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Biomedical subjects

M Ulmer

Publications and source records attributed to M Ulmer.

At least 19 recordsLinked to original sources

[Minimally invasive percutaneous epidural neurolysis in chronic radiculopathy. A prospective controlled pilot study to prove effectiveness].

The treatment of chronic back pain with sciatica is still an unsolved therapeutic challenge. Percutaneous minimally invasive neurolysis according to the Racz technique is increasingly applied and discussed controversially. So far there is no prospective randomized controlled study for evaluation of a possible treatment effect. In a prospective pilot study, 25 patients with monosegmental radiculopathy of the lumbar spine were treated with minimally invasive percutaneous epidural neurolysis according to Racz's technique. They all suffered from chronic disc herniations or failed back syndromes after surgery, all with radiculopathy. The average age of the patients was 51+/-16 years, the average duration of the symptoms was 28 months. Twelve weeks after the procedure patients had significant clinical improvement. The Oswestry score increased from 64+/-17 to 22+/-12 points. Subjective pain sensation according to the McNab score showed improvement too. None of the patients had worsening of the situation compared to preoperative findings. No clinically relevant complications were observed. The results are being used to design a clinical trial in accordance with good clinical practice guidelines to analyze the therapeutic efficacy of the procedure. The described technique is still a clinically experimental procedure. However, due to a low probability of side effects and due to the good results reported so far by most authors, the Racz catheter technique may be applied in certain patients with chronic radiculopathy refractory to conservative treatment.

Anesthesia, Epidural↗

[Successful treatment of gastroesophageal reflux with anterior partial fundoplication under celioscopy].

OBJECTIVE: To study the interest of partial fundoplication under laparoscopy, not only in terms of efficacy but also in the low rate of complications. METHODS: The study included all patients having undergone coelioscopic surgery for gastroesophageal reflux from January 1995 to February. A ventral semi-valve was created in all patients. Complications during surgery and post-surgical follow-up immediately after, six weeks later and then at distance were analyzed. RESULTS: The mean duration of surgery was 81 minutes (40-170 min.) and mean hospital stay 6.2 days (2-12 days). Twelve conversions were observed (9.6%) and post-surgical morbidity was of 9.7% after coelioscopy. At 6 weeks, 72 patients (63.7%) were satisfied with the operation, 13 patients (11.5%) complained of dysphagia and 5 (4.4%) of bloating. At distance, after a mean of 3.2 years (0.5-5.5 years), 72 patients (73%) were totally satisfied; 4 presented recurrent reflux (4.1%) and 3 patients (3.1%) complained of dysphagia. CONCLUSION: The results of laparoscopic surgery for gastroesophageal reflux with creation of a ventral semi-valve are encouraging. Pre-existing symptomatology is eradicated and post-surgical complications are clearly decreased.

Fundoplication↗

Expression, purification, and characterization of active recombinant prostate-specific antigen in Pichia pastoris (yeast).

BACKGROUND: Prostate-specific antigen (PSA), a member of the kallikrein family of serine proteases, is a chymotrypsin-like glycoprotein produced by the prostate epithelium. Elevated serum PSA (> 4 ng/ml) is a tumor marker for prostatic cancer and benign prostatic hypertrophy; increasing serum PSA over time is indicative of metastatic disease. It has been suggested that PSA may contribute to tumor metastasis through degradation of extracellular matrix glycoproteins, as well as cleavage of IGF binding protein-3, a modulator of IGF-1. To elucidate the role of PSA in the development and progression of prostatic cancer, it is necessary to have a reliable, cost-effective source of enzymatically active protein. Previous efforts to express recombinant PSA (rPSA) produced inactive proPSA, or mixtures of active and inactive PSA requiring activation by removal of the propeptide. We describe the expression of active recombinant mature PSA in yeast. METHODS: Stable chromosomal integration of a construct consisting of the yeast alpha-factor signal sequence preceding the mature PSA sequence resulted in secretion of rPSA. The rPSA was purified from the yeast cell culture supernatant to homogeneity by strong cation-exchange chromatography, and characterized by SDS-PAGE, Western analysis, electrospray mass spectrometry, N-glycanase digestion, N-terminal amino acid sequencing, and inactivation by a PSA-specific inhibitor. RESULTS: We report the production of active, mature rPSA in Pichia pastoris. Two forms of rPSA varying slightly in glycosylation were identified. The specific activity of the rPSA was equal to that of human seminal plasma PSA (0.56 micromol/min mg) as determined using a chromogenic substrate. CONCLUSIONS: Large-scale production of active rPSA will be useful in the exploration of PSA effects on tumor cell proliferation, migration and metastasis. In addition, a large supply of enzyme should facilitate the discovery of novel inhibitors for in vitro and in vivo evaluation, and may provide a reproducible source of rPSA for use as a standard in diagnostic testing.

Amidohydrolases↗

[Carcinomatous degeneration of augmentation enterocystoplasty].

Augmentation enterocystoplasties are performed increasingly frequently and their indications are no longer exclusively limited to small tuberculous bladders. One of the most serious complications of these procedures is malignant transformation, as reported in the present case. Carcinomatous degeneration is uncommon and usually occurs more than ten years after enterocystoplasty. Patients treated by this operation must be submitted to annual cystoscopy combined with guided biopsies at the slightest doubt. This surveillance should be started between the 5th and the 10th postoperative year.

Adenocarcinoma↗

Leptin is a four-helix bundle: secondary structure by NMR.

Leptin is a signaling protein that in its mutant forms has been associated with obesity and Type II diabetes. The lack of sequence similarity has precluded analogies based on structural resemblance to known systems. Backbone NMR signals for mouse leptin (13C/15N -labeled) have been assigned and its secondary structure reveals it to be a four-helix bundle cytokine. Helix lengths and disulfide pattern are in agreement with leptin as a member of the short-helix cytokine family. A three-dimensional model was built verifying the mechanical consistency of the identified elements with a short-helix cytokine core.

Amino Acid Sequence↗

A comparative study of cefepime and ceftazidime in the treatment of community-acquired lower respiratory tract infections.

Antibiotic treatment for community-acquired pneumonia must target Gram-positive pathogens, especially frequently isolated organisms such as Streptococcus pneumoniae. The severity of community-acquired pneumonia is often related to underlying factors. Occasionally it may be complicated by staphylococcal or Gram-negative bacillary infection. We have compared the safety and efficacy of cefepime 1 g bd with ceftazidime 1 g tds as empirical treatment in adults with community-acquired lower respiratory tract infections (LRTIs). One hundred and thirty-one patients with moderate to severe LRTIs were randomized to two treatment groups: 87 received cefepime and 44 received ceftazidime. The treatment groups were comparable with regard to sex, age and treatment duration. Of the 116 pathogens isolated, 57 were Gram-positive (46 strains of S. pneumoniae) and 59 were Gram-negative (33 strains of Haemophilus influenzae). Of the 111 patients evaluated, clinical cure rates were 87% (65/75) in the cefepime group and 86% (31/36) in the ceftazidime group. Pathogen eradication rates were 95% (74/78 and 36/37, respectively) in both groups. Both drugs were well tolerated and the incidence of adverse events in each group was comparable. Cefepime 2 g per day (1 g bd) was as safe and effective as ceftazidime 3 g per day (1 g tds) in the treatment of community-acquired LRTIs.

Adult↗

Treatment of Wegener's granulomatosis.

Treatment and outcome of 111 patients who fell ill with Wegener's granulomatosis (WG) between 1966 and 1990 were analysed retrospectively. Two regimens of treatment were distinguished: "conventional" treatment, i.e. daily application of cyclophosphamide/corticosteroids (FAUCI scheme) or azathioprine/corticosteroids or corticosteroids alone, and "stage-adapted" treatment, characterized by change of different treatments (e.g. cyclophosphamide pulse therapy, cotrimoxazole) according to the extent and activity of disease. In patients who received stage-adapted treatment, exacerbations occurred significantly more frequent than in conventionally treated patients, while lethal outcome was much more frequent in conventionally treated patients.

Adrenal Cortex Hormones↗

[Therapy of Wegener's granulomatosis. Experiences with conventional and stage-adjusted treatment in 111 patients over 24 years].

Treatment and outcome of 111 patients who fell ill with Wegener's granulomatosis (WG) between 1966 and 1990 were analysed retrospectively. The mean observation time after diagnosis had been 47 (1-288) months. At the time of diagnosis 37 patients suffered from locoregional symptoms only, whereas the disease was generalised in 74 patients. Two regimes of treatment were differentiated: "conventional" treatment, i.e. daily application of cyclophosphamide/prednisolone (FAUCI scheme) or azathioprine/prednisolone or prednisolone alone, and "stage-adapted" treatment, characterised by change of different treatments (e.g. cyclophosphamide pulse therapy, cotrimoxazole) according to the extent and activity of disease. In patients who received stage-adapted treatment, relapses occurred significantly more frequently than in conventionally treated patients. On the other hand, lethal outcome was much more frequent in conventionally treated patients.

Adult↗

Immunodiagnostic aspects of autoantibodies against myeloperoxidase.

The antigen specificity of autoantibodies causing perinuclear staining of granulocytes and monocytes (pANCA) was evaluated by analyzing 3000 sera, which were sent to us for screening of anticytoplasmic antibodies (ACPA, synonym: cANCA, anti-proteinase 3). In 620 sera, perinuclear staining was found. Antigen specificity was investigated by a myeloperoxidase ELISA and indirect immunofluorescence with Hep2 cells specific for antinuclear antibodies (ANA). Only 9.8% of the 620 sera showed reactivity with myeloperoxidase (AMPO), while 85.6% contained ANA which induced a pANCA-like staining. A further 4.6% of the 620 sera were neither ANA nor AMPO positive. Therefore, pANCA in general is only an indication that one should look for AMPO or other antilysosomal autoantibodies, when ANA have been excluded. To investigate the disease specificity of AMPO, we examined sera from patients with several well-defined autoimmune diseases. There were only very few positive results in collagen vascular diseases (3/114) (positive/total), primary systemic vasculitis (1/116) and clinically and histologically proven Wegener's granulomatosis (2/213). On the other hand, AMPO were present in patients with different forms of glomerulonephritis (45/192), especially crescentic glomerulonephritis (CGN) (34/79) without immune deposits in their biopsy specimen (3/30 showed trace deposits of IgM). There were, however, additionally 11 patients with symptoms resembling WG (who were cANCA negative, w/o characteristic WG biopsy), who had no obvious renal symptoms. These findings indicate that AMPO are primarily associated with idiopathic GN, especially CGN. Together with anti-proteinase-3 antibodies and anti-glomerular basement membrane antibodies they are an essential serologic parameter in the diagnosis of unclear systemic diseases with renal involvement.

Antibodies, Antineutrophil Cytoplasmic↗

[Cotrimoxazole in Wegener's granulomatosis--a prospective study].

During the last 3 years 34 patients with Wegener's granulomatosis (W. G.) were treated 37 times with co-trimoxazole (Co-trim). In 10 patients with locoregional disease the progression of W. G. could be stopped in each case. In 27 cases (24 patients) with generalized W. G. in complete remission achieved with cyclophosphamide and prednisolone (Cyc/Pred) a relapse occurred in more than 50% (14/27) of the cases.

Granulomatosis with Polyangiitis↗

Metabolic effects of acarbose in young healthy men.

To explore the long-term metabolic effects of acarbose in man, 6 healthy men (25 +/- 2 years; BMI: 21.6 +/- 2.7) were fed a controlled diet in a metabolic ward for 7 consecutive weeks. After an initial 3-week period to ensure a metabolic steady-state, they received 300 mg/d of acarbose (100 mg before each meal) for the remaining 4 weeks. Stool and urine collections were made over 7 d on weeks 3 and 7. Faecal excretion of water, nitrogen, carbohydrate, fat, zinc, magnesium, copper, chromium, iron, calcium and phosphorus and urinary excretion of nitrogen, urea and calcium were measured. In addition, fasting and postprandial blood glucose and insulin levels, as well as fasting triglycerides, total cholesterol, apolipoproteins (Apo) A-I, A-II, and B, zinc and copper, vitamins A, B1, B2, B6, C, and E concentrations were measured before and at the end of the acarbose period. Weight, food consumption, and water balance were not modified by acarbose. Faecal nitrogen excretion increased significantly but the nitrogen balance remained positive. Faecal excretion of carbohydrate, fat, iron and chromium were significantly increased by acarbose. Apos A-I and A-II decreased significantly. Plasma levels of vitamin B6 increased and vitamin A concentrations decreased with acarbose. This study provides new insights into the metabolic effects of acarbose with respect to nitrogen, mineral and vitamin metabolism.

Acarbose↗

Influence of chronic ethanol intake on obesity, liver steatosis and hyperlipidaemia in the Zucker fa/fa rat.

The effect of chronic alcohol intoxication on metabolic disturbances and fatty infiltration and degeneration was studied in genetically obese, hyperlipoproteinaemic, fa/fa Zucker rats. Sixteen obese Zucker (fa/fa) rats, sixteen lean Zucker rats (Fa/-) and sixteen Wistar rats, all male rats aged 7-8 weeks, were given either a control (C) diet (13% of energy from protein, 37% from fat, 50% from carbohydrate) or an ethanol (E) diet (13% of energy from protein, 37% from fat, 14% from carbohydrate, 36% from ethanol) for 4 weeks. The fa/fa rats given diet E consumed more energy than those given diet C, but after 4 weeks the weight gains and degrees of obesity were similar for both groups. With both diets, the developed hyperlipidaemia could be explained by the hyperinsulinaemia. Both hypertriglyceridaemia and hypercholesterolaemia were lower in fa/fa rats eating diet E than in those given diet C. Fatty infiltration of the liver, as assessed by hepatic triacyglycerol and cholesterol contents, was observed with both diets, but for fa/fa rats it was less extreme in those given diet E.

Adipose Tissue↗

Paradoxical effect of ethanol on liver lipogenesis in the genetically-obese Zucker rat.

Sixteen obese (fa/fa) Zucker rats, sixteen lean (Fa/-) Zucker rats and sixteen Wistar rats, all male rats aged 7-8 weeks, were given either a control (C) diet containing no ethanol or an ethanol (E) diet in which 36% of the energy was supplied by ethanol, for a period of 4 weeks. The activities of glucose-6-phosphate dehydrogenase (EC 1.1.1.49), glucose-6-phosphatase (EC 3.1.3.9) and glycerol kinase (EC 2.7.1.30) and the glycogen content in the livers of obese (fa/fa) rats were lower in animals given diet E than in those given diet C. As a result, hepatic lipogenesis and fatty degeneration of the liver were reduced in obese (fa/fa) rats given diet E.

Animals↗