New Operative Method for Fundal Variceal Bleeding: Fundectomy with Periesophagogastric Devascularization

Cirrhotic patients with gastric fundal bleeding occasionally require operative intervention. Fundal variceal bleeding may be controlled by performing a fundectomy in addition to periesophagogastric devascularization. For 23 patients with cirrhosis, preoperative nonsurgical intervention alone could not achieve definitive control of variceal bleeding from the gastric fundus, and periesophagogastric devascularization with the fundectomy—specifically resection of the varix-bearing lesion in the fundus—was performed. Direct inspection and palpation determined the area for the fundectomy, and resection was limited to the engorged varix-bearing area. The overall mortality rate was 26.1%. There were two postoperative deaths (18.2%) among 11 patients in the elective operation group and four deaths (33.3%) among 12 patients in the emergency operation group (p > 0.05). The mortality rates among class A, B, and C patients, following the Child-Pugh classification for hepatic functional reserve, were 0% (0/4), 23.1% (3/13), and 50.0% (3/6), respectively (p > 0.05). The patients who died had been transfused preoperatively with a mean of 13.0 ± 10.5 units, and those who survived received a mean of 6.00 ± 5.96 units (p > 0.05). Patients who were successfully stabilized by preoperative endoscopic intervention had significantly lower mortality (p < 0.001). During follow-up there was no recurrent bleeding from gastric varices, and there was only one case (4.35%) of hemorrhage from esophageal varices. Hence, periesophagogastric devascularization and fundectomy offers an alternative operative method for cirrhotic patients with variceal hemorrhaging from the gastric fundus.     

Protein intake at 9 mo of age is associated with body size but not with body fat in 10-y-old Danish children

BACKGROUND: During the complementary feeding period, infants shift from a daily protein intake (PI) of approximately 1 g/kg body wt to an intake 3-4 times as high. A high PI probably has both endocrine and physiologic effects and may increase the risk of obesity. OBJECTIVE: We examined the associations between PI in infancy and body size and composition in late childhood. DESIGN: We conducted an observational cohort study of 142 Danish healthy term infants (63 boys) born during 1987-1988. At 9 mo of age, diet, weight, length, skinfold thicknesses, insulin-like growth factor I, and serum urea nitrogen were determined. At 10 y of age, 105 children (51 boys) participated in a follow-up study. Diet, weight, height, skinfold thicknesses, percentage of body fat (dual-energy X-ray absorptiometry), insulin-like growth factor I, and serum urea nitrogen were determined. RESULTS: At 9 mo of age, PI (in g/d and percentage of energy) was strongly correlated with body size (length and weight) but not with measures of adiposity. PI at 9 mo of age was positively associated with height and weight but not with percentage of body fat at 10 y of age. Inclusion of parental body size in the models did not change the associations, but the significant associations were attenuated when body size at 9 mo of age was included. CONCLUSIONS: PI in infancy seems to stimulate early growth. This might explain part of the association between early PI and body size at 10 y of age, but a continuous effect of protein on growth during childhood cannot be excluded. PI in infancy was not associated with any measure of body fat at 10 y of age.     

Breastfeeding and risk of atopic dermatitis, by parental history of allergy, during the first 18 months of life

The role of breastfeeding in allergic diseases remains controversial. The authors studied the association between breastfeeding and development of atopic dermatitis during the first 18 months of life among children with and without a parental history of allergy. A cohort study of 15,430 mother-child pairs enrolled in The Danish National Birth Cohort was carried out between 1998 and 2000. Data on breastfeeding, atopic dermatitis, and potential confounders was obtained from telephone interviews conducted during pregnancy and when the children were 6 and 18 months of age. The cumulative incidence of atopic dermatitis was 11.5% at 18 months of age. Overall, current breastfeeding was not associated with atopic dermatitis (incidence rate ratio (IRR) = 0.91, 95% confidence interval (CI): 0.80, 1.04). Exclusive breastfeeding for at least 4 months was associated with an increased risk of atopic dermatitis in children with no parents with allergies (IRR = 1.29, 95% CI: 1.06, 1.55) but not for children with one (IRR = 1.11, 95% CI: 0.94, 1.31) or two (IRR = 0.88, 95% CI: 0.69, 1.13) parents with allergies (test for homogeneity, p = 0.03). The authors found no overall effects of exclusive or partial breastfeeding on the risk of atopic dermatitis. However, the effect of exclusive breastfeeding for 4 months or more depended on parental history of allergic diseases.     

Seasonal variation of dermatologic disease in the USA: a study of office visits from 1990 to 1998

BACKGROUND: Seasonal variation has been demonstrated in many diseases, including certain skin diseases. OBJECTIVE: To determine whether there is seasonal variation in dermatologic office visits in the USA. METHODS: Data on dermatologic office visits were obtained from representative visits to outpatient physicians in the USA from the National Ambulatory Medical Care Survey from 1990 to 1998. Office visit seasonality was examined for all skin conditions, and individually for the 15 most commonly diagnosed conditions. RESULTS: Office visits for skin conditions were seasonal (P = 0.002). The magnitude of variation can be roughly expressed by the following scheme: actinic keratosis (P = 0.0001) > acne (P = 0.0001) > folliculitis (P = 0.002) > dyschromia (P = 0.01) > seborrheic keratosis (P = 0.04) > psoriasis (P = 0.07) > seborrheic dermatitis (P = 0.09). Visits for skin cancer, not otherwise specified (skin cancer NOS), atopic dermatitis, cysts, common wart, wart, not otherwise specified (wart NOS), rosacea, contact dermatitis, and benign tumors showed no significant seasonal variations or trends. CONCLUSIONS: Dermatologic office visits are seasonal, with visits for individual diseases varying in their magnitude of seasonality. This seasonal variation may be a result of biological and nonbiological variables.     

Development of a quantitative liquid chromatography/electrospray mass spectrometric assay for a mutagenic tobacco specific nitrosamine-derived DNA adduct, O6-[4-Oxo-4-(3-pyridyl)butyl]-2'-deoxyguanosine

Liquid chromatography with electrospray tandem mass spectrometry (LC/ESI-MS/MS) was employed to quantify O6-[4-oxo-4-(3-pyridyl)butyl]-2'-deoxyguanosine (O6-pobdG), a mutagenic adduct formed by pyridyloxobutylating nitrosamines. Selected reaction monitoring (SRM) of the neutral loss of the sugar from protonated molecules of the adduct, [M + H - 116]+, was utilized for detection of O6-pobdG in pyridyloxobutylated DNA from both in vitro and in vivo sources. Quantitation was based on isotope dilution with synthetic O6-[1,2,2-2H3-4-oxo-4-(3-pyridyl)butyl]-2'-deoxyguanosine. The detection limits in this study were less than 5 fmol of pure standard and 50 fmol in 1.5 mg of DNA. This method was validated by comparing adduct levels measured with the LC/ESI-MS/MS method to those obtained with radiochemical methods in DNA alkylated with the model pyridyloxobutylating agent, [5-3H]4-(acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone ([5-3H]NNKOAc). The pyridyloxobutyl 2'-deoxyguanosine adduct coeluting with the deuterated standard disappeared when NNKOAc-treated DNA had been reacted with the repair protein, O6-alkylguanine-DNA alkyltransferase. This result confirms that the coeluting peak is solely O6-pobdG. Preliminary studies with liver DNA isolated from NNKOAc-treated mice demonstrated that this method can be used to quantify O6-pobG in DNA from in vivo sources. The improved sensitivity and specificity of adduct detection afforded by this LC/ESI-MS/MS method will allow us to explore the role of O6-pobdG in the toxicological properties of pyridyloxobutylating nitrosamines.     

Divergent proarrhythmic potential of macrolide antibiotics despite similar QT prolongation: fast phase 3 repolarization prevents early afterdepolarizations and torsade de pointes

Macrolide antibiotics are known to have a different proarrhythmic potential in the presence of comparable QT prolongation in the surface ECG. Because the extent of QT prolongation has been used as a surrogate marker for cardiotoxicity, we aimed to study the different electrophysiological effects of the macrolide antibiotics erythromycin, clarithromycin, and azithromycin in a previously developed experimental model of proarrhythmia. In 37 Langendorff-perfused rabbit hearts, erythromycin (150-300 microM, n = 13) clarithromycin (150-300 microM, n = 13), and azithromycin (150-300 microM, n = 11) led to similar increases in QT interval and monophasic action potential (MAP) duration. In bradycardic (atrioventricular-blocked) hearts, eight simultaneously recorded epi- and endocardial MAPs demonstrated increased dispersion of repolarization in the presence of all three antibiotics. Erythromycin and clarithromycin led to early afterdepolarizations (EADs) and torsade de pointes (TdP) after lowering of potassium concentration. In the presence of azithromycin, no EAD or TdP occurred. Erythromycin and clarithromycin changed the MAP configuration to a triangular pattern, whereas azithromycin caused a rectangular pattern of MAP prolongation. In 13 additional hearts, 150 microM azithromycin was administered after previous treatment with 300 microM erythromycin and suppressed TdP provoked by erythromycin. In conclusion, macrolide antibiotics lead to similar prolongation of repolarization but show a different proarrhythmic potential (erythromycin > clarithromycin > azithromycin). In the presence of azithromycin, neither EAD nor TdP occur. This effect may be related to a rectangular pattern of action potential prolongation, whereas erythromycin and clarithromycin cause triangular action potential prolongation and induce TdP.     

Effects of multimicronutrient supplementation on helminth reinfection: a randomized,controlled trial in Kenyan schoolchildren

A randomized, placebo-controlled, double-blind, two-by-two factorial trial was carried out among 977 schoolchildren from 19 primary schools in Nyanza Province, Kenya from February 1995 to February 1996. The interventions were multimicronutrient supplementation (vitamin A, 1000 micrograms; vitamin B1, 1.4 mg; vitamin B2, 1.6 mg; vitamin B6, 1.7 mg; vitamin B12, 2.0 micrograms; folate, 150 micrograms; niacin, 16 mg; vitamin C, 50 mg; vitamin D, 5 micrograms; vitamin E, 8 mg; iron, 18 mg; zinc, 20 mg; copper, 2.0 mg; iodine, 150 micrograms; selenium, 40 micrograms) and multihelminth chemotherapy (albendazole 600 mg in a single dose and/or praziquantel 40 mg/kg in a single dose). This paper reports the effects of the supplementation given on all school days on reinfection with hookworm, Ascaris lumbricoides, Trichuris trichiura and Schistosoma mansoni after 11 months. Baseline prevalence and geometric mean intensity for hookworm, A. lumbricoides, T. trichiura and S. mansoni in all children investigated were 54.7%, 13.8%, 45.6% and 70.0%, respectively and 8.6, 2.7, 5.9 and 19.4 eggs per gram (epg), respectively. Children received a mean of 2.3 multimicronutrient/placebo tablets per school week, giving a compliance rate of 46%. Children given multimicronutrients had a slightly, but significantly, lower intensity of S. mansoni reinfection compared with children given placebo (5.5 epg vs. 7.7 epg, P = 0.047). Multiple linear regression analyses controlling for baseline infection status confirmed this, as children who received micronutrients were reinfected with S. mansoni at only 69% of the intensity of those who received placebo. Multiple logistic regression analyses revealed that micronutrient supplementation was associated with a lower S. mansoni reinfection rate (odds ratio = 0.7) although this was only of borderline significance (P = 0.090). There were no significant differences in reinfection rates or intensities of hookworm, A. lumbricoides and T. trichiura. The effect on S. mansoni infection intensity is particularly interesting given the low compliance, suggesting that full micronutrient supplementation might have a role to play in S. mansoni control programmes.     

Synthesis of 1-boraadamantaneamine derivatives with selective astrocyte vs C6 glioma antiproliferative activity. A novel class of anti-hepatitis C agents with potential to bind CD81

A variety of amine complexes with 1-boraadamatane were synthesized and subsequently evaluated for an antiproliferative effect on CD81-enriched cell lines to provide evidence for binding and activation of CD81. CD81 is a member of the tetraspanin family of membrane proteins found in all cell lineages in the liver. CD81 signals for antiproliferation when bound by antibodies. It is known that the HCV-E2 envelope glycoprotein binds to the CD81 protein. While it is unclear whether virus entry into host cells is directly linked to virus attachment via CD81 for HCV, this step in the viral life cycle has recently proven to be an effective point of attack for other viruses including HIV and rhinoviruses. The aim of the current study concerns the synthesis of amantidine analogues by appending primary amines to 1-boraadamantane to evaluate such compounds for CD81-dependent antiproliferation of CD81-enriched cell lines (astrocyte) vs CD81-deficient cell lines (C6 glioma). If the antiproliferative effect of these amantidine analogues proves to be an effect of binding and activating CD81, then these compounds may have the potential to prevent or treat HCV infections. Each compound's potential for preventive and therapeutic activity stems from the compound's potential to block viral attachment, virus-cell fusion, or virus entry into host cells or to counter potential mechanisms of HCV immune evasion. Out of a library of over 500 compounds, including randomly selected small molecules and rationally designed small molecules, only the 1-boraadamantaneamine compounds and structurally similar analogues display a significant antiproliferative effect on the CD81-enriched astrocytes relative to the CD81-deficient cell lines. In fact, 1-boraadamantane.l-phenylalanine methyl ester complex (5), 1-boraadamantane.ethanolamine complex (8), and (S)-2-[(adamantane-1-carbonyl)amino]-3-phenylpropionic acid (15) show a dose-dependent, astrocyte-selective antiproliferative activity in the concentration range 0.1-10 microM. This is consistent with the binding and activation of CD81 and represents a 2-fold improvement compared to the clinically prescribed anti-HCV agent, amantidine, in the same concentration range. Consequently, the 1-boraadamantaneamine derivatives present a promising lead in the development of small molecules with potential to bind to CD81 and treat HCV infections.