Alterations in lipid peroxidation and T-cell function in women with hyperemesis gravidarum.

The objective of this study was to investigate serum adenosine deaminase (ADA) activity as a marker of T lymphocyte activation and parameters of oxidative stress and antioxidant defence in hyperemesis gravidarum (HG). Serum ADA activity, malondialdehyde (MDA), catalase (CAT) and glutathione peroxidase (GPx) levels were investigated in 40 pregnant women with the HG and 40 with healthy pregnancies, in a descriptive study. Although serum ADA and CAT were measured to be higher in HG group, the difference was not significant. Serum MDA and GPx levels were significantly elevated in women with HG when compared with those without HG. The significance of changes in lipid peroxidation and T-cell activation in the pathogenesis of HG and whether this is a cause or a compensatory reaction to HG requires further investigations with larger multicentre trials.

Apoptosis in raloxifene-treated postmenopausal women.

As raloxifene is a mixed estrogen receptor agonist and antagonist, it exerts different effects on apoptosis in different tissues. In this study, we aimed to evaluate apoptosis in the peripheral lymphocytes of postmenopausal women treated with raloxifene and compare it with untreated control subjects. In this way, we expected to deduce some results about the effect of raloxifene on the immune system and to serve as a guide for future studies on this newly proposed effect of a well-known agent. Twenty osteoporotic postmenopausal women treated with raloxifene for 12 months were included in this study. Another 20 osteoporotic postmenopausal women matched for age and postmenopausal years, but without any medication, were chosen as the control group. Apoptosis was evaluated using a morphological and DNA fragmentation assay, in the peripheral lymphocytes of these women. Our results revealed a decrease in the apoptosis percentages of the patients treated with raloxifene (14.6%) with respect to the control subjects (15.8%), but the difference was not statistically significant (p=0.467). This study indicated that raloxifene treatment had no apoptotic effect on peripheral human lymphocytes compared to controls.

Age-related changes in ovarian volume, antral follicle counts and basal follicle stimulating hormone levels: comparison between fertile and infertile women.

Our objective was to compare the relationship between age, basal follicle stimulating hormone (FSH) level and ultrasound-measured mean ovarian volume (MOV) and mean antral follicle counts (MFC) in a group of infertile and fertile women between the ages of 35 and 45 years. Menstrual cycle day 3 serum FSH, MOV and MFC were analyzed in 62 infertile and 53 fertile women. Basal FSH and MFC did not differ between infertile and fertile women, whereas MOV was significantly smaller in infertile women (p < 0.05). In the infertile group, there was a negative correlation between MOV and age (rho = -0.389, p < 0.05), between MOV and basal FSH (rho = 0.495, p < 0.01), and between MFC and age (rho = -0.553, p < 0.01). In the fertile group, there was a strong negative correlation between MOV and basal FSH (rho = -0.631, p < 0.01), and between MFC and basal FSH (rho = -0.710, p < 0.01). Mean basal FSH, MOV and MFC did not differ between subgroups of patients with different causes of infertility. In the infertile group, patients with small ovaries of volume less than 1.8 cm(3) (mean volume -1 SD) had higher mean basal FSH (p < 0.05) and lower MFC (p < 0.01) levels than patients with normal ovarian volume. In conclusion, transvaginal ultrasound (TVU) indices and indirect hormonal parameters of ovarian reserve were similar in infertile and fertile women aged between 35 and 45 years. It is suggested that, in infertile women above 35 years of age, TVU rather than hormonal parameters be preferred, based on our data showing a stronger association between age and TVU indices of ovarian reserve than between age and increase in basal FSH level. Thus, TVU assessment of ovarian volume and antral follicle counts is a practical and cost-effective, if not better, technique for ovarian reserve testing.

Comparison of different treatment modalities for postmenopausal patients with osteopenia: hormone replacement therapy, calcitonin and clodronate.

OBJECTIVE: To evaluate the effectiveness of hormone replacement therapy (HRT), clodronate, calcitonin and a clodronate plus calcitonin combination in postmenopausal patients with osteopenia. METHODS: One hundred postmenopausal patients with osteopenia, with bone mineral density (BMD) measurements at least one standard deviation below the mean value for young premenopausal subjects (T score < -1), were studied. They had no contraindications to HRT, clodronate or calcitonin use and were randomized to four different treatment groups. Patients in group I were treated with transdermal estradiol 50 micrograms/day and oral medroxyprogesterone acetate 10 mg/day during the last 12 days of the month; group II received oral clodronate 400 mg/day for 1 month out of every 3 months; group III received calcitonin nasal spray 100 IU/day; and patients in group IV were treated with oral clodronate 400 mg/day for 1 month out of every 3 months plus calcitonin nasal spray 100 IU/day. Elementary calcium 1000 mg/day was supplemented to patients in all groups. Spinal and femoral neck BMD measurements and markers of bone mineral metabolism were measured in each patient before treatment and 6, 12 and 18 months after treatment in 86 patients. RESULTS: Significant increases in mean lumbar spine BMD were found in the group receiving HRT, and at the end of 18 months there was a 2.69 +/- 0.76% increase, compared with baseline. Mean femoral neck BMD also increased by 2.22 +/- 0.57% in the HRT group; this was significantly different from baseline, resulting in a higher bone mass gain than in the other three groups. Increases in both lumbar spine and femoral neck BMD were found in patients treated with clodronate, although the only significant increase was observed in lumbar spine BMD at the end of 18 months. The mean changes in BMD were not significantly different, compared with the other groups, and at the end of 18 months there was a 2.20 +/- 0.58% increase at the lumbar spine. The mean vertebral and femoral neck BMD did not change significantly throughout the study period in patients receiving calcitonin. At the end of 18 months, there was a 0.13 +/- 0.52% decrease and a 0.11 +/- 0.49% increase in mean lumbar spine and femoral neck BMD, respectively, compared with baseline. The combination of clodronate plus calcitonin increased mean lumbar spine and femoral neck BMD by 2.08 +/- 1.05% and 1.46 +/- 1.09%, respectively, at the end of 18 months, but these increases were not significantly different from those in the groups where these agents were used alone. Significant decreases in bone resorption and in markers of bone formation were observed in all groups. CONCLUSION: HRT was found to be the most effective treatment regimen in postmenopausal patients with osteopenia, compared with clodronate, calcitonin and a clodronate plus calcitonin combination. Clodronate or calcitonin might be alternatives when HRT is contraindicated or refused by the patient; although calcitonin was found to be less effective. The clodronate plus calcitonin combination was not superior to either of these agents when used alone.

Comparison of meropenem with amikacin plus ceftazidime in the empirical treatment of febrile neutropenia: a prospective randomised multicentre trial in patients without previous prophylactic antibiotics. Meropenem Study Group of Turkey.

Eighty three patients with neutropenia and cancer were randomised to receive either 1 g meropenem tds or amikacin 15 mg/kg single dose daily plus ceftazidime 2 g tds. No prophylactic antibiotics were allowed before entry to the trial. Seventy seven patients were available for analysis. Infection was microbiologically or clinically documented in 53 episodes (69%). The overall success rate without adjustment was 49% in monotherapy, 37.5% in the combination group. These rates were increased to 65% and 56%, respectively when secondary infection episodes requiring a different class of chemotherapy were taken into account. Median duration for defervescence was 3 days in successfully treated patients in both groups. Only minor reversible side effects were noted in both treatment arms. Meropenem monotherapy seemed as effective and safe as amikacin plus ceftazidime for the empirical treatment of neutropenic cancer patients with fever.

A surveillance study of antimicrobial resistance of gram-negative bacteria isolated from intensive care units in eight hospitals in Turkey.

This study was carried out with the participation of eight hospitals in Turkey to determine the frequency of gram-negative bacteria isolated in intensive care units (ICU) and to compare their resistance rates to selected antibiotics. Aerobic gram-negative bacteria isolated from ICUs during 1996 were studied. Antibiotic susceptibilities to imipenem, ceftazidime, ceftazidime-clavulanate, ceftriaxone, cefotaxime, cefepime, cefodizime, cefuroxime, piperacillin/tazobactam, amoxycillin-clavulanate, gentamicin, amikacin and ciprofloxacin were determined by Etest. A total of 748 isolates were obtained from 547 patients. The majority of organisms were isolated from the respiratory (38.8%) and urinary tracts (30.9%). Pseudomonas spp. were the most frequently isolated gram-negative species (26.8%), followed by Klebsiella spp. (26.2%). Escherichia coli, Acinetobacter spp. and Enterobacter spp. were the other commonly isolated organisms. High resistance rates were observed for all antibiotics studied. Imipenem appeared to be the most active agent against the majority of isolates. Although resistance rates exceeded 50%, ciprofloxacin, cefepime and amikacin were found to be relatively effective. Extended-spectrum beta-lactamase (ESBL) production appeared to be a major mechanism of resistance to beta-lactam antibiotics. In contrast to ceftazidime-clavulanate, piperacillin/tazobactam showed poor activity against organisms thought to produce ESBL, suggesting the presence of an enzyme resistant to tazobactam action. This study has yielded high rates of resistance in aerobic gram-negative isolates from ICUs in Turkey. High resistance rates to all the other antibacterials studied leave imipenem as the only reliable agent for the empirical treatment of ICU infections in Turkey.

Clomiphene citrate challenge test in the assessment of ovarian reserve before controlled ovarian hyperstimulation for intracytoplasmic sperm injection.

The objective of this study is to evaluate the performance of clomiphene citrate (CC) challenge test to predict diminished ovarian reserve before controlled ovarian hyperstimulation for intracytoplasmic sperm injection (ICSI). The 198 women who underwent the CC challenge test fulfilled the following criteria; over 35 years of age, removal of one ovary or previous ovarian surgery, the presence of ovarian endometrioma or previous poor response to ovarian hyperstimulation. Of the patients tested, 141 were found to have a normal CC challenge test while 57 had an abnormal result. The cancellation rate of the cycle with a poor response was significantly higher in women with an abnormal test (36.8%) than in those with a normal test (19.8%) (P < 0.05). The sensitivity of CC test for cycle cancellation was found to be 43% with a specificity of 76%, positive and negative predictive values of 37 and 80%, respectively. The estradiol values on hCG day, the number of retrieved oocytes and metaphase II oocytes and the rate of transfer cycles were significantly lower in females with an abnormal test. Women with normal test results had higher pregnancy rates per embryo transfer than those with abnormal test results (21.5 vs. 13.3%) and the predictive value of an abnormal test for failing to conceive was 93% (53/57) with a sensitivity of 31%, specificity of 84% and negative predictive value of 15.6%. Of 57 women with an abnormal test result, 25 (43.8%) were abnormal due only to an elevated day 10 or 11 value of FSH, which could not be detected using only basal FSH screening. In this group, the cancellation rate (48 vs. 19.8%, P < 0.01), the rate of transfer cycles (48 vs. 72.3%, P < 0.05) and the mean number of retrieved oocytes (4.9 +/- 2.5 vs. 6.4 +/- 3.1, P < 0.01) were all significantly different from normal test group. Although the rate of pregnancies per started cycle (8 vs. 15.6%) did not show a statistically significant difference, this is most probably due to the low number of patients. In conclusion, an abnormal CC challenge test is a good predictor of diminished ovarian reserve and it is better than a basal FSH concentration on day 3. It provides valuable information for both patients as to their chances of achieving a pregnancy and also for the medical team deciding on options for stimulation protocols.

Effect of abnormal sperm head morphology on the outcome of intracytoplasmic sperm injection in humans.

The present study was designed to determine the efficacy of intracytoplasmic sperm injection (ICSI) using spermatozoa with abnormal head morphology in 17 cases with total teratozoospermia. A total of 160 oocytes were retrieved and 144 metaphase II oocytes were injected. The fertilization and cleavage rates were 50.7 and 93.2% respectively. Fertilization failure occurred in two couples. A total of 54 embryos were transferred and pregnancy rates per initiated and per embryo transfer cycle were 17.6 and 20.0% respectively, while the clinical pregnancy rates per initiated and embryo transfer cycle were 11.8 and 13.3%. The implantation rate was 3.7% (2/54). Out of two pregnancies achieved, one resulted in abortion in the first trimester. The ongoing pregnancy rates per initiated and embryo transfer cycle were 5.88% (1/17) and 6.6% (1/15) respectively. Although the implantation and ongoing pregnancy rates are very low, ICSI seems to be the only treatment modality in cases where teratozoospermia was total with 100% abnormal head morphology.

Trimethoprim/sulfamethoxazole-induced hypoglycemia in a malnourished patient with severe infection.

Hypoglycemia resulting from the combination of sulfonylurea and sulfonamides is a recognized drug interaction. Hypoglycemia induced by sulfonamides alone may be encountered less frequently. Because of their structural similarities to sulfonylureas, sulfonamides are liable to facilitate hypoglycemia by increasing insulin release in susceptible individuals. Sulfonamides can potentiate the hypoglycemic effect of sulfonylurea agents when given in combination. We describe a malnourished patient with severe infection who developed hypoglycemia during high-dose trimethoprim/sulfamethoxazole therapy. Elevated C-peptide concentrations during the hypoglycemic episode indicate that hypoglycemia resulted from increased endogenous insulin secretion. As malnourished patients are prone to hypoglycemia, we suggest that they should be monitored carefully if they are on sulfonamide therapy.

Outcomes of multifetal pregnancy reduction in multiple pregnancies achieved by intracytoplasmic sperm injection using ejaculated, testicular, or epididymal sperm.

OBJECTIVE: To report the pregnancy outcome after transabdominal multifetal pregnancy reduction in multiple pregnancies achieved by intracytoplasmic sperm injection. METHODS: One twin and 13 triplet pregnancies obtained by intracytoplasmic sperm injection underwent pregnancy reduction. Pregnancies were achieved with ejaculated sperm in 8, testicular sperm in 3, and epididymal sperm in 2 of these cases. All triplet pregnancies were reduced to twins at 10-12 weeks' gestation by transabdominal potassium chloride injection. A twin pregnancy with spina bifida affecting 1 fetus was reduced to singleton at 18 weeks of pregnancy. RESULTS: There was no failed procedure and no pregnancy loss within the first 4 weeks after the procedure. A complete miscarriage (7.1%) developed in 1 case at 17 weeks' gestation which was due most probably to the incompetent cervix. In utero fetal death occurred in 1 fetus of another reduced pregnancy. Three of the reduced pregnancies delivered at term, after 37 completed weeks, four premature deliveries occurred between 31 and 35 gestational weeks, and four pregnancies were ongoing beyond 25 weeks' gestation. A total of 16 fetuses, from seven twin and two singleton pregnancies, were delivered without perinatal mortality. CONCLUSIONS: Although the sample size was small, our experience indicates that the reduction of triplets obtained by sophisticated infertility treatments such as intracytoplasmic sperm injection using testicular or epididymal sperm seems to be a safe method and can be effectively used.

Bone loss rate in the lumbar spine: a comparison between natural and surgically induced menopause.

OBJECTIVE: To compare the bone loss between natural and surgically induced menopause by dual photon absorbsiometry (DPA) and quantitative computed tomography (QCT). METHODS: The study group included 365 women, who were in menopause for at least 6 months. Of all patients, 272 became menopausal naturally and 93 surgically. Spinal bone mineral density (BMD) of the women was determined by DPA in 201 patients and by QCT in 164. Regression analysis was used to correlate BMD and months since menopause. RESULTS: Measurements with DPA did not show any significant difference in bone loss between natural and surgical menopause patients, whereas in the group of patients of whom BMD is measured by QCT, a relatively increased bone loss rate is found in surgically induced menopause patients. CONCLUSIONS: Oopherectomized women seemed to suffer a relatively higher bone loss rate compared with natural menopause.

Pregnancies achieved with testicular and ejaculated spermatozoa in combination with intracytoplasmic sperm injection in men with totally or initially immotile spermatozoa in the ejaculate.

The efficacy of intracytoplasmic sperm injection (ICSI) employing testicular and ejaculated spermatozoa was assessed in 24 couples with totally or initially immotile spermatozoa. No criteria were employed in selecting which patients would be treated with testicular or ejaculated spermatozoa. The men were chosen at random. Testicular spermatozoa obtained by testicular sperm extraction were used in 14 and ejaculated spermatozoa were used in 10 of these couples. In all cases. asthenozoospermia was total in their basal semen sample. In 12 male partners, spermatozoa were totally immotile before and after Percoll gradient fractionation (totally immotile). In the remaining 12 men, spermatozoa initially showed a total absence of motility; however, some of the spermatozoa had showed very poor motility (0. 1%) after Percoll gradient fractionation and a 1.5-2.0 h incubation period (initially immotile). Of these 24 total asthenozoospermic males, 14 also had total teratozoospermia. The fertilization and cleavage rates in the testicular and ejaculated sperm groups were 53. 5 and 96.3 and 54.5 and 94.4% respectively. One cycle resulted in complete fertilization failure, and in 23 embryo transfer cycles a total of 10 pregnancies were obtained (41.6%). Eight pregnancies were achieved in the testicular sperm group, while only two pregnancies were obtained in the ejaculated sperm group. Four pregnancies, two from the ejaculated sperm group and two from the testicular sperm group, resulted in clinical abortions in the first trimester. Of the remaining six pregnancies, two have already resulted in healthy births and four pregnancies are now in the second or third trimester in the testicular sperm group. Using testicular spermatozoa in combination with ICSI can be an alternative mode of treatment in cases with totally or initially immotile spermatozoa in the ejaculate. Very low pregnancy rates have been obtained and no ongoing pregnancy has been achieved using ejaculated spermatozoa in these cases.

Fertility with testicular sperm extraction and intracytoplasmic sperm injection in non-obstructive azoospermic men.

In non-obstructive azoospermia spermatozoa can usually only be isolated from the testicles, and thus the most promising treatment model is testicular sperm extraction (TESE). Hormone concentrations, testicular volume determinations and testicular biopsy results are not uniform enough to select potential candidates for successful TESE and intracytoplasmic sperm injection (ICSI) approaches in advance. The aim of this study was to assess the efficacy of using ICSI with testicular spermatozoa in cases of non-obstructive azoospermia and to compare the inclusion criteria and sperm existence in the testicles in sperm obtainable and non-obtainable groups. All men showed either complete or incomplete (n = 14) maturation arrest in spermatogenesis, severe hypospermatogenesis (n = 10) or Sertoli cell-only syndrome (n = 5) in their testicular biopsies. Only 14 out of a total of 29 men provided enough spermatozoa for the ICSI procedure, while no spermatozoa were found in the testicular samples of the remaining 15 men. Out of 123 oocytes obtained from 14 females, 101 were injected with the husbands' testicular sperm cells. Total fertilization failure was observed in three cases. Of 39 oocytes fertilized, 38 cleaved. The fertilization and cleavage rates were 38.6 and 97.4% respectively. The pregnancy rate was 20.7% per initiated cycle. In the group from whom spermatozoa were obtainable, the pregnancy rate was 42.9% per initiated cycle and 54.5% per embryo transfer. A total of six pregnancies were achieved, of which two were twins and four were singletons. One singleton pregnancy resulted in abortion in the first trimester. There was no statistical difference concerning the serum follicle stimulating hormone concentration, testicular volume and biopsy results in groups in which spermatozoa were obtainable or not. In conclusion, although the association of TESE with ICSI obtained pregnancies for some patients with non-obstructive azoospermia, further studies are needed to determine the inclusion criteria for successful TESE.

High implantation and pregnancy rates with testicular sperm extraction and intracytoplasmic sperm injection in obstructive and non-obstructive azoospermia.

Thirty-two infertile couples with obstructive and non-obstructive azoospermia were included in this study. Testicular sperm extraction (TESE) was performed in 16 obstructive azoospermic cases where microsurgical sperm aspiration (MESA) or percutaneous sperm aspiration (PESA) were impossible because of totally destroyed epididymis and 16 non-obstructive azoospermia cases with severe spermatogenetic defect where the testicles were the only source of sperm cells. A total of 288 oocytes was obtained from 32 females and 84% were injected. The fertilization rates (FR) with 2 pronuclei (PN) and cleavage rate were 50.8 and 68.2% respectively. A total of 15 pregnancies was achieved (53% per embryo transfer), nine from the obstructive and six from the non-obstructive group. Four pregnancies resulted in clinical abortion (26.6%). The ongoing pregnancy rate was 39.2% per embryo transfer (ET) and 34.3% per started cycle. A high implantation rate was also achieved (26.6% in non-obstructive and 30% in obstructive azoospermia group). Using testicular spermatozoa in combination with ICSI in both obstructive and non-obstructive azoospermic groups, high implantation and pregnancy rates can be achieved.

Simultaneous bilateral tubal pregnancy after intracytoplasmic sperm injection.

Since the advent of assisted reproductive technology, the concern about ectopic implantation of embryos has increased dramatically. Simultaneous bilateral tubal pregnancy is the least common type of ectopic implantation of two embryos. In this report we present the first case of simultaneous bilateral tubal pregnancy after intracytoplasmic sperm injection (ICSI) and embryo transfer treatment. The present case had no risk factor for ectopic pregnancy. Therefore, for early diagnosis and management of such cases, close clinical follow-up and routine ultrasonography following ICSI are necessary.

Tolerability, safety and efficacy of two formulations of Parlodel--a slow release oral form (SRO) versus registered Parlodel capsules.

Twenty hyperprolactinemic patients who entered a randomized parallel-group, double-blind, double-dummy study were investigated regarding safety, tolerability and efficacy. Half of the patients received 5 mg Parlodel SRO plus placebo for Parlodel while the other half received 2.5 mg Parlodel b.i.d. and placebo for Parlodel SRO for a period of 15 days. In the second following period of 15 days, the daily dose was increased to 10 mg Parlodel administered either as a single dose of Parlodel SRO or two doses of Parlodel 5 mg. The plasma prolactin levels, clinical signs and symptoms of hyperprolactinemia, physical examination, blood pressure, heart rate assessments and adverse events were recorded during the study. Complete blood count, blood chemistry and standard ECG were performed before and at the end of treatment. In conclusion, both formulations are equally efficacious, well tolerated and safe. Due to the comfort of once-a-day administration and the excellent compliance, one could recommend to replace the b.i.d. or t.i.d. administration of Parlodel with the once-a-day Parlodel SRO in hyperprolactinemic patients.

Bone mineral density in Turkish postmenopausal women.

OBJECTIVE: To determine the bone mineral density curve in Turkish postmenopausal women and to evaluate the efficacy of estrogen replacement therapy in the prevention of bone loss. METHOD: Spinal bone mineral density was measured using dual photon absorptiometry in 118 postmenopausal women, prospectively. Parity, previous and current use of estrogen preparations were correlated with BMD using Student's t-test and the chi 2-test. RESULTS: With a mean BMD value of 0.967 +/- 0.013 g/cm2, 62.5% of our postmenopausal study population had a mean BMD value of < 1.0 g/cm2 and 33.7% were already osteoporotic (< 0.9 g/cm2). Bone loss was faster and more intense in the surgically menopausal than in the naturally menopausal group (P < 0.05). Parity after the fourth delivery dropped the mean BMD value (P < 0.05). Previous and current use of estrogen treatment seemed to decrease bone mineral loss in the postmenopausal years. CONCLUSION: Our data stress the need for locally obtained normal BMD values in every country in the world. High parity, surgical menopause and duration of 5 or more years of natural menopause are risk factors for bone loss. Estrogen replacement diminishes the annual bone loss.