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Biomedical subjects

M Merkel

Publications and source records attributed to M Merkel.

At least 37 records · Page 2Linked to original sources
PubMed1996

Inhaled prostacyclin (PGI2) versus inhaled nitric oxide in adult respiratory distress syndrome.

Inhalation of nitric oxide (NO) and prostacyclin (PGI2) may induce selective pulmonary vasodilation and-by improving ventilation-perfusion ratio in ventilated areas of the lung-increase Pao2 in patients with acute lung injury. To assess the therapeutic efficacy of both compounds, dose-response curves were established in patients with adult respiratory distress syndrome (ARDS). Patients received both PGI2 (doses of 1, 10, and 25 ng/kg/min) and NO (concentrations of 1, 4, and 8 ppm). Cardiorespiratory parameters were assessed at control, at each drug concentration, and after withdrawal of NO and PGI2. PGI2 resulted in a significant, dose-dependent and selective reduction of pulmonary artery pressure (PAP) from 35.1 +/- 6.3 mm Hg at control to 33.1 +/- 4.8 (1 ng/kg/min), 31.3 +/- 4.8 mm Hg (10 ng/kg/min) and 29.6 +/- 4.5 mm Hg (25 ng/kg/min), respectively. Inhaled NO reduced PAP from 34.5 +/- 5.6 to 32.1 +/- 5.9 mm Hg at 4 ppm, and to 31.8 +/- 6.1 mm Hg at 8 ppm, respectively, with no effect at 1 ppm. Pao2/Flo2 ratio increased from 105 +/- 37 to 125 +/- 56 mm Hg (range of increase: 0 to 57 mm Hg) at PGI2 10 ng/kg/min and to 131 +/- 63 mm Hg (range: -5 to 89 mm Hg) at 25 ng/kg/min with no effect at 1 ng/kg/min. NO improved Pao2 (e.g., from 116 +/- 47 to 167 +/- 86 mm Hg at 8 ppm) and reduced intrapulmonary shunt at all doses tested. We conclude that both inhaled PGI2 and NO may induce selective pulmonary vasodilation and increase Pao2 in severe ARDS.

APACHE↗
PubMed1995

[Dermatomyositis-like skin changes with long-term hydroxyurea (Litalir) therapy].

We report on dermatomyositis-like adverse cutaneous reactions following long-term maintenance therapy with hydroxyurea in two patients suffering from chronic myelogenous leukaemia (CML). In addition to non-specific side effects, such as xerosis, pruritus and hyperpigmentation, both patients presented with more specific skin changes, i.e. erythematous lesions, scaling, and partially atrophic areas distributed in a linear fashion on the dorsal aspects of the hands and fingers. In addition, teleangiectatic erythema of the face was present in both patients, and this was associated with oedema of the eyelids in one patient. Despite these dermatomyositis-like features there were no clinical signs of muscular involvement, and muscle-specific enzymes were within normal ranges. Skin biopsy specimens revealed an interface dermatitis characterized by a lichenoid cell infiltrate, vacuolar alteration of basal cells, necrotic keratinocytes within the spinous zone, focal hypergranulosis, ortho-hyperkeratosis and telangiectases in the upper part of the dermis. Analogous histopathological findings have been documented in lichen planus-like skin changes on the hands following hydroxyurea therapy. It seems doubtful whether there are actually any major differences between those skin changes described as dermatomyositis-like and those interpreted as lichen planus-like in patients receiving long-term hydroxyurea therapy.

Aged↗
PubMed1995

A 5' splice-region mutation and a dinucleotide deletion in the lysosomal acid lipase gene in two patients with cholesteryl ester storage disease.

Cholesteryl ester storage disease (CESD) results from inherited deficiencies of the lysosomal hydrolase, acid lipase (LAL; E.C. 3.1.1.13). To establish the molecular defects in LAL deficiency, two unrelated probands with severely reduced LAL activity were examined. DNA amplification by reverse-transcription polymerase chain reaction and subsequent sequence analysis of LAL cDNA identified two mutant alleles. Patient 1, presenting with hepatosplenomegaly, mildly elevated liver function tests, and hyperlipidemia, was homozygous for a deletion of nucleotides 823 to 894 of the LAL cDNA. This 72-bp deletion maintained the reading frame and resulted in a loss of 24 amino acids from the LAL protein. Analysis of genomic DNA revealed that the 72 bp corresponded to an exon of the LAL gene. A single G to A point mutation at the last exon position was observed in the genomic DNA of patient 1, indicating a splicing defect with consecutive exon skipping underlying the 72-bp deletion. Patient 2 was a compound heterozygote for the 72-bp deletion and a dinucleotide deletion at positions 967 and 968. This deletion resulted in a shifted reading frame carboxyterminal of codon 296, and 43 random amino acids followed the frame shift. A premature stop at codon 339 truncated the mutant LAL protein by 34 amino acids. Allele-specific hybridization confirmed that patient 1 was homozygous for the 72-bp deletion mutation, and that patient 2 was a compound heterozygote for the 72-bp deletion and the 2-bp deletion.

Adult↗
PubMed1994

Purification, characterization and molecular cloning of human hepatic lysosomal acid lipase.

Lysosomal acid lipase (LAL) is a hydrolase essential for the intracellular degradation of cholesteryl esters and triacylglycerols. This report describes a multi-step procedure for the purification of LAL from human liver. After solubilization with non-ionic detergent, acid hydrolase activity was purified 17000-fold to apparent homogeneity by sequential chromatography on Concanavalin A Sepharose, carboxymethyl-cellulose, phenyl Superose, Mono S cation exchange and Superose 12 gel-filtration columns. This procedure yielded two silver-staining protein bands of 56 kDa and 41 kDa on SDS/PAGE. Size-exclusion chromatography of the 41-kDa protein indicated that the enzyme was catalytically competent as a monomer of approximately 38 kDa. When assayed in the presence of cholesteryl oleate or trioleoylglycerol, purified acid lipase had Vmax values of 4390 nmol fatty acid.min-1.mg protein and 4756 nmol fatty acid.min-1.mg protein-1, and apparent Km values of 0.142 mM and 0.138 mM, respectively. The purified enzyme was most active at low pH (4.5-5.0) and required non-ionic detergent and ethylene glycol for optimal stability. Incubation of the 41-kDa acid lipase with endoglucosaminidase H reduced the molecular mass by 4-6 kDa, demonstrating Asn-linked glycosylation with high-mannose oligosaccharides. Deglycosylation did not affect enzymic activity, indicating that carbohydrates are not required for LAL activity. Based on partial peptide sequence, an oligonucleotide was synthesized and utilized to isolate LAL cDNA clones from a human liver cDNA library. A full-length LAL cDNA contained 2626 nucleotides and coded for a predicted protein of 372 amino acids, preceded by a 27 residue hydrophobic signal peptide. Hepatic LAL differed from fibroblast acid lipase at the N-terminus and revealed extensive similarities with human gastric lipase and rat lingual lipase, confirming a gene family of acid lipases. Northern hybridization using the complete LAL cDNA as a radiolabeled probe indicated striking differences in mRNA expression among human tissues. LAL mRNA was most abundant in brain, lung, kidney and mammary gland. Placenta and HeLa cells expressed intermediate amounts of LAL mRNA, while RNA extracted from liver and heart showed low levels of expression.

Amino Acid Sequence↗
PubMed1994

Principles of radical oesophageal surgery.

The standard procedure for cervical oesophageal carcinoma consists of partial pharyngectomy, laryngectomy with tracheostomy, resection of one thyroid lobe and complete oesophagectomy. For intrathoracic and abdominal carcinoma of the oesophagus, subtotal resection leaving a small cervical portion is sufficient. If the carcinoma has not exceeded the organ boundaries or is located below the tracheal bifurcation, the choice of resection either by transthoracic, transmediastinal or endoscopic methods is not critical with respect to the radical nature of the resection. In carcinoma located at or above the tracheal bifurcation a transthoracic approach is mandatory, but due to a significant hospital mortality and a low 5-year survival the question regarding valid indications for surgery remains open in most patients. With reference to the rules of radical surgery a "three-field" lymphadenectomy, which includes the resection of cervical, mediastinal and upper gastric lymph nodes, seems to be indispensable in all oesophageal carcinomas. Only some Japanese groups perform this procedure routinely or in selected cases. They report a positive correlation between the extent of lymph node dissection and the long-term survival. Since none of their studies is prospectively randomized, a certain bias could exist resulting in better results for extended lymphadenectomy. According to European experience, radical surgery of oesophageal carcinoma is more fiction than fact.

Anastomosis, Surgical↗
PubMed1991

[The role of Helicobacter pylori in the development of chronic gastritis and gastroduodenal ulcers].

To determine the correlation between Helicobacter pylori colonization of the gastric mucosa and the incidence of chronic gastritis as well as gastric and duodenal ulcer, 52 patients (26 women and 26 men) aged 19-77 years (mean 46 years) with gastrointestinal symptoms were studied. Biopsy specimens for histological and bacteriological examinations were taken during upper gastrointestinal tract endoscopies. Helicobacter pylori was found in 21 (40%) patients: 14 women and 7 men (p less than 0.05). The organisms were present more often in cases with chronic gastritis and duodenal ulcer (p less than 0.05). They were not identified in any of 7 persons with normal histologic features (p less than 0.01). Helicobacter pylori was found on the gastric mucosa in 6 (75%) of 8 patients with duodenal ulcer but in none of 5 cases after partial gastrectomy with the methods of Billroth I or Billroth II (p less than 0.05).

Adult↗
PubMed1989

[Bacterial flora of the surgically treated stomach].

In 33 patients operated on for peptic ulcer the pH and the bacterial flora of the gastric contents were studied. In 30 cases the pH of the gastric juice was increased, and parallelly the bacterial flora was more numerous. In 33 patients 139 various bacterial strains were cultured from gastric juice (70 strains of Enterobacteriaceae, 46 strains of cocci and Gram+ bacilli, 23 strains of fungi) in concentrations of 10(3)-10(7)/ml. In the light of literature data the authors discuss the clinical importance of excessive growth, qualitative and quantitative, of bacterial flora in the stomach as demonstrated during the operation.

Enterobacteriaceae↗
PubMed1988

Silent supraglottic carcinoma.

In a review of 51 consecutive patients with previously untreated squamous cell carcinoma of the supraglottic larynx, five (9.8%) patients were found to have no mucosal abnormality on initial evaluation by both computed tomography (CT) and direct laryngoscopy. All five patients who manifested submucosal disease had at least one endoscopic procedure done with a biopsy negative for cancer before definitive diagnosis, resulting in an average delay from initial endoscopy to diagnosis of 19.8 weeks. These inapparent or "silent" neoplasms present unique problems in regard to establishing a diagnosis by routine biopsy techniques, even though CT reliably demonstrates their presence. Early diagnosis requires aggressive biopsy techniques based on CT findings.

Aged↗
PubMed1987

Drug monitoring of etoposide (VP16-213). Correlation of pharmacokinetic parameters to clinical and biochemical data from patients receiving etoposide.

Pharmacokinetic parameters established in 15 patients receiving parenterally administered etoposide (80-120 mg . m-2) are reported. The etoposide assay by means of mass spectrometry after sample separation by thin-layer chromatography or high-pressure liquid chromatography used in this study has been described elsewhere. Peak plasma levels (9.5-63.3 micrograms . ml-1), the area under the curve (AUC) (2707-10192 micrograms . ml-1 . min-1), the mean transit time MTT (2.7-10.6 h), etoposide half-lives t1/2 alpha (0.10-0.52 h) and t1/2 beta (2.18-8.17 h), the volume of distribution at steady state (Vdss) (2.5-15.1 . l/m-2) and the systemic clearance (Cls) (10.1-35.1 ml min-1 . m-2) with the resulting mean values and standard deviations were determined. Our findings are compared with those of other authors, especially with regard to the method of detection used. This comparison indicates similar individual deviations and shorter half-lives with increasing specificity of the employed assay. Four patients studied on 3 consecutive days and, in one instance, during two different cycles of chemotherapy showed no sign of accumulation or of accelerated excretion of etoposide. There was little intrapatient variability. The pharmacokinetic parameters were correlated to clinical and laboratory findings. Statistical analysis indicated that the AUC was increased by prior cisplatin therapy and in patients with elevated levels of alkaline phosphatase. The Cls was decreased by prior cisplatin therapy, in obese patients, and by elevated alkaline phosphatase. The t1/2 beta of etoposide was increased in older patients. Linear regression analysis yielded a greater Vdss in patients with lower serum albumin levels, but this correlation has not yet been found to be statistically significant.

Adult↗
PubMed1986

Verrucous carcinoma of the cervix: a report of two cases and literature review.

Verrucous carcinoma of the cervix, like verrucous carcinoma of the vulva, is commonly misinterpreted as condyloma accuminata, resulting in a protracted delay of appropriate treatment. Since the correct diagnosis depends upon histological criterion which frequently belies the malignant nature of this lesion, conveyance to the pathologist of the history, physical findings, and clinical behavior of the lesion may facilitate early recognition. Aggressive surgical procedures including exenteration should be considered as primary treatment for large lesions and recurrent lesions when local excision fails. Radiotherapy is not usually an effective treatment for verrucous carcinoma and may induce malignant transformation. To date, 27 cases of verrucous carcinoma of the cervix have been reported. Two additional cases managed in recent years by the authors and a review of the world's literature about this uncommon lesion form the basis of this report.

Adult↗
PubMed1984

Computed tomography of upper aerodigestive tract squamous cell carcinoma. Assessment following induction chemotherapy.

One hundred forty-seven previously untreated patients with stage III or IV upper aerodigestive tract squamous cell carcinomas were examined by computed tomography (CT) prior to treatment. Computed tomography was used to observe the tumor response in 72 patients receiving induction chemotherapy (100 mg/sq m of cisplatin on days 1 and 21 and 135 mg/sq m of bleomycin sulfate on days 3 through 10). The CT findings in ten patients were correlated with serial histologic examination of the operative specimens. Our study indicates that CT is useful in following tumor response to chemotherapy, provided the physician is aware of the limitations of scanning as outlined herein.

Carcinoma, Squamous Cell↗