Hormonal and volume dysregulation in women with premenstrual syndrome

Premenstrual syndrome (PMS) presents with emotional and physical symptoms. Although the emotional symptoms have been extensively studied, the pathophysiology of the fluid-retention symptoms is not currently known. We tested the hypothesis that the fluid regulatory mechanisms are disturbed in PMS. Nine regularly menstruating women with PMS were compared with 9 healthy age-matched women. Hemodynamic parameters and upright plasma volume shift (extrapolated from changes in hematocrit), plasma renin activity (PRA), and plasma aldosterone and sex hormones were measured at different times during the menstrual cycle. During the early follicular and the midluteal phases, the plasma volume shift, supine and upright PRA, and plasma aldosterone were similar in both groups, and none of the participants had edema. However, during the late luteal phase, ankle edema was present only in women with PMS, and their maximal plasma volume shift was lower compared with controls (11.7+/-1.3 versus 15.6+/-0.6; P=0.004). The area under the curve (estimates the amount of the total plasma shift during 30 minutes standing) was 300+/-28 and 406+/-16 in PMS and controls, respectively (P=0.01). PRA and aldosterone levels were higher during the late luteal phase in women with PMS compared with controls (supine PRA: 1.4+/-0.3 [PMS] versus 1.1+/-0.4 [control; P value not significant], upright PRA: 3.9+/-0.08 versus 1.6+/-0.3 ng/mL per hour [P=0.015], supine plasma aldosterone: 131+/-30 versus 68+/-17 pg/mL [P=0.09], and upright plasma aldosterone: 208+/-40 versus 102+/-16 pg/mL [P=0.03]). We, therefore, conclude that women with PMS have increased plasma fluid-regulatory hormones and disturbed fluid distribution only during their late luteal menstrual phase.     

Vitamin D status in primary hyperparathyroidism

Background

Hypovitaminosis D worsens the manifestations of primary hyperparathyroidism (PHPT). Only a few studies have assessed the status of vitamin D in PHPT. The objective of this study was to determine the prevalence of 25(OH)D levels < 50 nmol/L in PHPT in comparison to a population without PHPT.

Methods

Subjects with PHPT were identified from the computerized database of the Clalit Health Services in Israel and were included only if they had an available serum 25(OH)D test result in 2009 and were not taking vitamin D supplements in 2008-2009 prior to the 25(OH)D test result. Subjects with renal failure were excluded (included n = 1180). All other subjects with an available 25(OH)D value in 2009 constituted the control group (n = 184,479).

Results

Subjects with PHPT and 25(OH)D < 50 nmol/L had higher levels of serum PTH, alkaline phosphatase, and calcium levels compared to those with 25(OH)D levels ≥ 50 nmol/L (P < 0.02). The mean serum 25(OH)D level was 47.7 ± 22.5 nmol/L compared to 52.1 ± 24.5 nmol/L in the control group (P < 0.001). 59.6% of subjects with PHPT had 25(OH)D levels < 50 nmol/L as compared to 49.5% in the control group (P < 0.001). Logistic regression, controlling for gender, ethnicity, age, and seasonality, showed that PHPT independently predicted 25(OH)D levels < 50 nmol/L; OR = 1.61(95% CI, 1.43-1.82).

Conclusions

Serum 25(OH)D levels < 50 nmol/L are frequent in PHPT, are more common than in controls, and are associated with more severe bone disease based on higher serum PTH and bone turnover biomarkers.     

Persistent gastric intramucosal ischemia in patients with sepsis following resuscitation from shock.

STUDY OBJECTIVES: (1) To determine the effects of resuscitation of patients with severe sepsis to conventional hemodynamic end points and normal blood lactate levels on postresuscitation sequential assessments of gastric intramucosal pH (pHi). (2) To determine whether trends in pHi are reflected in trends in systemic hemodynamic, oxygen utilization, and acid-base assessments. DESIGN: Prospective cohort study. SETTING: Medical ICU in an inner-city, university-based medical center. PATIENTS: Twelve recently admitted patients with severe sepsis and signs of circulatory shock who were successfully resuscitated to normal hemodynamic end points and lactate levels and who were also monitored with pulmonary artery catheters and gastric tonometers. INTERVENTIONS: Because of the observational nature of this study, no specific interventions were employed. The physician staff administered i.v. fluids and pharmacologic agents, during and after the resuscitative period, to treat infection and to achieve and maintain hemodynamic stability. Mechanical ventilation and supplemental oxygen were provided as needed. The hemodynamic and physiologic monitoring employed was determined by the managing physicians and established medical ICU routines. MEASUREMENTS AND RESULTS: A total of 12 patients were studied. Systemic hemodynamic, oxygen utilization, and acid-base assessments and pHi were recorded following resuscitation, and every 12 h thereafter. pHi decreased from 7.33 +/- 0.08 (mean +/- SD) following resuscitation to 7.26 +/- 0.04 at 24 h, 7.20 +/- 0.07 at 36 h (p < 0.05), and 7.24 +/- 0.08 at 48 h. Corresponding statistically significant and clinically relevant changes in systemic hemodynamic, oxygen utilization, and acid-base variables were not observed. The hospital mortality of this patient group was high (10 of 12; 83%). CONCLUSIONS: Gastric intramucosal acidosis develops and persists for at least 48 h in patients resuscitated from septic shock to conventional resuscitative end points, including the normalization of lactate levels. These regional changes were not reflected in corresponding changes in systemic acid-base and oxygen utilization variables. Direct determinations of pHi and therapy directed toward the resolution of splanchnic ischemia may be required to improve the outcome in these patients.     

Distinctive genetic signatures in the Libyan Jews

Unlinked autosomal microsatellites in six Jewish and two non-Jewish populations were genotyped, and the relationships among these populations were explored. Based on considerations of clustering, pairwise population differentiation, and genetic distance, we found that the Libyan Jewish group retains genetic signatures distinguishable from those of the other populations, in agreement with some historical records on the relative isolation of this community. Our methods also identified evidence of some similarity between Ethiopian and Yemenite Jews, reflecting possible migration in the Red Sea region. We suggest that high-resolution statistical methods that use individual multilocus genotypes may make it practical to distinguish related populations of extremely recent common ancestry.     

Absence of association of inherited thrombophilia with unexplained third-trimester intrauterine fetal death

OBJECTIVE: The purpose of this study was to investigate the alleged association between thrombophilia and unexplained third-trimester stillbirth. STUDY DESIGN: Case subjects were 37 women with a history of a third-trimester unexplained stillbirth. Control subjects were 46 volunteers, group-matched for ethnic origin, with no history of stillbirth, recurrent fetal loss, or thromboembolism. The pathology report of 34/37 placentas of case subjects was reviewed. RESULTS: The prevalence of at least 1 inherited thrombophilia among case subjects was 37.8% compared with 41.3% among control subjects. (OR = 0.87; 95%CI, 0.32-2.29). There was no significant difference between the groups with respect to the prevalence of any single inherited thrombophilia. There was, however, a significantly higher prevalence of antiphospholipid antibodies among case subjects compared with control subjects: 47.2% vs 8.7%, respectively (OR = 9.4; 95%CI, 2.5-42.3). No significant difference was noted in the prevalence of thrombopilia among subjects with or without placental infarcts. CONCLUSION: We did not find an association between unexplained third-trimester intrauterine fetal death and inherited thrombophilia; however, we did find such an association with antiphospholipid antibodies.     

Splanchnic vein thromboses associated with myeloproliferative neoplasms: An international,retrospective study on 518 cases

Myeloproliferative Neoplasms (MPN) course can be complicated by thrombosis involving unusual sites as the splanchnic veins (SVT). Their management is challenging, given their composite vascular risk. We performed a retrospective, cohort study in the framework of the International Working Group for MPN Research and Treatment (IWG-MRT), and AIRC-Gruppo Italiano Malattie Mieloproliferative (AGIMM). A total of 518 MPN-SVT cases were collected and compared with 1628 unselected, control MPN population, matched for disease subtype. Those with MPN-SVT were younger (median 44 years) and enriched in females compared to controls; PV (37.1%) and ET (34.4%) were the most frequent diagnoses. JAK2V617F mutation was highly prevalent (90.2%), and 38.6% of cases had an additional hypercoagulable disorder. SVT recurrence rate was 1.6 per 100 patient-years. Vitamin K-antagonists (VKA) halved the incidence of recurrence (OR 0.48), unlike cytoreduction (OR 0.96), and were not associated with overall or gastrointestinal bleeding in multivariable analysis. Esophageal varices were the only independent predictor for major bleeding (OR 17.4). Among MPN-SVT, risk of subsequent vascular events was skewed towards venous thromboses compared to controls. However, MPN-SVT clinical course was overall benign: SVT were enriched in PMF with lower IPSS, resulting in significantly longer survival than controls; survival was not affected in PV and slightly reduced in ET. MPN-U with SVT (n = 55) showed a particularly indolent phenotype, with no signs of disease evolution. In the to-date largest, contemporary cohort of MPN-SVT, VKA were confirmed effective in preventing recurrence, unlike cytoreduction, and safe; the major risk factor for bleeding was esophageal varices that therefore represent a major therapeutic target.