Dietary intake of advanced glycation end products (AGEs) and changes in body weight in European adults.

PURPOSE: Advanced glycation end products (AGEs) can be formed in foods by the reaction of reducing sugars with proteins, and have been shown to induce insulin resistance and obesity in experimental studies. We examined the association between dietary AGEs intake and changes in body weight in adults over an average of 5 years of follow-up. METHODS: A total of 255,170 participants aged 25-70 years were recruited in ten European countries (1992-2000) in the PANACEA study (Physical Activity, Nutrition, Alcohol, Cessation of smoking, Eating out of home in relation to Anthropometry), a sub-cohort of the EPIC (European Prospective Investigation into Cancer and Nutrition). Body weight was measured at recruitment and self-reported between 2 and 11 years later depending on the study center. A reference database for AGEs was used containing UPLC-MS/MS-measured Nε-(carboxymethyl)-lysine (CML), Nε-(1-carboxyethyl)-lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) in 200 common European foods. This reference database was matched to foods and decomposed recipes obtained from country-specific validated dietary questionnaires in EPIC and intake levels of CEL, CML, and MG-H1 were estimated. Associations between dietary AGEs intake and body weight change were estimated separately for each of the three AGEs using multilevel mixed linear regression models with center as random effect and dietary AGEs intake and relevant confounders as fixed effects. RESULTS: A one-SD increment in CEL intake was associated with 0.111 kg (95% CI 0.087-0.135) additional weight gain over 5 years. The corresponding additional weight gain for CML and MG-H1 was 0.065 kg (0.041-0.089) and 0.034 kg (0.012, 0.057), respectively. The top six food groups contributing to AGEs intake, with varying proportions across the AGEs, were cereals/cereal products, meat/processed meat, cakes/biscuits, dairy, sugar and confectionary, and fish/shellfish. CONCLUSION: In this study of European adults, higher intakes of AGEs were associated with marginally greater weight gain over an average of 5 years of follow-up.

Accelerator Measurements of Magnetically Induced Radio Emission from Particle Cascades with Applications to Cosmic-Ray Air Showers.

For 50 years, cosmic-ray air showers have been detected by their radio emission. We present the first laboratory measurements that validate electrodynamics simulations used in air shower modeling. An experiment at SLAC provides a beam test of radio-frequency (rf) radiation from charged particle cascades in the presence of a magnetic field, a model system of a cosmic-ray air shower. This experiment provides a suite of controlled laboratory measurements to compare to particle-level simulations of rf emission, which are relied upon in ultrahigh-energy cosmic-ray air shower detection. We compare simulations to data for intensity, linearity with magnetic field, angular distribution, polarization, and spectral content. In particular, we confirm modern predictions that the magnetically induced emission in a dielectric forms a cone that peaks at the Cherenkov angle and show that the simulations reproduce the data within systematic uncertainties.

pH regulation of the kinetic stability of the lipase from Thermomyces lanuginosus.

Thermomyces lanuginosus lipase (TlL) is a kinetically stable protein, resistant toward both denaturation and refolding in the presence of the ionic surfactant sodium dodecyl sulfate (SDS) and the nonionic surfactant decyl maltoside (DecM). We investigate the pH dependence of this kinetic stability. At pH 8, TlL remains folded and enzymatically active at multimillimolar surfactant concentrations but fails to refold from the acid urea-denatured state at submillimolar concentrations of SDS and DecM, indicating a broad concentration range of kinetic trapping or hysteresis. At pH 8, very few SDS molecules bind to TlL. The hysteresis SDS concentration range shrinks when moving to pH 4-6; in this pH range, SDS binds as micellelike clusters. Although hysteresis can be eliminated by reducing disulfide bonds, destabilizing the native state, and lowering the unfolding activation barrier, SDS sensitivity is not directly linked to intrinsic kinetic stability [its resistance to the general chemical denaturant guanidinium chloride (GdmCl)], because TlL unfolds more slowly in GdmCl at pH 6.0 than at pH 8.0. However, the estimated net charge drops from approximately -12 to approximately -5 between pH 8 and 6. SDS denatures TlL at pH 6.0 by nucleating via a critical number of bound SDS molecules on the surface of native TlL to form clusters. These results imply that SDS sensitivity is connected to the availability of appropriately charged regions on the protein. We suggest that conformational rigidity is a necessary but not sufficient feature of SDS resistance, because this has to be combined with sufficient negative electrostatic potential to avoid extensive SDS binding.

Mediterranean diet and incidence of hip fractures in a European cohort.

UNLABELLED: Prevention of hip fractures is of critical public health importance. In a cohort of adults from eight European countries, evidence was found that increased adherence to Mediterranean diet, measured by a 10-unit dietary score, is associated with reduced hip fracture incidence, particularly among men. INTRODUCTION: Evidence on the role of dietary patterns on hip fracture incidence is scarce. We explored the association of adherence to Mediterranean diet (MD) with hip fracture incidence in a cohort from eight European countries. METHODS: A total of 188,795 eligible participants (48,814 men and 139,981 women) in the European Prospective Investigation into Cancer and nutrition study with mean age 48.6 years (±10.8) were followed for a median of 9 years, and 802 incident hip fractures were recorded. Diet was assessed at baseline through validated dietary instruments. Adherence to MD was evaluated by a MD score (MDs), on a 10-point scale, in which monounsaturated were substituted with unsaturated lipids. Association with hip fracture incidence was assessed through Cox regression with adjustment for potential confounders. RESULTS: Increased adherence to MD was associated with a 7 % decrease in hip fracture incidence [hazard ratio (HR) per 1-unit increase in the MDs 0.93; 95 % confidence interval (95 % CI) = 0.89-0.98]. This association was more evident among men and somewhat stronger among older individuals. Using increments close to one standard deviation of daily intake, in the overall sample, high vegetable (HR = 0.86; 95 % CI = 0.79-0.94) and high fruit (HR = 0.89; 95 % CI = 0.82-0.97) intake was associated with decreased hip fracture incidence, whereas high meat intake (HR = 1.18; 95 % CI = 1.06-1.31) with increased incidence. Excessive ethanol consumption (HR high versus moderate = 1.74; 95 % CI = 1.32-2.31) was also a risk factor. CONCLUSIONS: In a prospective study of adults, increased adherence to MD appears to protect against hip fracture occurrence, particularly among men.

Incidence of and potential risk factors for gallstone disease in a general population sample.

BACKGROUND: Several epidemiological studies have been published, but there are few reports on relations between gallstone incidence, symptomatology and risk factors. METHODS: Of 621 randomly selected individuals aged 35-85 years in a general population who had been screened previously with ultrasonography and found to have no gallbladder stones, 503 (81.0 per cent) were re-examined after a minimum interval of 5 years. At baseline and re-examination, heredity for gallstone disease was explored and body mass index, digestive symptoms including abdominal pain, quality of life, alcohol and smoking habits, use of non-steroidal anti-inflammatory drugs and oestrogen, parity and blood lipid levels were recorded. RESULTS: Forty-two (8.3 per cent) of the 503 subjects developed stones. Subjects were followed for a total of 3025.8 person-years, yielding an incidence for newly developed gallstones of 1.39 per 100 person-years. A positive association for gallstone development was found only for length of follow-up and plasma low-density lipoprotein-cholesterol levels at baseline. Weekly alcohol consumption was inversely related to gallstone development. CONCLUSION: The incidence of gallstones in this population was 1.39 per 100 person-years. Gallstone development was related to length of follow-up and LDL-cholesterol levels, and inversely related to alcohol consumption.

Defined indications for elective cholecystectomy for gallstone disease.

BACKGROUND: This study examined symptomatology and quality of life following elective cholecystectomy for symptomatic gallstone disease with defined indications for surgery. METHODS: In this prospective study of 200 consecutive patients (161 women; median age 46.5 (range 24-79) years), strict indications for elective cholecystectomy were stipulated. Digestive symptoms and quality of life were recorded with a self-administered questionnaire before and at 3 and 12 months after surgery. RESULTS: Of 149 patients who experienced abdominal pain with typical location before surgery, 136 (91.3 per cent) reported total remission or reduced frequency of that type of pain 12 months later. Of 35 patients who reported atypical or multiple pain location before operation, 27 (77 per cent) experienced reduced frequency or disappearance of that type of pain. Frequency of pain episodes, atypical or multiple pain location, specific food intolerance and frequency of disturbing abdominal gas at baseline correlated positively with the frequency of abdominal pain episodes at 12 months after surgery. There was a tendency towards an inverse relation to age. CONCLUSION: The frequency of persistent abdominal pain after elective cholecystectomy was low among patients with typical pain location before surgery. Atypical pain location, and frequent pain episodes before operation significantly reduced the chance of becoming pain-free.

Thermochemistry of the specific binding of C12 surfactants to bovine serum albumin.

The specific binding to bovine serum albumin (BSA) of anionic and non-ionic surfactants with C12 acyl chains has been studied by high sensitivity isothermal titration calorimetry. This method proved particularly effective in resolving the binding of anionic surfactants into separate classes of sites with different affinity. For sodium dodecylsulfate (SDS) the measured binding curves could be rationalized as association to two classes (high affinity/low affinity) of sites comprising, respectively, three and six similar (i.e. thermodynamically equivalent), independent sites. Changes in the thermodynamic functions enthalpy, standard free energy, standard entropy and heat capacity could be discerned for each class of binding site, as well as for micelle formation. These data suggest that binding to low affinity sites (in analogy with micelle formation) exhibits energetic parameters; in particular, a large negative change in heat capacity, which is characteristic of hydrophobic interactions. The thermodynamics of high affinity binding, on the other hand, is indicative of other dominant forces; most likely electrostatic interactions. Other anionic ligands investigated (laurate and dodecyl benzylsulfonate) showed a behavior similar to SDS, the most significant difference being the high affinity binding of the alkylbenzyl sulfonate. For this ligand, the thermodynamic data is indicative of a more loosely associated complex than for SDS and laurate. BSA was found to bind one or two of the non-ionic surfactants (NIS) hepta- or penta(ethylene glycol) monododecyl ether (C12EO7 and C12EO5) with binding constants about three orders of magnitude lower than for SDS. Hence, the free energy of the surfactant in the weakly bound BSA-NIS complex is only slightly favored over the micellar state. The binding process is characterized by very large exothermic enthalpy changes (larger than for the charged surfactants) and a large, positive increment in heat capacity. These observations cannot be reconciled with a molecular picture based on simple hydrophobic condensation onto non-polar patches on the protein surface.

Biochemical properties of cloned lipases from the Pseudomonas family.

Three Pseudomonas lipases, representing three subfamilies, were analysed for pH optima, destabilization by EGTA and surfactants, phospholipase and cholesterolesterase side activities. All the Pseudomonas lipases tested showed alkaline pH optima. The Pseudomonas cepacia and the P. pseudoalcaligenes lipases were totally inhibited by EGTA at pH 9, and the latter was also fully inhibited at pH 7. The lipase from P. mendocina was not inhibited by EGTA at any of the pH values tested. These findings indicate that a calcium binding site exists in some of the Pseudomonas lipases. The P. pseudoalcaligenes, P. cepacia and P. mendocina lipases were inhibited by the anionic surfactant SDS at concentrations between 0.01-0.5 mg/ml. The P. pseudoalcaligenes and P. cepacia lipases were not inhibited by the nonionic surfactant Brij35 in concentration up to 1 mg/ml, whereas the lipase from P. mendocina was inhibited at 0.1 mg/ml. The P. pseudoalcaligenes and P. cepacia lipases were found to possess high cholesterol esterase activity. P. pseudoalcaligenes lipase was further found to have high phospholipase activity. Ten Pseudomonas lipase sequences were compared by automatic sequence alignment. On the basis of sequence identity we have classified Pseudomonas lipases into five subfamilies.

An analytical approach to the implementation of genetically modified crops.

Public scepticism towards genetically modified (GM) crops is increasing. To address this, the risks and benefits of GM crops must be examined across scientific disciplines, and be discussed with the authorities, the agricultural industry and the consumers. In a feasibility study we have systematically analysed the challenges of the development and marketing of GM crops in Europe. A life-cycle inventory was used together with established technology foresight techniques in an interdisciplinary and empirical framework. The approach taken in this study established a dialogue between stakeholders and provided a framework for discussions about the future direction of GM crops.

99mTc-HMPAO as a tracer of cerebral blood flow in newborn infants.

Studies on the kinetics of 99mTc-D,L-hexamethylpropylene amine oxime (99mTc-HMPAO) in adults have shown that it is not an ideal tracer of CBF because it underestimates high-flow areas. Knowledge of the kinetics of the tracer is important in evaluating the studies. The kinetics of 99mTc-HMPAO in infants may be different from that in adults, therefore, we examined the cerebral uptake and retention of 99mTc-HMPAO in neonates and estimated the degree of brain-to-blood back diffusion by comparing corresponding 133Xe flow images and 99mTc-HMPAO distribution images. In addition, we measured the urinary excretion of 99mTc-HMPAO. Regional CBF was measured using a mobile brain-dedicated, fast-rotating, four-head multidetector system specially designed for neonatal studies. Tracers were 99mTc-HMPAO (4 MBq/kg) and 133Xe (500 MBq/kg). Cerebral uptake and leak-out of 99mTc-HMPAO were measured by a single scintillation crystal placed over the frontoparietal part of the infant's head. The cerebral retention of 99mTc-HMPAO was analyzed in 50 infants. The mean gestational age and birth weight (95% confidence interval) were 34.4 weeks (32.2-35.7) and 2,326 g (1,954-2,995), respectively. The cerebral uptake of 99mTc-HMPAO was examined in 16 of the 50 infants, and activity during 24 h was monitored in five. In 11 infants, corresponding 133Xe studies were performed. Urinary excretion was studied in 12 infants. The maximal activity in the brain was reached 90s after i.v. injection and was 104% (98-111) of the stable level, which was reached approximately 3 min after the injection. The decay corrected leakout of the tracer during the following 24 h was 1.0% (0.4-1.5) per hour. The cerebral retention was calculated at 6.8% (6.1-7.6), highest in the group of ictal studies and lowest in premature infants with intracranial hemorrhage. The mean value of the fixation/clearance ratio alpha was estimated at 3.4 (2.8-4.4). The mean urinary excretion over 24 h was 19.5% (11.4-27.7) and was significantly related to renal function as indicated by serum urea (p = 0.02 r2 = 0.55). A four-compartment model describing the kinetics of 99mTc-HMPAO is shown to be valid in neonates. The cerebral retention of the tracer is higher in neonates because of higher extraction and lower initial back diffusion from brain to blood. In linearizing 99mTc-HMPAO distribution images, a smaller correction is necessary, and we propose a value of the correction factor of 3.4. In this way, 99mTc-HMPAO is a more reliable tracer of the distribution of CBF in neonates compared with adults. The urinary excretion is significantly reduced compared with adults, and the radiation dose to the bladder wall is reduced. The effective dose is 0.3 mSv/MBq/kg.

Gastric carcinoid associated with the syndrome of hypergastrinemic atrophic gastritis. A prospective analysis of 11 cases.

The prevalence of gastric carcinoid in fundic atrophic gastritis is probably greater than previously recognized. To help elucidate the clinicopathology of this syndrome, we report a series of 11 patients with solitary or multicentric carcinoid tumors. In these patients, basal gastrin levels and density of fundic mucosal endocrine cells were greater than that for patients with uncomplicated fundic atrophic gastritis (p = 0.02 and p = 0.002, respectively). The polypoid tumors, of which the largest measured 30 mm, frequently showed characteristic endoscopic features. They were all situated in the fundic mucosa, which showed micronodular endocrine cell hyperplasia. Small, endoscopically evident tumorlets, or "early carcinoids," limited to the lamina propria were observed in some patients. These lesions may represent intermediate stages between micronodules and invasive carcinoids, all of which infiltrated at least into the muscularis mucosae of the gastric wall. Although some consistent characteristics features were noted, there were structural variations. The cells were argyrophil but nonargentaffin and did not stain with conventional mucus stains. They did not stain significantly for carcinoembryonic antigen (CEA). The secretory product of these tumors remains to be identified. Ultrastructurally, some tumors were mainly composed of enterochromaffinlike (ECL) cells, but in other tumors most of the cells could not be classified.

Effects of gastric fundusectomy and antrectomy on gallbladder epithelial proliferation in the hamster.

BACKGROUND: Exogenous administration of cholecystokinin or its analog cerulein induces epithelial hyperplasia in the mouse gallbladder. The effects on the gallbladder of resectional surgery of the stomach with hormonal consequences are not known. METHODS: The effects of gastric fundusectomy and antrectomy on proliferation and growth of the gallbladder epithelium were studied in male Syrian golden hamsters during periods of 5 and 25 days. Sham-operated animals served as controls. RESULTS: Basal plasma gastrin concentrations were significantly increased after fundusectomy and significantly decreased after antrectomy, whereas basal plasma cholecystokinin concentrations were not significantly affected. Five days after fundusectomy, there was a significant increase in the tritiated thymidine DNA labeling index of gallbladder epithelial cells. On day 25, the gallbladder weight and total number of epithelial cells were significantly increased after fundusectomy. Antrectomy significantly decreased the gallbladder weight on day 25, whereas the labeling index and total number of epithelial cells were not significantly affected on days 5 and 25. CONCLUSIONS: These results suggest that gastric fundusectomy at least transiently induces gallbladder epithelial hyperplasia and hypertrophy in the hamster. Although achlorhydria and hypergastrinemia are prominent features, the actual mechanism behind this effect of fundusectomy on the gallbladder needs further clarification.

Evaluation of preoperative computed tomography in gastric malignancy.

Ninety patients with gastric malignancy underwent computed tomography (CT) before surgery. The CT findings regarding neoplastic invasion of adjacent organs and metastasis or enlarged lymph nodes were compared with the findings at laparotomy (85 cases) or autopsy (5 cases), thus permitting evaluation of the diagnostic accuracy of CT and its usefulness for predicting resectability. When present, neoplastic invasion of adjacent organs was overestimated or underestimated by CT in 21 cases. Invasion of adjacent organs according to CT was false positive in 17 cases and false negative in 11 cases. When liver metastasis or enlarged regional or distant lymph nodes were present, CT overestimated or underestimated their extent in 17 cases, and the diagnosis was false positive in one case and false negative in 33 cases. The positive and negative predictive values of CT concerning resectability of the tumor were 81% and 64%, respectively. Routine preoperative CT in gastric malignancy is concluded to be of limited value and surgical exploration, when feasible, remains the method of choice.

Profiling of bacterial flora in gastric biopsies from patients with Helicobacter pylori-associated gastritis and histologically normal control individuals by temperature gradient gel electrophoresis and 16S rDNA sequence analysis.

The aim of this study was to establish bacterial profiles in gastric biopsy specimens from patients with Helicobacter pylori-associated gastritis by means of temporal temperature gradient gel electrophoresis (TTGE) of PCR-amplified 16S rDNA fragments. Specimens from eight patients with asymptomatic gastritis and five histologically normal controls revealed a Helicobacter-specific band in the TTGE profile with increased amounts of Helicobacter-specific DNA in the biopsies from most of the gastritis patients. DNA from other genera including Enterococcus, Pseudomonas, Streptococcus, Staphylococcus and Stomatococcus was also found in the stomach. In the absence of gastric inflammation, Helicobacter spp. appeared to be part of a complex, presumably indigenous microbial flora found in the biopsy specimens from the stomach.

Identification of Helicobacter in gastric biopsies by PCR based on 16S rDNA sequences: a matter of little significance for the prediction of H. pylori-associated gastritis?

The aim of the present study was to correlate molecular evidence of the presence of Helicobacter pylori in gastric biopsy samples, based on analysis of 16S rDNA, vacuolating toxin (vacA), urease A (ureA) and cagA genes, with the clinical, histological and serological findings in patients with H. pylori-associated gastritis. Fresh biopsy samples were collected from the gastric antrum and corpus of 22 asymptomatic volunteers with or without H. pylori-associated gastritis. Total DNA was extracted from the biopsy material and subjected to 16S rDNA PCR amplification, Southern blotting and 16S rDNA sequence analysis of the PCR products. The vacA, ureA and cagA genes were characterised by PCR amplification and Southern blot analysis. Based on partial 16S rDNA sequence analysis, DNA belonging to the genus Helicobacter was detected in gastric biopsy samples from 20 of 22 subjects, including seven of nine histologically and serologically normal controls. Six of 20 partial 16S rDNA sequences revealed variations within variable regions V3 and V4 that deviated from those of the H. pylori type strain ATCC 4350T and, therefore, possibly represented other species of Helicobacter. VacA genes identical with those of the type strain were found predominantly in the subjects with H. pylori gastritis, and all the patients except one were found to be cagA-positive. There was no evidence of false positive PCR reactions. In conclusion, the PCR-based molecular typing methods used here were apparently too sensitive when applied to the detection of H. pylori in human gastric tissues. The lack of quantitative analysis makes them inappropriate as clinical tools for the diagnosis of H. pylori-associated gastritis, despite the fact that they provide a qualitative and sensitive tool for the detection and characterisation of H. pylori in the gastrointestinal tract.

Endogenous hypercholecystokininemia model in the hamster: trophic effect on the exocrine pancreas.

Using Syrian golden hamsters, we studied the effect of pancreaticobiliary diversion (PBD) on plasma cholecystokinin (CCK) and exocrine pancreatic tissue over 5, 10, and 24 days. As compared with sham-operated controls, PBD-operated animals had increased plasma CCK concentrations by 228, 318, and 207% at 5, 10, and 24 days, respectively. Correspondingly, pancreatic wet weight increased by 24, 61, and 87%; total pancreatic protein by 6, 57, and 73%; and total pancreatic DNA by 35, 52, and 98%, respectively. At 5 days, but not at 10 and 24 days, there was a significant increase in the pancreatic tissue DNA concentration (p less than 0.01) and [3]H-thymidine incorporation into DNA (p less than 0.02). Autoradiography showed increased [3]H-thymidine labeling index in acinar cells at 5 and 10 days after PBD (p less than 0.01 and p less than 0.005). Although not significant, ductal cell labeling index was also increased at 5 and 10 days. These findings provide evidence that, as in the rat, PBD in the hamster induces hypercholecystokininemia with ensuing pancreatic hyperplasia and hypertrophy. The hamster model may be useful for studies on the effect of endogenous CCK on pancreatic ductal cell carcinogenesis and diseases of the gallbladder, neither of which can be studied in the rat.

Effects of pancreaticobiliary diversion and gastric fundectomy on azaserine-induced pancreatic carcinogenesis in the rat.

The effects of pancreaticobiliary diversion (PBD) and gastric fundectomy on the pancreas in azaserine-treated rats were studied over 14 months. Sham-operated azaserine-treated animals served as controls. A significant increase in pancreatic weight and total DNA and protein content was found in PBD-operated and fundectomized animals. DNA flow cytometry showed a significantly increased ratio of tetraploid to diploid cells in pancreatic tissue in both experimental groups. Mean values of all these variables were significantly higher after PBD than after fundectomy. Acidophilic atypical acinar cell foci of the pancreas were observed in all of the experimental and 75% of the control animals. The volume density of these foci was significantly higher in each experimental group than in the controls. The volume density, radioactive thymidine labeling index, and mitotic index of the foci were significantly higher after PBD than after fundectomy. Changes consistent with pancreatic adenoma were diagnosed in the PBD group only. It is concluded that not only PBD with endogenous hypercholecystokininemia, but also fundectomy with endogenous hypergastrinemia lasting about half of the life span in rats, induces pancreatic hypertrophy and enhances the development of precancerous pancreatic changes after azaserine treatment. In comparison with PBD, fundectomy caused less pronounced changes and no observable neoplasia.

Randomised trial of pivampicillin plus pivmecillinam vs. pivampicillin in children and young adults with chronic obstructive pulmonary disease and infection with Haemophilus influenzae.

A prospective, randomised, single-blind comparative trial was carried out to determine whether double beta-lactam treatment with pivampicillin plus pivmecillinam is more effective than pivampicillin alone in the treatment of recurrent and chronic lung infections with Haemophilus influenzae in patients with chronic obstructive pulmonary disease (COPD) or cystic fibrosis (CF). Fifty-six children and young adults with COPD or CF were randomised to the clinical study. The patients were allocated at random to receive perorally either pivmecillinam, 40 mg/kg/day, combined with pivampicillin, 50 mg/kg/day, or pivampicillin 50 mg/kg/day alone for 14 days. A cross-over pharmacokinetic study using the same drugs was carried out in 10 CF patients to determine the antibiotic concentrations in serum and sputum after a single dose of each drug. The clinical study showed no significant differences in clinical scoring, lung function tests or adverse events after treatment with pivampicillin plus pivmecillinam or pivampicillin alone. Follow-up microbiological evaluation 2 and 6 weeks after the end of treatment showed that the offending pathogen was eradicated in 68% of the patients treated with pivampicillin plus pivmecillinam and in 67% of the patients treated with pivampicillin alone. Reinfection with another biotype was more common in the combination group (50% vs. 21%) than in the pivampicillin group. In the pharmacokinetic study the median peak serum concentration occurred two hours after intake of tablets. The efficacy of double beta lactam treatment in lung infections with H. influenzae appears to be equivalent to that of ampicillin on clinical lung symptoms, lung function tests, adverse effects and bacteriology.

A new case with hereditary xanthinuria: response to exercise.

The concentration of purines in plasma and urine from a 37-yr-old healthy man with a very low plasma urate concentration was measured by HPLC. A persistent increase in xanthine and a slight elevation of hypoxanthine was found. The metabolic response to intensive treadmill running and long distance running was investigated. The hypoxanthine concentration increased to about the same level as in healthy controls, but the elimination from plasma was considerably slower. The high xanthine level was practically unchanged by exercise.

Detection of spiral and coccoid forms of Helicobacter pylori using a murine monoclonal antibody.

Helicobacter pylori is the major cause of gastritis. The aim of this investigation was to develop a specific antibody, which recognizes both coccoid and spiral forms of Helicobacter pylori and to test this antibody on gastric biopsy sections known to harbour coccoid bacteria. Murine monoclonal antibodies against glycine-acid extracts of five strains of Helicobacter pylori were raised. Immunofluorescence and immunoelectron microscopy showed that one antibody of the IgG1 subclass was specific for both the spiral and coccoid forms. It reacted with a 28 kDa protein that was present in all the five strains tested. Using this antibody in an indirect immunofluorescence assay of formalin-fixed antral and corpus biopsy specimens from Helicobacter pylori-associated gastritis patients showed that nine of the nine antral and five of six corpus specimens harboured the coccoid form of Helicobacter pylori. This technique thus provides a rapid and specific detection of both the spiral and coccoid forms.