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Biomedical subjects

M Wunderlich

Publications and source records attributed to M Wunderlich.

At least 37 records · Page 2Linked to original sources
PubMed1994

Intersphincteric resection for low rectal tumours.

An abdominoperineal operation is described that extends rectal resection for low tumours into the intersphincteric plane with removal of the internal sphincter. Bowel continuity is restored by coloanal anastomosis. Of 38 patients who underwent surgery since 1984, 34 had low rectal cancer and four carcinoid or large villous adenoma. There was no mortality. Four patients developed local recurrence during a median observation period of 3 years. Continence was satisfactory in all patients. The median daily number of bowel movements during the first months after colostomy closure was 9 but decreased to 3 after 1 year and 1 after 2 years. Anal manometry demonstrated a significant reduction of mean resting pressure from 91.8 to 35.1 cmH2O with no recovery after 2 years (P < 0.0001). Squeeze pressure showed only a transient decrease.

Adult↗
PubMed1994

[Mild, moderate and severe dysplasia in exfoliative cytological studies of breast secretions in connection with use of oral contraceptives].

In our present material of 30,000 cytologically investigated mammary secretions we have found since 1980 in 1.55% mild, moderate and severe dysplasias. Due to the high number of women using long time oral contraceptive pills are further investigations necessary. Such women using gestagen accented pills in particular with the gestagen norethisterone acetate are charged with a significant high level of dysplasias in nipple discharge. After stopping or changing the contraceptives, these dysplasias seem to be reversible. These findings should therefore stimulate further intensive examinations, in order to detect in time possible dangerous side effects after long time using of oral contraceptive pills and to avoid them.

Adult↗
PubMed1993

In vivo control of redox potential during protein folding catalyzed by bacterial protein disulfide-isomerase (DsbA).

The formation of disulfide bonds in Escherichia coli is catalyzed by periplasmic protein disulfide-isomerase (DsbA). When the alpha-amylase/trypsin inhibitor from Ragi, a protein containing five intramolecular disulfide bridges, is secreted into the periplasm of E. coli, large amounts of misfolded inhibitor with incomplete or incorrect disulfides are accumulated. Folding of the inhibitor in the periplasm is not improved when DsbA is coexpressed and cosecreted. However, an up to 14-fold increase in correctly folded inhibitor is observed by co-expression of DsbA in conjugation with the addition of reduced glutathione to the growth medium. This peptide acts as a disulfide-shuffling reagent and can pass the outer membrane of E. coli. Since the influence of DsbA on the folding yield of the inhibitor is reduced in the presence of oxidized glutathione, the in vivo function of DsbA appears to be dependent on the ratio between oxidizing and reducing thiol equivalents in the periplasm. The high stability of thiol reagents against air oxidation during growth of E. coli allows the investigation of oxidative protein folding in vivo under controlled, thiol-dependent redox conditions.

Amino Acid Sequence↗
PubMed1993

Bacterial protein disulfide isomerase: efficient catalysis of oxidative protein folding at acidic pH.

Periplasmic protein disulfide isomerase (DsbA) is essential for disulfide formation in Escherichia coli. The tryptophan fluorescence of DsbA measures the redox state of the enzyme during catalysis of the oxidative folding of hirudin, a thrombin inhibitor containing three disulfide bonds and lacking tryptophan. With stoichiometric amounts of DsbA, reduced hirudin is rapidly oxidized in a process initially leading to random disulfides. Disulfide reshuffling involving reduced DsbA yields completely native inhibitor within 1 h, even at pH 4. Catalytic amounts of DsbA become essential for hirudin folding in the presence of redox buffers at acidic pH. The second-order rate constants of disulfide exchange reactions involving DsbA are several orders of magnitude above the known values for alkyl dithiols and disulfide oxidoreductases. DsbA preferably reacts with reduced, unfolded polypeptides. The reduction of DsbA by hirudin is faster by 1 order of magnitude than its reduction by the strong reductant dithiothreitol. Together, unusually fast disulfide interchange reactions and a preference for folding polypeptides appear to be responsible for the catalytic efficiency of DsbA and for disulfide formation in vivo at acidic pH.

Amino Acid Sequence↗
PubMed1993

The redox properties of protein disulfide isomerase (DsbA) of Escherichia coli result from a tense conformation of its oxidized form.

Periplasmic protein disulfide isomerase (DsbA) from Escherichia coli is a strongly oxidizing thiol reagent with one catalytic disulfide bridge and an intrinsic redox potential of -0.089 V. Gel filtration experiments and analytical ultracentrifugation studies demonstrate that DsbA is a monomeric protein with a molecular mass of 21.1 kDa, independent of its redox state. In order to investigate the molecular basis of its redox properties, the guanidinium.chloride-induced folding/unfolding equilibrium of the reduced and the oxidized form of the enzyme were compared. The transitions at pH 7.0 and 30 degrees C were found to be fully reversible and allowed the calculation of the free energy of stabilization of oxidized and reduced DsbA according to a two-state model for the unfolding transition. The analysis reveals that reduced DsbA is 22.7 (+/- 4.0) kJ/mol more stable than oxidized DsbA. This energetic difference is essentially independent of temperature, although the overall free energies of stabilization of both oxidized and reduced DsbA vary strongly between 20 and 30 degrees C as a consequence of changes in the cooperativity of the transitions The conformational tension of 22.7 (+/- 4.0) kJ/mol in oxidized DsbA quantitatively explains the oxidizing properties of the protein, as it causes a change of redox equilibrium constants between DsbA and thiols of about four orders of magnitude, corresponding to an increase of the standard redox potential of 0.118 (+/- 0.021) V. We conclude that the oxidizing properties of DsbA mainly result from a tense conformation of its oxidized form, that is converted to the relaxed, reduced state upon oxidation of thiols by DsbA. The results are discussed in terms of a general principle underlying the oxidizing properties of protein disulfide isomerases.

Chromatography, Gel↗
PubMed1993

Redox properties of protein disulfide isomerase (DsbA) from Escherichia coli.

The redox properties of periplasmic protein disulfide isomerase (DsbA) from Escherichia coli were analyzed by measuring the equilibrium constant of the oxidation of reduced DsbA by oxidized glutathione. The experiments are based on the finding that the intrinsic tryptophan fluorescence of DsbA increases about threefold upon reduction of the enzyme, which can be explained by the catalytic disulfide bridge quenching the fluorescence of a neighboring tryptophan residue. From the specific fluorescence of DsbA equilibrated in the presence of different ratios of reduced and oxidized glutathione at pH 7, an equilibrium constant of 1.2 x 10(-4) M was determined, corresponding to a standard redox potential (E'0) of DsbA of -0.089 V. Thus, DsbA is a significantly stronger oxidant than cytoplasmic thioredoxins and its redox properties are similar to those of eukaryotic protein disulfide isomerase. The equilibrium constants for the DsbA/glutathione equilibrium were found to be strongly dependent on pH and varied from 2.5 x 10(-3) M to 3.9 x 10(-5) M between pH 4 and 8.5. The redox state-dependent fluorescence properties of DsbA should allow detailed physicochemical studies of the enzyme as well as the quantitative determination of the oxidized protein by fluorescence titration with dithiothreitol and open the possibility to observe bacterial protein disulfide isomerase "at work" during catalysis of oxidative protein folding.

Disulfides↗
PubMed1993

[Drain fistulography. Radiological sphincter identification in high anal fistulae].

To warrant permanent surgical cure of high anal fistulae, while avoiding at the same time faecal incontinence due to inadvertent division of the puborectalis muscle, distinction between a trans- and suprasphincteric fistula track is essential. This differentiation is often crucial, since digital rectal palpation and conventional fistulography tend to be unreliable. Therefore we developed a radiological technique of imaging the anorectal fistulous track, "drain fistulography". After silicon drainage of the fistula the contrast visualization of anal canal, rectum and fistula drain allows to assess the topographic relation between fistula and anal sphincters as well as the sphincteric functional component above the fistula. A trans-sphincteric fistula track was demonstrated in 7 of 8 patients (5 with recurrent fistulae) by means of "drain fistulography", permitting complete laying open of each fistula in a second operation. In one patient a suprasphincteric fistula track was found and a "mucosal flap repair" was carried out. After a mean observation time of 53 months all patients are perfectly continent and free of recurrence. The method of "drain fistulography" is a valuable diagnostic tool to select the appropriate definitive surgical procedure in the treatment of high anal fistulae.

Adult↗
PubMed1992

[X-ray measurement of the level of rectal carcinomas and its dependence on the functional status of the pelvic floor].

The influence of the various functional states of the pelvic floor on the radiological assessment of the tumour levels and the distant tumour-free distance in rectum neoplasms was investigated. The parameters "anal canal length", "anorectal angle" and "impression of the puborectalis muscle" were measured in lateral distant views of the rectum in a series of healthy controls (n = 160). In addition, these parameters and the "distant tumour-free distance" were measured in patients with rectal cancer (n = 40). For each patient the lateral distant view at rest, during contraction and during maximal relaxation (straining) of the pelvic floor, were available for retrospective analysis. Depending on the various functional states of the pelvic floor, the differences between the same parameters were statistically significant (p less than 0.001). The average difference between the distal tumour-free distances during contraction and straining was 1.5 cm. Therefore, measurements of this distance in one lateral distant view exclusively may result in an inaccurate assessment of the tumour level. For the individual planning of extreme sphincter-saving surgery in low rectal cancer based on lateral distant view, the view at rest appears to be the most suitable. However, additional x-rays during contraction and maximal relaxation of the pelvic floor, respectively, should be available to identify the view at rest for an accurate assessment of the tumour level and to avoid misinterpretations which would have falsely influenced the planning of rectum surgery in 20% of our cases.

Adult↗
PubMed1991

How to set up your program in international health.

The foregoing delineation on the rationale, structure, and process for development of a program or institute in international health is not meant to be prescriptive. Flexibility, relevance, and sensitivity to the local context-the academic health center setting--are crucial, just as these characteristics are the hallmark of successful international projects. The present era offers significant challenges in improving the health and well-being of the world's population. Fortunately, there is an enlightened climate for the development of innovative and collaborative approaches to meet these challenges within a framework of social justice and overall human development. It is the unique and unparalleled opportunity for US academic health centers to work with international colleagues toward this goal.

Academic Medical Centers↗
PubMed1990

[Rectal cancer: prognostically relevant factors for the development of local recurrence following radical anterior resection].

The study was designed to detect criteria which influence the incidence of local recurrence after radical anterior resection for rectal cancer. Local recurrence developed in 18 patients (20%) out of 90. All patients entered a prospective clinical study for the detection of local recurrence (mean observation time: 50 months). The following criteria were evaluated retrospectively: age, sex, staging, grading, gross appearance of the tumour, lymphatic reaction, invasion of lymph and blood vessels, perineural invasion, mucus production of the tumour and width of the distal margin of clearance (measurement in cm in the specimen immediately after resection). Kaplan-Meier survival functions estimated the probability of staying free of local recurrence depending on the various criteria. Statistical significance was calculated using the tests of Breslow and Mantel. The incidence of local recurrence (%) depended on Dukes stage (A: 7%, B: 17%, C: 40%; p less than or equal to 0.03), grading (well differentiated: 5%, average: 20%, poorly differentiated: 55%; p less than or equal to 0.02), gross appearance (protuberant: 15%, infiltrating: 47%; p less than or equal to 0.006), lymphatic stroma reaction (yes: 10%, no: 45%; p less than or equal to 0.006), invasion of veins (yes: 75%, no: 20%; p less than or equal to 0.002), perineural invasion (yes: 52%, no: 17%; p less than or equal to 0.001) and the margin of clearance (less than 1 cm: 52%, 1-3 cm: 10%, greater than 3 cm: 15%; p less than or equal to 0.02 Mantel, p less than or equal to 0.05 Breslow between less than 1 cm vs. 1-3 cm and greater than 3 cm, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Lymphoid follicular hyperplasia in excluded colonic segments: a radiologic sign of diversion colitis.

Double-contrast barium enema (DCBE) studies showed lymphoid follicular hyperplasia (LFH) in excluded colonic segments after colostomy in 12 of 40 patients. In most patients with LFH, more than 80% of the excluded colon was affected. In eight patients, regression of LFH was demonstrated with DCBE studies after reanastomosis. This work suggests that LFH is the most common DCBE study finding in diversion colitis.

Adult↗
PubMed1989

Dislocated Atkinson tubes: removal and repositioning with a balloon catheter.

Atkinson tubes are inserted endoscopically for palliation of obstructing esophageal carcinoma. A technique was developed to reposition or remove dislocated tubes that involves the use of a dilation balloon catheter. The technique was successful in treating three partially dislocated tubes and one of two completely dislocated tubes (tubes completely dislodged into the stomach). The only complication occurred in two patients who coughed up a small amount of blood.

Aged↗
PubMed1988

Results of a rigorous follow-up system in colorectal cancer.

Results of a computer-aided follow-up programme for patients with colorectal cancer are analyzed. Between 1978 and 1987 1293 patients underwent this programme, the drop-out rate was 17%. 299 recurrences in 168 patients were discovered (40% local recurrence, 29% liver metastases and 31% others). Fifty-one per cent of patients with local recurrence and 47% with liver metastases were symptom free. Radical surgery could be performed in 50% of local recurrences and in 26% of liver metastases. The three year survival rate after radical surgery for recurrence was 35% for local recurrences and 33% for liver metastases, the five-year-survival rate 23% and 15%, respectively.

Cohort Studies↗
PubMed1988

Rectal cancer: factors influencing the development of local recurrence after radical anterior resection.

The study was designed to select criteria which influence the incidence of local recurrence after radical anterior resection for rectal cancer. Local recurrence developed in 18 patients (20%) out of 90. All patients entered a prospective clinical study for the detection of local recurrence (mean observation time: 50 months). The following criteria were evaluated retrospectively: age, sex, staging, grading, gross appearance of the tumour, lymphatic reaction, invasion of lymph- and blood vessels, perineural invasion, mucus production of the tumour and width of the distal margin of clearance (measurement in cm in the specimen immediately after resection). The incidence of local recurrence (%) depended on Dukes stage (A: 7%, B: 17%, C: 40%; p less than or equal to 0.03), grading (well differentiated: 5%, average: 20%, poorly differentiated: 55%; p less than or equal to 0.02), gross appearance (protuberant: 15%, infiltrating: 47%; p less than or equal to 0.006), lymphatic stroma reaction (yes: 10%, no: 45%; p less than or equal to 0.006), invasion of veins (yes: 75%, no: 20%; p less than or equal to 0.0002), perineural invasion (yes: 52%, no: 17%; p less than or equal to 0.001) and the margin of clearance (less than 1 cm: 52%; 1-3 cm: 10%, greater than 3 cm: 15%; p less than or equal to 0.02 Mantel, p less than or equal to 0.05 Breslow between less than 1 cm vs 1-3 cm and greater than 3 cm, respectively). Local recurrence was not related to age, sex and mucus production of the tumour. Unfavourable morphological criteria may help to define groups with a higher risk of developing local recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1988

[Therapy of fetal cardiac arrhythmia ante partum and sub partu].

After representation of importance and pathophysiology of fetal tachycardias a short review is given about principles and ways of the intrauterine cardioversion. They are the base for the following detailed description of the present therapeutical possibilities of fetal arrhythmias (sinustachycardia, paroxysmal supraventricular tachycardia and atrial flutter) under consideration of literature and own experience. Concluding recommendations about behaviour in case of fetal tachyarrhythmias are given.

Anti-Arrhythmia Agents↗
PubMed1988

Compliance--a joint effort of the patient and his doctor.

Non-compliance is the reason why in 25-50% of cases treatment of seizures is only partially successful. We have tried to throw some light on the reasons for noncompliance in the behaviour of the doctor as well as the patient. It is not possible simply to prescribe compliance - even though the result is a decrease in attacks; reliability must be learnt. Responsible patients and compassionate doctors are a pre-condition for reliability. Both doctor and patient are committed to treating and healing. This can only be achieved by mutual trust and understanding. A doctor who can make clear to his patient that he is dependent on the patient's co-operation will be more successful than a doctor who does not. Self-help groups can help the patient to recognise his difficulties and take responsibility for himself by coming to terms with his illness. Self-help groups cannot produce compliance; compliance is a result of group work. The doctor - patient relationship has been the subject of much thought, discussion and theorizing recently. In all of this compliance is the key factor.

Anticonvulsants↗