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Biomedical subjects

C Ziegler

Publications and source records attributed to C Ziegler.

15 recordsLinked to original sources

Gynecologic history of women with inflammatory bowel disease.

OBJECTIVE: To describe the gynecologic history of women with inflammatory bowel disease. METHODS: Questionnaires were sent to the 1000 women age 20-60 who had been hospitalized for inflammatory bowel disease at the Cleveland Clinic Foundation during 1989-1993. There were 692 responses, and those from 662 women who had undergone surgery for inflammatory bowel disease were analyzed. Of the 117 women who had undergone hysterectomy, 85 responded to follow-up questionnaires. RESULTS: Three hundred sixty women had Crohn disease, 251 had ulcerative colitis, and 51 had inflammatory bowel disease of indeterminate or unknown type. Menstrual abnormalities were reported by 58%. Symptomatic vaginal discharge, reported by 40%, was more likely to occur in those with Crohn disease than with ulcerative colitis (odds ratio [OR] 2.09, 95% confidence interval [CI] 1.47-2.99; P < .001). Infertility was reported by 25% of the women in this series. Abdominal pain with sexual intercourse (50% overall) was more common in women with Crohn disease than in those who had ulcerative colitis (OR 1.64, 95% CI 1.13-2.40; P = .01), but pain with penetration (55% overall) did not differ statistically by type of inflammatory bowel disease. Half of the women reported the loss of pleasure or desire for sex. Ovarian cysts had been diagnosed in 39% of women and resulted in surgical treatment in 57% of these. One hundred seventeen women (18%) had undergone hysterectomy, 52 (44% of total) at age 35 or younger. CONCLUSION: Gynecologic conditions are common in women with inflammatory bowel disease, including menstrual abnormalities, vaginal discharge, infertility, and gynecologic surgery. All physicians providing care for women with inflammatory bowel disease should be familiar with the frequency and nature of concurrent gynecologic conditions.

Adult

Quinolones as an alternative treatment of chlamydial, mycoplasma and gonococcal urogenital infections.

We report the results of several trials aimed at evaluating the quinolones in urogenital infections. In Chlamydia trachomatis infections, ofloxacin (200 mg b.i.d. for 10 days) gave a cure rate of 98% (n = 66), and fleroxacin (400 mg s.i.d. for 7 days) provided a cure rate of 89% (n = 19). A double-blind study comparing fleroxacin (600 mg s.i.d.) to doxycycline (100 mg b.i.d.) for 7 days showed similar high cure rates for both regimens (100%; n = 23). In Mycoplasma hominis infections, ofloxacin (200 mg b.i.d. for 10 days) yielded a cure rate of 86% (n = 50) for M. hominis and 55% (n = 43) for Ureaplasma urealyticum. Gonococcal infections (n = 122) were all cured by a single dose of 200 mg ofloxacin. Both ofloxacin and fleroxacin were well tolerated and may be recommended for patients with chlamydial or uncomplicated gonococcal infections, although 600 mg fleroxacin showed a higher incidence of adverse events compared to doxycycline.

4-Quinolones

On the pathogenesis of anaemia and leukopenia in filarial (Litomosoides carinii) infection of Mastomys natalensis.

Mastomys natalensis infected with the filarial parasite Litomosoides carinii show anaemia and leukopenia. Alterations start with the onset of microfilaraemia. Anaemia is temporally macrocytic (up to 80 days after infection), subsequently normocytic and hypochromic, accompanied by reticulocytosis. Increased intravascular haemolysis (i) and functional disorders of the haemopoetic system (ii) are involved in the pathogenesis. i: Circulating erythrocytes showed increased osmofragility. Hypoglycaemia demonstrated in parasitaemic animals may be one reason. ii: Histological and electron microscopical investigations of the bone marrow revealed markedly enhanced haemopoiesis in infected animals. However, a high proportion of cells was found pathologically altered already beginning in the late prepatency and increasing in the further course of infection. Thus, dyshaemopoiesis may result in the production of morphologically and functionally aberrant cells which are rapidly eliminated by the MPS which is highly activated in L. carinii infected M. natalensis.

Anemia

Peritoneal surface-active material in continuous ambulatory peritoneal dialysis (CAPD) patients.

Phospholipids have been demonstrated to be present in the peritoneal dialysis effluent of 34 patients on continuous ambulatory peritoneal dialysis (CAPD). The phospholipids present have been characterized by chromatography and their relative concentrations are fairly consistent from patient to patient. The predominant phospholipid is phosphatidylcholine (81%). Surface activity of this phospholipid has been demonstrated. The concentration of total phospholipid correlates with the time the patient had been on CAPD. It is lower in those patients who have been on dialysis longer.

Chromatography, Gas

Agents for the treatment of brain edema. 2. [(2,3,9,9a-Tetrahydro-3-oxo-9a-substituted-1H-fluoren-7-yl)oxy]+ ++alkanoi c acids and some of their analogues.

Our initial paper discussed brain edema resulting from traumatic head injury and the need for specific and effective agents to treat the disorder and disclosed a novel approach for the discovery of a drug of this kind. The current study describes the synthesis of a series of [(2,3,9,9a-tetrahydro-3-oxo-9a-substituted-1H-fluoren-7-yl)oxy]alk anoic acids and their analogues. These compounds were evaluated in an in vitro cerebrocortical tissue slice assay for their relative potencies in inhibiting K+ + HCO3- induced swelling. Structural modification at a number of sites in the "lead" compound revealed that significant biological activity was inherent only within a very narrow range of structural types. The observation that nearly all the biological activity resided in one of the two enantiomers demonstrated the marked stereospecificity of the most active compounds. One of the most potent compounds, (R)-(+)-[(5,6-dichloro-2,3,9,9a-tetrahydro-3-oxo-9a-propyl-1H-fluoren -7-yl) oxy]acetic acid ((+)-5c), exhibited a dose-response relationship in the in vivo acceleration/deceleration brain edema assay, and the data from the two highest doses were statistically significant. Electron microscopic examination demonstrated that the perivascular astroglial swelling that arises from this procedure is abolished in the animals treated with (+)-5c. This compound is currently being evaluated for its clinical efficacy and safety in the treatment of traumatic head injury.

Animals

Influence of effectors of the complex-type-oligosaccharide biosynthesis on the formation of proteokeratan sulfate in bovine cornea.

The structural similarity of the inner core of complex-type prosthetic oligosaccharides of N-asparagine glycoproteins and of the linkage region between the polysaccharide part and the protein chain of cornea proteokeratan sulfate makes their biosynthesis via a common route an attractive hypothesis. To test this, a tissue culture system was established to determine the rate of proteokeratan sulfate biosynthesis in bovine cornea and to measure the influence of several effectors of the dolichol pathway on this rate. Addition of dolichyl phosphate enhanced the formation of proteokeratan sulfate. Tunicamycin, 2-deoxy-D-glucose, bromoconduritol and deoxynojirimycin inhibited this process. Swainsonine probably led to the formation of a keratan sulfate with hybrid structure. The results support that the linkage region of cornea proteokeratan sulfate is synthesized via the assembly of a glucosylated dolichyl pyrophosphoryl oligosaccharide, its transfer to protein and subsequent processing by glycosidases.

1-Deoxynojirimycin

Inhibitors of glycolic acid oxidase. 4-Substituted 3-hydroxy-1H-pyrrole-2,5-dione derivatives.

An extensive series of novel 4-substituted 3-hydroxy-1H-pyrrole-2,5-dione derivatives has been prepared and studied as inhibitors of glycolic acid oxidase (GAO). Compounds possessing large lipophilic 4-substituents are, in general, potent, competitive inhibitors of porcine liver GAO in vitro. Methylation of the nitrogen or the 3-hydroxy substituent reduced potency dramatically, indicating the requirement for the two acidic functions on the 1H-pyrrole-2,5-dione nucleus. In rat liver perfusion studies, with three representative compounds, concentration-dependent inhibition of the conversion of [1-14C]glycolate to [14C]oxalate was observed. Chronic oral administration to ethylene glycol fed rats of the 4-(4'-bromo[1,1'-biphenyl]-4-yl) derivative (83) was shown to effect a significant reduction in urinary oxalate levels over a 58-day period.

Alcohol Oxidoreductases

The carbohydrate-protein-binding region in proteokeratan sulfate from bovine cornea is not sulfated.

Peptidokeratan sulfate from bovine cornea was degraded without prior desulfation by hydrazinolysis and nitrous acid deamination and the products were reduced and labelled with NaB3H4. The chain disaccharide units gave, as expected, galactosyl-2,5-anhydromannitol disaccharides with no, one and two sulfate groups, respectively. Desulfation during the degradation procedure was less than 25%. The fraction of the degradation products containing the binding region was identified by its mannose content and size, further separated by mannose-specific affinity chromatography and high-voltage electrophoresis and analysed. 94% of its mannose was found in uncharged oligosaccharides. This indicates that the binding region oligosaccharide bears no sulfate groups.

Animals

Agents for the treatment of brain injury. 1. (Aryloxy)alkanoic acids.

Blunt and ischemic injuries of the brain have been shown to result in swelling that is predominantly limited to a single cell type, the astrocyte, within the complex cellular mosiac of cerebral gray matter. Evaluation of various diuretic (aryloxy)acetic acids in vitro using incubating cat brain slices and primary astrocyte cultures identified compounds with marked ability to inhibit brain tissue swelling. Some of the compounds significantly reduced the mortality and morbidity following acceleration/deceleration brain injury in anesthesized cats. A variety of (indanyloxy)alkanoic acids were synthesized which were analogous to the dually active (indanyloxy)acetic acids. Some of the 4-(indanyloxy)butanoic acids were found to be devoid of diuretic activity but to possess equal or greater activity than the dually active compounds in the in vitro and in vivo brain assays. Selected examples from both the (indanyloxy)acetic and 4-(indanyloxy)butanoic acid series showed marked chiral effects, with one enantiomer generally exhibiting a much greater activity than the other. A clinical study of severely head-injured patients treated with ethacrynic acid demonstrated a significantly improved outcome when compared to controls. These data suggest a clinical advantage for the nondiuretic (aryloxy)alkanoic acids which possess in vitro and in vivo activities in the cat brain assays that are comparable or superior to dually active compounds.

Animals

[Bf-immunofixation on cellogel membranes (author's transl)].

A method for the determination of Bf phenotypes of means of immunofixation after electrophoresis on cellogel membranes is reported. In comparison to immunofixation after agarose gel thin layer electrophoresis, this method shows an equal separation quality, but requires only about 1/5 of the monospecific anti-Bf serum, and results can be obtained after only 5 h. The gene frequencies calculated from our material (BfS 0.7994, BfF 0.1850, BfSO,7 0.0085, BfF1 0.0071) are in good accordance with investigations about other European populations.

Berlin