Maternal deaths and their causes in Ankara, Turkey, 1982-2001

This study was carried out to determine the incidence and causes of maternal deaths about a 20-year period at the Zekai Tahir Burak Women's Health Education and Research Hospital (ZTBWHERH), Ankara, Turkey. All maternal deaths from January 1982 to July 2001 were reviewed and classified retrospectively. Using a computer-generated list, 348 patients admitted to the Labour Department of ZTBWHERH during 1982-2001 were selected as controls. Medical records were reviewed for demographic data, history of antenatal care, route of delivery, referral history, and perinatal mortality. Cases and controls were compared, and standard tests were used for calculating odds ratio (OR) and 95% confidence interval (CI) for the association of demographic and delivery characteristics. During this period, there were 174 maternal deaths and 430,559 livebirths, giving a maternal mortality ratio of 40.4/100,000 livebirths. The mortality rate declined from 85.1/100,000 in 1982 to 11.6/100,000 in 2001. One hundred thirty (74.7%) deaths were due to direct obstetric causes and 24 (13.7%) were abortion-related, while 20 (11.4%) were due to indirect obstetric causes. The most common cause of direct obstetric deaths was pre-eclampsia/eclampsia, followed by obstetric haemorrhage and embolism. Abortion-related sepsis and haemorrhage, anesthesia-related deaths, obstetric sepsis, acute fatty liver of pregnancy, and ectopic pregnancy accounted for other causes of deaths. Cardiovascular disease was the leading indirect cause of death. Referral, lack of antenatal care, and foetal death at admittance were associated with 8-, 3-, and 6-fold increased risk of maternal mortality respectively (OR 8.89, 95% CI 5.7-13.8; OR 3.74, 95% CI 2.5-5.5; OR 6.38, 95% CI 3.1-13.1). Although maternal mortality ratios have declined at the hospital, especially in the past five years, the rate is still high, and further improvements are needed. The problem of maternal mortality remains multifactorial. Short-term objectives should be focused on improving both medical and administrative practices. Improving the status of women will necessarily remain a long-term objective.     

Intrarenal arteriovenous fistula causing a "pseudonutcracker effect"

We report a case in which an intrarenal arteriovenous fistula caused the nutcracker effect. Color Doppler sonography of the left renal artery showed a peak systolic velocity of 150 cm/second and renoaortic ratio of 2.1. The left renal vein was significantly dilated, and the adjacent renal artery was kinked. A stenosis in the left renal vein at the aorto-mesenteric bifurcation was demonstrated, with a maximum velocity of 201 cm/second. Renal Doppler evaluation showed an area of high-velocity, low-resistance arterial flow consistent with an arteriovenous fistula in the inferior half of the left kidney. Angiography confirmed the fistula. The fistula was successfully occluded by coil embolization. Follow-up sonography showed almost complete obliteration of the fistula, regression of the renal vein dilatation, and a reduction in renal venous and arterial flow velocities. Given the reversibility of the fistula's effects, we suggest the term "pseudonutcracker effect" to describe this case.     

Serum leptin levels are associated with tamoxifen-induced hepatic steatosis

PURPOSE: Tamoxifen, used in breast cancer treatment, may induce hepatic steatosis. It has been suggested that leptin, which has a relationship with body fat stores, may be involved in the pathogenesis of hepatic steatosis. In this study, we compared serum leptin levels in tamoxifen-treated patients with and without hepatic steatosis. METHODS: Thirty-four women with breast cancer receiving tamoxifen were included in the study. Serum samples were obtained from the patients before and 3 months after tamoxifen therapy. RESULTS: Increased hepatic steatosis was detected in 15 of 34 (44%) patients after 3 months of tamoxifen therapy. Serum leptin levels were found to be significantly elevated in patients with increased hepatic steatosis (37.3 +/- 17.7 to 50.5 +/- 22.4 ng/ml, p = 0.023) compared to (48.2 +/- 20.2 to 42.6 +/- 14.9 ng/ml, p > 0.05) after tamoxifen treatment. CONCLUSION: Leptin may play a role in tamoxifen-induced hepatic steatosis. The exact mechanism involved should be investigated in further studies.     

Prognostic value of serum IL-18 and nitric oxide activity in breast cancer patients at operable stage

Interleukin-18 (IL-18) is a multifunctional cytokine that was previously termed interferon-gamma-inducing factor. It has been suggested that serum IL-18 level may be used as a prognostic factor in some cancer types. Nitric oxide is a potent biologic molecule involved in the pathogenesis of cancer. In this study, we measured serum IL-18 and nitrate + nitrite levels in 56 patients with nonmetastatic breast cancer and 14 control subjects. Serum IL-18* and nitrate + nitrite** levels were significantly higher in patients with breast cancer when compared to the control subjects (*p < 0.05, **p < 0.001). Serum IL-18 levels were significantly higher in patients whose tumor size was greater than or equal to 5 cm when compared to patients whose tumor size was less than or equal to 2 cm (p < 0.05). Patients who were axillary lymph node negative (ALN) had lower serum IL-18 levels when compared to patients with positive ALN (p < 0.001). Serum IL-18 levels were significantly higher in patients with stage IIB or IIIA when compared to patients with stage I or IIA (p < 0.05). There was no significant difference in serum nitrate + nitrite levels in terms of age, tumor stage, estrogen receptor, and menopausal and ALN status (p > 0.05). In conclusion, serum IL-18 level may be a useful marker to predict prognosis of patients with breast cancer in complete remission after surgery. Long-term follow-up is required to clarify this hypothesis.     

Phase II Study of Lonidamine and Diazepam in the Treatment of Recurrent Glioblastoma Multiforme

Recurrent glioblastoma multiforme (GBM) is resistant to most therapeutic endeavours, with low response rates and survival rarely exceeding 6 months. There are no standard chemotherapeutic regimens and new therapeutic approaches have to be found. We report an open-label, uncontrolled, multicentre phase II trial of lonidamine (LND) and diazepam in 16 patients with GBM at first relapse and a Karnofsky performance status 70. The treatment regimen consisted of LND 450mg/day and diazepam 15mg/day orally of every 28-day cycle until progression or unacceptable toxicity. Patients received a median of three cycles (range, 1–12). No complete or partial response was observed. Therefore, according to the design of the study, no additional patients were enrolled and the trial was closed. Nevertheless, seven stabilizations (50%) were observed. Median time to progression was 8 weeks (range, 5–19 weeks). Median overall survival from recurrence was 15 weeks (range, 14–61 weeks). No grade 3–4 toxicity, except somnolence, was observed and there were no therapy-related deaths. Dose reduction for diazepam due to somnolence (grade III) was performed in 9 patients. The combination of LND and diazepam is well tolerated. LND and diazepam, acting on two distinct mitochondrial sites involved in cellular energy metabolism, may exert a cytostatic effect on tumour growth as shown by the high percentage of stable patients. The LND–diazepam at the used dosing schedule did not show a complete or partial response. LND plus diazepam may be interesting in the adjuvant setting or associated to chemotherapy to act on different targets and increase the therapeutic index.     

In vivo genotoxic effect of cadmium chloride in mice leukocytes using comet assay.

The alkaline single cell gel electrophoresis (SCGE) or "comet" assay under alkaline conditions was used to measure DNA damage in the leukocytes of Swiss Albino male mice exposed to cadmium chloride (CdCl(2)). The effect of CdCl(2) was studied after a single acute oral administration of a range of doses starting from 0.5 to 128.0 mg/kg b.wt of CdCl(2).The samples of whole blood were collected from each mouse at 24, 48, 72, and 96 h post-treatment to study single/double strand breaks in DNA. A significant increase in mean comet tail length indicating DNA damage was observed with CdCl(2) at 24 h post-treatment (P<0.05) with CdCl(2) when compared to controls. A gradual decrease in the mean tail length was observed at 48 h post-treatment indicating repair of the damaged DNA. The mean tail length showed a dose-related increase and time-dependent decrease after treatment with CdCl(2) when compared to controls. The study also confirms that the comet assay is a sensitive and rapid method to detect DNA damage caused by heavy metal like Cadmium (Cd).     

In vivo genotoxic effects of mercuric chloride in rat peripheral blood leucocytes using comet assay

DNA damage induced by Mercuric chloride (HgCl2) in leucocytes of Wistar albino male rats has been studied in vivo. The comet assay or the alkaline single cell gel electrophoresis (SCGE) assay was used to measure the DNA damage. The rats were administered orally with doses ranging from 0.0054, 0.0108, 0.0216, 0.0432 to 0.0864 mg/kg body weight (b.wt.) of HgCl2. The assay was performed on whole blood at 24, 48, 72 h, 1st and 2nd week. The reason leucocytes were used was to reflect biomarker studies in humans. A significant increase in mean comet tail length indicating DNA damage was observed at all time intervals with HgCl2 except in 2nd week post treatment when compared to controls. The mean comet tail length revealed a clear dose dependent increase from 0.0054 to 0.0432 mg/kg b.wt. A maximum increase in mean comet tail length was observed at 0.0432 mg/kg b.wt. 24 h after treatment. From 48 h post treatment, the mean comet tail lengths of all the doses gradually decreased and by week 2 of post treatment, they had approached control levels, pointing to repair of the damaged DNA. These findings suggest that the comet assay is a highly sensitive technique to study DNA damage caused by metals.