Pituitary responsiveness to LH-RH during gestation and puerperium in the rhesus monkey

Pituitary gonadotropin response to luteinizing hormone-releasing hormone (LH-RH; 150 micrograms, administered intravenously) was studied during pregnancy and the early postpartum period in rhesus monkeys. Challenge tests were performed approximately every three weeks during pregnancy and every two weeks after delivery, in breast-feeding and non breast-feeding animals. It was found that the response to the releasing factor was completely abolished as early as day 20 after conception. This absence of pituitary responsiveness to LH-RH continued throughout pregnancy. The return of the response during the puerperium occurred as early as day 15 post-delivery in non-breast-feeding monkeys, but remained abolished up of the response to LH-RH in FSH and LH concentration was observed, in that LH levels increased 70%-90%, whereas FSH levels increased only 20%-30%. Serum prolactin (PRL) levels in breast-feeding animals presented a slight increase the first week post-delivery and thereafter, and decreased gradually until they reached normal levels four weeks post-delivery. In contrast, concentrations of serum PRL in non-breast-feeding animals decreased abruptly to normal levels within the first week post-delivery. These results demonstrate that, due to its similarity to the human, the rhesus monkey is an excellent animal model in which to study pituitary function during pregnancy and the puerperium.     

Immunization with a combination of merozoite surface proteins 4/5 and 1 enhances protection against lethal challenge with Plasmodium yoelii

It is widely believed that subunit vaccines composed of multiple components will offer greater protection against challenge by malaria, and yet there is little experimental evidence to support this view. We set out to test this proposition in the Plasmodium yoelii challenge system in rodents by comparing the degree of protection conferred by immunization with a mixture of merozoite surface proteins to that conferred by single proteins. We therefore examined a defined protein mixture made of the epidermal growth factor-like domains of P. yoelli merozoite surface protein 1 (MSP1) and MSP4/5, the homologue of P. falciparum MSP4 and MSP5. In the present study we demonstrate that this combination of recombinant proteins dramatically enhances protection against lethal malaria challenge compared to either protein administered alone. Many mice immunized with the MSP4/5 plus MSP1(19) combination did not develop detectable parasitemia after challenge. Combined immunization with MSP1(19) and yMSP4/5, a product characterized by lower protective efficacy, also greatly enhanced protection by reducing peak parasitemias and increasing the numbers of survivors. In some combination trials, levels of antibodies to MSP1(19) were elevated compared to the MSP1(19) alone group; however, improved protection occurred regardless of whether boosting of the anti-MSP1(19) response was observed. Boosting of anti-MSP1(19) did not appear to be due to contaminating endotoxin in the EcMSP4/5 material since enhanced protection was observed in C3H/HeJ mice, which are endotoxin insensitive. Collectively, these experiments show that multiantigen combinations offer enhanced levels of protection against asexual stage infection and suggest that combinations of MSP1, MSP4, and MSP5 should be evaluated further for use in humans.     

Rare association of ovarian implantation site for patients with heterotopic and with primary ectopic pregnancies after ICSI and blastocyst transfer

Two cases of patients with ruptured ovarian pregnancies (P1 = ovarian heterotopic and P2 = primary ovarian ectopic) after intracytoplasmic sperm injection and blastocyst transfer are presented. Laparoscopy was performed on day 40 and day 27 after transfer in cases P1 and P2 respectively. In both cases the ectopic pregnancies were located on the left ovary and were successfully removed by laparoscopy preserving the ovaries. In case P1 the intrauterine pregnancy was not affected. A healthy boy was born after 37 weeks of pregnancy. In this way, potential fertility of the patients and the intrauterine pregnancy were maintained. These cases occurred during a series of blastocyst transfers in which 129 pregnancies were obtained. There were no cases of ovarian ectopic/heterotopic pregnancies from January 1996 to September 1999 in 814 pregnancies obtained from day 2 or day 3 embryo transfers. Because the ovarian ectopic pregnancies occurred in patients with day 5 embryo transfer who otherwise did not have any predisposing factors for ectopic pregnancy, it is advisable to conduct a large scale analysis of future data about the possible association between blastocyst-stage embryo transfer and the somewhat higher risk of unexpected complications of clinical outcome.     

Reference charts for weight gain and body mass index during pregnancy obtained from a healthy cohort

Objective. To create reference charts for weight gain and body mass index (BMI) in pregnancy derived from longitudinal data obtained in a representative sample of the Argentinean population.

Methods. A prospective cohort of 1439 healthy pregnant women was selected from antenatal clinics in seven different urban regions in Argentina. Serial anthropometric measurements were made at weeks 12, 16, 20, 24, 28, 32, 36 and in the last pre-natal control. Centile curves of body weight and BMI by gestational age were developed using the LMS method.

Results. Mean weight gain at 38 weeks of gestation was 11.9 ± 4.4 kg. There were no differences in total weight gain between women who enter pregnancy with low, normal or overweight; only those women with a pre-pregnancy BMI in the range of obesity showed a significantly lower weight gain (10.2 ± 4.8 kg). At 12 weeks of pregnancy, BMI values of the 10th, 50th and 90th centiles were 19.3, 22.8 and 29.0, and at 38 weeks these values were 23.3, 27.4 and 33.8, respectively.

Conclusion. This BMI for gestational age chart, based on women who delivered normal birth weight infants and processed with modern statistical methods, represents an improvement in pre-natal care monitoring.     

Fat-Free Mass Depletion and Inflammation in Patients with Bronchiectasis

Fat-free mass depletion has been related to increased inflammatory activity and to increased morbidity and mortality in chronic respiratory diseases. The aims of our study were to determine the nutritional status and serum levels of adipocytokines and inflammatory cytokines in patients with bronchiectasis of any etiology and their relation with respiratory parameters. A cross-sectional study was designed that included patients aged >14 years with diagnostic criteria for bronchiectasis. Anthropometric parameters; a diet questionnaire; hand grip dynamometry; levels of leptin, adiponectin, interleukin-6 (IL-6), tumor necrosis factor-α, and ultrasensitive C-reactive protein; as well as respiratory parameters (ie, clinical, radiologic, and spirometric values) were assessed. Ninety-three clinically stable patients were recruited, 43 with cystic fibrosis, 31 with noncystic fibrosis bronchiectasis, and 19 with cystic fibrosis transmembrane conductance regulator-related bronchiectasis. Fat-free mass depletion was present in 31% of patients, with no differences according to the etiology of the bronchiectasis. Correlations were found between inflammatory cytokines (ie, IL-6) and exacerbations, bronchorrea, forced expiratory volume in 1 second, and Bhalla score. Patients with worse respiratory disease severity, malnutrition, and diabetes had significantly higher levels of IL-6. Adiponectin correlated significantly and positively with fat mass and fat mass index and negatively with fat-free mass, fat-free mass index, and hand dynamometry. Leptin correlated positively with body mass index, fat mass and fat mass index, and negatively with fat-free mass, fat-free mass index, and dynamometry. Patients with bronchiectasis present a high percentage of fat-free mass depletion, independent of the etiology of the disease. The levels of inflammatory cytokines (especially IL-6) may be useful markers of disease severity. Adiponectin levels were higher in patients with fat-free mass depletion.     

Leptomeningeal relapse of multiple myeloma following allogeneic stem cell transplantation

Progressive multiple myeloma may manifest features of 'de-differentiation', including a plasmablastic appearance, failure to secrete paraprotein, extramedullary involvement, and resistance to treatment. A 44-year-old woman with kappa-light chain myeloma underwent allogeneic stem cell transplantation (SCT). Twenty months later she developed paraspinal plasmablastic myeloma in the absence of paraprotein in urine or myeloma in the marrow. The paraspinal masses responded to chemotherapy. At 30 months she developed myelomatous meningitis, which proved resistant to intrathecal chemotherapy, irradiation, and donor lymphocyte infusion (DLI). The leptomeningeal disease led to death at 38 months. This is the first report of leptomeningeal relapse of myeloma after allografting.     

Depression and anxiety symptoms in bronchiectasis: associations with health-related quality of life

Background and purpose

Bronchiectasis causes pulmonary infections and loss of lung function, resulting in chronic respiratory symptoms and worsening health-related quality of life. The aims of this study were to measure symptoms of depression and anxiety in a sample of patients with bronchiectasis and evaluate their relationship to health outcomes and health-related quality of life.

Methods

This cross-sectional study included adolescents and adults with bronchiectasis. Patients completed the hospital anxiety and depression scale and the St. George respiratory questionnaire. Health outcome data, including clinical, radiological and spirometric values, were recorded from medical charts.

Results

Ninety-three participants with bronchiectasis of any aetiology were recruited: 20 % had elevated depression-related scores and 38 % had elevated anxiety-related scores. Increased symptoms of depression and anxiety were significantly associated with age; anxiety was associated with more frequent exacerbations. Regression analyses indicated that after controlling for demographic (gender and age) and clinical variables (exacerbations frequency, daily sputum, aetiology and spirometry), both depression and anxiety symptoms predicted significantly worse health-related quality of life. In comparison with other predictors, psychological symptoms explained the largest amount of variance in health-related quality of life.

Conclusions

Symptoms of depression and anxiety were significant predictors of health-related quality of life in patients with bronchiectasis, independently of respiratory involvement, gender, age or other variables.     

Selection of the most common chromosome abnormalities in oocytes prior to ICSI

So far, all preimplantation genetic diagnosis (PGD) protocols in use produce results after the eggs have been fertilized. However, these approaches are not acceptable for patients with moral objections to the generation and discard of supernumerary zygotes or embryos. In these circumstances, only those oocytes to be replaced may be inseminated. The purpose of this study was to develop a PGD protocol to diagnose first polar bodies (PBs) prior to Intracytoplasmatic Sperm Injection (ICSI) in order to inseminate only those oocytes found to be chromosomally normal. PB biopsy was performed 1 hour after ovum pick up, and after fixation, the PBs were analysed by FISH and the eggs inseminated by ICSI no later than 7 hours after retrieval. One third (33.3%) of the PBs were aneuploid. Fifty-four normal and 12 non-resolved oocytes were injected by ICSI, of which 65% became 2-PN zygotes. Embryo transfer on day 2 was possible in all 10 patients (average maternal age 35.2+/-3.2, range 29-39 years), of which 6 became pregnant with 8 fetuses (28.6% or 8/28 transferred embryos). The results indicate that PB analysis of some common chromosome abnormalities is feasible within time limits imposed by ICSI insemination (6 hours or less).