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Biomedical subjects

C Witt

Publications and source records attributed to C Witt.

At least 73 records · Page 4Linked to original sources
PubMed2000

Analysis of local strain in aluminium interconnects by energy filtered CBED

Energy filtered convergent beam electron diffraction (CBED) was used to investigate localised strain in aluminium interconnects. The quantitative analysis of the experimental patterns is based on a multi-step evaluation procedure which is the main subject of the present paper. The improvements which were made to the analysis method aim at increasing both the automation and the accuracy. The detection of the higher order Laue zone (HOLZ) line positions is performed by means of the Hough transform. The required sub-pixel resolution can be achieved routinely and the achievable accuracy is only limited by the line width and the amount of noise in the patterns. The determination of the strain state is performed via a refinement algorithm which is based on varying the strain state in the sample coordinate system and simulating the patterns for the individual grains until a best fit with the experiment is obtained. For the simulation we have developed a new correction scheme in which the dynamical effects are treated separately for each individual HOLZ line. The results show that the main source of the observed strains is the difference in thermal expansion coefficients. The strain is substantially reduced underneath a hillock in the interconnect. Asymmetries in the strain distribution around the hillock show that the unidirectional diffusion during electromigration tests causes peak strains in areas next to the hillock which may be possible failure sites.

Journal Article↗
PubMed2000

An analysis of the safety of the single dose, two drug regimens used in programmes to eliminate lymphatic filariasis.

This review of the safety of the co-administration regimens to be used in programmes to eliminate lymphatic filariasis (albendazole + ivermectin or albendazole + diethylcarbamazine [DEC]) is based on 17 studies conducted in Sri Lanka, India, Haiti, Ghana, Tanzania, Kenya, Ecuador, the Philippines, Gabon, Papua New Guinea, and Bangladesh. The total data set comprises 90,635 subject exposures and includes individuals of all ages and both genders. Results are presented for hospital-based studies, laboratory studies, active surveillance of microfilaria-positive and microfilaria-negative individuals, and passive monitoring in both community-based studies and mass treatment programmes of individuals treated with albendazole (n = 1538), ivermectin (9822), DEC (576), albendazole + ivermectin (7470), albendazole + DEC (69,020), or placebo (1144). The most rigorous monitoring, which includes haematological and biochemical laboratory parameters pre- and post-treatment, provides no evidence that consistent changes are induced by any treatment; the majority of abnormalities appear to be sporadic, and the addition of albendazole to either ivermectin or DEC does not increase the frequency of abnormalities. Both DEC and ivermectin show, as expected, an adverse event profile compatible with the destruction of microfilariae. The addition of albendazole to either single-drug treatment regimen does not appear to increase the frequency or intensity of events seen with these microfilaricidal drugs when used alone. Direct observations indicated that the level of adverse events, both frequency and intensity, was correlated with the level of microfilaraemia. In non microfilaraemic individuals, who form 80-90% of the 'at risk' populations to be treated in most national public health programmes to eliminate lymphatic filariasis (LF), the event profile with the compounds alone or in combination does not differ significantly from that of placebo. Data on the use of ivermectin + albendazole in areas either of double infection (onchocerciasis and LF), or of loiais (with or without concurrent LF) are still inadequate and further studies are needed. Additional data are also recommended for populations infected with Brugia malayi, since most data thus far derive from populations infected with Wuchereria bancrofti.

Albendazole↗
PubMed2000

Sleep apnea syndrome in patients with cardiac pacemaker.

BACKGROUND: Heart rhythm disturbances are cardiac side effects in patients with sleep-disordered breathing (SDB), which in itself is considered to be a risk factor for bradycardic rhythm disturbances. OBJECTIVE: We analyzed the prevalence and degree of SDB in patients who received a cardiac pacemaker due to bradycardic rhythm disturbances and investigated the relationship between the severity of an underlying SDB and the type of heart rhythm disturbance. METHODS AND RESULTS: 192 patients (100 males, 92 females, mean age 62.2 +/-12.2 years) were studied using the portable screening device MESAM IV. The respiratory disturbance index (RDI) was calculated visually. The mean RDI in all patients was 9.13+/-11. 09/h, 11.7+/-13.15/h in males and 6.33+/-7.42/h in females. The prevalence ratio of SDB between men and women was 1.7:1, with significant differences in the respective severity (p<0.05). The screening showed a prevalence of SDB (RDI >10/h) of 32.3%. The highest prevalence was found in the group of patients with atrial fibrillation and bradycardia. However, there were no significant differences compared to other types of rhythm disturbances. The RDI in the population studied depended on age and body mass index, but not on the existence or type of rhythm disturbance and not on concomitant diseases. CONCLUSION: The prevalence of SDB in cardiac pacemaker patients is similar to that in patients of comparable age without a pacemaker. A heart rhythm disturbance does not seem to be an independent risk factor for development of SDB. Nevertheless, the differential diagnosis of bradycardic rhythm disturbances in this age group should include a screening for sleep apnea.

Age Distribution↗
PubMed2000

Increased interleukin-10 and macrophage inflammatory protein-1 alpha release from blood monocytes ex vivo during late-phase response to allergen in asthma.

BACKGROUND: We determined the effect of late-phase responses to allergen challenge of mildly allergic asthmatic patients on the expression and release of the cytokines IL-10 and MIP-1alpha from peripheral blood monocytes. METHODS: Sixteen mildly allergic asthmatics were exposed to increasing concentrations of allergen aerosol. Nine demonstrated an early response alone (single responders), while seven had an early followed by a late response (dual responders). Monocytes were isolated from venous blood before and 24 h after allergen challenge, and placed in short-term culture for determination of IL-10 mRNA expression by reverse-transcription polymerase chain reaction and protein release. MIP-1alpha protein release was measured by radioimmunoassay. RESULTS: IL-10 mRNA expression was significantly higher in dual responders than early responders alone, for unstimulated monocytes or for monocytes exposed to lipopolysaccharide or IL-1beta. In addition, the release of IL-10 and MIP-1alpha from monocytes of dual responders was also enhanced. CONCLUSIONS: Circulating monocytes are primed to release more of the cytokines, IL-10 and MIP-1alpha, in dual but not in single responders, at 24 h after allergen. They may contribute to allergen-induced inflammatory responses in the airways.

Adult↗
PubMed1999

I-band titin in cardiac muscle is a three-element molecular spring and is critical for maintaining thin filament structure.

In cardiac muscle, the giant protein titin exists in different length isoforms expressed in the molecule's I-band region. Both isoforms, termed N2-A and N2-B, comprise stretches of Ig-like modules separated by the PEVK domain. Central I-band titin also contains isoform-specific Ig-motifs and nonmodular sequences, notably a longer insertion in N2-B. We investigated the elastic behavior of the I-band isoforms by using single-myofibril mechanics, immunofluorescence microscopy, and immunoelectron microscopy of rabbit cardiac sarcomeres stained with sequence-assigned antibodies. Moreover, we overexpressed constructs from the N2-B region in chick cardiac cells to search for possible structural properties of this cardiac-specific segment. We found that cardiac titin contains three distinct elastic elements: poly-Ig regions, the PEVK domain, and the N2-B sequence insertion, which extends approximately 60 nm at high physiological stretch. Recruitment of all three elements allows cardiac titin to extend fully reversibly at physiological sarcomere lengths, without the need to unfold Ig domains. Overexpressing the entire N2-B region or its NH(2) terminus in cardiac myocytes greatly disrupted thin filament, but not thick filament structure. Our results strongly suggest that the NH(2)-terminal N2-B domains are necessary to stabilize thin filament integrity. N2-B-titin emerges as a unique region critical for both reversible extensibility and structural maintenance of cardiac myofibrils.

Actin Cytoskeleton↗
PubMed1999

Degradation and protein release properties of microspheres prepared from biodegradable poly(lactide-co-glycolide) and ABA triblock copolymers: influence of buffer media on polymer erosion and bovine serum albumin release.

The aim of the present study was to investigate the influence of the chemical insertion of poly(ethylene oxide), PEO, into a poly(lactide-co-glycolide), PLG, backbone on the mechanisms of in vitro degradation and erosion of the polymer. For this purpose microspheres prepared by a modified W/O/W double emulsion technique using ABA triblock copolymers, consisting of PLG A-blocks attached to central PEO B-blocks were compared with microspheres prepared from PLG. Due to their molecular architecture the ABA triblock copolymers differed in their erosion and degradation behavior from PLG. Degradation occurred faster in the ABA polymers by cleavage of ester bonds inside the polymer backbone. Even erosion was shown to start immediately after incubation in different buffer media. By varying pH and ionic strength of the buffer it was found that both mass loss and molecular weight decay were accelerated in alkaline and acidic pH in the case of the ABA triblock copolymers. Although the pH of the medium had a moderate influence on the degradation of PLG, the molecular weight decay was not accompanied by a mass loss during the observation time. In a second set of experiments we prepared bovine serum albumin, BSA, loaded microspheres from both polymers. The release of BSA from ABA microspheres under in vitro conditions parallels the faster swelling and erosion rates. This could be confirmed by electron paramagnetic resonance, EPR, measurements with spin labeled albumin where an influx of buffer medium into the ABA microspheres was already observed within a few minutes. In contrast, PLG microspheres revealed a burst release without any erosion. The current study shows that the environmental conditions affected the degradation and erosion of the pure polymer microspheres in the same way as the release of the model protein. This leads to the conclusion that the more favorable degradation profile of the ABA triblock copolymers was responsible for the improvement of the release profile.

Animals↗
PubMed1999

Respiratory arousals in mild obstructive sleep apnea syndrome.

The objective of the study is to identify patients with mild sleep apnea by counting not only apneas and hypopneas, but also mild respiratory events, which do not fulfill apnea or hypopnea criteria, but result in an arousal (Type-R arousal). Arousals related to body movements (Type-M arousal) were separately counted. The influence of nasal continuous positive airway pressure (nCPAP) on respiratory and movement arousals was analyzed. Daytime sleepiness before and after nCPAP and its relationship to arousal types was investigated using the Multiple Sleep Latency Test (MSLT) and a standardised questionnaire. Twenty-two patients with a mean age of 43.6 +/- 9.2 years underwent polysomnographic evaluation on a baseline night, and during three nights with nCPAP. On the baseline night, subjects presented with a mean RDI of 10.5 +/- 7.2/h, an apnea index (AI) of 1.2 +/- 1.5/h, a hypopnea index (HI) of 9.3 +/- 6.6/h, a R index of 5.2 +/- 5.9/h, and a M index of 9.7 +/- 5.6/h. Use of nCPAP lowered the RDI (p < 0.001) and the R index (p < 0.01). Mean sleep latency in the MSLT increased with nCPAP (p < 0.05) and the patient's subjective well being improved (p < 0.01). Correlation analysis revealed a relationship between Type-R arousals and RDI and HI (r = 0.5, p < 0.01) as well as between questionnaire scores and mean sleep latency. The decrease of Type-R indicates the positive effect of nCPAP. Arousal analysis and detection of mild respiratory events associated with arousals are helpful in investigating the sleep structure and in objectifying clinical symptoms and treatment success in patients with mild OSAS.

Adult↗
PubMed1999

Pulmonary function following laparoscopic or conventional colorectal resection: a randomized controlled evaluation.

BACKGROUND: Laparotomy causes a significant reduction of pulmonary function, and atelectasis and pneumonia occur after elective conventional colorectal resections. OBJECTIVE: To evaluate the hypothesis that pulmonary function is less restricted after laparoscopic than after conventional colorectal resection. DESIGN: A randomized clinical trial. SETTING: The surgical department of an academic medical center. PATIENTS: Sixty patients underwent laparoscopic (n = 30) or conventional (n = 30) resection of colorectal tumors. The 2 groups did not differ significantly in age, sex, localization or stage of tumor, or preoperative pulmonary function. MAIN OUTCOME MEASURES: Forced vital capacity, forced expiratory volume in 1 second, peak expiratory flow, mid-expiratory phase of forced expiratory flow, and oxygen saturation of arterial blood. RESULTS: The forced vital capacity (mean +/- SD values: conventional resection group, 1.73+/-0.60 L; laparoscopic surgery group, 2.59+/-1.11 L; P<.01) and the forced expiratory volume in 1 second (conventional resection group, 1.19+/-0.51 L/s; laparoscopic surgery group, 1.80+/-0.80 L/s; P<.01) were more profoundly suppressed in the patients having conventional resection than in those having laparoscopic surgery. Similar results were found for the peak expiratory flow (conventional resection group, 2.51+/-1.37 L/s; laparoscopic resection group, 3.60+/-2.22 L/s; P<.05) and the midexpiratory phase of forced expiratory flow (conventional resection group, 1.87+/-1.12 L/s; laparoscopic surgery group, 2.67+/-1.76 L/s; P<.05). The oxygen saturation of arterial blood, measured while the patients were breathing room air, was lower after conventional than after laparoscopic resections (P<.01). The recovery of the forced vital capacity and forced expiratory volume in 1 second to 80% of the preoperative value took longer in patients having conventional resection than in those having laparoscopic resection (P<.01). Pneumonia developed in 2 patients having conventional resection, but no pulmonary infection occurred in the laparoscopic resection group (P>.05). CONCLUSIONS: Pulmonary function is better preserved after laparoscopic than after conventional colorectal resection. Pulmonary complications may be reduced after laparoscopic resections because of the better postoperative pulmonary function.

Aged↗
PubMed1999

Temporary tracheobronchial stenting in malignant lymphoma.

BACKGROUND: Temporary stenting is a new strategy in the treatment of malignant airway stenoses. Patients receive stents as primary palliation followed by tumor-specific therapy in order to reduce the stenosis and subsequently remove the stent. METHODS: We investigated this strategy of temporary airway stenting in 5 consecutive patients with malignant lymphoma (Non-Hodgkin's lymphoma, n = 3; Hodgkin's lymphoma, n = 2) who presented with severe dyspnoea. Nine stents (six Strecker, three Dumon stents) were implanted into the trachea or main bronchi. After stenting, patients underwent tumor-specific therapy (chemotherapy, n = 4; percutaneous radiotherapy, n = 1). RESULTS: Clinical improvement of dyspnoea and stridor was observed in each patient after stent implantation. In 4 patients (80%), stents could easily be removed after successful tumor-specific therapy, which led to reduction of stenosis after a mean interval of 26 days (14 to 52 days). One patient died during chemotherapy 6 days after stenting. CONCLUSIONS: The results show that temporary stenting is a valuable strategy in chemo- and radiosensitive malignancies, as it ameliorates the patients' respiratory condition until tumor-specific therapy is effective, and prevents poststenotic complications. It integrates stent implantation in a multi-therapy concept.

Adolescent↗
PubMed1999

Matching for TNF microsatellites is strongly associated with matching for other non-HLA MHC sequences in unrelated bone marrow donor-recipient pairs.

The use of unrelated donors for bone marrow transplantation is associated with an increased morbidity and mortality when compared with HLA identical siblings. We have demonstrated previously that matching of unrelated donors and recipients for TNFa microsatellites is correlated with lower CTLp frequencies. Matching of unrelated donors and recipients for other non-HLA sequences in the major histocompatibility complex has been reported to result in less graft-versus-host disease and improved survival. It has been argued that matching for non-HLA sequences in the MHC in addition to the HLA genes themselves results in matching for the entire MHC and is therefore the equivalent of providing an HLA identical sibling donor. In order to test this hypothesis we have examined TNFa microsatellites of unrelated donor recipient pairs in whom matching for HLA loci, non-HLA sequences near HLA B (beta-block markers) and non-HLA sequences near DRB1 (delta-block markers) had been determined. All 17 patients who were matched for HLA and non-HLA markers were also matched for TNF microsatellites. This data supports the idea that matching for HLA genes and non-HLA markers results in matching at all other loci in the MHC.

Bone Marrow Transplantation↗
PubMed1999

A new bronchoscopic method to measure airway size.

Bronchoscopic evaluation of stenosis is limited due to radial distortion of bronchoscopic images and the unknown distance between the endoscope and the stenotic area. The purpose of this study was the development and validation of a method for measuring cross-sectional areas in large airways. Distance measurements were performed using a laser probe inserted into the working channel of a bronchoscope. The laser probe was positioned to the locus of interest in the airway, a ring of light (helium/neon) projected on to the luminal wall and the images acquired using an electronic bronchoscope. The images taken were distortion-corrected by means of a computer program. The method was validated by simulating airways using tubes of known diameter. Additionally, distortion-corrected bronchoscopic images were compared with distortion-free videoscopic image analysis of tracheal slices taken from pigs. In the case of the plastic tubes, Pearson's correlation coefficient (r) as well as the intraclass correlation coefficient (ICC) were slightly higher (r=0.99, p<0.01, ICC=0.97) than the correlation of cross-sectional areas between bronchoscopic and videoscopic images of tracheal slices (r=0.88, p<0.01, ICC=0.87). This concept allows accurate and reproducible determination of cross-sectional areas in large airways.

Animals↗
PubMed1999

Plasmacytoid monocytes appear in the bronchoalveolar lavage: differences between smokers and nonsmokers.

The primary purpose of this study was to describe the expression pattern of the surface antigens CD68, CD36, 27E10, G16/1, and RM3/1 on bronchoalveolar lavage (BAL) cells of smokers and nonsmokers. We found a cell type, morphologically similar to lymphocytes, which showed a strong expression of the monocyte markers CD68 and CD36. We therefore recognized these cells as plasmacytoid monocytes (PM). Hereby we report the appearance of PM in the BAL and its dependency of smoking. The study was conducted in 40 patients with various lung diseases and normal subjects. Sixteen patients and normal subjects were smokers and 24 were nonsmokers. There was a significant increase of PM in the BAL of smokers compared to nonsmokers. However we could not find a disease-related increase of PM in the BAL. This is the first report demonstrating the occurrence of PM in the BAL. Our data support the monocytic origin of PM and suggest an involvement in T cell-mediated responses of the lung.

Antibody Specificity↗
PubMed1999

The genetic basis for the association of the 8.1 ancestral haplotype (A1, B8, DR3) with multiple immunopathological diseases.

An individual's major histocompatibility complex (MHC) ancestral haplotype (AH) is the clearest single determinant of susceptibility to MHC associated immunopathological disease, as it defines the alleles carried at all loci in the MHC. However, the direct effects of any of the 150-200 genes that constitute the MHC are difficult to determine since recombination only occurs at defined hotspots. This review concerns the 8.1 AH (HLA-A1, C7, B8, C4AQ0, C4B1, DR3, DQ2), which is carried by most Caucasians with HLA-B8. It is associated with accelerated human immunodeficiency virus (HIV) disease, and susceptibility to insulin-dependent diabetes mellitus (IDDM), systemic lupus erythematosus, dermatitis herpetiformis, common variable immunodeficiency and IgA deficiency, myasthenia gravis and several other conditions. We have mapped susceptibility genes for HIV, IDDM and myasthenia gravis to the central MHC between HLA-B and the tumour necrosis factor or complement genes. Here we consider which of the remaining 8.1-associated diseases are more closely associated with HLA-DR3 and/or DQ2. Several candidate genes in the central MHC have the potential to modulate immune or inflammatory responses in an antigen-independent manner, as is seen in studies of cultured cells from healthy carriers of the 8.1 AH. Hence these genes may act as a common co-factor in the diverse immunopathological conditions associated with the 8.1 AH.

Animals↗
PubMed1999

Pulmonary involvement in diffuse cutaneous systemic sclerosis: broncheoalveolar fluid granulocytosis predicts progression of fibrosing alveolitis.

OBJECTIVE: The clinical course of fibrosing alveolitis (FA) in patients with systemic sclerosis (SSc) may vary considerably from stable condition for years to continuous fatal progression. This prospective study aimed at identifying the prognostic value of bronchoalveolar lavage fluid (BALF) analysis in FASSc. METHODS: Seventy three consecutive patients with SSc and clinical signs of pulmonary involvement were enrolled. Every patient underwent clinical examination, lung function tests, computed tomography (CT), gallium scan, echocardiography, and bronchoalveolar lavage (BAL). Forty nine patients, 26 with pathological and 23 with normal BALF findings were prospectively followed up for two years and re-evaluated annually. RESULTS: At baseline, 51 subjects (70%) showed radiological signs of lung fibrosis and/or alveolitis by CT and diffusion capacity for carbon monoxide (DLco) was decreased in 47 patients (64%). Thirty five patients (48%) had pathological BALF findings. BALF differential counts included BALF granulocytosis in 18, BALF lymphocytosis in 12, and a mixed increase of both granulocytes and lymphocytes in five patients. On follow up, a progression of FA with a significant decrease of DLco was only observed in patients with BALF granulocytosis. In contrast, patients with BALF lymphocytosis or normal BALF cell count had stable lung function parameters during the study period. In none of our patients echocardiography showed evidence of pulmonary hypertension. CONCLUSION: BALF granulocytosis predicts progression of FA with deterioration of lung function, which is most sensitively monitored by DLco. Immunosuppressive treatment is recommended in patients with granulocytic FASSc.

Bronchoalveolar Lavage Fluid↗
PubMed1998

A rapid protocol for cardiac troponin T gene mutation detection in familial hypertrophic cardiomyopathy.

Mutations in the human cardiac troponin T gene (TNNT2) are associated with familial hypertrophic cardiomyopathy (FHC) linked to chromosome 1q3 (CMH2). Mutation analyses of TNNT2 have been restricted to RNA-based screening methods because only the TNNT2 cDNA sequence was known. We characterized the genomic structure of 15 TNNT2 exons spliced into the adult isoform. A protocol for rapid mutation detection based on direct sequencing of large PCR-amplified genomic DNA fragments revealed a known TNNT2 mutation (Phe110Ile) in one of 30 FHC probands. Three polymorphic short tandem repeat elements (D1S477, D1S2622, and D1S1723), useful for FHC pedigree analyses at CMH2, were shown to be physically tightly linked to TNNT2.

Cardiomyopathy, Hypertrophic↗