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Biomedical subjects

N Wolf

Publications and source records attributed to N Wolf.

At least 55 records · Page 3Linked to original sources

Gastric aspiration technique for pH recording: a critical evaluation of this method.

The most often used methods for the measurement of intragastric acidity are repeated mostly hourly aspirations of gastric contents or continuous pH measuring with an electrode. Intragastric pH, volume of aspirated gastric juice and total acid secretion have been tested over relatively short periods of time (2-12 h) and through an entire 24-hour period. Nearly every clinical antiulcer drug which neutralizes acidity or inhibits acid secretion has been investigated with this method. pH monitoring with the gastric aspiration procedure is a reliable and reproducible method. There is a remarkable global agreement in the results. While pH electrodes provide an alternative means of measuring pH, they have the disadvantage of not allowing measurement of volume and/or acid secretion.

Anti-Ulcer Agents↗

[Inhibition of 24-hour acidity by nizatidine].

In a randomized, double-blind, placebo-controlled, comparative cross-over study, we studied the effect of four H2-receptor antagonists on intragastric 24-hour acidity, nocturnal volume and acid output. Ten healthy male volunteers were administered 300 mg or 150 mg nizatidine, 800 mg cimetidine, 300 mg ranitidine, 40 mg famotidine, or placebo on several days, in each case at 9:000 PM. Nocturnal intragastric H+ concentration (mmol/l) (11:00 PM to 7:00 AM) was significantly reduced by all H2 blockers compared with placebo. We obtained the following inhibition rates: Cimetidine 67%; ranitidine 95%; famotidine 89%; nizatidine 80% (300 mg) and 69% (150 mg). Nocturnal acid (mmol/l) and volume output (ml/h) were also significantly (compared with placebo) inhibited by all four H2-receptor antagonists. Inhibition of nocturnal acid secretion was almost identical on nizatidine 300 mg nocte, ranitidine 300 mg nocte, famotidine 40 mg nocte, and cimetidine 800 mg nocte. Nizatidine 300 mg nocte and 150 mg nocte exclusively reduced acid secretion at night, without an aftereffect into the following day (8:00 AM to 6:00 PM). These results suggest that the clinical efficacy of these H2-receptor antagonists is identical with respect to healing peptic ulcer disease and providing freedom from pain. It is generally accepted today that gastric acid inhibitors used in the treatment of peptic ulcer disease should interfere with daytime gastric acid secretion as little as possible, particularly since the acid protects the stomach from bacteria ingested with the food during the day.

Cimetidine↗

[Anal canal carcinoma: diagnosis--therapy--prognosis].

78 patients with anal canal carcinoma were treated between 1970 and 1988 at the University Hospital Erlangen. 48 patients (35 women, 13 men) were treated by surgery alone, 44/48 by abdominoperineal resection, 4/48 by local excision. Median age was 63 years, median follow-up 8.5 years. The overall local recurrence rate was 16.7%, the overall five-year-survival was 51%. 30 patients received a combined radio-chemotherapy. The small pelvis was treated with a.-p./p.-a. fields up to a total dose between 42 and 50 Gy. Two courses of chemotherapy consisting of 5-FU (800 to 1000 mg/m2 days 1 to 4 and 29 to 32) and Mitomycin C (10 mg/m2 days 1 and 29) were administered. Two months after completion of treatment 83% had a biopsy proven complete remission. After a median follow-up of 15 months 87% are alive with NED, 74% are continent. The combined regimen of radio-chemotherapy is considered as the treatment of the choice for anal canal carcinoma. Abdominoperineal resection is only performed in patients with non response or local recurrent disease.

Antineoplastic Combined Chemotherapy Protocols↗

[Single evening administration of a new antimuscarinic agent telenzepine in therapy of acute duodenal ulcer. Results of a randomized double-blind comparative study versus pirenzepine].

A multicenter, double-blind, randomized controlled study was conducted in 314 duodenal ulcer patients to compare the efficacy and safety of the antimuscarinics telenzepine and pirenzepine in the treatment of duodenal ulcer. Patients received telenzepine 3 mg (156) once-daily at bedtime or 50 mg pirenzepine (158) two times daily for 2 weeks. If ulcerous lesions persisted treatment was extended to 4 weeks. Efficacy was assessed by relief of ulcer pain and endoscopic findings of ulcer healing. Safety was determined on the basis of side effects and results of laboratory tests. The 2- and 4-week healing rates achieved with telenzepine were 21.1 and 67.3%, respectively, and with pirenzepine they were 20.0 an 69.0%, respectively; the differences in healing rates for the two drugs were not statistically significant. Similarly both drugs provided satisfactory relief of pain. The incidence of untoward effects was 24.5% with telenzepine and 29.7% with pirenzepine, dryness of mouth being most prominent (20.4 vs. 19.3%). With telenzepine blurred vision was reported in a significantly lower rate compared to pirenzepine (0.7 vs. 4.2%, p less than 0.05). Clinically relevant abnormal laboratory tests were not observed. The present study shows for the first time that the newly developed antimuscarinic drug telenzepine is in a single nocturnal dosage regimen (3 mg nocte) as effective as pirenzepine (50 mg bid) in the treatment of duodenal ulcer.

Adult↗

The use of carbon dioxide fiberoptic laser catheter for atrial septostomy.

The development of optical fibers capable of transmitting laser energy has encouraged the experimental use of laser irradiation for the treatment of acquired cardiovascular disorders. One of the key questions is which combination of laser source, energy parameters, and transmitting fiberoptic would be best suited for intravascular use. In most experiments argon, neodymium-YAG, and excimer lasers, coupled to suitable optical fibers, have been used. We now describe the use of a carbon dioxide fiberoptic laser catheter for the creation of an atrial septal defect. Silver halide infrared transmitting fibers were inserted into standard 6 French cardiovascular catheters. This laser catheter system, capable of transmitting several watts of pulsed CO2 laser energy, was initially used to create atrial septal defects in isolated dog hearts to determine the best energy parameters. Atrial septostomy was later performed successfully in four of five anesthetized dogs. The thermal damage extended 50 to 60 micron beyond the "holes" created by the laser irradiation in the interatrial septum. Thus, pulsed CO2 laser irradiation, delivered through optical fibers, can create an atrial septal defect.

Animals↗

Maternal-effect lethal mutations on linkage group II of Caenorhabditis elegans.

We have analyzed a set of linkage group (LG) II maternal-effect lethal mutations in Caenorhabditis elegans isolated by a new screening procedure. Screens of 12,455 F1 progeny from mutagenized adults resulted in the recovery of 54 maternal-effect lethal mutations identifying 29 genes. Of the 54 mutations, 39 are strict maternal-effect mutations defining 17 genes. These 17 genes fall into two classes distinguished by frequency of mutation to strict maternal-effect lethality. The smaller class, comprised of four genes, mutated to strict maternal-effect lethality at a frequency close to 5 X 10(-4), a rate typical of essential genes in C. elegans. Two of these genes are expressed during oogenesis and required exclusively for embryogenesis (pure maternal genes), one appears to be required specifically for meiosis, and the fourth has a more complex pattern of expression. The other 13 genes were represented by only one or two strict maternal alleles each. Two of these are identical genes previously identified by nonmaternal embryonic lethal mutations. We interpret our results to mean that although many C. elegans genes can mutate to strict maternal-effect lethality, most genes mutate to that phenotype rarely. Pure maternal genes, however, are among a smaller class of genes that mutate to maternal-effect lethality at typical rates. If our interpretation is correct, we are near saturation for pure maternal genes in the region of LG II balanced by mnC1. We conclude that the number of pure maternal genes in C. elegans is small, being probably not much higher than 12.

Animals↗

Temporal and spatial pattern of differences in microtubule behaviour during Drosophila embryogenesis revealed by distribution of a tubulin isoform.

Immunofluorescence staining of Drosophila embryos with a monoclonal antibody specific for acetylated alpha-tubulin has revealed that acetylated and nonacetylated alpha-tubulin isoforms have different patterns of distribution during early development. Acetylated alpha-tubulin was not detected in either interphase or mitotic spindle microtubules during the rapid early cleavage or syncytial blastoderm divisions. Acetylated alpha-tubulin was first observed as interphase lengthened at the end of syncytial blastoderm, and at cycle 14 was localized to a ring of structures clustered around the interphase nuclei. These structures probably represent a set of stable microtubules involved in nuclear elongation. Absence of detectable acetylated alpha-tubulin prior to cellular blastoderm seems to be due to rapid turnover of microtubule arrays rather than to lack of the enzyme required for modification, since acetylated alpha-tubulin appeared in early embryos when micro-tubules were stabilized by taxol treatment or anoxia. Because acetylated alpha-tubulin seems to be characteristic of stable microtubule arrays, the appearance of the antigen at cycle 14 represents a fundamental change in microtubule behaviour in the somatic cells of the embryo. Acetylated alpha-tubulin was not detected in pole cells during the blastoderm or early gastrula stages, indicating that acetylation of alpha-tubulin is not merely a consequence of cellularization. After the onset of gastrulation, interphase microtubule arrays in most cell types contain acetylated alpha-tubulin. However, cells in mitosis lack antibody staining. The resulting unstained patches reveal the stereotyped spatial pattern of cell division during gastrulation. Although the cells that give rise to the amnioserosa have acetylated alpha-tubulin in their interphase arrays at early gastrulation, by germ band elongation these large, plastic cells completely lack staining with anti-acetylated alpha-tubulin. In contrast, differentiated cell types such as neurones, which have arrays of stable axonal microtubules, stain brightly with the specific antibody. Although acetylated and nonacetylated alpha-tubulin are present in roughly equal amounts by the late stages of embryogenesis, acetylated alpha-tubulin is partitioned into the pellet during centrifugation of extracts of embryos homogenized at 4 degrees C.

Animals↗

[Function-preserving treatment of anal cancer using simultaneous radio- and chemotherapy].

Since 1985, twelve patients with anal carcinoma underwent simultaneous radiation and chemotherapy as primary treatment. The primary tumor region and the regional lymph drainage area received a total dose of 30 Gy over three weeks or 50 Gy over five weeks. During the first week of radiotherapy, 5-fluorouracil (1000 mg/m2 daily for four days by continuous infusion), and mitomycin (10 mg/m2 on day 1) were administered; four weeks later, a second cycle at the same dosage followed. This treatment schedule was well tolerated by all patients and all tumors responded. In only one patient was the tumor still palpable at the end of the treatment period. In eight patients a biopsy was obtained from the primary tumor region four weeks after treatment had ended: in six of them no further operative treatment was necessary, because no evidence of tumor was found in the biopsy. It is concluded from these results that simultaneous radiation and chemotherapy is the best primary treatment of anal carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗

Expression of chimeric genes in Caenorhabditis elegans.

We have shown the expression of transformed genes in the nematode Caenorhabditis elegans using a new gene fusion system. Vectors consisting of the flanking regions of a collagen gene (col-1) or a major sperm protein gene of C. elegans fused to the Escherichia coli uidA gene, encoding beta-glucuronidase, were microinjected into worms and found to be propagated as high-copy extrachromosomal tandem arrays. We have detected beta-glucuronidase activity in transformed lines, and have shown that the activity is dependent upon the correct reading frame of the construction and on the presence of the worm sequences. The enzyme activity was shown to be encoded by the chimeric beta-glucuronidase gene by co-segregation analysis and by inactivation with specific antisera. Expression is at a very low level, and seems to be constitutive. We have used histochemical techniques to visualize the enzyme activity in embryos.

Animals↗

[Indications for thymectomy].

An absolute indication for thymectomy exists in all cases with tumors of the thymus gland, however, preoperative differentiation between benign and malignant lesions is not always possible even with modern imaging methods. In extensive tumors of questionable operability preoperative transthoracic needle biopsy (guided by CAT-scan) is recommended. After establishing the histological diagnosis, preoperative radio- and/or chemotherapy can be considered. Certain immunological diseases are a relative indication for thymectomy. Its value is proven in myasthenia gravis, questionable however in ulcerative colitis and erythroblastopenia. Systemic lupus erythematosus is a contraindication.

Autoimmune Diseases↗

Two loci required for cytoplasmic organization in early embryos of Caenorhabditis elegans.

We have identified five new alleles, including an amber allele, at each of two loci (zyg-11 II and zyg-9 II) previously identified by temperature-sensitive strict maternal-effect lethal mutations. Genetic analysis indicates that each of these genes is expressed specifically during oogenesis and encodes a protein product whose function is required only during embryogenesis. Temperature-pulse experiments suggest that the time of action of both products is during the one-cell stage of embryogenesis. Phenotypic analysis reveals that mutations in both loci lead to disorganization of the cytoplasm in early embryos and to abnormalities in at least one of the meiotic divisions. Mutations at the zyg-9 locus appear to specifically affect microtubule function in one-cell embryos while zyg-11 mutations affect many cytoplasmic properties.

Alleles↗

[Creative arts activity in manually handicapped patients].

Congenital or acquired conditions directly or indirectly causal in total or partial impairment of manual function are set out. The possibilities for creative-expressive activity, using various techniques, nothwithstanding manual disabilities are pointed out. In Cefischer, who until his war-related loss of both upper limbs had been a renowned cartoonist, a comparison of his works, drawn initially by hand and later with the mouth, reveals his characteristic style of expression having remained the same. Further examples are given of creative expression in the presence of manual disability even under extreme circumstances (such as 11 years of confinement to the Iron Lung). Arts and crafts work of persons with leprosy-related manual handicaps are mentioned; typewriter graphics as a method inaugurated by Basset is presented as used in young people with total manual disability. Partial disability of manual function due to arthritis was present in Renoir, Jawlensky, and Grandma Moses, the course of their conditions is described over time. Contents and form of their pictures, after long years of being manually disabled, do not reveal any essential changes in comparison to their earlier ones.

Art↗

[Intragastric acidity under the prostaglandin E2 analog trimoprostil. Increased inhibitory effect through administration after meals].

In this double-blind cross-over study the effect of trimoprostil (trimethyldesoxyprostaglandin E2), an orally effective prostaglandin E2 analogue, on 24-h intragastric H+-activity, nocturnal acid output, nocturnal volume secretion and meal stimulated gastrin secretion was determined in 12 healthy male volunteers. On three different days the subjects received four times a day either placebo or 1.5 mg trimoprostil 30 min before or 30 min after meals. Trimoprostil administered before or after meals reduced 24-h intragastric acidity by 27.0 and 53.9%. Nocturnal acid output was inhibited by 32.7 and 55.6%. Nocturnal volume secretion and meal stimulated gastrin secretion remained unaffected. The study shows that the antisecretory activity is significantly increased when trimoprostil is given after meals.

Administration, Oral↗

[Experiences with totally implantable catheter systems in home parenteral nutrition].

Totally implantable catheter systems have proved their qualification in patients treated with intravenous chemotherapy. These systems appear to have also advantages in patients requiring home parenteral nutrition. The risks of infection can be minimized, daily dressing changes are not necessary, and the cosmetic appearance is not influenced.

Adolescent↗