Appendicectomy, childhood hygiene, Helicobacter pylori status, and risk of inflammatory bowel disease: a case control study

Aims—To examine the relation between inflammatorybowel disease and appendicectomy, childhood domestic hygiene, andHelicobacter pylori infection.
Methods—Case control study involving 213 patientswith ulcerative colitis, 110 with Crohn's disease, and 337 controlshaving elective surgery.
Results—Nine patients with ulcerative colitis(4.5%) reported a previous appendicectomy compared with 57 controls(19%) (odds ratio (OR) 0.20, 95% confidence interval (CI) 0.1-0.4,p<0.0001). The inverse association was unaffected by excludingoperations performed after the age of onset of ulcerative colitis andwas stronger for appendicectomy performed before age 20 (OR 0.14). Noassociation with appendicectomy was found for Crohn's disease and noassociations with tonsillectomy for either disease. The availability ofa fixed hot water supply in early childhood (before age 11) wasassociated with Crohn's disease (OR for hot water not always versusalways available 0.56, 95% CI 0.3-0.9, p=0.02) but not withulcerative colitis. No other aspect of domestic hygiene before or afterage 11 was associated with either Crohn's disease or ulcerativecolitis. Although H pylori seroprevalence was positively associated with overcrowding (p<0.001) and the absence of running hotwater in childhood it was not associated with the presence of eitherCrohn's disease or ulcerative colitis. H pyloriseroprevalence was no lower in patients who had been exposed tosulphasalazine than in controls or those not exposed.
Conclusions—Our findings confirm the stronginverse association between previous appendicectomy and the developmentof ulcerative colitis and suggest that the protective effect is greaterfor appendicectomy performed in childhood.

Keywords:inflammatory bowel disease; appendicectomy; tonsillectomy; childhood hygiene; Helicobacter pylori; sulphasalazine

     

MODES OF INACTIVATION OF NEUROHYPOPHYSIAL HORMONES: SIGNIFICANCE OF PLASMA DISAPPEARANCE RATE FOR THEIR PHYSIOLOGICAL RESPONSES

Analogues of oxytocin and deaminooxytocin with 4-glutamine replaced by 4-glutamic acid methyl ester readily lose their uterotonic activity when incubated with rat serum, presumably by hydrolysis to the much less active 4-glutamic acid derivatives. On the other hand, inactivation of the deaminooxytocin analogue in the rat uterus, as demonstrated by the 'oil-bath'technique, is only slightly more rapid than that of deaminooxytocin and distinctly slower than that of oxytocin. Its in situ/in vitro ratio of uterotonic activity is less than 0.1 whereas that for deaminooxytocin is about 3 and also the persistence of the uterotonic effect in situ is slightly less than that of deaminooxytocin. The results with these 'rapidly inactivated'analogues can be used as proof of some predictions of the three-compartment model for tissue distribution of neurohypophysial hormones and its influence upon the time course of a biological response published earlier. The potential use of analogues of neurohypophysial hormones as probes for inactivation mechanisms and the results thus far obtained are discussed.     

Twenty-four-hour ambulatory blood pressure in community-dwelling elderly men and women,aged 60-102 years

OBJECTIVE: To investigate ambulatory blood pressure in elderly people, including 'old elderly' subjects, aged over 80 years. DESIGN: Cross-sectional study of community-dwelling, elderly subjects. METHODS: Subjects were healthy, self-caring, and living independently. Those who were taking medication affecting blood pressure were excluded. Conventional blood pressure was the mean of two measurements. Ambulatory blood pressure monitoring was performed using the SpaceLabs 90207 device. Daytime and night-time blood pressure were defined by fixed clock intervals. RESULTS: Seventy-five 'young elderly', aged 60-79 years, (39 men, 36 women) and 81 'old elderly' aged 80 years and older (37 men, 44 women) underwent 24-h ambulatory blood pressure monitoring. Systolic blood pressure (SBP) was related to age, correlation coefficients between age and SBP were 0.31, 0.25 and 0.31, respectively, for conventional SBP, daytime SBP and night-time SBP (P < 0.01 for all). There was no correlation between age and diastolic blood pressure. Blood pressure levels were similar in men and women. Mean conventional blood pressure, daytime blood pressure and night-time blood pressure were found to be 149/81, 138/82 and 119/69 mmHg, respectively, in the 'young elderly' and 162/82, 147/83, and 133/71 mmHg, respectively, in the 'old elderly (P < 0.01 for SBP). The night : day SBP ratio was significantly higher in the 'old' elderly compared with the 'young' elderly (0.90 versus 0.86, respectively; P < 0.01). CONCLUSIONS: Ambulatory blood pressure levels in healthy, community-dwelling 'old elderly' are higher than those reported for younger adults and reflect the prominent age-related rise in SBP associated with advanced old age. Advanced old age is associated with a diminished nocturnal dip in blood pressure.     

Response to 2'-deoxycoformycin after failure of interferon-alpha in nonsplenectomized patients with hairy cell leukemia

Two patients with hairy cell leukemia with massive splenomegaly and severe pancytopenia were treated with recombinant alpha-A interferon (IFN-alpha-2a). There was no significant response to a trial of IFN- alpha-2a (11 and 20 weeks) with respect to blood counts or spleen size. Subsequent treatment with 2'-deoxycoformycin (dCF) for 8 consecutive weeks (4 mg/m2/wk) resulted in normalization of spleen size and a normalization of peripheral blood counts and bone marrow in one patient. The second patient demonstrated a reduction in spleen size and improved blood counts following 9 weeks of dCF therapy but eventually became refractory. This demonstrates that dCF is non-cross-resistant with interferon and confirms the efficacy of dCF in nonsplenectomized patients.     

Evaluation of drugs for elimination of leukemic cells from the bone marrow of patients with acute leukemia

Relatively nonmyelotoxic drugs and drug combinations were investigated for their ability to eliminate malignant cells from human bone marrow. In vitro 90% inhibitory concentration (IC90) doses were established on granulocyte macrophage colony-forming units (GM-CFU) in culture of bone marrow by using the GM-CFU assay for the following drugs: 4- hydroperoxycyclophosphamide (4-HC), Adriamycin, L-asparaginase, bleomycin, hydrocortisone, VP-16, spirogermanium, Taxol, and vincristine. The leukemic cell kill efficiency of these drugs at IC90 doses was compared with that of 4-HC on acute lymphoid leukemia (ALL) cell lines by using the limiting-dilution assay. Under these conditions, no single drug was superior to 4-HC. To increase the in vitro effect in leukemic cell kill, combinations of vincristine with hydrocortisone, Adriamycin, VP-16, and 4-HC were investigated. Vincristine at 1 to 5 micrograms/mL increased the marrow cytotoxicity of hydrocortisone, Adriamycin, and VP-16, but it was protective (subadditive) with 4-HC. Vincristine and 4-HC in combination was additive to supraadditive on ALL cell lines, increased the leukemic cell kill by one to two logs above 4-HC alone at IC90 doses (P less than .05), and was not affected by the addition of excess marrow cells. The recommended doses for chemopurging in clinical studies are vincristine, 1 to 5 micrograms/mL, plus 4-HC, 5 micrograms/mL.     

Effects of monoclonal antibody therapy in patients with chronic lymphocytic leukemia

A phase I clinical trial was initiated to treat patients with stage IV B-derived chronic lymphocytic leukemia (CLL) with the IgG2a murine monoclonal antibody T101. This antibody binds to a 65,000-mol wt (T65) antigen found on normal T lymphocytes, malignant T lymphocytes, and B- derived CLL cells. All of the patients had a histologically confirmed diagnosis of advanced B-derived CLL and were refractory to standard therapy, and more than 50% of their leukemia cells reacted with the T101 antibody in vitro. The patients received T101 antibody two times per week, over two to 50 hours by intravenous administration in 100 mL of normal saline containing 5% human albumin. Twelve patients were treated with a fixed dosage of 1, 10, 50, or 100 mg, and one patient was treated with 140 mg of antibody. It was demonstrated that patients given two-hour infusions of 50 mg developed pulmonary toxicity, with shortness of breath and chest tightness. This toxicity was eliminated when infusions of 50 or 100 mg of T101 were prolonged to 50 hours. All dose levels caused a rapid but transient decrease in circulating leukemia cell counts. In vivo binding to circulating and bone marrow leukemia cells was demonstrated at all dose levels with increased binding at higher dosages. Antimurine antibody responses were not demonstrated in any patients at any time during treatment. Circulating free murine antibody was demonstrated in the serum of only the two patients treated with 100 mg of antibody as a 50-hour infusion and the patient treated with 140 mg of antibody over 30 hours. Antigenic modulation was demonstrated in patients treated at all dose levels but was particularly apparent in patients treated with prolonged infusions of 50 and 100 mg of antibody. We were also able to demonstrate antigenic modulation in lymph node cells, which strongly suggests in vivo labeling of these cells. Overall, T101 antibody alone appears to have a very limited therapeutic value for patients with CLL. The observations of in vivo labeling of tumor cells, antigenic modulation, antibody pharmacokinetics, toxicity, and antimurine antibody formation may be used in the future for more effective therapy when drugs or toxins are conjugated to the antibody.     

Nutritional Factors Associated with Antenatal Depressive Symptoms in the Early Stage of Pregnancy Among Urban South Indian Women

Many women of reproductive age from developing countries have poor nutritional status, and the prevalence of depression during pregnancy is high. The objective of the present study was to assess the prevalence of antenatal depressive symptoms in early pregnancy, and to identify the demographic and nutritional factors associated with these symptoms in a sample of urban South Indian pregnant women. This cross-sectional study was the baseline assessment of a prospective randomized controlled trial of vitamin B₁₂ supplementation in urban pregnant south Indian women between the ages of 18 and 40 years (www.clinicaltrials.gov: NCT00641862). 365 women in their first trimester of pregnancy were screened for depressive symptoms at an urban clinic in Karnataka, South India, using the Kessler Psychological Distress Scale (K-10). Nutritional, clinical and biochemical factors were also assessed. Mean (SD) age of the cohort was 22.6 (3.7) years and mean (SD) BMI was 20.4 (3.3) kg/m². 121 (33 %) of the women in the 1st trimester had symptoms consistent with depression (K-10 score >6). In multivariate log binomial regression analysis, presence of antenatal depressive symptoms in the first trimester were positively associated with vomiting, prevalence ratio (PR) = 1.54 (95 % CI 1.10, 2.16) and negatively with anemia, PR = 0.67 (95 % CI 0.47, 0.96). Nutrient intakes, serum vitamin B₁₂, methylmalonic acid, homocysteine and red cell folate levels were not associated with measures of depression. Antenatal depressive symptoms in early pregnancy are highly prevalent in urban Indian women and are more common in women with vomiting and without anemia. In this cross-sectional data, blood concentrations of vitamin B₁₂ and folate were not associated with depressive symptoms. The relationship between nutritional status and depressive symptoms may require larger and longitudinal studies.