Management of sphenoid sinus cerebrospinal fluid rhinorrhea: making use of an extended approach to the sphenoid sinus.

OBJECTIVES: Specific information addressing the management of cerebrospinal fluid (CSF) fistulas that originate from within the sphenoid sinus remains scant. The objective of this study was to review the cause and management of CSF rhinorrhea arising from the sphenoid sinus. STUDY DESIGN AND SETTING: This is a retrospective chart review of 12 cases of CSF rhinorrhea arising from the sphenoid sinus that occurred in 11 patients. All patients were treated at a single institution between 1994 and 1999. RESULTS: All patients were managed surgically with sphenoid sinus fat obliteration using an endoscopic sublabial, transseptal approach. This approach was successful for all 12 cases, with median duration of follow-up of 18 months. CONCLUSIONS: Endoscopically assisted transseptal repair of CSF fistulas that originate within the sphenoid sinus offers an alternate approach to previously described methods of repair in this region. Advantages include wide access to the entire sphenoid sinus, improved access to laterally pneumatized regions within the sphenoid sinus, and rostral mucosal closure over the repair within the sinus.     

Lethal effects of CCl4 and its metabolism by Mongolian gerbils pretreated with chlordecone, phenobarbital, or mirex.

Gerbils are much more sensitive to the hepatotoxic and lethal effects of CCl4 than rats as indicated by 48-hr LD50 values (0.08 vs 2.8 ml/kg). On the other hand, gerbils are refractory to chlordecone (CD) potentiation of CCl4 toxicity. To investigate the possible mechanism underlying the high sensitivity of gerbils to CCl4 lethality, the metabolism of CCl4 was studied in gerbils pretreated with dietary CD, phenobarbital (PB), or mirex (M) at 10, 225, and 10 ppm, respectively. The hepatic content of 14CCl4, the expiration of 14CCl4 and 14CCl4-derived 14CO2, and lipid peroxidation were measured and the results were compared with the previous data for rats. After the 15-day dietary pretreatment, male gerbils (60-80 g) received 14CCl4 (0.08 ml/kg; sp act 0.04 mCi/mmol) ip in corn oil and the radioactivity present in the expired air was collected for 6 hr. More than 80% of the parent compound as represented by the 14C-label in the toluene trap was expired in 6 hr regardless of the pretreatments. Expiration of 14CO2 measured during the 6 hr after 14CCl4 administration in control gerbils was 3.5-fold more than that in rats and was significantly increased in pretreated groups (M greater than PB greater than CD). PB and M pretreatments resulted in a significant increase of 14C-label bound to the nonlipid fraction of the liver as compared with CD-treated or control gerbils. The radiolabel present in the livers of control gerbils was 5-fold higher than that of rats. In vivo lipid peroxidation measured as diene conjugation in lipid extracts from the livers was lower in gerbils than in rats, and none of the pretreatments significantly affected lipid peroxidation. The serum alanine aminotransferase and aspartate aminotransferase were significantly elevated at 6 hr after CCl4 injection in all groups of gerbils. These data indicate that the more extensive metabolism of CCl4, as represented by 14CO2 formation and 14C-label bound to hepatic tissue, in gerbils as compared with rats, may partially explain the high sensitivity of gerbils to CCl4 toxicity. However, the enhanced metabolism of CCl4 found in CD-, PB-, or M-pretreated gerbils did not lead to amplified hepatotoxic and lethal effects of CCl4. The reason gerbils may be refractory to CD amplification of CCl4 injury might be associated with other factors yet to be investigated.     

ACARDIAC TWIN FETUS WITH SEVERE HYDROPS FETALIS AND BILATERAL TALIPES VARUS DEFORMITY

Twin reversed-arterial-perfusion syndrome (TRAPS) is a rare complication of monochorionic twin pregnancies. TRAPS is characterized by the hemodynamic dependence of a “recipient” twin from a “pump” twin. The “recipient” twin exhibits lethal abnormalities, such as acardia and acephaly. Circulatory failure of the normal twin derives from the existence of arterio-arterial and veno-venous anastomoses within the placenta that allow retrograde perfusion of the acardiac twin by blood coming from the normal twin. Acardiac twinning is the most extreme manifestation of the twin-twin transfusion syndrome. This occurs in 1 in 100 monozygotic twin pregnancies and 1 in 35,000 births. We report a case of diamnionic monochorionic female twins in which the acardiac twin demonstrated severe hydrops fetalis and bilateral talipes varus deformity. Cesarean section was performed on a 27-year-old hypertensive gravida 2, para 1 mother for fetal indications at 32 6/7 weeks gestation. The acardiac fetus had a two-vessel umbilical cord measuring 43.5 cm in length and 0.8 cm in diameter. The proximal end inserted into the root of the normal twin's umbilical cord in an acute angle forming a “v” close to the placental disc. Structures rostral to the thorax were absent except for a round mass of flesh with three small buds in place of the head and neck, and bilateral upper extremities. Only the kidneys, right adrenal, small and large intestine, and rudimentary urinary bladder were present. Both feet demonstrated talipes varus deformity. The fetus was severely hydropic. The subcutaneous fat measured 4.5 cm in maximum thickness. The normal twin had a protracted course complicated with respiratory distress syndrome, moderate secundum atrial septal defect with left to right shunt, and thrombocytopenia of prematurity. The baby was eventually discharged after approximately 1 month. At the time of this report, 5 months postpartum, the neonate is growing and developing normally. To our knowledge, this is the first report of severe hydrops fetalis and talipes varus deformity in an acardiac twin.     

Protection of chlordecone-potentiated carbon tetrachloride hepatotoxicity and lethality by partial hepatectomy

Chlordecone (CD) pretreatment is known to markedly potentiate CCl₄ hepatotoxicity. Previous studies have shown that prior exposure to CD obtunds the increased hepatocellular regeneration and repair observed in non-treated rats challenged with a single, low dose of CCl₄. These observations allowed us to hypothesize that suppression of hepatic regeneration and tissue repair by CD + CCl₄ combination treatment might be involved in this interaction. To test this hypothesis, CCl₄ hepatotoxicity was evaluated in actively regenerating livers using CD-treated (10 ppm in the diet for 15 days), surgically partially hepatectomized (PH) male Sprague-Dawley rats. Rats undergoing no surgical manipulation (CTRL) and sham operation (SH) were included as appropriate controls. Surgical manipulations were conducted on day 15 of the dietary protocol. Based on liver-to-body weight ratios (LW/BW), mitotic indices, hepatic cytochrome P-450 content, and hepatic glutathione (GSH and GSSG) levels, PH-induced hepatocellular regeneration was not affected by pretreatment with CD. Thus, the PH model was considered valid for assessing the effects of CD + CCl₄ combination treatment. CCl₄ (100 l/kg; i.p.) was administered 1, 2, 4 or 7 days after the surgical manipulations. Hepatotoxicity was assessed 24 h later by measuring LW/BW and serum enzymes (SGPT, SGOT and ICD) in all four groups. Hepatic histopathological, histomorphometric and lethal effects were assessed in animals receiving CCl₄ 1 or 7 days after the surgical manipulations. CCl₄-induced increases in LW/BW were observed in CD + PH rats receiving CCl₄ 4 or 7 days post-PH, but not in the 1 or 2 day post-PH groups in which the hepatocellular regeneration was maximal. CCl₄-induced serum enzyme elevations were significantly less in the CD + PH rats as compared to CD + SH. This decrease in the serum enzyme elevations was most prominent in the 1 day post-PH group, where the hepatocellular mitotic activity was most pronounced. CCl₄ lethality, assessed in the 1 day post-surgical manipulation group, was also decreased in the CD + PH rats in comparison to CD + SH rats. Such a protection was not observed in rats receiving CCl₄ 7 days post-PH. These data are consistent with and are supportive of the hypothesis that a suppression of otherwise normally stimulated hepatocellular regeneration following low-dose CCl₄ administration is involved in the marked amplification of CCl₄ toxicity by CD.Abbreviations CD chlordecone - GSH reduced glutathione - GSSG oxidized glutathione - PH partial hepatectomy - SH shamhepatectomy - CTRL control, not surgically manipulated - N normal diet - LW/BW liver weight-to-body weight ratio - SGPT serum glutamic; pyruvic transaminase - SGOT serum glutamic oxaloacetic transaminase - ICD isocitrate dehydrogenase These studies were made possible by a grant from the US Environmental Protection Agency R-811072A preliminary report of these findings was presented at the 70th Annual Meetings of the Federation of American Societies for Experimental Biology at St. Louis, MO (Fed Proc 45: 1051, 1986)A. N. Bell is a Predoctoral Toxicology Trainee and Robert A. Young is a Postdoctoral Trainee supported by Toxicology Training grant from National Institute of Environmental Health Science ES-07045     

Role of apoptosis in HIV disease pathogenesis

After approximately one and a half decades of intensive studies, the exact mechanisms to explain HIV-mediated cytopathicity are still enigmatic and need closer scrutiny. There has been a dichotomy between virological and immunological viewpoints in understanding HIV-mediated cytopathicity, the former emphasizing a killing of infected cells by HIV-1 and the latter emphasizing indirect mechanisms wherein HIV or its soluble component(s) alter CD4 T-cell function and induce susceptibility to apoptosis. Accumulating evidence points to the notion that apoptosis might be a major contributor to the depletion of CD4 T-cells in HIV infection. This review summarizes current information about the regulatory mechanisms of T-cell apoptosis and the role of apoptosis in HIV pathogenesis with the goal of providing an integrated view of HIV cytopathicity.     

Reliability of CD4 quantitation in human immunodeficiency virus-positive children: implications for definition of immunologic response to highly active antiretroviral therapy

Our objective was to develop data-based algorithms for definition of immunologic response to AIDS therapies in pediatric patients, taking account of T-cell subset measurement errors. The study design involved cross-protocol analysis of 2,148 enrollees in six completed Pediatric AIDS Clinical Trials Group trials. We used standard quantitation of T-cell subsets; linear modeling with mean-dependent measurement error variance was used to develop 95% tolerance limits for change in CD4%. For individuals with a CD4% of approximately 25%, the measurement error-based 95% tolerance interval ranges from 15% to 35%, whereas for individuals with a CD4% of approximately 5%, the tolerance interval ranges from 3% to 7%. When pairs of CD4% measures taken within a time interval of less than 30 days are averaged to estimate steady-state CD4%, tolerance interval width decreases by approximately 30%. A simple graphical tool that provides a data-based criterion for immunologic response over and above variation ascribable to T-cell measurement error is provided. Variability in CD4% due to measurement error is substantial, increases with level of CD4%, and complicates assessment of immunologic response to therapy. Replicates of CD4% measures could be used to improve precision of interpretation of CD4% measures.     

Phase 1 trial of the topical microbicide BufferGel: safety results from four international sites

AIM: To evaluate the safety of BufferGel (ReProtect LLC, Baltimore, MD), a spermicidal microbicide that acidifies semen and maintains the protective acidity of the vagina, in a high-dose tolerance trial. METHODS: HIV/STD negative, sexually abstinent, and sexually active women in India, Thailand, Malawi, and Zimbabwe were asked to insert one applicator ( approximately 5 ml) of BufferGel vaginally twice per day for 14 days. Sexually active women agreed to have sex (while using BufferGel and nonlubricated condoms) at least twice per week. RESULTS: In total, 98 women (30 sexually abstinent and 68 sexually active) were enrolled. Overall compliance with product use was 93%. Epithelial abnormalities detected by pelvic examination or colposcopy were uncommon (8 cases in 271 examinations). Irritation was reported by approximately one quarter of the women (0.58 events per woman-week) but was generally mild and of short duration. The prevalence of bacterial vaginosis (BV) fell significantly, from 30% at enrollment to 6% at one week, and 7% at two weeks of BufferGel use. Thirty-two women acquired microscopically detectable yeast during BufferGel exposure, but only 3 developed symptomatic vaginitis. CONCLUSION: BufferGel appears to be safe and well tolerated by the cervicovaginal epithelium. Its effect on BV and yeasts merits further study.