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Biomedical subjects

F Noll

Publications and source records attributed to F Noll.

At least 19 recordsLinked to original sources

Phospholipid monolayer of plant lipid bodies attacked by phospholipase A2 shows 80 nm holes analyzed by atomic force microscopy.

In plant storage tissue, lipid bodies are composed of triacylglycerides and surrounded by a phospholipid monolayer which is stabilized by oleosins. At the onset of lipid body mobilization, cells express phospholipase A2, which partially degrades the monolayer and thus provides access for the subsequently acting triacylglyceride degrading enzymes. Analyzing the lipid body surface by atomic force microscopy we show that, at the stage of maximal phospholipase A2 expression, the monolayer contains holes of approximately 80 nm in width and 2.45 +/- 0.46 nm in depth. Non-contact mode imaging was performed with a lateral resolution of approximately 10 nm and a vertical resolution of less than 0.1 nm. The depth of the holes corresponds to the width of the monolayer, while the width of the channels is sufficiently large to provide access to 100 kDa enzymes, such as lipoxygenase and lipases.

Cucumis sativus↗

Intravesical therapy with pertussis toxin before radical cystectomy in patients with bladder cancer: a Phase I study.

OBJECTIVES: To ascertain the side effects of intravesical instillation of pertussis toxin (PTX) because it inhibits tumor cell motility in vitro and in vivo and seems to be a promising therapeutic approach against cancer. METHODS: We initiated a Phase I study and measured the effect of intravesical instillation of PTX before radical cystectomy. Study end points were PTX-related side effects. PTX was instilled at five dose levels, starting with 14 microg and continuing to 72 microg. RESULTS: Fifteen patients, with a median age of 64 years, were included in the study. Intravesical instillation of PTX was without local or systemic side effects (grade 0, according to National Cancer Institute toxicity criteria). CONCLUSIONS: Treatment with PTX was safe and well tolerated without any significant local or systemic toxicity in dosages up to 72 microg. Therefore, the influence of PTX on local tumor should be evaluated in a Phase II study.

Administration, Intravesical↗

Therapy of superficial bladder carcinomas.

Treatment of superficial bladder carcinoma was derived by several large randomized trials. This group of cancers is stratified by differentiation grade and stage in three groups of different risk profiles (Ta G1-2 vs. T1 G1-2 vs. Tis/T1 G3). Standard therapy is fractionated transurethral resection (TUR). Adjuvant therapy after transurethral resection is not indicated in primary Ta G1-2 tumors because there is a low recurrence rate and no risk of tumor progression. The recurrence rate can be decreased up to 15% in recurrent Ta or T1 G1-2 tumors by intravesical therapy with mitomycin C (20 mg/instillation) or adriamycin (50 mg/instillation). Therapy should be limited to early (within 24 h post-TUR) and short-term treatment (4 x weekly, 5 x monthly). Alternatively, patients can be treated by intravesical BCG (strain Connaught or strain RIVM). Maintenance therapy is advantageous according to recurrence rate. Tumors with great malignant ability (Tis or T1 G3) will be treated initially with adjuvant BCG. Patients who fail are candidates for radical cystectomy within 3-6 months after initial diagnosis. There is no need - except in clinical trials - for the administration of unverified or not admitted drugs.

Carcinoma, Transitional Cell↗

Transurethral sphincterotomy in quadriplegic patients: long-term-follow-up.

Sphincterotomy was the treatment of choice in spinal cord injured patients with reflex bladder activity and detrusor sphincter dyssynergia after World War II. However, nowadays the conversion of a spastic bladder into a low pressure reservoir by medication or operatively has become a more favourable bladder management. Only in quadriplegic patients who are not able to perform self-catheterization, this treatment modality seemed to be an alternative. With twelve o'clock sphincterotomy, urodynamic parameters of the lower urinary tract can be brought to favourable measures (leak-point, residuals). However, the reoperation rate for the maintenance of these urodynamic results is high (57%). Laser sphincterotomy seems to be advantageous in this respect, as it reduces the need for resphincterotomy significantly. Additionally, 14% of the patients needed operations, which made condom fixation possible. Upper tract could only be preserved if sphincterotomy is done early enough. Patients who do not empty completely while in the wheelchair are at risk to develop a hydronephrosis.

Adult↗

Immunoenzymometric assay of human glycogen phosphorylase isoenzyme BB in diagnosis of ischemic myocardial injury.

With a new immunoenzymometric assay we measured human glycogen phosphorylase isoenzyme BB (GPBB) in 116 healthy individuals, 14 patients with stable angina, 107 nontraumatic chest pain patients on admission to the emergency department [45 acute myocardial infarction (AMI), 49 unstable angina, 13 other diseases], and in serial samples from 41 AMI patients. GPBB was compared with creatine kinase (CK), CKMB mass, myoglobin, and cardiac troponin T. Receiver-operating characteristic plots demonstrated the significantly greater (P < or = 0.012) discriminatory power of GPBB to detect acute ischemic coronary syndromes compared with all other tested markers. GPBB was the most sensitive marker for detection of AMI during the first 4 h after onset of chest pain, and only GPBB was increased above the upper reference limit (7 micrograms/L) on admission in patients who had unstable angina at rest and reversible ST-T alterations. This and the high early sensitivity of GPBB are most likely explained by its function as a key enzyme of glycogenolysis.

Adult↗

Early release of glycogen phosphorylase in patients with unstable angina and transient ST-T alterations.

OBJECTIVE: To determine whether transient ST-T alterations in patients with unstable angina are associated with an increase in plasma glycogen phosphorylase BB concentrations on admission to hospital. DESIGN: Prospective screening of patients with unstable angina for markers of myocardial cell damage. SETTING: Accident and emergency department of university hospital. PATIENTS: 48 consecutive patients admitted for angina pectoris (18 with transient ST-T alterations). None of the patients had acute myocardial infarction according to standard criteria. MAIN OUTCOME MEASURES: Creatine kinase and creatine kinase MB activities, creatine kinase MB mass concentration, and myoglobin, cardiac troponin T, and glycogen phosphorylase BB concentrations on admission. RESULTS: All variables except for creatine kinase and creatine kinase MB activities were significantly higher on admission in patients with unstable angina and transient ST-T alterations than in patients without. However, glycogen phosphorylase BB concentration was the only marker that was significantly (p = 0.0001) increased above its discriminator value in most patients (16). In the 18 patients with transient ST-T alterations creatine kinase MB mass concentration and troponin T and myoglobin concentrations were significantly (p = 0.0001) less commonly increased on admission (in five, three, and two patients, respectively). CONCLUSIONS: The early release of glycogen phosphorylase BB may help to identify high risk patients with unstable angina even on admission to an emergency department. Glycogen phosphorylase BB concentrations could help to guide decisions about patient management.

Angina, Unstable↗

Urethral stricture repair: results in 179 patients.

From 1977 till April 1990 169 operative reconstructions of urethral strictures were carried out in this clinic. 49 patients with a short stricture (less than 2 cm) underwent excision and end to end anastomosis. In 18 patients with a long stricture (2-6 cm) one stage urethroplasty with a transverse distal penile or preputial island of skin flap was used. 102 patients with extensive or otherwise problematic strictures were subjected to two-stage mesh skin graft urethroplasty. In 10 patients with a short stricture we have recently implanted a new urethral stent in the strictured area after visual urethrotomy. During a long-time follow-up a good anatomical and functional result was achieved in all but 2 patients who underwent an excision and end to end anastomosis. In the island flap urethroplasty group a restricture occurred in one patient, and mesh graft urethroplasty was successful in all but 3 patients. In the urethral stent patients the primary results are excellent.

Adolescent↗

[Urethroplasty using a free dermo-epidermal of preputial mesh graft: Meshgraft urethroplasty].

Long urethral strictures raise serious problems in terms of appropriate treatment. Reconstruction techniques using scrotal skin have a high recurrence rate. In order to avoid complications, a dermoepidermal or preputial Meshgraft was used to reconstruct a new urethra in two stages. In the first stage, the graft was raised and transplanted onto the open urethra. 8 to 12 weeks later, in the second stage, the new urethra is closed. Since 1977, Meshgraft urethroplasty has been performed in 128 patients, using the skin of the foreskin (n = 75) or medial surface of the thigh (n = 53). A good anatomical and functional result was obtained in all but three cases, regardless of the graft donor site. This operative technique constitutes a very effective method for the lasting treatment of long or complicated urethral strictures, for example in patients with spinal cord injuries.

Adolescent↗

Novel antibody coating of a magnetizable solid phase for use in enzyme immunoassays.

Novel kinds of magnetizable particles have been prepared using the interaction between the complexing groups of phosphonic acid and polyvalent metal ions on the surface of Fe3O4 particles. After modification of monoclonal and polyclonal antibodies by the bifunctional chelating agent 2-(4-diazophenyl)-1-hydroxyethane-1,1-bisphosphonic acid, antibodies were immobilized at a ratio of 5-10 mg antibody molecules per ml Fe3O4 particles without loss of immunological reactivity. Very sensitive and fast immunoenzymometric assays for the quantitative determination of human interferon-alpha 1 and mouse immunoglobulins were developed using such particles. The advantages of the method include immobilization of proteins on magnetizable carriers without chemical modification of the carrier and the short assay time compared to conventional immunoenzymometric assays.

Animals↗

Characterization of human tissue-type plasminogen activator with monoclonal antibodies: mapping of epitopes and binding sites for fibrin and lysine.

The study defines interactions between human tissue-type plasminogen activator (t-PA) and 21 mouse monoclonal antibodies (mAb). Characterization includes epitope distribution, reactivity of different forms of t-PA with antibodies, and modification of t-PA function by antibody binding. Eighteen antibodies are directed against t-PA A-chain. These antibodies recognize four distinct epitopes (A, B, C, D) and one partially overlapping epitope (D'). The remaining three antibodies are directed against two different epitopes (E, F) on catalytically active t-PA B-chain. A-chain reactive antibodies do not bind to the reduced form of t-PA, while B-chain reactive antibodies bind to reduced and deglycosylated t-PA forms. The latter antibodies associate more tightly with sc t-PA than with tc t-PA and have a higher affinity for t-PA-PAI 1 complex as compared to free t-PA. The analysis of functional effects of antibodies reveals that antibodies directed against all above defined epitopes inhibit interactions between t-PA and fibrin: a) binding of t-PA to fibrin, b) fibrinolytic activity of t-PA, and c) fibrin activation of sc t-PA amidolytic activity. The observations support the assumption that several sites of t-PA are involved in fibrin binding and that fibrin-bound t-PA is closely surrounded by the fibrin mesh. Many antibodies quench also binding of t-PA to lysine-Sepharose. Experiments with free, non-fixed lysine confirm strong competition between lysine and mAb 16 and 18, directed against epitope A, and mAb 29, binding to epitope F.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

[Wall-stent for treatment of bulbar urethral stricture and DSD in spastic bladder].

Since may 1989 a urethral Wallstent has been used for the treatment of short urethral strictures and for DSD in paraplegic patients with reflex bladder activity. Forty-nine patients have now been followed-up, which exceeds the 6-month margin. Out of these, 25 suffered from a short stricture of the bulbous urethra and 24 had spastic bladders with severe DSD. Eighteen of the 25 patients with strictures had previous unsuccessful direct vision urethrotomies; 17 in the DSD group had undergone failed sphincterotomies. In all but 2 cases the infravesical obstruction could be treated effectively solely by stent implantation. The results obtained equal those of a well-performed end-to-end anastomosis of the bulbous urethra or a 12, o'clock sphincterotomy.

Adult↗

[Is down-staging of advanced bladder cancer by neoadjuvant chemotherapy possible?--MVEC protocol].

In 22 patients with advanced transitional cell carcinoma of the bladder, neoadjuvant chemotherapy according to the MVEC regimen was given. Subsequent radical cystectomy showed down-staging in 7 patients (32%). The preoperative clinical staging revealed regression of the bladder cancer in 77% of all cases. Down-grading was seen in only 2 patients. Because of the discrepancy between preoperative clinical staging and the histopathological staging after radical cystectomy, invasive tumour surgery is necessary even when clinical staging has not revealed a tumour after chemotherapy.

Aged↗

Purification of monoclonal antibodies by hydroxylapatite HPLC and size exclusion HPLC.

Monoclonal antibodies of both the IgG and the IgM type were purified by hydroxylapatite HPLC (HA-HPLC) under very mild conditions. The IgM type antibodies, which were isolated from ascites fluid and separated from other proteins also by means of size exclusion HPLC. It was shown that the most frequently observed disadvantage of HA-HPLC, that is the relative short life of the columns (P. Steffen (1989) GIT Fachz. Lab., Suppl. 3/89 (Chromatogr.), 50-90), is due to microbial contamination rather than lower mechanical stability. In order to monitor column performance, a test was developed based on the use of standard proteins under isocratic separation conditions. This allows a direct comparison between the respective performances of columns made from different materials, hydroxylapatite or fluoroapatite, from different sources and with different particle sizes. A problem which often occurs with HA-HPLC in the case of IgM antibody isolation, namely precipitation of the antibodies at low salt concentrations at the beginning of a chromatographic run, was avoided by adding sodium chloride to both separation buffers.

Antibodies, Monoclonal↗

[The AS800 artificial sphincter for the treatment of female incontinence].

From 1983 to May 1991, the artificial sphincter AS800 has been applied in 106 female patients for the treatment of complicated cases of urinary incontinence. Of these, 80 remained in continuous follow-up and have now been followed up for at least 1 year, with a mean of 3.8 years. In 40 of our female patients the urethra was afunctional secondary to failure of previous anti-stress-incontinence procedures. Neurogenic incontinence with sphincteric involvement affected 30, while 10 of the patients had congenital sphincter anomalies or traumatic sphincter weakness. Following implantation of the artificial sphincter, 86.3% of these patients are completely continent and do not need a pad. With regard to emptying, 81.3% are able to empty their bladder without residual urine after opening the sphincter, and 8 have to perform clean intermittent catheterization (CIC) once or twice daily in addition. A further 7 void exclusively by CIC. As preparation for implantation of the AS800 sphincter, 24 additional procedures were performed, including 5 antireflux operations and 6 bladder-flap procedures. In 38 of 80 patients a total of 62 revisions were performed. Infection and erosion were the most common reasons for revision, accounting for 48.2% of all revisions. The next most common reason was tissue atrophy underneath the cuff. However, 25% of the revisions were due to device failures, most often cuff leakage.

Adolescent↗

Ileumaugmentation and alloplastic sphincter implants.

A total of 46 patients with reflex bladder activity who failed conservative treatment underwent bladder augmentation in some cases in combination with the implantation of an artificial sphincter. Twenty were a result of a spinal cord injury and 26 had myelomeningocele. Acceptable continence has been achieved in 42 patients. In order to accomplish this 39 simple bladder augmentations with ileum, 5 total bladder replacements and 2 augmentations with sigma were performed. Additionally 6 antireflux operations, 8 bladder-flap procedures and 26 implantations of an artificial sphincter were carried out. Overall patient satisfaction was 88 percent.

Adolescent↗