Leg raise increases pressure in lower and upper esophageal sphincter among patients with gastroesophageal reflux disease.

The purpose of this study was to determine the relation between posturally increased intra-abdominal pressure and lower/upper esophageal sphincter pressure changes in patients with gastroesophageal reflux disease. We used high resolution manometry to measure pressure changes in lower and upper esophageal sphincter during bilateral leg rise. We also examined whether the rate of lower and upper esophageal sphincter pressure would increase during leg raise differentially in individuals with versus without normal resting pressure. Fifty eight patients with gastroesophageal reflux disease participated in the study. High resolution manometry was performed in relaxed supine position, then lower and upper esophageal sphincter pressure was measured. Finally, the subjects were instructed to keep their legs lifted while performing 90-degree flexion at the hips and knees and the pressure was measured again. Paired t-test and independent samples t-test were used. There was a significant increase in both lower (P < 0.001) and upper esophageal sphincter pressure (P = 0.034) during leg raise compared to the initial resting position. Individuals with initially higher pressure in lower esophageal sphincter (>10 mmHg) exhibited a greater pressure increase during leg raise than those with initially lower pressure (pressure ≤10 mmHg; P = 0.002). Similarly individuals with higher resting upper esophageal sphincter pressure (>44 mmHg) showed a greater pressure increase during leg raise than those with lower resting pressure (≤44 mmHg; P < 0.001). The results illustrate the influence of postural leg activities on intraesophageal pressure in patients with gastroesophageal reflux disease, indicating by means of high resolution manometry that diaphragmatic postural and sphincter function are likely interrelated in this population.

Real-space path integration is impaired in Alzheimer's disease and mild cognitive impairment.

INTRODUCTION: Path integration (PI) is an important component of spatial navigation that integrates self-motion cues to allow the subject to return to a starting point. PI depends on the structures affected early in the course of Alzheimer's disease (AD) such as the medial temporal lobe and the parietal cortex. OBJECTIVES: To assess whether PI is impaired in patients with mild AD and amnestic mild cognitive impairment (aMCI) and to investigate the role of the hippocampus, entorhinal and inferior parietal cortex in this association. METHODS: 27 patients with aMCI, 14 with mild AD and 18 controls completed eight trials of Arena Path Integration Task. The task required subjects with a mask covering their eyes to follow an enclosed triangle pathway through two previously seen places: start-place1-place2-start. Brains were scanned at 1.5T MRI and respective volumes and thicknesses were derived using FreeSurfer algorithm. RESULTS: Controlling for age, education, gender and Mini-Mental State Examination score the aMCI and AD subjects were impaired in PI accuracy on the pathway endpoint (p=0.042 and p=0.013) compared to controls. Hippocampal volume and thickness of entorhinal and parietal cortices explained separately 36-45% of the differences in PI accuracy between controls and aMCI and 28-31% of the differences between controls and AD subjects. CONCLUSIONS: PI is affected in aMCI and AD, possibly as a function of neurodegeneration in the medial temporal lobe structures and the parietal cortex. PI assessment (as a part of spatial navigation testing) may be useful for identification of patients with incipient AD.

Effect of donepezil in Alzheimer disease can be measured by a computerized human analog of the Morris water maze.

BACKGROUND: Drug development for Alzheimer disease (AD) is challenged by the success in animal models tested in the Morris water maze (MWM) and the subsequent failures to meet primary outcome measures in phase II or III clinical trials in patients. The human variant of MWM (hMWM) enables us to examine allocentric and egocentric navigation as in the MWM. OBJECTIVE: It was the aim of this study to examine the utility of a computerized hMWM to assess the effects of donepezil in mild AD. METHODS: Donepezil 5 mg/day was started after initial hMWM testing in the treated group (n = 12), and after 28 days, the dose was increased to 10 mg/day. The performance after 3 months was compared to that of a non-treated group (n = 12). RESULTS: Donepezil stabilized or improved the spatial navigation performance after 3 months, especially in the allocentric delayed recall subtask (p = 0.014). CONCLUSIONS: The computerized hMWM has the potential to measure the effects of donepezil in mild AD. It is a sensitive cognitive outcome measure in AD clinical trials.

Treatment of coronary bifurcation lesions: stent-covering of the side branch with and without PCI of the side branch: a retrospective analysis of all consecutive patients.

BACKGROUND: Treatment of coronary bifurcation lesions is a complex problem. METHODS: This retrospective single-center study included all consecutive patients with PCI of coronary bifurcations with stent covering of the side branch (SB) between January 2008 - August 2011. RESULTS: Our study group (n = 98) was group A (n = 64, 65.3%) and group B (n = 34, 34.7%). Mean follow-up was 14.1 (group A) vs 12.3 (group B, p = ns) months. CONCLUSION: In patients with coronary bifurcations a simpler strategy has a significantly lower MACE. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01538186.

Midlife dietary patterns and mortality in the population-based study of Swedish twins.

BACKGROUND: We examined midlife dietary patterns in relation to (1) sociodemographic and health-related characteristics and (2) survival. METHODS: A two-step cluster analysis of a 12-item food questionnaire was used to derive dietary patterns in a cohort of 16 649 members of the Swedish Twin Registry, a prospective, population-based study of twins. The average age at baseline (1967) was 55.5 years; the follow-up for all-cause mortality extended until 2011 (26.8±12.35 years or 345,127 person-years) via death records. RESULTS: Four dietary patterns (classes) distinguishable by demographic and health characteristics emerged: Moderate Intake and Starch Diet (Class 1), Moderate Intake Diet with Low Flour-Based Foods (Class 2), Meat and Starch Diet (Class 3) and Low Meat Intake Diet (Class 4). Membership in Class 3 was associated with 7% increased risk of mortality compared with Class 2 independent of baseline age, cohort, sex and body mass index. These results were mostly explained by sociodemographic and lifestyle factors. When follow-up was restricted to those in the study for 20+ years, both Classes 1 and 3 conferred increased risk of mortality compared with Class 2, independent of covariates. Analyses conducted within twin pairs revealed similar results. CONCLUSIONS: Midlife diet over-represented by meat and starch-based foods may increase the risk of mortality, whereas the diet low in starch may be beneficial. These results appear to be independent of factors shared by twins, as well as at least partially a function of social and lifestyle factors, particularly marital status and smoking.

From Morris Water Maze to computer tests in the prediction of Alzheimer's disease.

BACKGROUND: Spatial navigation performance in the Hidden Goal Task (HGT), a real-space human analogue of the Morris Water Maze, can identify amnestic mild cognitive impairment (aMCI) patients with memory impairment of the hippocampal type, a known indicator of incipient Alzheimer's disease (AD). OBJECTIVE: Contrast results from computer versus real-space versions of the HGT. METHODS: A total of 42 aMCI patients were clinically and neuropsychologically classified into: (1) memory impairment of the hippocampal type--the hippocampal aMCI (HaMCI; n = 10) and (2) isolated retrieval impairment--the nonhippocampal aMCI (NHaMCI; n = 32). Results were compared to the control (n = 28) and AD (n = 21) groups. RESULTS: The HaMCI group, although similar to the NHaMCI group with respect to overall cognitive impairment, performed poorer on the computer version of the HGT and yielded parallel results to the real-space version. The two versions were strongly correlated. CONCLUSIONS: Both versions of the HGT can reliably identify aMCI with pronounced memory impairment of the hippocampal type. The computer version of the HGT may be a useful, relatively inexpensive screening tool for early detection of individuals at a high risk of AD.

Etiology of acute gastroenteritis in children requiring hospitalization in the Netherlands.

Infectious gastroenteritis causes a considerable burden of disease worldwide. Costs due to gastroenteritis are dominated by the hospitalized cases. Effective control of gastroenteritis should be targeted at the diseases with the highest burden and costs. For that, an accurate understanding of the relative importance of the different bacterial, viral, and parasitic pathogens is needed. The objective of the present study was to determine the incidence and etiology of gastroenteritis requiring hospital admission in the Netherlands. Six hospitals enrolled patients admitted with gastroenteritis for approximately one year over the period May 2008 to November 2009. Participants provided questionnaires and a fecal sample, and the hospital filled out a clinical questionnaire. In total, 143 children hospitalized for gastroenteritis and 64 matched controls were included in the study. Overall incidence of gastroenteritis requiring hospitalization was estimated at 2.92 per 1,000 children aged 0-17 years per year, with the highest incidence in children under the age of 5 years. The full diagnostic panel of pathogens could be studied in fecal samples of 96 cases. One or more pathogens were found in 98% of these cases. Co-infections were observed relatively often (40%). Viruses were detected in 82% of the samples, with rotavirus being most common (56%), bacteria in 32% and parasites in 10%. The present study emphasizes the importance of viral pathogens, especially rotavirus, in hospitalizations of children with gastroenteritis. Policies to reduce (costs of) hospitalizations due to gastroenteritis should therefore be first targeted at rotavirus.

Human analogue of the morris water maze for testing subjects at risk of Alzheimer's disease.

BACKGROUND: Patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (MCI) have difficulties with spatial orientation. OBJECTIVE: To test hypothesis that spatial navigation is impaired early in MCI patients representing the presymptomatic stage of AD. METHODS: We tested patients with probable AD (n = 21), MCI, further classified according to Petersen's criteria as amnestic MCI (aMCI) single domain (n = 11), aMCI multiple domain (n = 31), or nonamnestic MCI (n = 7). The aMCI group was also stratified using cued recall according to Dubois' criteria into memory impairment of the hippocampal type (n = 10) and isolated memory retrieval impairment-nonhippocampal (n = 32) and also according to ApoE4 status into E4+ (n = 12) and E4- (n = 30). These patients and controls (n = 28) were tested in the human variant of the Morris water maze. Depending on the subtest, the subjects could use the egocentric or allocentric (hippocampus-dependent) navigation. RESULTS: The AD and aMCI multiple domain groups were impaired in all subtests. The aMCI single domain group was impaired in allocentric subtests. The hippocampal MCI group performed poorer than the nonhippocampal MCI group and similarly to the AD group. The ApoE4+ group was as bad as the AD group when compared with the E4- group. CONCLUSION: aMCI subjects represent a very heterogeneous population, and spatial memory or cued recall examination can add more value to aMCI classification. ApoE4+ patients are more impaired than ApoE4- patients.

Influence of water quality on cholesterol induced systemic pathology.

Reduced systemic pathology was identified in cholesterol-fed rabbits administered distilled water compared to animals drinking local tap water; this included pathology of the liver and spleen. Studies directed at determining the effect of the trace metals aluminum, copper and zinc on cholesterol-induced systemic pathology were undertaken. As previously reported copper added to distilled drinking water (0.12 PPM) increased Alzheimer-like pathology in the brain, but did not augment pathology of the spleen or liver. Aluminum added to distilled water (0.36 PPM) administered to drink exacerbated cholesterol-induced hepatic pathology but not splenic pathology, and addition of 0.36 PPM zinc to the distilled drinking water failed to affect pathology of either the liver or spleen. The overall increase in both central and systemic pathology observed among cholesterol-fed rabbits administered tap water seems to be due to different trace metal contaminants occurring in tap water.

[Non-respiratory cyanosis in the newborn]. / Niet-respiratoire cyanose bij de pasgeborene.

Four term babies, three boys and one girl, became cyanotic shortly after birth. In two cases the cause was maternal use of drugs: methemoglobinaemia due to use of a chromate and depression of the nervous system due to clomipramine. They recovered. A third child suffered cerebral infarction and was left with decreased left-arm function. The fourth child had a hypoplastic left heart and died. Central cyanosis in a newborn should be cause for concern. A thorough case history should be taken and extensive physical examination carried out. In case of doubt additional diagnostic tests should be performed.

[Mycobacterium haemophilum as the cause of lymphadenitis in the neck in an otherwise healthy boy]. / Mycobacterium haemophilum als veroorzaker van lymphadenitis colli bij een niet-zieke jongen.

In an 8.5-year-old boy with severe recurring unilateral swelling of the neck, infection with Mycobacterium haemophilum was established. In addition to the more usual causative agents, cervical lymphadenopathy in children can, in rare cases, be caused by M. haemophilum. The skin tests did not differentiate between Mycobacterium avium and Mycobacterium tuberculosis infection. There was no evidence of specific immune deficiencies. The swelling did not respond to treatment with four tuberculostatic drugs (rifampicin, isoniazid, pyrazinamide and ethambutole), nor to repeated surgical excision. Finally, M. haemophilum grew on the culture despite sub-optimal culture conditions. Thereupon the patient was treated with co-trimoxazole and recovered in two weeks. This is the first patient with cervical lymphadenopathy caused by M. haemophilum to be described in the Netherlands. M. haemophilum grows on an iron-rich medium at a relatively low temperature (30-32 degrees C). In cases of cervical lymphadenopathy, it is advisable to consider M. haemophilum as a cause and to adjust the culture conditions accordingly.

Atypical progeroid syndrome: an unknown helicase gene defect?

We describe a boy with chromosomal breakage syndrome, who died of hepatocellular carcinoma at the age of 17 years. Other findings included growth retardation, bilateral cataracts, premature graying of hair and elevated levels of urinary hyaluronic acid. Intellectual functions were normal. Although some manifestations were suggestive of Werner syndrome, the diagnosis could not be confirmed by molecular investigations. Therefore, this patient probably represents a provisionally unique syndrome, perhaps due to a mutation in a related (helicase) gene.

Deficits in controlled processing may predict dementia: a twin study.

This study tested for differential patterns of cognitive decline in 33 twin pairs for which both were nondemented, but 1 member of the pair went on to develop dementia. Compared with their nondemented twin partners, twins who later developed dementia already showed poorer performance on tests of memory and attention, visuospatial-reasoning skills, and perceptual speed and the Mini-Mental State Examination (MMSE). The authors suggest that this cluster of tests reflects deficits in controlled rather than automatic cognitive processes. Nondemented twin partners of the twins who became demented were also compared with 33 matched controls selected from pairs in which both members remained nondemented. Nondemented twin partners scored lower than matched controls on tests of verbal ability, memory and attention, and perceptual speed and the MMSE. This finding indicates that nondemented twin partners of demented twins are at elevated risk themselves for becoming demented, and further suggests that certain areas of cognition are compromised prior to diagnosis of dementia.

Interleukin-12 has a role in mediating resistance of murine strains to Tyzzer's disease.

Clostridium piliforme induces enterohepatic disease in many domestic and laboratory animal species. Susceptibility to infection is known to vary with the immune status and strain of the host, but little is known about specific immune mechanisms that regulate this disease. To evaluate host control of C. piliforme infection, we examined the role of interleukin-12 (IL-12) both in the control of and in the response to murine C. piliforme infection. For this study, 3-week-old C. piliforme-resistant C57BL/6 or -susceptible DBA/2 mice were infected intravenously with either the toxic H1 or the nontoxic M1 C. piliforme isolate. Serum and liver samples were collected prior to C. piliforme inoculation (day 0) and at days 1, 3, 7, 14, and 28 postinoculation. Evaluation of hepatic IL-12 p40 mRNA expression by reverse transcription-PCR and of total-IL-12 protein levels in serum by enzyme-linked immunosorbent assay revealed that C. piliforme induced elevations in both hepatic p40 mRNA and serum total-IL-12 levels at all times postinoculation. Elevations were similar with both toxic and nontoxic C. piliforme isolates. Levels of total IL-12 in serum were significantly (P < 0.05) higher in C57BL/6 mice than in DBA/2 mice. Additional experiments were performed in which polyclonal antibody treatment was used to neutralize IL-12 in mice of both strains prior to intravenous inoculation with toxic C. piliforme H1. IL-12 neutralization increased the severity of Tyzzer's disease at day 3 postinoculation in both mouse strains, but the degree of increase was greater in C57BL/6 mice than in DBA/2 mice.

Effects of neutrophil, natural killer cell, and macrophage depletion on murine Clostridium piliforme infection.

Clostridium piliforme infection (Tyzzer's disease) induces enterohepatic disease in many domestic and laboratory animals. Murine susceptibility to Tyzzer's disease varies with host strain, age, and immune status However, little is known about the role of the immune system in control of this disease. To investigate the role of host immunity in Tyzzer's disease, mice were depleted of either neutrophils, natural killer cells, or macrophages by antibody administration or chemotherapy. After depletion, DBA/2 mice, which are naturally susceptible to C. piliforme, or naturally resistant C57BL/6 mice were inoculated intravenously with C. piliforme. Animals were euthanized 3 days postinoculation and evaluated for gross and histologic lesions and hepatic bacterial load. In juvenile DBA/2 or C57BL/6 mice, depletion of either neutrophils or natural killer cells increased severity of disease. In adult mice, depletion of natural killer cells significantly increased severity of Tyzzer's disease in the resistant (C57BL/6) but not in the susceptible (DBA/2) strain. Macrophage depletion did not alter the course of infection in either mouse strain. These studies indicate an important role for neutrophils and natural killer cells in the pathogenesis of murine Tyzzer's disease. The role of macrophages in murine C. piliforme infection will require further evaluation.

Lesions of experimental genital Tritrichomonas foetus infections in estrogenized BALB/c mice.

Ninety-seven BALB/c mice were inoculated intravaginally with 8.0 x 10(5) Tritrichomonas foetus organisms, using either isolate ATCC 30003 or field isolate MU Y22 2 days after estrogenization with 15 micrograms 17 beta-estradiol. Reproductive tracts were examined at several time points post-inoculation to determine gross and histologic responses to trichomonad infection as compared to estrogenized, uninfected control animals. The two isolates varied greatly in ability to maintain chronic infection; no ATCC 30003-inoculated animals remained culture-positive beyond 7 weeks post-inoculation, whereas MU Y22-inoculated animals were infected for greater than 26 weeks. Lesions were seen in 40-60% of animals prior to 10 weeks post-inoculation and included moderate uterine dilation and glandular atrophy, uterine gland abscesses, pyometra, intramural perivascular lymphoid infiltrates, and ovarian bursitis. The severity of lesions was independent of the T. foetus isolate. Lesions became more severe at 10 weeks post-inoculation, and at 10 and 26 weeks post-inoculation, lesions were seen in 60% and 75% of animals, respectively. In addition to lesions described above, epithelial changes were marked at these late necropsies, including ulceration, flattening, hypertrophy, and squamous metaplasia. The lesions seen in these mice closely resemble those described in natural bovine infection, suggesting that the estrogenized BALB/c mouse is an excellent model for study of bovine trichomoniasis.

Cerebrospinal larva migrans due to Baylisascaris procyonis in a guinea pig colony.

Four guinea pigs from a colony of approximately 50 animals were examined for progressive neurologic disease of 5 days' duration. Signs of neurologic dysfunction included cachexia, stupor, hyperexcitability, lateral recumbency, and opisthotonos. Results of gross pathologic, microbiologic, and serologic examinations were unremarkable. Histologic examination of cerebral and cerebellar sections revealed multifocal malacia and regions of eosinophilic granulomatous inflammation. Cross-sections of nematode larvae, identified as Baylisascaris sp., most likely B. procyonis, the raccoon ascarid, were seen in the brain of some affected animals. An intact Baylisascaris larva was recovered from a symptomatic animal when cerebral tissue was processed by the Baermann extraction technique. Results of further investigation indicated that wood shavings used for the guinea pigs had been contaminated by raccoon feces, some of which contained numerous B. procyonis eggs. The bedding source for this colony was changed and, to date, no new cases of neurologic disease have been seen. This report emphasizes the potential insidious entrance of B. procyonis into well-managed laboratory animal facilities.