Molecular evidence for Mycobacterium avium subspecies paratuberculosis (MAP) in Crohn's disease correlates with enhanced TNF-alpha secretion.

BACKGROUND: Support for a role of Mycobacterium avium subspecies paratuberculosis in Crohn's disease is largely based on epidemiological evidence, as no data on mechanisms linking the presence of M. avium subspecies paratuberculosis with gut damage is available. AIMS: To determine whether the presence of M. avium subspecies paratuberculosis contributes to the pathogenesis of Crohn's disease by promoting cytokine secretion within gut mucosa. PATIENTS AND METHODS: A total of 235 subjects were recruited: 63 with Crohn's disease, 53 with ulcerative colitis, 45 with irritable bowel syndrome and 74 normal controls. M. avium subspecies paratuberculosis status was defined by nested PCR using IS900 sequence. Gut mucosal organ cultures were established to detect cytokine secretion patterns. RESULTS: Significantly higher tumour necrosis factor-alpha concentrations were found in culture supernatants for Crohn's disease compared to ulcerative colitis (p<0.05), irritable bowel syndrome (p<0.01) and controls (p<0.0001). When tumour necrosis factor-alpha levels were correlated with the presence of M. avium subspecies paratuberculosis, significantly greater concentrations were only found in M. avium subspecies paratuberculosis-positive Crohn's disease patients (p<0.05). Tumour necrosis factor-alpha levels in M. avium subspecies paratuberculosis-positive Crohn's disease were significantly higher than in M. avium subspecies paratuberculosis-positive ulcerative colitis (p<0.01), M. avium subspecies paratuberculosis-positive irritable bowel syndrome (p<0.05) and M. avium subspecies paratuberculosis-positive controls (p<0.01) and all M. avium subspecies paratuberculosis-negative specimens. CONCLUSIONS: The data link M. avium subspecies paratuberculosis with a pathogenic mechanism in Crohn's disease and is consistent with abnormal macrophage handling of M. avium subspecies paratuberculosis.

Anti-mycobacterial therapy in Crohn's disease heals mucosa with longitudinal scars.

BACKGROUND: A possible causative link between Crohn's disease and Mycobacterium avium ss paratuberculosis has been suggested. AIM: To report unique scarring in Crohn's disease patients treated with anti-Mycobacterium avium ss paratuberculosis therapy. PATIENTS: A retrospective review of 52 patients with severe Crohn's disease was conducted. Thirty-nine patients who had at least one follow-up colonoscopy during treatment were included. METHODS: Patients received rifabutin (up to 600 mg/day), clofazimine (up to 100 mg/day) and clarithromycin (up to 1 g/day) - anti-Mycobacterium avium ss paratuberculosis therapy - for 6 months to 9 years. Ramp-up dosing was used. Colonoscopies and histological analyses monitored progress. RESULTS: Twenty-two patients (56.4%, 22/39) healed with unusual scarring, which appeared as branched, ribbon-like, elevated lines. In 2/6 patients (33.3%) who had > 3 years of treatment after scarring occurred, scars receded, becoming imperceptible as full healing occurred. Histologically, a marked reduction in inflammation occurred in 15/39 patients (38.5%). Of these, 6/15 patients (40%) displayed restoration of normal mucosa. Longitudinal scarring occurred in 12/15 patients (80%) with improved histology. CONCLUSIONS: The presence of scarring fading to normal mucosa on anti-MAP therapy implies a more profound healing not seen with standard anti-inflammatory and immunosuppressant drugs. Longitudinal scarring and consequent healing with normal histology should become a standard treatment goal for Crohn's disease.

Efficacy and safety of rifabutin-containing 'rescue therapy' for resistant Helicobacter pylori infection.

BACKGROUND: Current 'rescue' therapies provide inadequate Helicobacter pylori eradication rates because of antibiotic resistance. AIM: To test the efficacy of a modified triple regimen combining rifabutin, pantoprazole and amoxicillin as rescue therapy for patients in whom eradication of H. pylori had failed standard clarithromycin-based triple therapy. METHODS: One hundred and thirty patients (mean age 51.7 +/- 14.8 years) who had failed one or more eradication attempts with omeprazole, clarithromycin and amoxicillin were treated for 12 days with rifabutin 150 mg daily, amoxicillin 1 g or 1.5 g t.d.s, and pantoprazole 80 mg t.d.s. RESULTS: The intention-to-treat and per-protocol eradication rates were 90.8/90.8%. Metronidazole or/and clarithromycin resistance had no significant impact on H. pylori eradication rates. A higher overall eradication rate of 96.6% (95% CI: 92.1-101%) was obtained in patients treated with a regimen containing 1.5 g amoxicillin t.d.s compared with 90.7% (95% CI: 82-98.6%) using a regimen with 1 g amoxicillin t.d.s but the difference was not significant. Side-effects reported in 40% of patients were mild. CONCLUSION: A 12-day course of low dose of rifabutin with an increased dose of amoxicillin and pantoprazole is well-tolerated and highly effective against dual-resistant H. pylori infection after failure of triple therapy.

T-cell-receptor repertoire in chronic plaque-stage psoriasis is restricted and lacks enrichment of superantigen-associated V beta regions.

Preferential usage of certain T-cell receptors by the lymphocytic infiltrate in psoriasis might indicate the involvement of an antigen in the pathogenesis of this disease. However, to date there are no data on the complete T-cell-receptor V alpha and V beta repertoire in psoriatic patients. We therefore compared the usage of T-cell-receptor variable regions in blood and skin of 10 patients with chronic plaque-stage psoriasis by means of semiquantitative polymerase chain reaction. Additionally, HLA class II alleles were analyzed by means of sequence-specific oligonucleotide typing. A considerable restriction of the T-cell-receptor repertoire was observed in the skin, where up to 20% of the variable regions present in the blood were not detectable. This was true for both alpha- and beta-chains. However, no interindividually constant pattern of T-cell-receptor restriction was deducible. Inconsistently, a certain preferential usage of some beta chains occurred within the cutaneous compartment. This report on the complete T-cell-receptor V alpha and V beta repertoire in psoriasis documents the restricted receptor repertoire of infiltrating T cells and a lack of enrichment of superantigen-associated V beta regions. Thus superantigens seem not to play a pathogenetically relevant role in chronic plaque-stage psoriasis.

Expression of catalytically active radish 3-hydroxy-3-methylglutaryl coenzyme A reductase in Escherichia coli.

Two fragments of a cDNA encoding radish 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) were cloned into the vector pET-8c and expressed in Escherichia coli. The large fragment, encoding both the membrane and the cytosolic domains, was expressed at low level, essentially as an insoluble protein without enzymatic activity. In contrast, the fragment encoding only the cytosolic domain was expressed at a high level in a catalytically active form. The amount of soluble active enzyme in cell-free extracts of E. coli dramatically increased when the temperature during the induction was lowered from 37 degrees C to 22 degrees C.

Fish oil (Eicosapen) is less effective than metronidazole, in combination with pantoprazole and clarithromycin, for Helicobacter pylori eradication.

BACKGROUND: In vitro omega-3-fatty acids (Eicosapen) are bacteriostatic to Helicobacter pylori and have a variety of immuno-modulating effects. AIM: To investigate the efficacy and tolerability of eicosapen (E) as an antibiotic-sparing component of a triple H. pylori eradication regimen in non-ulcer dyspepsia patients in a randomized, double-blind trial. METHODS: Non-ulcer dyspepsia patients (n=199), with a normal upper endoscopy and a positive (13)C-urea breath test (UBT) were randomly assigned to either pantoprazole, clarithromycin and metronidazole (PCM) or pantoprazole, clarithromycin and eicosapen (PCE) for 7 days. Four weeks after treatment, H. pylori eradication was determined by UBT. Symptoms were followed up to 16 months. RESULTS: In the intention-to-treat population, PCM eradicated infection in 78% but PCE was successful in only 34% (P < 0.001). Symptomatic improvement occurred in both groups, and was not related to H. pylori eradication. CONCLUSION: Eicosapen is unlikely to be useful in H. pylori eradication regimens.

Clinical trials with the cholinergic drug RS 86 in Alzheimer's disease (AD) and senile dementia of the Alzheimer type (SDAT).

The muscarinic agonist RS 86 was administered to patients with Alzheimer's disease (AD) and senile dementia of the Alzheimer type (SDAT) in a series of controlled clinical trials. Daily doses were up to 3.0 mg orally for a maximum duration of 18 weeks. RS 86 produced typical peripheral cholinergic effects, but appeared to be better tolerated than similar drugs, such as physostigmine and arecoline. Positive clinical changes with regard to cognitive functions, mood, and social behavior were seen in a minority of AD and SDAT patients. Psychometric tests suggested improvement of functions entailing a speed component. RS 86 is a suitable drug for further clinical experiments in AD and SDAT.

Aspects related to mevalonate biosynthesis in plants.

We purified and characterized a membrane-associated enzyme system from radish (Raphanus sativus L.) that is capable of converting acetyl-CoA into 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA). The enzyme system apparently comprises acetoacetyl-CoA thiolase (EC 2.3.1.9) and HMG-CoA synthase (EC 4.1.3.5). Its activity in vitro can be strongly stimulated by FeII. When ferrous ions are applied chelated with ethylenediaminetetraacetate, citrate or adenosine 5-triphosphate (ATP), the stimulation is further increased. Stimulation is due to a higher catalytic efficiency as indicated by an increase in Vmax, whereas the affinity of the enzyme towards acetyl-CoA remains constant (Km = 6 micro M). A considerable portion of HMG-CoA lyase activity is associated with the same membranes. HMG-CoA lyase (EC 4.1.3.4) is also solubilized and partially co-purified. Its activity requires comparatively high concentrations of Mg2+. The conversion of HMG-CoA to mevalonic acid is catalyzed by HMG-CoA reductase (EC 1.1.1.34) that is associated with the same membranes. By cDNA encoding the Arabidopsis HMG-CoA reductase, we isolated a corresponding gene from a cDNA library newly established from etiolated radish seedlings. This full-length cDNA, referred to as lambda cRS3, encodes a polypeptide 583 amino acids with a molecular mass of about 63 kDa. The hydropathy profile suggests the presence of two hydrophobic membrane-spanning domains within the N-terminal 165 amino acids. The carboxy-terminal part, where the catalytic site resides, is highly conserved in all eukaryotic HMG-CoA reductase genes sequenced so far.

[The resources of the social network of single person households during acute illness. Basic data for home care planning in an influenza epidemic]. / Die Tragfähigkeit der sozialen Netze von Einpersonenhaushalten bei akuter Krankheit. Basisdaten zur Spitexplanung bei Grippepandemie.

UNLABELLED: 230 single persons living in the city of Zurich, 60% aged 18-45, 10% 45-65 and 22% older than 64 years; 70% males were subject to an enquiry. The questioned persons mostly live in two-room-apartments, on average for 11 years, they are single for 8.5 years on average. Solely 5.4% have no living relatives but 32% see them only irregularly (same for all age groups) and 4% are not persistently in touch with friends or acquaintances. 36% were needing help in the past because of sickness or accident. They got it from neighbours (38%), friends, acquaintances (36%), family members (17%) and from home care organisations (9%). In case of a heavy wave of influenza only 14% would not help their neighbours, they would help an average of four neighbours but also they would surely not help four neighbours. The answering persons know 23 singles (= 10%) who presumably would not get any help and 20 (= 9%) who would decline help. 90% of the questioned persons believe, that they would get help by family members or friends, even if those live far away, but still 29% expect help from home care organisations, of the questioned over 64 years old even 52%. CONCLUSION: 10-30% of city singles need help in form of home care in case of an acute illness like heavy influenza.

[Epidemiology of dementia and regional health care concepts for dementia patients and relatives]. / Epidemiologie der Demenz und regionale Versorgungskonzepte für Demenzkranke und ihre Angehörigen.

The prevalence of dementia varies according to the definitions used but shows always an exponential increase with age, a doubling by every five years increase from 60-95 years. Due to the aging of the baby boom generation a doubling of dementia prevalence in the next 50 years is to be expected. Alzheimer's disease is the most frequent cause of dementia. Combinations with vascular, Lewybody, frontotemporal and other causes of dementia are much more frequent than first considered. They all give rise to severe dementia despite only mild Alzheimer changes in the brain. However, a therapeutic response may be expected from cholinergic therapy. Since this pharmacotherapy of dementia only leads to a limited delay of 6-10 months in the progression of dementia, combinations with psychosocial measures such as caregiver-education and care-planning are necessary. We therefore need centers of excellence, such as memory clinics or psychogeriatric counselling centers throughout Switzerland.

[Pharmacotherapy and milieu therapy in senile dementia]. / Pharmakotherapie und Milieutherapie der senilen Demenz.

A causal therapy is temporarily effective in one quart and permanently effective in one eighth of patients with senile dementia after precise differential diagnostic evaluation. A careful examination of the different aspects of cognition allows in all cases the recognition of the specific primary cognitive deficits and of the preserved cognitive skills. Communication of this knowledge to the relatives and the professional caregivers allows an adequate adaptation of the human and physical environment to the needs and skills of the demented. This will diminish secondary behaviour changes. The same goal has the specific pharmacotherapy of these symptoms. To minimalize side-effects, psychopharmaca in the aged have to be used less frequently, with lower doses, for shorter periods and with less different substances.

[Headache as a symptom of angina]. / A fejfájás mint anginatünet.

The authors report two cases where headaches was the only manifestation of severe myocardial ischemia. They had high degree coronaria sclerosis which was demonstrated by angiocardiography in one patient and at autopsy in the second patient. These findings suggest that in the mechanism of headache angina rather the pain perception than generalized vasospasm plays an important role.

[The use of adenosine in the diagnosis and treatment of cardiac arrhythmias]. / Adenozin alkalmazása a szívritmuszavarok diagnosztikájában és kezelésében.

The authors investigated the effect of adenosine or ATP on narrow QRS tachycardia in 56 pts, 3 pts with wide QRS tachycardia 9 pts with suspected latent preexcitation and 10 pts with PVC suspected to be ventricular parasystole. After the bolus iv. administration of adenosine or ATP every SVT was stopped related to AV node (44 pts), but in the rest twelve related to atrial origin of SVT only one automatic atrial tachycardia could be stopped. From the 9 patient suspected to have concealed WPW 2 pts had delta wave during the effect of adenosine, and in four pts parasystole was demonstrated among the pts had varying coupling interval PVC. None of the pts who had wide QRS tachycardia was the tachycardia stopped, but in two cases the supraventricular origin--atrial flutter and tachycardia--was discovered. The authors emphasize the favourable effect of adenosine in narrow complex tachycardia and suggest that it can given safely in wide QRS tachycardia of unknown origin either. The diagnostic effect of adenosine can be used in sinus rhythm too if latent preexcitation or ventricular parasystole is suspected.

[Falls as a side effect of drugs]. / Sturz als Nebenwirkung von Medikamenten.

Because of the smaller functional resources, the risk for falls in elderly persons is significantly increased when they take sedative anxiolytics with long half life, antipsychotics, antidepressants and, not so well documented, antihypertensives. Nonpharmacological strategies are, therefore, the treatment of choice for insomnia, depression and agitation in the elderly.

[Health care needs, brain functional ability, social behavior and social attendant circumstances of elderly patients in community and institutionalized geriatric care in the city of Zurich]. / Pflegebedürftigkeit, Hirnleistungs-fähigkeit, Sozialverhalten und soziale Begleitumstände von Alterspatienten in der offenen und institutionalisierten Alterspflege in der Stadt Zürich.

All aged persons being helped by community nursing-services, the house-helper service, the housekeeper service, or living in a home for the aged or in an apartment for seniors in a representative area of the city of Zurich are compared to all patients in nursing-homes of the city. This study included the size of social network measured by the number of different regular visitors, the number of different medications taken daily, the cognitive abilities measured by the Mini Mental Status, the activities of daily living and the social skills rated by the care-givers as well as the intensity of the care given. The groups were similar in age and sex-distribution but the nursing-home patients differed significantly in all other parameters from the others. In contrast, no significant differences could be found between persons receiving care in their homes and those in institutions for the aged.

[Remarks on the drug treatment of demented patients]. / Bemerkungen zur medikamentösen Behandlung Dementer.

Drug holidays are mandatory during longlasting therapy of demented patients with neuroleptics because of slowed drug-metabotisme and high succeptability for sedative side effects. Despite claims to the contrary nootropic drugs are no effective therapy of dementia in every day praxis. Based on the cholinergic hypothesis of Alzheimer's typ dementia and on the results of pilotstudies, cholinergic therapies will probably improve effectively the behavior of some dements on the future.

[Phototherapy of behavioral disorders as a sequela of disordered circadian rhythm in dementia in the elderly--difficulties in practical clinical applications]. / Lichttherapie von Verhaltensstörungen als Folge gestörter zirkadianer Rhythmen bei dementiellen Alterspatienten--Schwierigkeiten der praktisch-klinischen Anwendbarkeit.

The behavioral disturbances of 16 nursing home patients with a history of sundowning behaviour and dementia were treated with light therapy instead of psychopharmacological medication. After the withdrawal of the before established medication a very individual, heterogenous deterioration of the symptoms was noted. A significant improvement of the behaviour was not found by light therapy in any patient. The problems in practical handling and possible consequences of further investigation are discussed.

[Comparative study between the Folstein mini-mental state and the Zurich variant in demented and non-demented patients]. / Vergleichsuntersuchung zwischen dem "Mini-Mental State" nach Folstein und dessen Zürcher Variante bei dementen und nichtdementen Patienten.

The "Mini-Mental State" examination developed by Folstein is a well established psychometric test in the assessment of senile dementia. We applied a modified version, the Zurich variant of the Folstein-MMS. A comparative study with both tests in a total of 53 patients (25 with dementia, 28 without dementia) of the Käferberg nursing home revealed highly correlating scores (r = 0.878, p less than 0.001).

[Movement patterns of demented and non-demented nursing home patients using the Involuntary Movements and Extrapyramidal Scale. Effects of pharmacotherapy]. / Untersuchung des Bewegungsmusters von dementen und nichtdementen Krankenheimpatienten mit der "Involuntary Movements and Extrapyramidal Scale". Effekte der Pharmakotherapie.

We applied the involuntary movements and extrapyramidal scale in 54 patients (41 with dementia, 13 without dementia) of the Käferberg nursing home. Increased severity of parkinsonism was negatively correlated with Mini-Mental State scores (mnestic function r = 0.479, p less than 0.001/spatial function r = -0.617, p less than 0.001) and with activities of daily living scores (r = 0.635, p less than 0.001). Increased severity of parkinsonism and impaired memory are associated with poor performance in activities of daily living.

[Duplication of hospitalizations of nursing home residents from 2007 to 2009--a retrospective analysis]. / Verdoppelung der Hospitalisationen von Pflegeheimpatienten von 2007 bis 2009 - eine retrospektive Analyse.

AIM: To demonstrate why the number of hospitalizations of nursing home residents has doubled although several studies have established that hospitalizations do not diminish their mortality rate. METHODS: Retrospective analysis of medical databasis from 815 patients of the eight nursing homes of Zürich, thereof 180 were hospitalized in 2007, 234 in 2008 and 401 in 2009. The reasons for a hospitalization have been classified in nine categories. RESULTS: The category "fall with fractures" with a proportion of 29% contributes most to the augmentation of hospitalizations, followed by the categories "ambiguous condition" with 24% and "improving quality of life" with 17%. Hospitalizations for the sustained optimization of quality of life explain 62% of the increased hospitalization rate. CONCLUSION: Nursing home residents are not hospitalized to keep them longer alive, but to optimize their quality of life.