Differential effects of chronic ethanol feeding on cytochrome P-448- and P-450-mediated drug metabolism in the rat

The effects of chronic ethanol feeding on cytochrome P-448- and P-450-mediated drug metabolism have been studied both in vivo and in vitro in the rat, using caffeine, phenacetin, antipyrine and aminopyrine as test substrates. N-Demethylation of aminopyrine (P-450 mediated) was increased both in vivo and in vitro in rats after chronic ethanol feeding (P < 0.05) whereas in vivoN-demethylation of caffeine and O-dealkylation of phenacetin (P-448 mediated) were unchanged in the same animals. N-rmDemethylation of antipyrine was increased by both phenobarbital and 3-methylcholanthrene pretreatment and by chronic ethanol feeding (P < 0.05), possibly due to cytochrome P-450 induction. Furthermore, the Michaelis affinity constants. K_m, for hepatic microsomal aminopyrine N-demethylase and antipyrine N-demethylase were lower in chronic ethanol-fed animals (P < 0.05), suggesting a qualitative change in the enzymes resulting in greater substrate affinity. These findings suggest a differential effect of chronic ethanol feeding on the induction of cytochrome P-450- and cytochrome P-448-mediated drug metabolism, with a greater effect on the former microsomal system.     

Prophylactic dexamethasone for postoperative nausea and vomiting in pediatric strabismus surgery: a dose ranging and safety evaluation study

In this double-blind, randomized, placebo-controlled study, we evaluated the efficacy and safety of different doses of prophylactic IV dexamethasone for postoperative nausea and vomiting (PONV) in 168 children (aged 2-15 yr) scheduled for strabismus surgery. Patients received IV dexamethasone 0.25 mg/kg (D 0.25), 0.5 mg/kg (D 0.5), 1.0 mg/kg (D 1), or saline (S) immediately after induction of general anesthesia. Patients were discharged 24 h after surgery. Nausea and vomiting were assessed at 0-2, 2-6, and 6-24 h after surgery. Blood glucose was measured preoperatively and at 4 h after study drug administration. Wound healing and infection were assessed after 1 wk. More patients in group S had vomiting at 0-2, 2-6, and 6-24 h (P = 0.001, P = 0.003, and P = 0.04, respectively) and required larger doses of rescue antiemetics compared with the dexamethasone groups. Fewer patients in the dexamethasone groups (6, 3, and 6 in D 0.25, D 0.5, and D 1, respectively) had severe PONV compared with group S (P = 0.001). No significant increase in postoperative blood glucose levels was observed and wound healing was satisfactory in all four groups. The results suggest that dexamethasone 0.25 mg/kg is more effective than saline and equally effective compared with larger doses for preventing PONV for pediatric strabismus surgery.     

Vitamin D and bone mineral density status of healthy schoolchildren in northern India

BACKGROUND: Current data on the prevalence of vitamin D deficiency in India are scarce. OBJECTIVE: We assessed the calcium-vitamin D-parathyroid hormone axis in apparently healthy children from 2 different socioeconomic backgrounds in New Delhi, India. DESIGN: Clinical evaluation for evidence of vitamin D deficiency was carried out in 5137 apparently healthy schoolchildren, aged 10-18 y, attending lower (LSES) and upper (USES) socioeconomic status schools. Serum calcium, inorganic phosphorus, alkaline phosphatase, 25-hydroxyvitamin D [25(OH)D], and immunoreactive parathyroid hormone were measured in 760 children randomly selected from the larger cohort. Bone mineral density of the forearm and the calcaneum was measured in 555 children by using peripheral dual-energy X-ray absorptiometry. RESULTS: Clinical evidence of vitamin D deficiency was noted in 10.8% of the children. Children in the LSES group had a significantly (P < 0.01) lower 25(OH)D concentration (10.4 +/- 0.4 ng/mL) than did those in the USES group (13.7 +/- 0.4 ng/mL). Concentrations of 25(OH)D <9 ng/mL were seen in 35.7% of the children (42.3% in LSES; 27% in USES; P < 0.01). Boys had significantly (P = 0.004) higher 25(OH)D concentrations than did girls. There was a significant negative correlation between the mean serum immunoreactive parathyroid hormone and 25(OH) D concentrations (r = -0.202, P < 0.001). Mean forearm bone mineral density was significantly (P < 0.01) higher in the USES group than in the LSES group. CONCLUSION: A high prevalence of clinical and biochemical hypovitaminosis D exists in apparently healthy schoolchildren in northern India.     

Unsafe abortion: a neglected tragedy. Review from a tertiary care hospital in India

AIM: With 16% of the world's population, India accounts for over 20% of the world's maternal deaths. The maternal mortality ratio, defined as the number of maternal deaths per 100 000 live births is incredibly high at 408 per 100 000 live births for the country. Abortion has been legalized in India for the past three decades. However, the share of unsafe abortion as a cause of maternal mortality continues to be alarming. The objective of the present study is to identify the magnitude of problem of unsafe abortion in India. METHODS: Emergency gynecologic admissions to a tertiary care center in North India over a 15-year period (1988-2002) were reviewed to evaluate the demographic and clinical profile of patients admitted as a result of unsafe abortion. The records were analyzed with regard to the age group, parity and marital status of the abortion seekers, the indication of abortion, the methods used, qualification of abortion providers, complications and fatality rate. RESULTS: The majority of women who were admitted with diagnosis of unsafe abortion were in the third decade of their lives. They were married, multiparous women living with their spouses. Sixty percent of the women had approached unqualified abortion providers who used primitive methods of pregnancy termination. All the women were admitted with serious complications of unsafe abortions and one-fourth of them succumbed to the complications. CONCLUSION: Unsafe abortion constitutes a major threat to the health and lives of women. This study highlights the need to focus more directly on the needs and preferences of women who seek abortion as well as on the accessibility of contraceptives and skills of the providers of abortion services, in order to improve the quality of abortion care.     

Pain relief following Arthroscopy - a comparative study of Intra-articular Bupivacaine,Morphine and Neostigmine

Pain after arthroscopy is quite distressing. Intra-articular bupivacaine produces transient analgesia and reports of analgesia using intra-articular opioids have produced conflicting results. Recently, spinal administration of neostigmine was shown to produce dose-dependant analgesia. However, this was limited by adverse effects. The purpose of this study was to compare the effects on intra-articular neostigmine, bupivacaine and morphine. 75 patients were randomized to receive intra-articular saline, bupivacaine, morphine, neostigmine and bupivacaine-neostigmine after arthroscopic surgery under spinal anaesthesia. Visual analog pain scores (VAS), duration of analgesia as defined as time for first demand for parenteral opioids and the total subsequent consumption of morphine was evaluated. Intra-articular bupivacaine resulted in significant VAS reduction at one and four hours as compared to those receiving intra-articular saline and morphine. Analgesia lasted longer after 500ugm intra-articular neostigmine as compared with bupivacaine, morphine or saline. The need for supplementary analgesia was lowest in the neostigmine group as compared to the other groups. No significant difference was found if bupivacaine was added to neostigmine. Among all the groups, no significant side-effects were observed.Key Words: Arthroscopy, Bupivacaine, Morphine, Neostigmine     

Should decisions on internal mammary lymph node irradiation be based on current lymphoscintigraphy techniques for sentinel lymph node identification?

BACKGROUND: Treatment of internal mammary lymph node (IMN) metastases remains controversial because of the difficulty in predicting involvement, potential treatment-related morbidity, and questionable efficacy. Lymphoscintigraphy with sentinel lymph node biopsy offers a means to identify occult involvement of IMN, allowing appropriate patient selection for IMN treatment. METHODS: The authors retrospectively reviewed 262 lymphoscintigraphies (LS) of 248 patients treated at the University of Florida (Gainesville, FL) between 1998 and 2002. Tumor characteristics were assessed for their value in predicting IMN drainage and their association with IMN radiation. RESULTS: Lymph flow to the IMN was documented with LS in 23 of 262 tumor specimens (9%). Flow to the IMN was not correlated with any of the five factors: tumor location, tumor size, lymphovascular invasion, pathologic lymph node status, and laterality of the involved breast (right vs. left breast). Identification of IMN flow increased from 5.7% to 10.1% with the use of a deep injection technique. IMN radiotherapy was used more frequently in patients with larger tumors (15 of 188 in Tis/T1 vs. 31 of 70 in T2-T4; P<0.0001) and positive lymph nodes (17 of 91 in lymph node-negative patients vs. 28 of 66 in lymph node-positive patients; P<0.0001). In patients with T2N0 tumors (n=32), IMN radiotherapy was used more frequently with medial tumors (5 of 11 [45%]) than with lateral tumors (4 of 21 [19%]). CONCLUSIONS: The incidence of flow to the IMN documented with the current LS technique was low compared with other LS and extended radical mastectomy series. Histopathologic information was obtained for the sentinel IMN when IMN flow was identified on the LS. In the absence of histopathologic information, treatment decisions should continue to be based on clinical factors known to be correlated with occult IMN involvement.