Fruits, vegetables, and hMLH1 protein-deficient and -proficient colon cancer: The Netherlands cohort study.

BACKGROUND: Clinical and pathologic differences exist between colon carcinomas deficient and proficient in the mismatch repair protein hMLH1. Animal and in vitro studies suggest that fruits, vegetables, folate, and antioxidants are associated with colonic expression of mismatch repair genes.METHODS: Associations between consumption of fruits and vegetables and hMLH1 protein-deficient and -proficient colon cancer were evaluated in the Netherlands Cohort Study on diet and cancer using a case-cohort approach. A self-administered food frequency questionnaire was completed, in 1986, by 120,852 individuals ages 55 to 69 years. Using immunohistochemistry, hMLH1 protein expression was assessed in colon cancer tissue obtained from 441 patients who were identified over 7.3 years of follow-up excluding the initial 2.3 years. Incidence rate ratios (RR) were estimated for hMLH1 protein-deficient and -proficient colon cancer.RESULTS: hMLH1 protein expression was absent in 54 tumors (12.2%) and present in 387 tumors. Fruit consumption was associated with hMLH1 protein-deficient colon cancer [highest versus lowest tertile, RR, 0.46; 95% confidence interval (95% CI), 0.23-0.90; P(trend) = 0.029] but not with hMLH1 protein-proficient tumors (highest versus lowest tertile, RR, 1.03; 95% CI, 0.78-1.35; P(trend) = 0.81). Total consumption of vegetables was not associated with either type of tumor (hMLH1 protein deficient: RR, 0.86; 95% CI, 0.45-1.65; P(trend) = 0.67; hMLH1 protein proficient: RR, 0.94; 95% CI, 0.72-1.23; P(trend) = 0.72). No associations were observed for folate, fiber, antioxidants, or subgroups of vegetables.CONCLUSION: These analyses indicate that an inverse association between consumption of fruits and colon cancer may be confined to the subgroup of tumors with a deficient mismatch repair system.     

GSTP1 and GSTA1 polymorphisms interact with cruciferous vegetable intake in colorectal adenoma risk.

The possible interplay between cruciferous vegetable consumption, functional genetic variations in glutathione S-transferases (GST) M1, T1, P1, and A1, and colorectal adenomas, was investigated in a Dutch case-control study. The GSTM1 and GSTT1 deletion polymorphisms, and the single nucleotide polymorphisms in GSTP1 (A313G) and in GSTA1 (C-69T) were assessed among 746 cases who developed colorectal adenomas and 698 endoscopy-based controls without any type of colorectal polyps. High and low cruciferous vegetable consumption was defined based on a median split in the control group. High consumption was slightly positively associated with colorectal adenomas [odds ratio (OR) 1.15; 95% confidence interval, 0.92-1.44]. For GSTP1, a positive association with higher cruciferous vegetable intake was only apparent in individuals with the low-activity GSTP1 genotype (GG genotype, OR 1.94; 95% confidence interval, 1.02-3.69). This interaction was more pronounced in men, with higher age and with higher meat intake. The GSTA1 polymorphism may have a modifying role as well: the OR for higher intake compared with lower intake was 1.57 (0.93-2.65) for individuals homozygous for the low expression variant (TT genotype). This seemed to be stronger with younger age and higher red meat intake. Cruciferous vegetable consumption and the combined GSTA1 and GSTP1 genotypes showed a statistically significant interaction (P = 0.034). The GSTM1 and GSTT1 genotypes did not seem to modify the association between cruciferous vegetable intake and colorectal adenomas. In conclusion, GSTP1 and GSTA1 genotypes might modulate the association between cruciferous vegetable intake and colorectal adenomas.     

Formulation of a liquid ovine Fab-based antivenom for the treatment of envenomation by the Nigerian carpet viper (Echis ocellatus).

Most antivenoms are required for use in tropical or sub-tropical countries where temperatures may be high and refrigerated storage unavailable or unreliable. Although freeze-dried products can be expected to have maximal storage stability, many antivenoms are manufactured in liquid form to lower their cost and ease their use. We developed a liquid formulation of an existing freeze-dried antivenom against the carpet viper (Echis ocellatus) for use in Nigeria. When Fab fragments, prepared from antisera raised in sheep, were exposed to pH between 3.0 and 8.0, time and temperature dependent precipitation of some populations of the Fab product occurred over the range 4.5-7.0. Formulation of the Fab fragments in acetate buffer (20 mM) at pH 4.0 provided a clear, colourless, particle-free and stable product which retained neutralising potency for at least one year at 4 degrees C and room temperature. An accelerated study indicated stability for at least 4 weeks at 37 degrees C which may be considered equivalent to four years at 4 degrees C. The presence of sugars (sorbitol at 20 g/l or mannitol at 50 g/l) or sodium chloride (153 mM) had no effect in stabilising Fab at high temperature (37 degrees C) and, in agreement with the prediction of these accelerated studies, no beneficial effect of mannitol was found in real-time studies after one year.     

Effects of prednisolone and deflazacort on osteocalcin metabolism in sheep

Summary Glucocorticoids adversely affect bone and mineral metabolism through a number of mechanisms, including inhibition of bone formation. Deflazacort is a glucocorticoid which has been reported to be relatively bone-sparing. We compared the effects in oophorectomized sheep of deflazacort and prednisolone on the metabolism of osteocalcin (OC), a marker of osteoblast function. An [¹²⁵I]OC infusion method was used to measure the OC plasma clearance rate (PCR) and OC plasma production rate (PPR).Six-day intravenous infusion of deflazacort and prednisolone (in the dose range 0.007–1.00 mg/hour) induced dose-dependent decreases in OC PPR which were of a similar pattern but significantly different magnitude (P < 0.02); deflazacort demonstrated a potency about 150% that of prednisolone. Both steroids decreased plasma OC levels on a dose-related basis but at the lower doses 0.05 mg/hour (P < 0.05) and 0.013 mg/hour (P < 0.0005), deflazacort caused greater decrements. OC PCR was significantly increased only by higher doses of deflazacort (1.00 mg/hour, 0.25 mg/hour;P < 0.05). Deflazacort and prednisolone increased both postabsorptive plasma glucose and plasma calcium levels, but there were no significant differences between their effects.We conclude that plasma OC levels and OC PPR in sheep were more sensitive to the effects of deflazacort than to prednisolone. At high doses, the depressive effect of deflazacort on plasma OC levels may have been due in part to an increased OC PCR which was not evident with prednisolone treatment. However, the agents appeared to have a similar dose-dependent hyperglycemic effect, and both caused a small dose-dependent increase in plasma calcium. These findings indicate that prednisolone had similarly potent effects on both bone and glucose metabolism while deflazacort exhibited differential potency on the two systems. The greater potency of deflazacort on bone in sheep may be due to species differences in steroid metabolism or steroid-receptor interaction.     

Development and initial experience with a manually controlled spring wire device ("Cordostat") to aid in difficult funipuncture

Funipuncture has evolved as a useful tool in prenatal diagnosis and treatment. The ease with which it can be performed depends on placental implantation site, amniotic fluid volume, fetal presentation and activity, gestational age, and operator experience. Under select circumstances, such as hydramnios, oligohydramnios/anhydramnios, a back-up fetus/posterior placenta, or gestation of fewer than 20 weeks, funipuncture can be difficult or impossible. We have developed a new instrument, the "Cordostat," which can help the operator perform difficult funipuncture by providing stabilization and allowing intrauterine manipulation of the umbilical cord. The instrument consists of a deflecting wire guide threaded through a 19.5-guage trochar needle, which can be manually controlled to coil around and stabilize a free loop of cord. Conventional funipuncture can then be performed through a second uterine puncture. We describe use of this instrument in 12 patients undergoing second-trimester induced abortion.     

Carcinoid metastatic to breast diagnosed by fine-needle aspiration biopsy

We report a patient in whom fine-needle aspiration biopsy of a breast mass, clinically suspected to be a mammary adenocarcinoma, established the diagnosis of a carcinoid metastatic to breast. The aspirate smears resembled a primary breast carcinoma; however, subtle cytomorphologic differences were present. Ultrastructural and immunohistochemical studies of the aspirate material confirmed the diagnosis of metastatic carcinoid.     

Asthma morbidity during pregnancy can be predicted by severity classification

BACKGROUND: The 1993 National Asthma Education Program Working Group on Asthma and Pregnancy defined asthma severity as mild, moderate, or severe on the basis of symptoms and spirometry, but no studies have evaluated the relationship between this classification system and subsequent asthma morbidity during pregnancy. OBJECTIVE: The objective of this study was to evaluate the relationship between asthma severity classification during pregnancy and gestational asthma exacerbations. METHODS: Asthma severity was defined according to the 1993 classification, adjusted to include medication requirements, in a volunteer sample of 1739 pregnant asthmatic patients who were less than 26 weeks' gestation. RESULTS: Initial asthma classification (mild, moderate, or severe) was significantly related to subsequent asthma morbidity during pregnancy (hospitalizations, unscheduled visits, corticosteroid requirements, and asthma symptoms during labor and delivery). Exacerbations during pregnancy occurred in 12.6% of patients initially classified as mild, 25.7% of patients classified as moderate, and 51.9% of patients classified as severe (P <.001). Asthma morbidity was similar, whether patients were classified as moderate or severe by symptoms and spirometry or by medication requirement. Thirty percent of initially mild patients were reclassified as moderate-severe during pregnancy, and 23% of the initially moderate-severe patients were reclassified as mild later in pregnancy; asthma morbidity in these patients changed accordingly. CONCLUSION: The National Asthma Education Program Working Group on Asthma and Pregnancy classification of asthma severity, adapted to include medication use, predicts subsequent asthma morbidity during pregnancy.     

Accelerated epigenetic aging in adolescents living with HIV is associated with altered development of brain structures

Journal of NeuroVirology - We recently demonstrated that adolescents perinatally infected with HIV-1 (PHIV+) have accelerated aging as measured by a highly accurate epigenetic biomarker of aging...