The spectrum of aldolase B (ALDOB) mutations and the prevalence of hereditary fructose intolerance in Central Europe

We investigated the molecular basis of hereditary fructose intolerance (HFI) in 80 patients from 72 families by means of a PCR-based mutation screening strategy, consisting of heteroduplex analysis, restriction enzyme digest, DNA single strand electrophoresis, and direct sequencing. For a subset of patients mutation screening with DHPLC was established which turned out to be as fast and as sensitive as the more conventional methods. Fifteen different mutations of the aldolase B (ALDOB) gene were identified in HFI patients. As in smaller previous studies, p.A150P (65%), p.A175D (11%) and p.N335K (8%) were the most common mutated alleles, followed by c.360_363delCAAA, p.R60X, p.Y204X, and c.865delC. Eight novel mutations were identified in eight families with HFI: a small indel mutation (c.1044_1049delTTCTGGinsACACT), two small deletions (c.345_372del28; c.841_842delAC), two splice site mutations (c.113-1G>A, c.799+2T>A), one nonsense mutation (c.612T>G (p.Y204X)), and two missense mutations (c.532T>C (p.C178R), c.851T>C (p.L284P)). By mutation screening for the three most common ALDOB mutations by DHPLC in 2,000 randomly selected newborns we detected 21 heterozygotes. Based on these data and after correction for less common and private ALDOB mutations, HFI prevalence in central Europe is estimated to be 1:26,100 (95% confidence interval 1: 12,600-79,000).     

Segmental heterogeneity of swelling-induced Cl transport in rat small intestine

The effect of cell swelling induced by hypotonic media was studied in segments of rat small intestine. In the Ussing chamber, exposure to a hypotonic medium caused a decrease in short-circuit current (I _sc) and potential difference (V ^ms) in the jejunum, whereas the ileum responded with an increase in I _sc and V ^ms. The transition from one pattern to the other was located about in the middle of the small intestine. Tissue conductance decreased in both segments, probably due to a reduction of paracellular shunt conductance induced by the cell swelling. Voltage scanning experiments revealed that the observed decrease in total tissue conductance in the ileum was caused solely by a decrease in local conductance in the villus region while the crypt conductance did not change, suggesting that the decrease in paracellular conductance of the crypts is compensated by an increase in cellular conductance. The response in both segments was dependent on the presence of Cl⁻ and was blocked by the Cl⁻ channel blocker 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB). It was not affected by the neurotoxin tetrodotoxin. In the jejunum the swelling-induced decrease in I _sc was reduced in the presence of the cyclooxygenase inhibitor, indomethacin, or the lipoxygenase inhibitor, nordihydroguaiaretic acid. In the ileum the Cl⁻ secretion induced by hypotonicity was blocked by the K⁺ channel blocker quinine and was reversed into a decrease in I _sc when serosal Ca²⁺ was zero. We conclude that the observed volume regulatory changes are initiated in the jejunum by an eicosanoid-mediated opening of basolateral Cl⁻ channels and in the ileum by a Ca²⁺-mediated opening of K⁺ channels which enhances apical Cl⁻ efflux. Received: 27 June 1995/Received after revision: 8 December 1995/Accepted: 28 December 1995     

Death or illness of a family member,violence, interpersonal conflict,and financial difficulties as predictors of sickness absence: longitudinal cohort study on psychological and behavioral links

OBJECTIVE: Although an association between stressful life events and health problems has been demonstrated, the underlying mechanisms have remained unclear. We examined whether psychological problems and health-risk behaviors underpin the health effects of different event categories. METHOD: The initially healthy participants were 2991 (796 men, 2195 women) municipal employees who had taken no sick leave in 1995. In 1997, they completed a questionnaire requesting information on recent life events and psychological and behavioral factors. The outcome was recorded sickness absences in 1998. RESULTS: In men, the death or serious illness of a family member, violence, and financial difficulties increased the risk of later sickness absence. According to structural equation modeling, violence and financial difficulties also induced psychological problems such as anxiety, mental distress, and lowered sense of coherence. Psychological problems were associated with heightened cigarette and alcohol consumption, which in turn increased sickness absence. A corresponding structural model did not fit the data in relation to death or serious illness of a family member. In women, life events were associated with psychological problems and smoking but not sickness absence. CONCLUSIONS: Longitudinal evidence suggests that increased psychological problems and behaviors involving risk to health partially mediate the effect of stressful life events on health, as indicated by sickness absence. This model received support among men and for the event categories of violence and financial difficulties. Women were less affected by stressful life events than men.     

Significance of extrapancreatic findings in computed tomography (CT) of acute pancreatitis

Computed tomography (CT) has proven reliable in the early detection of acute haemorrhagic pancreatitis. In the present study the extrapancreatic changes at CT were studied in 60 patients with acute pancreatitis. The CT findings were correlated to the early "prognostic signs" by Ranson and the clinical course of the disease. All the patients with minor extrapancreatic changes recovered without complications. When moderate to severe extrapancreatic changes were seen the incidence of haemorrhagic pancreatitis and the risk of development of pseudocyst or abscess was high. In these patients a dynamic contrast enhanced CT should be done in order to select the patients with haemorrhagic pancreatitis.     

Parent Support Programmes for Families Who are Immigrants: A Scoping Review

Journal of Immigrant and Minority Health - Parental support is of paramount importance in the promotion of positive parenting, strengthening parenthood and protecting children from disadvantages...     

Alcohol reduces prefrontal cortical excitability in humans: a combined TMS and EEG study.

The effects of alcohol (0.8 g/kg) on the prefrontal cortex were studied in nine healthy subjects using the technique of transcranial magnetic stimulation (TMS) combined with electroencephalography (EEG). A total of 120 magnetic pulses were delivered with a figure-of-eight coil to the left prefrontal cortex at the rate of 0.4-0.7 Hz. The EEG was recorded simultaneously with 60 scalp electrodes (41 electrodes were used for analysis); the TMS-evoked activation was estimated by the area under the global mean field amplitude (GMFA) time curve. TMS caused changes in EEG activity lasting up to 270 ms poststimulus. Alcohol decreased GMFA at 30-270 ms poststimulus (713+/-303 vs 478+/-142 microV ms; p=0.007). Alcohol-induced differences were most pronounced at anterior electrodes. These results suggest that alcohol reduces the excitability in the prefrontal cortex.     

Synchronous primary carcinomas of the ampulla of vater and ascending colon in a patient with multiple flat adenomas

Multiple primary cancers occurring in the same patients have been reported to represent 1.8–3.9% of all cancers. The majority of all patients reported to have had a combination of simultaneous neoplastic changes in the ampulla of Vater and the colon showed familial adenomatous polyposis (FAP) syndrome. Variants of familial adenomatous polyposis coli are: attenuated adenomatous polyposis coli (AAPC, previously also known as flat adenoma syndrome) and multiple adenoma coli. AAPC is characterized clinically by many, but usually fewer than 100, colonic lesions that are characteristically slightly elevated and plaque-like, with a reddish surface and sometimes central depression. Genetically it represents an extremely rare variant of FAP. Another group of individuals, so-called multiple adenoma patients, have a phenotype similar to AAPC, but most have no demonstrable germ-line adenomatous polyposis coli mutation, as do patients with FAP or AAPC. However, there have been only a few reports that discussed concurrent neoplastic changes in the ampulla of Vater and colon in patients with multiple colonic flat adenomas, but without the florid phenotype of classical FAP. We present rare clinical course of a patient with multiple (more than 60) flat adenomas in the proximal colon and two primary cancers: of the ampulla of Vater and of the ascending colon. This patient and his family history did not show polyposis compatible with FAP or hereditary nonpolyposis colorectal cancer (HNPCC) syndrome.     

Inefficient central nervous system delivery limits the use of ibuprofen in neurodegenerative diseases.

Chronic use of non-steroidal anti-inflammatory drugs may reduce the risk or delay the onset of Alzheimer's disease. To date, only limited information exists on the brain distribution of these drugs. The objective of this study was to determine the absolute brain delivery of ibuprofen by using constant in vivo infusion in rats. Ibuprofen was infused to steady-state concentrations both in plasma and brain tissue. Ibuprofen levels in plasma and brain tissue were measured by RP-HPLC after the plasma and the brain samples were purified by protein precipitation and solid phase extraction, respectively. Results indicate that both plasma and brain concentrations reached steady-state within 6h, and that the brain to plasma ratio of ibuprofen was only 0.02. Thus, limited brain penetration prevents the possible use of ibuprofen in treating or preventing neurodegenerative disorders such as Alzheimer's disease.