Biomedical subjects

K Jahnke

Publications and source records attributed to K Jahnke.

At least 73 records · Page 4Linked to original sources

PubMed1996

Purification and characterization of dihydropyrimidine dehydrogenase from Alcaligenes eutrophus.

Dihydropyrimidine dehydrogenase from Alcaligenes eutrophus was purified to homogeneity using ammonium sulfate fractionation and chromatography on phenyl-Sepharose, MonoQ-Sepharose, and 2,5-ADP-Sepharose. The enzyme is a homotetramer with a subunit molecular mass of 52 kDa. The absorption spectrum of the bacterial dihydropyrimidine dehydrogenase has maxima in the 300- and 400-nm region, suggesting a flavoprotein. The enzyme contains 4 mol FMN, about 24 mol iron and acidlabile sulfide per mole of protein, implying a flavoprotein with FeS centers. The bacterial dehydrogenase is NADPH dependent with B-side stereospecificity. The initial velocity patterns of the bacterial dehydrogenase together with isotope exchange at equilibrium and a quantitative analysis of the product and dead-end inhibition data suggest a rapid equilibrium random kinetic mechanism, which is in contrast to results obtained for dihydropyrimidine dehydrogenase from pig liver. The pig liver enzyme adheres to a nonclassical two-site ping-pong kinetic mechanism [B. Podschun, P. F. Cook, and K. D. Schnackerz (1990) J. Biol. Chem. 265, 12966-12972], whereas for the bovine enzyme a rapid equilibrium random kinetic mechanism was proposed based on steady-state kinetic data [D. J. T. Porter and T. Spector (1993) J. Biol. Chem. 268, 19321-19327].

Alcaligenes↗

PubMed1996

[The time span between symptom onset and starting treatment in head and neck tumors].

The interval between the onset of symptoms in patients with head and neck cancers and the introduction of treatment was evaluated. During a 1-year period, patients were interviewed to determine the duration of any delays from the onset of complaints until the first visit to a doctor. Also asked was how long it took to be referred to an ENT specialist and actual referral to our department. We then determined the interval from diagnosis to the introduction of therapy. It was found that the delay of patients who went directly to an otorhino-laryngologist was shorter (median, 8 weeks) than that of patients who first went to their family doctors (median, 13 weeks) (P < 0.02). The latter then took an additional 4 weeks before sending patients to an otorhinolaryngologist. Referral from the ENT specialist to our department took another 2 weeks, as well as our staging and pre-therapeutic management. Our findings show that the patient himself is the critical factor in delaying diagnosis and therapy. Tumor patients with greater professional qualification went to their doctors earlier (P < 0.0001) or more often went directly to an ENT specialist (P < 0.002). Consultations of physicians without experience in otorhinolaryngology caused yet further delays.

Adult↗

PubMed1996

[Golden tube wire for temporary or permanent implantation].

Abnormal eustachian tube function has been a major problem in improving hearing with middle ear surgery. In 13 patients, a newly developed gold tube conductor was placed in the eustachian tube via the middle ear cavity. Patients were examined 2-50 months postoperatively, at which time middle ear aeration was found to be significantly improved in 11 of the cases.

Adolescent↗

PubMed1996

[Rhinosurgery in diseases of the orbits].

The rhinosurgical procedures in different orbital diseases are discussed. Special attention is directed to the application of endoscopic and microsurgical techniques. We describe the different stages of orbital involvement in 106 patients. Computer-tomography has proven to be most effective informing the extent of sinus disease as well as orbital inflammation, because of this an immediate stage-dependent therapy can be commenced. Indications for endonasal, extranasal or for combined approaches are given. In two patients with blindness due to mycosis we performed an exenteration of the orbit. The advantages of extranasal and endonasal techniques for decompression of the orbit are discussed. Successful approaches for the extranasal microsurgical removal of orbital tumors are described. The results demonstrate that the surgically decompressed optic nerve has a favourable prognosis. Pathogenesis, diagnostic procedures, indications and microsurgical techniques of the traumatized optic nerve are discussed. The long-term follow up results of our optic nerve decompression cases are presented.

Endoscopy↗

PubMed1995

[Surgery of cholesteatoma of the ear canal].

Aseptic necrosis and cholesteatoma of the external auditory canal can be stages of the same pathological entity. The majority of these patients suffered from symptoms similar to those of external otitis. It is suggested that minor mechanical trauma, e.g. cotton lip swabs, plays a role in the pathogenesis of external ear canal cholesteatoma. During the last 10 years we have been surgically treating 22 patients with diagnosis of aseptic necrosis and cholesteatoma of the bony external auditory canal. All 22 patients registered significant postoperative improvement.

Adult↗

PubMed1995

[Meniere disease as an autosome dominant hereditary disease].

Within one year (1993) we found a positive family history in five out of forty-eight new patients with Menière's disease, corresponding to a frequency of 10.4%. We found between two and seven cases in each of five families. The disease followed a dominant autosomal hereditary pattern over two to four generations. Audiometric and vestibulometric examination confirmed the diagnosis. Clinical emphasis was placed on trigger factors such as infections, physical and psychological stress, the autonomic system, and metabolic and endocrinological disorders. There was no evidence of a significantly high incidence of any single trigger factor. The most important result of this study, which also included human leucocyte antigen (HLA) typing, is the fact that HLA A2 was represented in 90% of patients with positive family history of Menière's disease and in 75% of patients with solitary Menière's disease in contrast to only 28.9% in the average European population. The frequency of HLA B44 was 70% in family-linked Menière's disease and 37.5% in single Menière's disease. The frequency in the average European population is 12.3%. What is even more striking is the combination HLA A2 B44, occurring with respective frequencies of 60%, 37%, and 5%. These results suggest a multi-factor etiology of Menière's disease combined with a genetic predisposition, which might be caused by mutations on the short arm of chromosome 6.

Adult↗

PubMed1995

Tragal cartilage in the primary reconstruction of defects resulting from a nasal septal abscess.

Immediate reconstruction of nasal septal sequestration following a septal abscess with autologous tragal cartilage graft is the method of choice in children and adolescents. On one hand autologous tissue is used, thus foreign body reaction with rejection or irregular resorption does not occur. On the other hand further defects in the posterior septal segment with additional damage to growth zones do not arise. Furthermore local tissue is saved, thus it will be available later, in case revision surgery will be necessary. But in contrast to costal cartilage tragal cartilage is easy to obtain in reconstruction of the nasal septum. No visible or functional defect arise at the donor site.

Abscess↗

PubMed1995

Experimental results concerning the reconstruction of the stapes superstructure with bioactive ceramics.

We examined the feasibility of rebuilding a stable stapes superstructure in the middle ear for a new articulated ossicular chain by using bioactive ceramic and glass ceramic in guinea pigs. The ceramic implants were placed on the stapes footplate without touching the tympanic membrane, thus protecting it against relative movements. The implants were removed together with the stapes footplate after six weeks, three and six months respectively. After six weeks, histological evidence of bony connections between all ceramic implants and the remnants of the crurae were found, being more pronounced after three and six months. We propose a new implant for the reconstruction of the stapes superstructure.

Animals↗

PubMed1995

[Macroglossia as the initial symptom of amyloidosis].

Amyloidosis is a term that describes a heterogeneous group of disorders in which various tissues contain the characteristic insoluble fibrillar protein known as amyloid. A number of different forms of presentation have been described and include senile, familial or hereditary, systemic, localized, secondary and primary forms. We now report our management of a 79-year old woman who suffered from primary A-lambda-light chain amyloidosis. Amyloid changes first presented in the tissues of the tongue and floor of mouth and were seen clinically as a macroglossia. Further investigation led to a primary diagnosis of multiple myeloma IIa, as categorized by Durie and Salmon. Several cases have been reported to date describing secondary development of macroglossia due to long-term known and treated multiple myeloma. However, there has been only one report of macroglossia as a primary finding leading to the diagnosis of multiple myeloma.

Aged↗

PubMed1995

[Fatal outcome after retrograde insufflation of the eustachian tube].

This case report describes a lethal complication of retrograde air insufflation through the Eustachian tube after myringotomy. A 35-year-old woman presented with otalgia and hearing loss in her left ear, which had occurred after an upper respiratory infection. Otoscopy showed a middle ear effusion. A myringotomy was performed under mask anesthesia in a private clinic. During subsequent retrograde Eustachian tube insufflation, the patient experienced sudden convulsions, followed by cardiac and respiratory arrest. The patient then died some hours later from generalized cardiac and circulation break-down in the intensive care unit of a nearby hospital. The cause of the cardiac and circulation collapse could not be defined completely, but it is believed than an anatomical variant of the tegmen tympani was responsible for the tragic outcome because of an air embolus.

Adult↗

PubMed1994

[Cancers in medial neck cysts--3 case reports].

1% of thyroglossal duct cysts are supposed to develop carcinoma. In most cases papillary carcinoma is found deriving from ectopic thyroid tissue. As far as squamous cell carcinomas are concerned, worldwide only eleven cases have been reported so far. In this article, three cases of carcinoma in a thyroglossal duct cyst are presented (1 case of squamous cell carcinoma, 2 cases of papillary carcinoma). The diagnostic procedures as well as the therapeutic strategies are discussed. The diagnosis of a thyroglossal duct cyst should be confirmed by ultrasonography. This can provide information about the presence or absence of a normal thyroid gland and makes radioisotope scanning unnecessary.

Adult↗

PubMed1994

E-cadherin as a functional marker of the differentiation and invasiveness of squamous cell carcinoma of the head and neck.

The cell-cell-adhesion molecule E-cadherin is necessary for the maintenance of the epithelial cellular structure. We were able to show a correlation between decreasing E-cadherin expression, dedifferentiation and increased invasiveness in a cell line model. We studied 73 squamous cell carcinomas from the upper aerodigestive tract using the immunofluorescent method to demonstrate expression of E-cadherin. Decreased E-cadherin expression correlated with a decreased grade of differentiation and an increased lymph node metastatic rate. This confirms the significance of E-cadherin as a marker for differentiation and invasiveness of squamous cell carcinoma of the pharynx and larynx.

Cadherins↗

PubMed1994

[Accelerated hyperfractionated radiotherapy combined with simultaneous chemotherapy in locally advanced pharyngeal and oral carcinomas].

PURPOSE: To evaluate the feasibility and effectiveness of a concurrent radio-chemotherapy regimen for locally advanced carcinomas of the pharynx and floor of the mouth. PATIENTS AND METHODS: Since January 1990, 97 patients with locally advanced carcinomas of the naso-, oro-, hypopharynx and the oral cavity in UICC stages III and IV were treated according to an accelerated hyperfractionated radiotherapy schedule with concurrent chemotherapy. The primary tumor and positive lymph nodes received a total dose of 72 Gy in 6 weeks. In the first 3 weeks, large fields were irradiated 5 times per week with 2 Gy per fraction. Thereafter, treatment was accelerated, giving 2 daily fractions of 1.4 Gy with minimal intervals of 6 hours. Target volumes were reduced after 49.6 and 59.4 Gy, excluding clinically uninvolved lymph node regions of low and high risk. On day 1, 350 mg/m2 5-FU and 50 mg/m2 folinic acid were given as intravenous bolus followed by continuous infusion of 350 mg/m2 5-FU and 100 mg/m2 folinic acid, days 1 to 5. 10 mg/m2 mitomycin C was given on day 5 and 36 of the treatment. Salvage surgery was offered for residual disease 5 to 6 weeks after the end of radiotherapy. PATIENT CHARACTERISTICS: 70 male, 27 female; age: 27 to 81 years; T2/T3/T4: 7/30/60; N0/N1/N2/N3: 20/18/53/6; nasopharynx/oropharynx/hypopharynx/oral cavity: 16/33/36/12. Median follow-up is 26 months. RESULTS: Overall survival and recurrence-free survival at 2 years were RESULTS: Overall survival and recurrence-free survival at 2 years were 68 +/- 5% and 74 +/- 5%. Multivariate analysis revealed a significant influence of the geometric mean neck node diameter or the N-stage on loco-regional control and survival. T-stage, tumor volume, or tumor localisation did not become significant. Acute toxicity of this schedule was acceptable but required optimised supportive care. Treatment related grade 4+ late toxicity of mucosa, soft tissue and bone were observed with a cumulative frequency of 13% at 2 years. Two patients died during a phase of severe leuko- or thrombocytopenia. CONCLUSION: This phase I to II trial shows favourable results using an intensified treatment radio-chemotherapy protocol. A phase III study is now planned, comparing this regime with an accelerated hyperfractionated radio-therapy alone to an increased total dose of 77.6 Gy.

Adult↗

PubMed1993

Acid-base catalytic mechanism of dihydropyrimidinase from pH studies.

The pH dependence of kinetic parameters and solvent deuterium isotope effects have been used to probe the mechanism of the dihydropyrimidinase from the liver of pig and calf. The V/K for 5,6-dihydrouracil (DHU) (or the alternative substrate glutarimide) measured with either the native zinc or cadmium-substituted enzymes decreases at both low and high pH giving pK values of about 7.5-8 and 9-10. The low pK value observed in V is perturbed significantly to lower pH (approximately 6), and the high pK is not observed. The binding of glutarate monoamide is optimum when the group with a pK of 7.7 is protonated, and this same group must be protonated for the reverse reaction, that is, formation of DHU from N-carbamoyl-beta-alanine. These data are consistent with a general base mechanism and in addition suggest that the enzyme is present initially with a water bound to the active site zinc. The enzymic general base with a pK of 7.5-8 is required to activate water for nucleophilic attack on the C-4 of 5,6-dihydrouracil which is directly coordinated to the active site zinc. The second group with a pK of 9-10 likely reflects Zn-water ionization of the free enzyme. The water bound to the active site Zn is displaced by reactant binding, and thus the pK of 9-10 is not observed in the V profile. Solvent deuterium isotope effects are near unity on the V/K for the natural substrate 5,6-dihydrouracil, but a finite effect of 1.6 is observed on V.(ABSTRACT TRUNCATED AT 250 WORDS)

Amidohydrolases↗

PubMed1993

Acid base catalytic mechanism of the dihydropyrimidine dehydrogenase from pH studies.

Primary deuterium (NADPH(D)), solvent deuterium, and multiple isotope effects and the pH dependence of kinetic parameters have been used to probe the mechanism of the dihydropyrimidine dehydrogenase from pig liver. Isotope effect and pH-rate data suggest a rate-determining reductive half-reaction in which reduction of the flavin by NADPH has only a minor rate limitation (DV approximately D(V/KNADPH) approximately 1.1), while protonation of the flavin at N-1 occurring in a step following reduction is slow (D2OV = 3, while D2O(V/KNADPH) = 2). An enzymatic general acid with a pK of 8.2 is required to protonate N-1 of the flavin. In the second half-reaction, uracil is reduced at C-6 by flavin and protonated on the opposite face at C-5 by an enzymatic general acid with a pK of 9. The hydride transfer from N-5 of the flavin to C-5 of uracil is facilitated by an enzymatic general base with a pK of 5.6 that accepts a proton from N-1 of the flavin. There is also evidence from the pH dependence of V and the V/K for reduced dinucleotide substrates that a second enzyme residue with a pK of 6.4 must be unprotonated for optimum activity, but is not essential for activity. None of the functional groups reflected in the V/KNADPH pH-rate profile have a role in binding, while both of those observed in the V/Kuracil profile have a role in binding as shown by the pH dependence of the dissociation constants for the competitive inhibitors ATP-ribose and 2,6-dihydroxypyridine.

Animals↗

PubMed1993

[Reconstruction of the stapes superstructure with bioactive ceramics].

In this study we examined the feasibility of rebuilding a stable stapes superstructure for a new articulated ossicular chain by using bioactive ceramics. Dense hydroxylapatite and ceravital were tested in guinea pigs. The ceramic prosthesis was placed on the remnants of the footplate to create a bony connection without touching the tympanic membrane, thereby protecting it from relative movements. The implants were explanted together with the stapes footplate at six weeks and three months, respectively. Histologically, bony connections were found between all ceramic implants and the remnants of the crura even at six weeks and became more pronounced after three months.

Animals↗

PubMed1993

[Otosclerosis in the elderly. The effect of stapes-plasty on hearing ability and hearing aid management].

We examined 105 patients who underwent partial stapedectomies at the age of 65 years or older as treatment for combined hearing losses due to otosclerosis. Among other things investigated was the influence of the operation on the hearing of both the operated and unoperated ears, as well as on tinnitus existing preoperatively and the use of a hearing aid. Findings showed that tinnitus decreased or vanished in 75% of the cases. Sixty-one percent of the patients needed a hearing aid continuously preoperatively, with 48% not needing it post-operatively and 13% using it only occasionally. The degree of sensorineural hearing loss had by the other patients was so severe that the use of a hearing aid was also necessary post-operatively. However, in some of these cases, a successful use of a hearing aid became possible for the first time due to the surgical improvement in hearing.

Aged↗

PubMed1992

[Tympanoplasty].

The first goal of tympanoplasty as treatment for chronic otitis media is to obtain a clean, disease-free ear, the second one hearing improvement. Prerequisite for success is the sufficient functioning of the inner ear as well as of the Eustachian tube. Therefore, patients very often have to undergo adjuvant treatment such as adenotomy, rhino-surgery and surgery of the paranasal sinuses. Microsurgery of the ear has become very refined. Thus even after removal of extensive inflammation it is now possible to rebuild the middle ear using various proved as well as newly developed biomaterials. Often a two-stage procedure is advisable for cholesteatoma surgery. In this disease meticulous postoperative care and longterm follow-ups are very important.

Cholesteatoma↗