steroid treatment may be beneficial, the esophageal strictures usually require mechanical dilatation to relieve submucosal fibrosis. This entity should be considered in any patient who has an esophageal disorder in the presence of either a strong history of allergy or peripheral eosinophilia.

Increased concentrations of eicosanoids and platelet-activating factor in menstrual blood from women with primary dysmenorrhea.

Prostanoids, leukotrienes and platelet-activating factor were measured by radioimmunoassay in menstrual blood of seven women with primary dysmenorrhea and five healthy controls. The eicosanoids and PAF concentrations in dysmenorrheic patients were significantly higher than those found in healthy women (P less than 0.005 for PGF2 alpha, 11-dehydro-TXB2, 2,3-dinor-TXB2 and LTC4/D4; P less than 0.001 for PAE; P less than 0.05 for PGE2 and 2,3-dinor-6-keto-PGF1 alpha). Whereas no relationship could be found between the concentrations of PGF2 alpha, PGE2, 11-dehydro- and 2,3-dinor-TXB2 and severity of primary dysmenorrhea, a close correlation between LTC4/D4 and PAF and severity of the disease was observed, particularly in patients who responded poorly to therapy with prostaglandin synthetase inhibitors. We conclude that the hyperstimulation of myometrial activity is not caused by selective stimulation of one metabolic pathway of arachidonic acid, but rather by an overall stimulation of phospholipid metabolism. The assessment of prostanoids, leukotrienes and PAF in menstrual blood many be useful as a direct index of primary dysmenorrhea, and the development of their antagonists may have therapeutic implications in improved treatment of the disease.

Peritoneal mesothelioma: an unusual cause of esophageal achalasia.

Secondary esophageal achalasia due to malignancy is a rare condition; only 53 such cases have been reported to date. Sixty-two percent of the cases were due to gastric adenocarcinoma. Mesothelioma of the peritoneum is an uncommon neoplasm. The usual presenting symptoms are abdominal pain, abdominal mass, or abdominal distention. The patient we are reporting had peritoneal mesothelioma which presented with dysphagia and weight loss, in addition to the radiological and manometric picture of achalasia. Secondary achalasia was suspected clinically, and was confirmed by computed tomography and laparotomy. The diagnosis of peritoneal mesothelioma was made only by histopathological examination. We are not aware of any other report documenting the association of peritoneal mesothelioma and achalasia.

Measurement of shoulder related disability: results of a validation study.

OBJECTIVE: To develop and validate a questionnaire to quantify disability associated with shoulder symptoms. METHODS: A set of questions relevant to shoulder symptoms from a general disability interview was developed and the questionnaire applied to a cross-sectional population survey and a prospective study of general practice attenders. Subjects included adults who reported current shoulder pain in a population survey and patients from three general practices who attended with shoulder symptoms during a six month period. The main outcome measures were: frequency of problems with daily living related to shoulder symptoms, total score on 22-item disability questionnaire, and measures of shoulder movement. RESULTS: A higher proportion (80%) of patients attending their general practitioner with shoulder symptoms had five or more disabilities compared with subjects reporting shoulder pain in a community survey (34%). The ranked frequency with which each disability was reported was similar in the two groups, although sleep disturbance was the most common problem in consulters. Self-reported disability is correlated with measures of restricted shoulder movement. CONCLUSION: This disability questionnaire was simple to complete and should prove useful for both general practice and population-based studies of shoulder pain.

Menstrual migraine: a possible pathogenic implication of platelet function.

It has been suggested that migraine is a blood disorder caused by a primary abnormality of platelet behaviour. We have studied in different phases of the cycle of 11 healthy normal women and 13 patients suffering from menstrual migraine: 1. The platelet aggregation induced in vitro by ADP, collagen and ristocetin; 2. The platelet sensitivity to prostacyclin (PSP); 3. The platelet content of 5-hydroxytryptimine (5-HT); 4. The possible correlation between these parameters and the plasma concentration of progesterone. The results demonstrate that in patients with menstrual migraine the platelet response to various aggregating agents is not modified compared to the controls, whereas there is a different response of the PSP to the modulating effect of plasma progesterone. Moreover, in the same patients the platelets have an increased capability of accumulating 5-HT during the perimenstrual phase of the cycle. This suggests that platelet dysfunction may play a role in the pathogenesis of menstrual migraine.

24-hour blood pressure monitoring to evaluate the effects of nifedipine in pre-eclampsia and in chronic hypertension in pregnancy.

OBJECTIVE: To investigate the effect of 7 to 14 days of therapy with nifedipine (sustained-release preparation) on the 24-hour blood pressure patterns of pregnant women with pre-eclampsia or chronic hypertension, and to test the utility of blood pressure monitoring in modulating the timing and dosage of the drug. DESIGN: 24-hour automatic blood pressure monitoring of pregnant women with pre-eclampsia or chronic hypertension before and after nifedipine treatment. SETTING: Centre for Prevention, Diagnosis and Treatment of Hypertension in Pregnancy, University of Turin, Italy. POPULATION: Sixteen pregnant women with pre-eclampsia and 17 with chronic hypertension. METHODS: 24-hour blood pressure monitoring was performed before the beginning of the therapy and after 7 to 14 days of treatment with sustained-release nifedipine. MAIN OUTCOME MEASURES: Chronobiological analysis of systolic and diastolic blood pressure values was performed; MESOR, amplitude, acrophase, hyperbaric index, percent time elevation and significance of rhythm were calculated before and after treatment. RESULTS: 6336 blood pressure measurements were analysed. Systolic and diastolic MESOR values were significantly decreased after nifedipine treatment both in pre-eclampsia and in chronic hypertension. However, the antihypertensive effect of nifedipine in pre-eclampsia was especially pronounced during evening and night, while in chronic hypertension it was more constant during the 24-hour period. 24-hour blood pressure monitoring allowed adjustment, when necessary, to the timing and dosage of nifedipine in accordance with the blood pressure patterns of each patient, using the hyperbaric index and percent time elevation as objective parameters for the evaluation of treatment efficacy. CONCLUSIONS: 24-hour blood pressure monitoring is a good method to optimise treatment, and confirms that nifedipine is useful for the control of maternal blood pressure in pregnancy.

Platelet sensitivity to prostacyclin in normal subjects, and in patients with benign and malignant tumours of the breast.

Platelet sensitivity to prostacyclin (PG12) was determined in normal male and female subjects, and in patients with benign and malignant tumours of the breast. The IC50 overall mean values for PG12 on ADP-induced platelet aggregation were similar for normal men and women, being 0.97 +/- 0.05 ng ml-1 and 0.83 +/- 0.07 ng ml-1 respectively. However, there were significant differences in the IC50 values for women in the 1st (0.81 +/- 0.06 ng ml-1) vs. 2nd (1.37 +/- 0.13 ng ml-1) phase of the menstrual cycle; post-menopausal women gave similar values to normal males and to pre-menopausal women in the 1st phase of the cycle. No significant differences were found between normal subjects and patients with benign or malignant tumours of the breast when account was taken of the status of the patient in relation to the phase of the menstrual cycle and the menopause. The importance of the hormonal status in evaluating changes in platelet sensitivity in patients with breast cancer is strongly emphasised.

Relevance of prostaglandins in true menstrual migraine.

Eighteen patients suffering from true menstrual migraine and 12 control subjects were studied. We evaluated in different phases of the menstrual cycle and during the migraine crisis the peripheral plasma concentrations of 6-keto-PGF1 alpha (the stable metabolite of PGI2), thromboxane B2 (the stable metabolite of thromboxane A2), PGF2 alpha and PGE2. The mean values of 6-keto-PGF1 alpha in menstrual migraine sufferers are lower than in normal women throughout the whole cycle. The difference between the trends observed in the two groups is statistically significant (p less than 0.05). The plasma levels of TXB2 and of PGF2 alpha are similar in the two groups investigated, both in basal conditions and during the attack. The plasma concentrations of PGE2 are slightly lower in migraineurs in basal conditions than in normals. However, during the crisis they increase significantly (p less than 0.05). In conclusion, among all the parameters considered, PGE2 seems to play the most important role during the pain phase of the attack. The results of the present study suggest that a deficit of PGI2, one of the most important protecting agents against ischemia, might be a typical feature of menstrual migraine and might cause in these patients a vascular hypersensitivity to different ischemic stimuli.

Production of prostacyclin, 6-keto-PGF1 alpha and thromboxane B2 by human umbilical vessels increases from the placenta towards the fetus.

The aim of this study was to investigate the production of prostacyclin (PGI2) and thromboxane B2 (TXB2) by incubated samples of umbilical arteries and veins taken at different distances (2, 10, 20, 30 cm) from the placenta to provide additional information relevant to the haemodynamics of umbilical blood flow. The production of PGI2, and 6-keto-PGF1 alpha (the stable metabolite of PGI2), was higher in both veins and arteries as the distance from the placenta at which the vessels were sampled was increased. A similar correlation between production by venous rings and distance from the placenta was observed for TXB2, but there was no apparent gradient of TXB2 production by the samples of arterial rings. No statistically significant variations were discernible in the ratio of 6-keto-PGF1 alpha:TXB2 (approximately 50 in the veins and approximately 20 in the arteries) in relation to the sampling distance. The significance of these high ratios is discussed in relation to umbilical blood flow and fetal well-being and development.

Vitamin E supplementation in preeclampsia.

An oxidant/antioxidant imbalance has been suggested among the pathogenetic factors involved in preeclampsia. As vitamin E is one of the most important antioxidant body components, a nonrandomized controlled trial was undertaken in 36 preeclamptic patients in order to evaluate the effect of vitamin E supplementation (100-300 mg/day per os) on fetal and maternal outcome. Fetal mortality was similar in 14 patients treated with conventional therapy plus oral vitamin E supplementation (35%) and in 22 patients treated with conventional therapy only (36%). Furthermore, in both groups of patients proteinuria increased, and increased dosages of antihypertensive drugs were called for in order to control blood pressure. We conclude that, with these dosages and in case of an already established disease, vitamin E does not improve fetal outcome in severe preeclampsia. Furthermore, it does not show favorable effects on maternal hypertension and proteinuria.

Increased activity of 6-phosphogluconate dehydrogenase and glucose-6-phosphate dehydrogenase in purified cell suspensions and single cells from the uterine cervix in cervical intraepithelial neoplasia.

The activities of 6-phosphogluconate dehydrogenase and glucose-6-phosphate dehydrogenase have been measured in squamous epithelial cells of the uterine cervix from normal patients and cases of cervical intraepithelial neoplasia (CIN). A biochemical cycling method, which uses only simple equipment and is suited to routine use and to automation, was applied to cells separated by gradient centrifugation. In addition, cells were examined cytochemically, and the intensity of staining in the cytoplasm of single whole cells was measured using computerised microcytospectrophotometry. Twenty per cent of cells in samples from normal patients (n=61) showed staining intensities above an extinction of 0.15 at 540 nm, compared to 71% of cases of CIN 1 (n=14), 91% of cases of CIN 2 (n=11) and 67% of cases of CIN 3 (n=15). The cytochemical data do not allow definitive distinctions to be made between different grades of CIN whereas the biochemical assay applied to cell lysates shows convincing differences between normal samples and cases of CIN. There are no false negatives for CIN 3 (n=14) and CIN 2 (n=10) and 11% false negatives for CIN 1 (n=9) and 14% of false positives for normal cases (n=21). The results of this preliminary study with reference to automation are discussed [corrected].