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Biomedical subjects

A Köhler

Publications and source records attributed to A Köhler.

At least 55 records · Page 3Linked to original sources
PubMed1997

Adaptational changes in kinetic parameters of G6PDH but not of PGDH during contamination-induced carcinogenesis in livers of North Sea flatfish.

Kinetic parameters of glucose-6-phosphate dehydrogenase (G6PDH) and phosphogluconate dehydrogenase (PGDH) were determined in situ in livers of marine flatfish flounder that were caught in unpolluted areas in the open sea and in the highly polluted river Elbe (Germany). Analysis was performed quantitatively in liver sections using valid enzyme histochemical methods and image analysis. G6PDH but not PGDH was strongly affected by contaminant exposure and subsequent carcinogenesis. G6PDH showed a gradual decrease in Vmax and Km for glucose-6-phosphate in extralesional normal-looking liver tissue. Hepatocellular carcinomas also showed a low Km, whereas the Vmax was upregulated. These findings are interpreted as follows: prolonged challenges of the livers by pollutants inhibit or inactivate G6PDH and this is compensated for by reduction in Km. In carcinomas, G6PDH levels are upregulated but the low Km values are kept to increase the NADPH production capacity required in cancer cells showing that posttranslational regulation processes are important to control cellular metabolism under various environmental conditions.

Adaptation, Physiological↗
PubMed1997

[Opioids and driving ability].

INTRODUCTION: Clinical observations of patients under oral opioid treatment suggest that the initially appearing central side effects such as sedation, dizziness or drowsiness decrease after a few weeks of treatment. However, it is still unclear whether long-term treatment with opioids impairs complex psychomotor functions such as driving a car. METHODS: Twenty patients on stable dosages of oral opioids were examined using a driving simulator. The patients were regular car drivers and not older than 70 years. Additionally, every patient had to complete a questionnaire for mental condition and vigilance and the "d II" letter cancellation task. Control groups tested in the same way were: patients before an elective operation after taking benzodiazepines for sedation, volunteers after alcohol consumption (0.80 per thousand ), physicians on call with less than 4 h of sleep and healthy volunteers without any medication. RESULTS: Some of the patients treated with opioids reacted as fast as medication-free volunteers. There were no significant differences between the reaction times of older patients (>50 years) receiving opioids in comparison to the group of older healthy volunteers. The same result was obtained in the letter cancellation task. No differences could be seen between medication-free volunteers and patients receiving opioids with regard to tasks of visual or motor control skills. The volunteers under influence of alcohol and the patients under benzodiazepines had a considerable decrease in performance. CONCLUSIONS: Long-term therapy with opioids does not inevitably impair complex skills, but the decision to permit driving a car can only be made in the individual case. PRACTICAL RECOMMENDATIONS: At the beginning of therapy with opioids the physician has to fulfil his duty to inform the patient of any possible dangers of treatment. From the medical point of view, driving must be prohibited until a stable opioid dosage is reached. Any changes in dosage (increase, reduction), change of the opioid and poor general condition independent of the opioid therapy must result in prohibition of car driving. Continuous control of the therapy with documentation is a duty of the physician. The written documentation should include the patients' physical and mental condition, side effects and the therapeutic result. From the medical point of view, driving can be possible when dosage treatment and general condition remain stable. In any case, the doctor has to remind the patient of the responsibility of critical self-examination. In doubt, special performance investigation should be taken into consideration.

English Abstract↗
PubMed1997

In vivo morphology of woven, collagen-sealed Dacron prostheses in the thoracic aorta.

BACKGROUND: Long-term changes in knitted Dacron grafts inserted into the infrarenal aorta have been addressed by a number of studies indicating their potential for postoperative dilatation. In contrast, the behavior of woven, collagen-presealed, double-velour Dacron grafts used to replace the thoracic aorta is not known. METHODS: Forty-five patients were examined at a mean of 32.4 +/- 14.8 months after insertion of woven, collagen-coated, Dacron double-velour prostheses (Meadox woven with Hemashield, Meadox, Oakland, NJ) in the thoracic position under highly standardized conditions using spiral computed tomography. RESULTS: Compared with a manufactured diameter of 26 mm, all grafts showed an increase of 1 to 5 mm (mean, 3.0 +/- 1.2 mm [11.6% +/- 4.4%]; p < 0.0001) with greater enlargement of the ascending than of the descending aortic portions (p = not significant). A further statistically significant progressive dilatation failed to occur. Degenerative changes, including false aneurysm formation, could be excluded. CONCLUSIONS: Woven, collagen-coated Dacron prostheses are considered a safe replacement material for the thoracic aorta.

Aortic Dissection↗
PubMed1997

Extraanatomic thoracic aortic bypass grafts: indications, techniques, and results.

OBJECTIVE: Even in the age of extensive aortic replacement special circumstances may warrant the insertion of extraanatomic thoracic aortic bypass grafts. Our experience with 17 patients is analyzed. METHODS: Between 1988 and 1994, ten female and seven male patients (mean age 37.5 years, range 9-69 years) were treated for the following indications: (1) complex CoA (n = 5); (2) reoperation for CoA (n = 6); (3) extensive aortic occlusive disease (n = 4); and (4) complicated aneurysm (n = 2). Routing of the grafts was: ascending-descending aorta (8); ascending-abdominal aorta (4); left subdavian artery- descending aorta (2); descending-descending aorta (2); and descending-abdominal aorta (1). Eight procedures were reoperations. In four patients concomitant cardiac operations were performed: one aortic valve replacement, one patch plasty of the LCA, and two composite graft replacements of aortic valve and ascending aorta, one of them with CABG. RESULTS: Three early deaths occurred. two after emergency operation in thoracic aneurysm under dire conditions (one perforation, one infection), one after ascending-abdominal aortic grafting with multiple branch revascularization. The underlying pathology was relieved successfully in all 14 survivors. In the two patients with concomitant aortic valve and isthmic stenosis, critical anterior motion of the mitral valve, presumably because of the massive afterload reduction of the left ventricle, complicated the perioperative course. One patient was reoperated because of aneurysm 4 years after descending-descending aortic grafting for complex CoA with poststenotic dilatation. CONCLUSIONS: In complex aortic coarctation or hypoplasia extraanatomic bypass grafts are expedient and effective procedures, especially for reoperation. Their use in the treatment of aneurysmal lesions remains an exception.

Adolescent↗
PubMed1997

Isovolemic hemodilution with a bovine hemoglobin-based oxygen carrier: effects on hemodynamics and oxygen transport in comparison with a nonoxygen-carrying volume substitute.

OBJECTIVE: Stroma-free hemoglobin solutions have been shown to maintain oxygen transport in the absence of red blood cells. This study was designed to investigate the impact of such solutions on hemodynamics and oxygen transport during progressive isovolemic hemodilution within and even beyond a clinically relevant range of hematocrit values. DESIGN: Prospective, randomized experimental study comparing a bovine hemoglobin-based oxygen carrier (bHBOC) with a conventional nonoxygen-carrying volume substitute (hydroxyethyl starch [HES]). SETTING: Animal laboratory of a university cardiovascular research center. PARTICIPANTS: Splenectomized full-grown foxhounds, anesthetized with pentobarbital and piritramid. INTERVENTIONS: Twelve splenectomized foxhounds were anesthetized and mechanically ventilated. Catheters were placed for hemodilution, arterial and venous blood sampling, and hemodynamic measurements. The baseline hematocrit (Hct) value was adjusted to 0.35 by an initial isovolemic exchange of blood for identical volumes of HES (10% HES 200/0.5). Thereafter, the hematocrit was progressively reduced by isovolemic hemodilution using either HES (n = 6) or bHBOC (n = 6). MEASUREMENTS AND MAIN RESULTS: Hemodynamic and laboratory parameters of oxygen transport were measured at Hct values of 0.30, 0.20, and 0.10. Oxygen content was directly estimated using an oxygen-specific fuel cell. Arterial oxygen content at an Hct value of 0.10 nearly doubled in bHBOC-treated dogs as compared with HES-diluted animals (p < 0.001). This gain in oxygen-carrying capacity was completely negated by a decrease in cardiac output (-32% Hct 0.35 v Hct 0.30; p < 0.001) immediately on the first infusion of bovine hemoglobin. Thus, oxygen delivery was significantly lower as compared with HES-treated dogs at Hct 0.30 and 0.20, but remained stable at a level of 60% of baseline until Hct was 0.10. Both the pulmonary and the systemic vascular resistances increased. CONCLUSIONS: Isovolemic hemodilution with bHBOC did not improve systemic oxygen delivery in comparison with a nonoxygen-carrying diluent (HES) in a range of Hct values down to 0.10. Unchanged mixed venous lactate levels and stable oxygen consumption indicate sufficiently maintained oxygen delivery. This might become advantageous in patients who are unable to adequately increase cardiac output during hemodilution.

Animals↗
PubMed1997

AND-1, a natural chimeric DNA-binding protein, combines an HMG-box with regulatory WD-repeats.

Using a specific monoclonal antibody (mAb AND-1/23-5-14) we have identified, cDNA-cloned and characterized a novel DNA-binding protein of the clawed toad, Xenopus laevis, that is accumulated in the nucleoplasm of oocytes and various other cells. This protein comprises 1,127 amino acids, with a total molecular mass of 125 kDa and a pI of 5.27. It is encoded by a mRNA of approximately 4 kb and contains, in addition to clusters of acidic amino acids, two hallmark motifs: the amino-terminal part harbours seven consecutive 'WD-repeats', which are sequence motifs of about 40 amino acids that are characteristic of a large group of regulatory proteins involved in diverse cellular functions, while the carboxy terminal portion possesses a 63-amino-acid-long 'HMG-box', which is typical of a family of DNA-binding proteins involved in regulation of chromatin assembly, transcription and replication. The DNA-binding capability of the protein was demonstrated by DNA affinity chromatography and electrophoretic mobility shift assays using four-way junction DNA. Protein AND-1 (acidic nucleoplasmic DNA-binding protein) appears as an oligomer, probably a homodimer, and has been localized throughout the entire interchromatinic space of the interphase nucleoplasm, whereas during mitosis it is transiently dispersed over the cytoplasm. We also identified a closely related, perhaps orthologous protein in mammals. The unique features of protein AND-1, which is a 'natural chimera' combining properties of the WD-repeat and the HMG-box families of proteins, are discussed in relation to its possible nuclear functions.

Animals↗
PubMed1996

Isolation, characterization, and organ-specific expression of two novel human zinc finger genes related to the Drosophila gene spalt.

The region-specific homeotic gene spalt (sal) of Drosophila specifies head and tail as opposed to trunk segments. During later stages of ontogenesis, sal is also expressed and required in a small number of tissues and organs in the developing embryo. sal encodes a zinc finger protein of unusual but characteristic structure. We made use of these unique features to isolate sal-like genes from humans. Here we report the isolation and molecular characterization of two sal-like transcription units, termed Hsal1 and Hsal2, which are located on chromosomes 16q12.1 and 14q11.1-q12.1, respectively. Their transcripts are expressed in a limited number of adult organs, including the brain. While Hsal2 is evenly expressed in different brain areas, Hsal1 transcripts preferentially accumulate in the corpus callosum and the substantia nigra. In the fetal brain, transcripts of both genes were detected in neurons. The arrangement of sal-like zinc finger domains and their high degree of sequence similarity suggest a novel and conserved subfamily of human zinc finger transcription factors that is closely related to the Drosophila gene product encoded by the gene sal.

Adult↗
PubMed1996

[Defecation flowmetry. A new study technique for evaluating the evacuation function of the rectum].

In a prospective study carried out on 78 patients with chronic constipation (31, with slow transit, 47 with obstructive defecation disorders) the evacuation function of the rectum during defecation was assessed by defecoflowmetry. These patients were compared to a control group of normal volunteers (n = 32). The following parameters were evaluated: defecation and retention volume, defecation fraction, defecation time, maximum flow, mean flow rate and time to maximum flow. As expected, there was no difference in evacuation function between the group of patients with slow transit and the control group. Significant differences, however, existed between the two types of constipation, as well as between obstructive defecation disease and controls, regarding all parameters mentioned above. Evacuation function depends neither on rectal neck pressure nor on intrarectal pressure. In patients with obstructive defecation disorders, three subgroups were discernable: one with prolonged time of defecation and satisfactory evacuation, one with prolonged time of defecation and poor evacuation, and one small group of patients who were not able to defecate. Each group is based on a different underlying pathomechanism. We conclude that changes in evacuation function of the rectum refer either to volume or to time of defecation, or to both. Changes are found only in obstructive type constipation, not in slow transit constipation. Therefore, defeconflowmetry as a dynamic procedure can be used in screening for the classification of chronic constipation.

Adult↗
PubMed1996

[Anodermal advancement flap-plasty as alternative treatment method to endorectal closure techniques in therapy of high anal fistulas. A prospective study of 31 patients].

From January 1992 until April 1995, 31 patients with trans- and suprasphincteric anal fistulae (transsphincteric n = 21; suprasphincteric n = 4; transsphincteric in Crohn's disease n = 6) underwent a fistulectomy followed by closure of the internal opening by suture and anocutaneous flap. All patients had undergone previous operations, some several times. The recurrence rate of 13% appeared to be low after a short follow-up. Continence was only negligibly impaired, although the anal resting pressure and contraction pressure were significantly reduced. In five patients a shortened prewarning period was noticed. Also in Crohn's fistulae the results were equivalent when the surgical treatment was performed in a non-inflammatory period.

Adult↗
PubMed1996

Molecular characterization of breakpoints in patients with holoprosencephaly and definition of the HPE2 critical region 2p21.

Holoprosencephaly (HPE) is a common developmental defect involving the brain and face in humans. Cytogenetic deletions in patients with HPE have localized one of the HPE genes (HPE2) to the chromosomal region 2p21. Here we report the molecular genetic characterization of nine HPE patients with cytogenetic deletions or translocations involving 2p21. We have determined the parental origin of the deleted chromosomes and defined the HPE2 critical region between D2S119 and D2S88/D2S391. As a first step towards cloning the HPE2 gene which is crucial for normal brain development we have constructed a YAC contig which spans the smallest region of deletion overlap. Several of these YACs could be identified which span three different 2p21 breakpoints in HPE patients. These YACs narrow the HPE2 critical region to less than 1 Mb and are now being further analyzed to identify the gene causing holoprosencephaly on chromosome 2.

Base Sequence↗
PubMed1996

Assignment of genes encoding GABAA receptor subunits alpha 1, alpha 6, beta 2, and gamma 2 to a YAC contig of 5q33.

A gene cluster consisting of the four gamma-aminobutyric acidA (GABAA) receptor subunit genes GABRA1, GABRA6, GABRAB2, and GABRG2 was assigned to a yeast artificial chromosome (YAC) contig of 5q33. Two of the 26 YACs of the contig are positive for all four subunit genes. The order of the GABR subunit genes with respect to known anonymous gene loci is cen-D5S380 - D5S403 - D5S529 - GABRB2 - GABRA1/A6 - GABRG2-D 5S422-tel. This novel YAC contig lies between known YAC contigs of 5q34/q35 and 5q31-q33.

Chromosome Banding↗
PubMed1996

[Endo-anal and transperineal continence preserving closure techniques in surgical treatment of Crohn fistulas. A prospective long-term study of 186 patients].

UNLABELLED: Our aim was to review the results and to investigate the prognosis in a prospective study of aggressive surgical treatment in 186 patients (59% women, 41% men, age 18 to 65 years) treated during the past 9 1/2 years by conventional laying open of the fistula (n = 71), endorectal advancement flap repair (n = 89) and by fistulectomy without internal sphincterotomy (n = 37). 54 (29%) patients had intersphincteric, 57 (30.5%) transsphincteric, 10 (5.5%) suprasphincteric, 37 (20%) low rectovaginal and 28 (15%) had complex fistulas without internal opening. Four sphincter saving techniques were performed by the high and fistulas (n = 89) with primary occlusion of the intraanal ostium and endorectal mucosal flap (n = 29), endorectal advancement flap (n = 41), anodermal flap (n = 8) and transperineal repair with levator interposition (n = 11). Postoperatively 18 cases (20.2%) of suture leakage occurred, 27% in the mucosal flap group, 17.6% in the advancement flap group, 12.5% in the anodermal group, and 27% in the transperineal group. A complete primary healing of perianal wounds was noted in 73% of the patients within 6 months. The presence of rectal disease (n = 77) did not adversely influence the rate and duration of healing. Persistent or recurrent fistula occurs in 29 patients (15.6%), 22% in the sphincter saving group, 4% in the intersphincteric group and 32% in the complex type of fistulas. Disturbance of continence was observed in 9 patients (4.8%). Postoperatively, there was no significant change in resting anal pressure and maximum voluntary conctraction pressure in any fistula group (n = 104). CONCLUSION: The presented clinical and functional long term results of patients with Crohn's fistulas underline the importance of experience in the treatment of perianal fistula disease. A successful treatment depends primarily on an aggressive therapeutic strategy and the appropriate method of operation.

Adolescent↗
PubMed1995

Clinical and molecular genetic findings in five patients with Miller-Dieker syndrome.

Five patients with type 1 lissencephaly, typical features of Miller-Dieker syndrome and apparently normal karyotypes were investigated for microdeletions in chromosome 17p13.3. Analysis of loci D17S5 and D17S379 by polymerase chain reaction and fluorescence in situ hybridization revealed a deletion in three cases. No deletion was observed in the remaining two cases. Given the almost identical clinical picture of the five patients, the great variation in the molecular findings argues against Miller-Dieker syndrome being a contiguous gene syndrome.

Abnormalities, Multiple↗
PubMed1995

Assignment of the dystonia-parkinsonism syndrome locus, DYT3, to a small region within a 1.8-Mb YAC contig of Xq13.1.

A YAC contig was constructed of Xq13.1 in order to sublocalize the X-linked dystonia-parkinsonism (XDP) syndrome locus, DYT3. The contig spans a region of approximately 1.8 Mb and includes loci DXS453/DXS348/IL2R gamma/GJB1/CCG1/DXS559. For the construction of the contig, nine sequence-tagged sites and four short tandem repeat polymorphisms (STRPs) were isolated. The STRPs, designated as 4704#6 (DXS7113), 4704#7 (DXS7114), 67601 (DXS7117), and B4Pst (DXS7119) were assigned to a region flanked by DXS348 proximally and by DXS559 distally. Their order was DXS348/4704 #6/4704 #7/67601/B4Pst/DXS559. They were applied to the analysis of allelic association and of haplotypes in 47 not-obviously-related XDP patients and in 105 Filipino male controls. The same haplotype was found at loci 67601 (DXS7117) and B4Pst (DXS7119) in 42 of 47 patients. This percentage of common haplotypes decreased at the adjacent loci. The findings, together with the previous demonstration of DXS559 being the distal flanking marker of DYT3, assign the disease locus to a small region in Xq13.1 defined by loci 67601 (DXS7117) and B4Pst (DXS7119). The location of DYT3 was born out by the application of a newly developed likelihood method for the analysis of linkage disequilibrium.

Adult↗
PubMed1995

[Transanal rectal advancement flap versus mucosa flap with internal suture in management of complicated fistulas of the anorectum].

A prospective study was carried out on 55 patients with complicated anal fistulas (41 transsphincteric, 5 suprasphincteric and 9 rectovaginal) to evaluate the value of two sphincter-conserving techniques with primary occlusion of the internal ostium and endorectal advancement flap (group A, n = 34) or mucosal flap (group B, n = 21). Ten of the patients had Crohn's disease. Both techniques consist in one-stage fistulectomy without drainage of the intersphincteric space. The inflamed proctodeal and granulation tissue was carefully cleared. The site of the former primary orifice of the fistula was adapted by means of two or three peranally performed single stitches. The peranally applied suture included the layers of the internal anal sphincter muscle only. A mobilized flap of rectal wall (group A) and rectal mucosa and submucosa (group B) about 4 cm x 3 cm in size was stitched below the muscular sphincter. The perianal part of the wound was left to heal by second intention. Postoperatively there were 16 cases of suture leakage (23.5% in group A, and 38% in group B), and 19 patients (26% or 47% in both groups) had to have revision surgery because of recurrent fistula or sutur leakage; 2 patients (3.6%) developed incontinence with intermittent fecal soiling. Complete incontinence was not observed in any patient. No significant difference in clinical and functional results was determined between the two groups.

Anal Canal↗
PubMed1995

[Media sclerosis: a case of pseudohypertension].

A 51-year-old diabetic showed symptoms of a hypertensive crisis with a systolic blood pressure above 300 mmHg. The antihypertensive therapy failed and the Doppler-pressure values were also too high for all limb arteries. Duplex-sonography and soft-x-ray examination showed a mediasclerosis of arms and legs. The true pressure, measured at the still compressable arteries of the fingers was relatively low. There was symptomatic improvement after completion of the antihypertensive therapy.

Arm↗
PubMed1995

[What is the role of the pubococcygeal and puborectal muscles in patients with obstructive defecation disorders? An electromyography study].

BACKGROUND: We believe that the M. levator ani plays little or no role in obstructed defaecation, and that the concept of "paradoxical" puborectalis muscle activity is misleading. The main aim of the study was to investigate the function of the pubococcygeal muscle during simulated defaecation and to compare this with the electromyographic activity of the puborectal muscle. METHODS AND RESULTS: In a prospective electromyographic study of 18 women (average age 53 years) with obstructive defecation disorder the activity of the pubococcygeal muscle and the puborectal muscle was investigated at rest, during contraction and straining. The control group consisted of 18 healthy women with an average age of 54 years. The function of the pubococcygeal muscle and the puborectal muscle was largely the same in both, study and control group. No statistically significant differences in the amplitude were found between the two groups at rest during contraction and maximum strain. CONCLUSION: We therefore conclude that the increase in activity of the voluntary muscle of the pelvic floor observed on electromyography during defaecation does not indicate automatically a pathologic condition but is a possible functional state at this moment.

Adult↗