Does nausea and vomiting of pregnancy play a role in the association found between maternal caffeine intake and fetal growth restriction?

The aim of this study was to explore the relationships between nausea and vomiting in pregnancy and (a) fetal growth restriction; and (b) maternal caffeine metabolism and fetal growth restriction. A cohort of 2,643 pregnant women, aged 18-45 years, attending two UK maternity units between 8 and 12 weeks gestation, was recruited. A validated tool assessed caffeine intake at different stages of pregnancy and caffeine metabolism was assessed from a caffeine challenge test. Experience of nausea and vomiting of pregnancy was self-reported for each trimester. Adjustment was made for confounders, including salivary cotinine as a biomarker of current smoking status. There were no significant associations between fetal growth restriction and nausea and vomiting in pregnancy, even after adjustment for smoking and alcohol intake. There were no significant differences in the relationship between caffeine intake and fetal growth restriction between those experiencing symptoms of nausea and vomiting and those who did not, for either the first (p = 0.50) or second trimester (p = 0.61) after adjustment for smoking, alcohol intake and caffeine half-life. There were also no significant differences in the relationship between caffeine half-life and fetal growth restriction between those experiencing symptoms of nausea and vomiting and those who did not, for either the first trimester (p = 0.91) or the second trimester (p = 0.45) after adjusting for smoking, alcohol intake and caffeine intake. The results from this study show no evidence that the relationship between maternal caffeine intake and fetal growth restriction is modified by nausea and vomiting in pregnancy.

Effects of linoleic acid and mitogenic stimulation on the fatty acid composition of human lymphocytes.

Perturbation of the fatty acid composition of human lymphocytes in vitro was investigated by addition of linoleic acid complexed to bovine serum albumin (BSA-LA) and by mitogenic stimulation with phytohaemagglutinin (PHA). BSA-LA resulted in a 45% increase in linoleic acid in phosphatidylethanolamine (PE) and over 100% in phosphatidylcholine (PC) in peripheral blood cells. Supplementation with BSA-LA in PHA-stimulated lymphocytes produced even greater changes: 100% increase in linoleic acid content for PE and over 300% for PC. There was a large decrease in oleic acid: 40% for PE and almost 100% in PC. Significant decreases in arachidonic acid occurred in both phospholipid fractions. PHA alone also altered membrane phospholipid fatty acid composition, with reductions in palmitic, stearic and linoleic acid for PE and increases in oleic acid and arachidonic acid (almost 100%). For PC, there were large decreases in stearic (40%), linoleic (30%) and arachidonic (40%) acids, together with an increase in oleic acid (65%). Cells supplemented with linoleic acid grown in the presence of PHA, compared with those grown in linoleic acid-supplemented medium alone, showed a 40% decrease in palmitic acid and a 55% increase in arachidonic acid in PE. For PC, there were large decreases in stearic acid (40%) and arachidonic acid (57%). Antibody-induced redistribution of surface molecules ('capping') was inhibited by some 14% after incubation with BSA-LA. However, no consistent alterations in PHA-induced cell proliferation were observed. These data suggest that profound alterations of membrane fatty acid composition occur spontaneously during the mitotic cycle, and may be further induced by experimental manipulation, without gross perturbation of cell function.

Detection of kidney reactive antibodies at crossmatch in renal transplant recipients.

We have investigated retrospectively sera from 70 renal allograft recipients for the presence of antibodies binding to a preanastomosis biopsy of the donor kidney by an indirect immunoperoxidase technique. All recipients had a negative T cell lymphocytotoxic crossmatch. A positive immunoperoxidase crossmatch for kidney-reactive antibodies was seen in 13/70 (18.6%) recipients--6 reacting with endothelium, 4 with epithelium, and 3 with both cell types. Neither the presence of these antibodies nor their pattern of staining correlated with recipient graft outcome. Following transplantation endothelial reactive antibodies developed in 15/43 (35%) patients, whereas tubular epithelial antibodies occurred in 5/43 (12%). The antibodies were persistent and accompanied graft failure in 10/14 (71%) patients, while transient antibodies were only associated with graft failure in 2/12 (17%) recipients. Development of lymphocytotoxic antibodies did not correlate with the presence of renal reactive antibodies or eventual graft outcome. Smooth muscle and antinuclear antibodies in recipient sera prior to transplantation were associated with improved graft survival. Eluates of 8/14 rejected grafts confirmed the presence of renal reactive antibodies, with patterns of staining similar to those observed in recipient sera. Antibodies in 7/8 recipients were shown by absorption studies to have HLA class I and/or II specificity, the remaining recipient having proximal tubular brush border antibodies.

The effect of feeding on the bile salt-independent canalicular secretion in dogs.

Mongrel dogs were prepared by cholecystectomy, ligation of the lesser pancreatic duct, and insertion of cannulas into the duodenum and stomach. During experiments on the unanesthetized dogs, bile was collected by cannulating the common bile duct through the duodenal cannula. Canalicular secretion was estimated by the biliary clearance of erythritol. Feeding caused increased bile flow, increased erythritol clearance, decreased bile salt concentration, and unchanged bile salt output. These findings indicate that feeding stimulated the bile salt-independent canalicular secretion.

Fatty acid composition of plasma and erythrocyte phospholipids in preterm infants.

Erythrocyte and plasma phospholipid fatty acids were determined in preterm babies at 0, 6 and 10 weeks. There were highly significant changes in fatty acid composition between birth and 6 weeks in both plasma and erythrocyte phospholipids, the changes being more numerous and quantitatively greater in phosphatidyl choline. There was little further change by 10 weeks. Linoleic acid increased by approximately 100% at 6 weeks in plasma phosphatidyl ethanolamine and 200% in phosphatidyl choline. In erythrocyte phosphatidyl ethanolamine, linoleic acid increased by approximately 150% at 6 weeks and in phosphatidyl choline increased 170%. Arachidonic acid decreased by 54%. The essential fatty acid status of the preterm babies studied using contemporary feeding regimes was satisfactory and by 6 weeks phospholipid fatty acid profiles were comparable with published data for normal healthy breast-fed infants.

Adult asthma assessment in an accident & emergency department.

Poor initial assessment contributes to morbidity and mortality in acute severe asthma. We have audited this aspect of management in an A & E department over a single 6-month senior house officer employment cycle. The use of a cheap and simple stamp highlighting important clinical features of asthma was associated with a significant improvement in early assessment.

Effects of aerial applications of cypermethrin and demeton-S-methyl on nontarget arthropods of wheat.

Cypermethrin (Ripcord) and demeton-S-methyl (Duratox) were each applied to large fields of winter wheat by fixed-wing aircraft. The numbers of soil surface- and foliar-dwelling arthropods were estimated at intervals before and after treatment in both the treated and an untreated control field, using pitfall traps and a D-Vac suction sampler. Cereal aphids were the major group of phytophagous insects collected from all of the trial sites. Both compounds caused an initial decline in their numbers immediately after spraying but a significant "resurgence" in aphid populations was observed in the demeton-S-methyl-treated field towards the end of the study. The major groups of entomophagous arthropods collected from the fields were Carabidae, Staphylinidae, Linyphiidae, Empididae, and Braconidae. With the exception of the effects of cypermethrin on linyphiids and demeton-S-methyl on empids, both of the treatments had only minor, short-lived effects on these entomophages. Neither of the compounds had any significant, long-term effects on general feeding (e.g., detritivorous) arthropods.

Contamination and effects in freshwater ditches resulting from an aerial application of cypermethrin.

Cypermethrin (Ripcord) was applied at 25 g ai ha-1 by fixed-wing aircraft to a large field (11.6 ha) of winter wheat bordered on three sides by drainage ditches. About 60% of the nominal application rate was deposited on the crop and about 6% (maximum) was deposited over the water surface. The amount of spray drift deposited upwind declined sharply with increasing distance from the treated field. Downwind, the spray drift was small but occurred over a much greater distance. Very low (0.03 micrograms liter-1 maximum) concentrations of cypermethrin were found in subsurface water samples and these declined rapidly after spraying. Bioassay tests, using a sensitive indicator species, confirmed that only a small amount of cypermethrin contamination had occurred in the ditch adjacent to the downwind perimeter of the field. Frequent sampling of the zooplankton and macroinvertebrate fauna of the ditches indicated that there were no marked biological effects resulting from the cypermethrin application. Only a few air-breathing corixids and the highly susceptible water mites showed minor short-term reductions in abundance after spraying. No effects were observed on either caged or indigenous fish stocks and no significant residues of cypermethrin were found in fish tissues.

Cost of a roller skating rink to the local accident and emergency department.

A 14 month retrospective study was undertaken to determine the cost implications of the opening of a roller skating rink to the local hospital accident and emergency department (A and E). A total of 398 patients attended following injury at the roller skating rink, of whom 384 were included in the study. The estimated cost of their injuries was determined by the hospital accounts department. The average cost per patient attending the A and E department following roller skating injury was about 100 pounds. The total cost to the A and E department of all injuries sustained at the rink over this period was 38,412 pounds. The cost implications of opening a roller skating rink for the A and E department are considerable. If proposals for self-budgeting are applied, A and E departments will have to seek additional funding if such leisure facilities are opened in their vicinity.

Immunoglobulin production by coeliac biopsies in organ culture.

The production of immunoglobulins by jejunal mucosa during organ culture has been studied. In 18 untreated coeliac patients the amounts of IgA, secretory IgA and IgM in the culture medium were higher than in those from 17 normal controls. The results in 15 treated coeliac patients did not differ from the control subjects. Mucosal biopsies from patients with serum IgA deficiency produced very little IgA, but large amounts of IgG and IgM. The addition of neither Frazer's gluten fraction III, nor alpha-gliadin to the culture system stimulated any additional increased secretion of immunoglobulins from the untreated coeliac patients. Production of IgA and IgM by the small bowel mucosa continues during organ culture, but that of IgG appears insignificant.

An in vitro test for cows' milk protein intolerance?

The clinical features and results of standard laboratory investigations have been studied in children with cows' milk protein intolerance and the results compared with an in vitro test, examining the degranulation of peripheral blood basophils to cows' milk antigen. Of 67 children investigated, 26 had probable intolerance to cows' milk, and maximal basophil degranulation responses in these children were significantly increased (p less than 0.01). The most striking differences were those observed between children with definite cows' milk protein intolerance and control individuals (p less than 0.002). Of 14 children with definite cows' milk intolerance clinically, only 4 had negative responses. The basophil degranulation test may be a valuable, simple and inexpensive investigation in the diagnosis of cows' milk protein intolerance and perhaps also in other conditions in which food sensitivity plays a part.

The early anaemia of the premature infant: is there a place for vitamin E supplementation?

1. The efficacy of oral vitamin E supplementation in preventing the early anaemia of the premature infant was assessed in a 10-week double-blind trial. Forty-two babies received either a placebo or 5 or 15 mg supplementary vitamin E/d with oral feeding. No infant received less than the recommended vitamin E:polyunsaturated fatty acid (E:PUFA) value of 0.6. No iron supplement was given. 2. Weekly full blood counts were taken, and plasma vitamin E assay and in vitro haemolysis tests performed on blood sampled on day 1, and also at 6 and 10 weeks of age. All blood withdrawn and transfused and all feeds were documented. 3. Thirty-six (86%) of the babies had a plasma vitamin E level at birth below the accepted adult norm, i.e. less than 5200 micrograms/l. At 6 weeks of age thirty-three (79%) and at 10 weeks thirty-five (83%) of the babies had levels within the normal adult range. No baby showed either clinical or haematological evidence of a vitamin E deficiency state during the trial. 4. It is concluded that in the absence of Fe supplementation and observing the minimum recommended E:PUFA value, contemporary feeding practices allow for the absorption of sufficient vitamin E by the premature baby to prevent the development of an early haemolytic anaemia. 5. No significant relation was found between plasma vitamin E levels and the degree of peroxide haemolysis.

Degradation of albumin in meningococcal sepsis.

We postulate that the proteolytic degradation of albumin into fragments could link the rapidity of the shock, rash, and hypocalcaemia associated with meningococcal sepsis. We examined urine of children with meningococcal disease and urine from control children with no sepsis and found albumin fragments of about 45 kDa, 25 kDa, and less than 20 kDa only in the urine of children with meningococcal sepsis and associated purpura. Exogenous or endogenous proteases, or both, may be released in severe meningococcal sepsis and, in association with an inadequate antiprotease response, result in albumin degradation. This may be a contributory factor to the rapid shock, hypocalcaemia, and rash seen in meningococcal sepsis.

Initial evaluation of low-dose phenobarbital as an indicator of compliance with antimalarial drug treatment.

Since poor compliance with antimalarial therapy is often suspected but difficult to prove, this study attempted to establish a model for predicting the plasma concentration of phenobarbital (given in low doses in conjunction with the drug) as an indicator of compliance. Phenobarbital was chosen because its value had been demonstrated as a marker of compliance in long-course therapies, any significant departure from steady-state concentrations (achieved with full compliance) indicating one or more missed doses. Therapy for uncomplicated malaria varies from 5 days with artesunate to 7 days with quinine + tetracycline. Volunteers with confirmed falciparum malaria were randomized into 5 groups and given malaria therapy as well as phenobarbital daily for 3-7 days. Plasma samples for determination of phenobarbital concentrations were taken just prior to the daily dose of phenobarbital. Although there was a clear and predictable individual pattern of blood concentrations following each dose of phenobarbital, inter-individual variation in blood levels was significant and reduced their predictive value beyond the second day's dose. The cause of the variations is not clear; it could be attributable to different sources of the drug, previous intake of phenobarbital by the patient, or differences in drug absorption and disposition in malaria patients. Results for the 5-day artesunate regimen suggest that phenobarbital may be useful as a marker of compliance if the patient stops medication after 3 days; clear differences were evident at the end of the course of treatment between plasma phenobarbital concentrations in individuals completing the 5-day course and those who stopped after 3 days. For the quinine-tetracycline regimen, results suggest that it may be possible to discriminate between subjects where there is a 3-day difference in treatment. Phenobarbital is a better discriminant when dosing is every 24 hours as with artesunate, rather than the 8-hourly regimen for quinine-tetracycline. When measuring compliance for malaria treatment, if it is important to know what proportion of patients reach 3, 5 or 7 days of compliance, then phenobarbital might have a role to play in this assessment, but further investigations in more patients would be required. Alternatively, different markers could be used for the doses to be given on these days and, as long as the patient does not mix the doses for the different days, sequential doses and determination of compliance could be based on an "all or none" detection of the marker rather than on drug levels.

The effect of drug packaging on patients' compliance with treatment for Plasmodium vivax malaria in China.

A study conducted in 1994 showed that the use of blister packs containing antimalarial drugs significantly increased patients' compliance, compared with traditional means of dispensing drugs in a paper envelope. The present study assessed patients' compliance and compared the difference between 3-day chloroquine and 8-day primaquine courses of treatment for vivax malaria. The level of real compliance was determined by making the drugs with phenobarbital, and measuring its level in the blood following treatment. The results show that blister packaging significantly improved patients' compliance (p < 0.001) over traditional means of dispensing antimalarial drugs; there was no difference in treatment compliance between 3-day and 8-day courses when the drugs were in blister packs. However, with ordinary packaging the treatment compliance rate for an 8-day course was significantly less than for a 3-day course (P < 0.05).

Effect of eradication of Helicobacter pylori on gastric juice ascorbic acid concentrations.

Ascorbic acid, the reduced form of vitamin C, may protect against gastric cancer and is secreted by the normal stomach. Secretion is impaired in Helicobacter pylori (H pylori) associated chronic gastritis. This study examined if eradication of H pylori improves gastric juice ascorbate values. Fasting gastric juice and plasma samples were collected at endoscopy from patients participating in trials of H pylori eradication for duodenal ulcer disease and intestinal metaplasia before and up to 15 months after attempted eradication. Ascorbic acid and total vitamin C concentrations were determined by high performance liquid chromatography. In 12 patients in whom H pylori was successfully eradicated gastric juice ascorbate and total vitamin C concentrations and the ratio of juice to plasma vitamin C rose after treatment. Analysis after treatment suggested that the rise was greatest in patients with high final plasma vitamin C concentrations, even though these did not change with treatment. By contrast, in 22 patients in whom H pylori eradication was unsuccessful there were no significant changes in juice or plasma concentrations after treatment. It is concluded that successful eradication of H pylori improves secretion of vitamin C into gastric juice. It is speculated that this increases protection against gastric cancer.

Systemic and local antibody responses to gastric Campylobacter pyloridis in non-ulcer dyspepsia.

Antibody titres to Campylobacter pyloridis in serum and gastric juice were estimated by an enzyme linked immunosorbent assay (ELISA) to whole organisms obtained from bacterial culture in 39 patients with non-ulcer dyspepsia. Whereas 20 of the 21 patients with chronic gastritis had gastric C pyloridis, 17 patients with no C pyloridis had normal histology in the gastric antrum and body. Significantly raised serum IgG and IgA antibody titres to C pyloridis were found in colonised patients with gastritis. Patients with raised IgG antibody to C pyloridis were also shown to have significantly raised titres to other Campylobacter species, suggesting antigenic cross reactivity. Gastric juice antibodies were also studied and IgA titres to C pyloridis were detected in a proportion of patients with gastritis, together with low levels of IgM, but no IgG.