Pronounced bronchial hyper-responsiveness and asthma severity

Summary. Fifty-six asthmatics from an asthma ward or from an asthma out-patient clinic were challenged with two low concentrations (0–03 and 0–012 mg) of metacholine chloride in order to assess the relationship between pronounced hyper-responsiveness and asthma severity in a clinical setting. Only inhaled bronchodilators were stopped before challenge. Asthma severity was assessed retrospectively and prospectively on the basis of treatment, number of days in hospital, intensive care, number of emergency visits and days on sick-leave. The results show that pronounced hyper-responsiveness (n= 28) is not associated with asthma severity. It is concluded that a single simplified test of pronounced bronchial hyper-responsiveness, performed without taking into consideration the actual state of the disease and without stopping all medication, is of no help in identifying the patients with the clinically most severe asthma and worst prognosis.,     

Long-term benefit to pallidal deep brain stimulation in a case of dystonia secondary to pantothenate kinase-associated neurodegeneration.

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive disorder with onset in childhood and rapid progression. There is no causative and insufficient symptomatic drug therapy. Deep brain stimulation (DBS) of the internal pallidum (GPi) has been reported to improve motor function. Most case reports, however, are limited to short observational periods. The impact of DBS on the progression and life expectancy in PKAN is unknown. We present a 5-year outcome and video documentation of bilateral GPi-DBS of an adolescent patient suffering from genetically defined PKAN.     

Felodipine or Hydrochlorothiazide/Triamterene for Treatment of Hypertension in the Elderly: Effects on Blood Pressure, Hypertensive Heart Disease, Metabolic and Hormonal Parameters

Trenkwalder P, Plaschke M, Aulehner R, Lydtin H. Felodipine or Hydrochlorothiazide/Triamterene for Treatment of' Hypertension in the Elderly: Effects on Blood Pressure, Hypertensive Heart Disease, Metabolic and Hormonal Parameters.

The aim of the study was to compare the antihypertensive efficacy of either felodipine or the diuretic combination hydrochlorothiazide/triamterene in a group (n = 65) of elderly (≥70 years) hypertensives (office blood pressure ≥ 60/95 mmHg) with special regard to ambulatory blood pressure monitoring, hypertensive heart disease and metabolic parameters. This was a randomized, double-blind study with a treatment period of 6 months. Reduction of office and 24-hr ambulatory blood pressure was comparable with both treatment regimens; after 6 months, 18 of 29 patients in the felodipine group (62%) and 20 of 27 patients in the diuretic group (74%; p = 0.4) were controlled. While episodes of ischemic type ST-segment depression were significantly reduced in the felodipine group (from 49 to 9 episodes), there was no significant change in the diuretic group (from 24 to 21 episodes). Both regimens decreased left ventricular wall thickness, but the decline in left ventricular muscle mass index was significant only for felodipine. Felodipine did not induce any change in metabolic or hormonal parameters; the diuretic combination significantly increased serum creatinine, uric acid, plasma renin activity, and plasma prorenin. Thus, the antihypertensive efficacy of felodipine and the diuretic combination was comparable in elderly hypertensives; only felodipine, however, improved parameters of hypertensive heart diesease and showed a neutral metabolic and hormonal profile.     

In vivo monitoring of age-related changes in rat brain using quantitative diffusion magnetic resonance imaging and magnetic resonance relaxometry

Ghrelin is a novel peptide that stimulates the release of growth hormone from the pituitary and is involved in hypothalamic feeding regulation. A pre-embedding immunostaining technique was used to study the ultrastructure and synaptic relationships of ghrelin-containing neurons in the rat arcuate nucleus (ARC). Ghrelin-like immunoreactive (ghrelin-LI) neurons were found in the ARC, and were especially abundant in its ventral part. At the electron microscopic level, ghrelin-LI neurons received afferent synapses from many unknown axon terminals. Ghrelin-LI products in the immunoreactive cell bodies, processes, and axon terminals were detected mainly in dense granular vesicles about 110 nm in diameter. Ghrelin-LI presynaptic axon terminals often made synapses with unknown immunonegative neurons. These results suggest that ghrelin acts to regulate food intake through synaptic connections in hypothalamic neuronal networks.     

Chromosome aberrations in B-cell chronic lymphocytic leukemia: reassessment based on molecular cytogenetic analysis

In B-cell chronic lymphocytic leukemia (B-CLL) clonal chromosome aberrations are detected in approximately 40–50% of tumors when using conventional chromosome banding analysis. Most studies find trisomy 12 to be the most frequent chromosome aberration, followed by structural aberrations of the long arm of chromosomes 13 and 14. Trisomy 12 and the ”14q+” marker are associated with shorter survival times, while the patients with 13q abnormalities have a favorable outcome, similar to those with a normal karyotype. The development of molecular cytogenetic techniques has greatly improved our ability to detect chromosome aberrations in tumor cells. Using fluorescence in situ hybridization, chromosome aberrations can be detected not only in dividing cells but also in interphase nuclei, an approach referred to as interphase cytogenetics. The prevalence of specific aberrations in B-CLL is currently being reassessed by interphase cytogenetics. By far the most frequent abnormality are deletions involving chromosome band 13q14, followed by deletions of the genomic region 11q22.3-q23.1, trisomy 12, deletions of 6q21-q23, and deletions/mutations of the TP53 tumor suppressor gene at 17p13. The evaluation of the true incidence of these aberrations now provides the basis for more accurate correlations with clinical characteristics and outcome. Deletions/mutations of the TP53 gene have been shown to be associated with resistance to treatment and to be an independent marker for poor survival. 11q deletions have been associated with extensive nodal involvement, rapid disease progression, and short survival times. Whether trisomy 12, 13q14, and 6q deletions have a prognostic impact awaits further study. The application of these molecular cytogenetic techniques will also contribute to the identification of the pathogenetically relevant genes that are affected by the chromosome aberrations in B-CLL. Received: 2 February 1998 / Accepted: 31 March 1998     

Ten novel MSH2 and MLH1 germline mutations in families with HNPCC

Hereditary nonpolyposis colorectal cancer (HNPCC) is one of the most common hereditary cancer-susceptibility syndromes. Germline mutations in mismatch repair genes are associated with the clinical phenotype of HNPCC. We report ten novel germline mutations, three in MSH2 and seven in MLH1. All but one mutation have been found in families fulfilling criteria of the Bethesda guidelines; four of them additionally fulfilled the Amsterdam criteria I or II. Eight mutations were considered pathogenic and predictive diagnostics in healthy family members at risk shall be undertaken; these include five frameshift mutations leading to premature stop codons, in MSH2: c.1672delT (p.S558Xfs) and c.2466_2467delTG (p.C822X) and in MLH1: c.1023delG (p.R341Xfs), c.1127_1128dupAT (p.K377Xfs) and c.1310delC (p.P437Xfs); three mutations leading to splice aberrations, in MSH2: c.1661G>C (r.1511_1661del) and in MLH1: c.677+3A>C (r.589_677del) and c.1990-2A>G predicted to result in a splice site defect. The remaining two mutations are unclassified variants with assumed pathogenicity: one missense mutation in the highly conserved ATPase domain of MLH1 (c.122A>G [p.D41G]) and one in-frame insertion of twelve nucleotides in MLH1 (c.2155_2156insATGTGTTCCACA [p.I719delinsNVFHI]). These two mutations were not found in 102 alleles of healthy control individuals. The corresponding tumors from all patients showed a high level of microsatellite instability (MSI-H). Immunohistochemistry (IHC) revealed complete loss of expression of the affected protein in the tumor cells from all but three patients. The tumors from the patients with the mutations c.1127_1128dupAT and c.1990-2A>G showed a reduction of expression of the MLH1-protein, rather than complete loss. In the tumor from the patient with the missense mutation c.122A>G [p.D41G] a normal expression of the proteins coded by MLH1 and MSH2 was noticed.     

The relationship between indicators of building dampness and respiratory health in young Swedish adults

Several epidemiological studies have indicated that building dampness affects the respiratory health of the inhabitants. In this study we investigated the relationship between building dampness and respiratory symptoms in young Swedish adults. In 1993, as a part of the European Community Respiratory Health Survey stage II, subjects were invited to participate in a detailed interview-led questionnaire, spirometry, methacholine challenge and measurement of total and specific IgE. A total of 1853 of the 2084 selected subjects participated in this study (88.9%). One hundred and thirty-six (7.4%) subjects reported water damage in their homes in the last year and 318 (17.3%) subjects reported visible molds during the same period. Seventy-four (4%) subjects reported both water damage and visible molds in the last year. This subgroup, with 74 subjects had significantly more attacks of breathlessness both when resting (OR 3.2 (95% CI 1.4-7.2)) and after effort (OR 2.7 (95% CI 1.3-5.6)) compared to subjects reporting no water damage or molds. Long-term cough was also more common in this group (OR 2.2 (95% CI 1.2-4.0)). This study adds evidence to a relationship between damp buildings and respiratory symptoms.     

Diversification of Clonal Complex 5 Methicillin-Resistant Staphylococcus aureus Strains (Rhine-Hesse Clone) within Germany

Since 1995, a methicillin-resistant Staphylococcus aureus (MRSA) clone has spread in southern Germany. The strain was assigned to the Rhine-Hesse pulsed-field gel electrophoresis (PFGE) type by the staphylococcal reference center and was highly similar to epidemic clones known to belong to clonal complex 5 (CC5; USA100) based on multilocus sequence typing (MLST). Here we analyzed a defined collection of strains assigned to the Rhine-Hesse/USA100 PFGE type. Using sequence-based typing methods (MLST, spa), the isolates were divided into two distinct clusters, ST5 and its single-locus variant ST225. These two lineages are not distinguishable by PFGE or phage typing. Most of the ST5 isolates were derived from patients and volunteers from the Tübingen area in southwest Germany, whereas the ST225 isolates were mostly from other locations in Germany. The locally restricted ST5 isolates were shown to contain different SSCmec islands and exhibited different antibiotic resistance profiles. In contrast, the ST225 isolates form a highly homogenous group and are emerging all over Germany. The two lineages are clearly distinguishable by their phage content and spa type: ST5 strains from Tübingen are characterized by a Sa7int phage that carries the virulence gene sak, which codes for staphylokinase, and ST225 isolates are characterized by a Sa1int phage. In conclusion, based on sequence typing and phage content, CC5 strains can be subdivided into two distinct lineages with different epidemicities.