Toremifene, a new agent for treatment of mastalgia: an open study

OBJECTIVE: Endocrine agents have been widely used in the treatment of mastalgia. Toremifene is an agent that predominantly has antiestrogenic properties with minimal estrogenic activities. This study was aimed at investigating this drug in the treatment of mastalgia and to evaluate its tolerability and efficacy. METHODS: Seventeen premenopuasal women with a mean age of 37.7 years complaining of moderate to severe mastalgia received toremifene 60 mg daily. The treatment period was 12 weeks. 70% of patients had cyclical and 30% had noncyclical mastalgia. RESULTS: All women with cyclical mastalgia responded to toremifene compared with only 75% of those with non-cyclical mastalgia. Four patients withdrew from the study after 4 weeks because of side effects, accounting for 23.5% of patients in the study. CONCLUSION: This small study has shown that toremifene is an effective agent in the treatment of mastalgia, but a high incidence of side effects makes it ineligible as an agent of choice for treatment of mastalgia.     

Pretreatment cystatin C in children with malignancy: can it predict chemotherapy-induced glomerular filtration rate reduction during the induction phase?

BACKGROUND: Monitoring of kidney function is essential during chemotherapy. Serum creatinine is of limited value in early detection of renal insufficiency. The cystatin C level has been proved to be a good marker for detection of mild reduction in glomerular filtration rate. PURPOSE: To evaluate the validity of the pretreatment serum cystatin C level in predicting significant reduction of the glomerular filtration rate during the induction phase of chemotherapy. PATIENTS AND METHODS: Serum levels of cystatin C and creatinine and corrected creatinine clearance were assessed in 34 children with different types of malignancy just before the start of chemotherapy and again in 33 of them 1 month later. Patients were compared with 14 healthy controls of matched age and sex. RESULTS: Before chemotherapy, all patients when compared with controls had normal levels of cystatin C (P = 0.1) and creatinine (P = 0.62) and normal corrected creatinine clearance (P = 0.76). One month after chemotherapy, patients showed a significant increase in their cystatin C levels (P < 0.001) and a significant decrease in their corrected creatinine clearance (P < 0.001). However, creatinine levels did not change significantly (P = 0.65). Corrected creatinine clearance negatively correlated significantly with both cystatin C and creatinine levels (r = -0.622, P < 0.001; r = -0.346, P = 0.045, respectively) before chemotherapy and also 1 month after chemotherapy (r = -0.577, P < 0.001; r = -0.45, P = 0.009, respectively). When pretreatment levels of cystatin C and creatinine were used to predict patients who developed a reduction in corrected creatinine clearance of more than 20% after therapy, only the cystatin C level was statistically significant (P = 0.03). A cutoff point of 0.57 mg/L with sensitivity of 77.8%, specificity of 63%, and overall accuracy of 74% was suggested. CONCLUSIONS: Children with malignant diseases develop significant reduction in their glomerular filtration rate during the induction phase of chemotherapy, although their serum creatinine level may not change significantly. Cystatin C, as a more sensitive marker than creatinine for the assessment of glomerular filtration rate, can be used to predict patients who would have a higher risk of renal impairment during the induction phase of chemotherapy and who thus would require more frequent renal function assessment to consider adjustment of the chemotherapy dose if indicated.     

Totally tubeless percutaneous nephrolithotomy in selected patients

PURPOSE: Significant early postoperative discomfort after percutaneous procedures is usually secondary to nephrostomy tubes and externalized ureteral catheters. We describe our modification of the traditional percutaneous nephrolithotomy (PCNL) approach that we name "totally tubeless PCNL." PATIENTS AND METHODS: Between June 2000 and May 2001, 60 consecutive PCNLs were performed at our centers. At the end of the surgery, we omitted the nephrostomy tube and removed the externalized catheter in selected patients: no solitary kidney, stone size <3 cm, and without any obstructions or arterial bleeding. A total of 30 patients underwent totally tubeless PCNL (group 1). We compared their results with those of a control group of 30 patients who underwent standard PCNL (group 2). The incidence of complications, analgesic requirements, length of hospitalization, and time to return to normal activities were compared in the two groups. RESULTS: In both groups, PCNL was performed successfully without any significant complications. A 90% stone-free rate was achieved in both groups, and in the remaining patients, small residual stones (<4 mm) were detected. No urinoma was demonstrated by postoperative ultrasound scanning in group 1. The average length of hospitalization was 1.5 days for group 1 and 3 days for group 2. The average analgesic requirements were 30 mg of pentazosin in group 1 and 90 mg in group 2. No transfusion was needed. There were three complications: 2 patients (6.6%) had urinary tract infection in group 1 and 1 (3.3%) in group 2. All were managed medically. CONCLUSIONS: Omitting the percutaneous nephrostomy tube and removing ureteral catheter at the end of surgery in selected patients were safe and accompanied by significantly reduced postoperative discomfort, length of hospitalization, and analgesic requirements. Further studies are needed to determine the role of this technique.     

Pregnancy-related admissions to the intensive care unit

We conducted a retrospective review of obstetric patients admitted to the intensive care unit at Al-Ain hospital during period January 1(st) 1997 to December 31(st) 2002, in order to identify the indications for admission and the outcome. A total of 60 patients were admitted during the six years. The frequency of admission was 2.6 per 1000 deliveries and obstetric patients represented 2.4% of all ICU admissions. Admission was planned in 11 patients (18%) and unplanned in 49 (82%). The mean (+/-SD) duration of stay in ICU was 1.6+/-1.5 days. The leading indications for admission were haemorrhage (28.4%) and preeclampsia/eclampsia (25%). Of the 60 admissions, 47 (78.4%) followed surgery. The mean APACHE II score was 5.0+/-3.0. Twenty-two patients (37%) had blood transfusions, and only two (3.3%) required ventilation. Of the 60 patients only 28 (46.7%) were deemed to have severe illness necessitating intensive care; the remaining 32 patients were suitable for high dependency care. The mean APACHE II score and duration of stay were significantly higher in these patients. There were two deaths, representing 3.3% of obstetric intensive care unit admissions. Our findings highlight the need for establishing a high dependency unit to avoid unnecessary admission to the intensive care unit and to ensure proper management.     

Blood levels of trace elements, electrolytes, and oxidative stress/antioxidant systems in epileptic patients

Epileptic patients exhibited variably altered status of trace elements, electrolytes, and free radical scavenging enzyme activities. We investigated the effect of epilepsy and long-term antiepileptic drug therapy on the serum level of some trace elements (zinc, selenium, and copper), electrolytes (calcium, magnesium, sodium, and potassium), and antioxidants (glutathione peroxidase, and uric acid) and plasma levels of lipid peroxidation index (malondialdehyde), total antioxidant capacity, and ceruloplasmin. Seventy epileptic patients and fourteen controls were recruited in this study. In the treated group (particularly with valproate), we reported increases in the levels of zinc, calcium, sodium, malondialdehyde, and glutathione peroxidase and decreases in the levels of copper, total antioxidant capacity, and ceruloplasmin with no difference in selenium, magnesium, and potassium. However among untreated epileptics, uric acid level was increased and total antioxidant capacity was markedly lowered. We conclude that the above parameters balance differs in epileptics comparable to controls and hence their correlation to seizures pathophysiology and their degree of control or resistance to antiepileptic drug therapy. Better regulation of the lipid peroxidation and antioxidants and fewer disturbances in mineral metabolism were observed in monotherapy versus polytherapy and with carbamazepine versus valproate therapy.     

Sex and estrus cycle differences in the modulatory effects of morphine on seizure susceptibility in mice

PURPOSE: To evaluate the effects of sex and estrus cycle on biphasic anticonvulsant and proconvulsant modulation of seizure threshold by morphine. METHODS: The threshold for the clonic seizures (CST) induced by acute intravenous administration of gamma-aminobutyric acid (GABA)-antagonist pentylenetetrazole (PTZ) was assessed in male and female mice. Estrus cycle was assessed by vaginal smears. The effect of removing circulating sex hormones was assessed by gonadectomy. RESULTS: At baseline, diestrus females had a higher CST compared with males and estrus females. Morphine at lower doses (0.5-3 mg/kg) had a significant anticonvulsant effect in males and estrus females compared with that in vehicle-treated controls, whereas female mice in diestrus phase showed a relative subsensitivity to this effect. Morphine at higher doses (30 and 60 mg/kg) significantly decreased CST in males and diestrus females, with less relative effect in estrus mice. In both phases, morphine exerted stronger effects in males compared with females. Ovariectomy brought the baseline CST to the male level and resulted in significant expression of both phases of morphine effect but did not abolish the sex difference in responsiveness to morphine. CONCLUSIONS: The biphasic modulation of seizure threshold is subject to both constitutive sex differences in sensitivity to morphine and hormonal fluctuations during the estrus cycle.