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Biomedical subjects

A Walch

Publications and source records attributed to A Walch.

31 records · Page 2Linked to original sources
PubMed1999

[Squamous epithelial carcinoma-associated necrolytic migratory erythema].

A 59-year-old Caucasian man suffered from persistent disseminated necrolytic skin lesions for 8 months. They failed to respond to a variety of therapeutic regimens but then cleared spontaneously within a few days. After one week an invasive squamous cell carcinoma of the hypopharynx became clinically apparent. At autopsy, the expected glucagonoma often associated with necrolytic migratory erythema was not found.

Carcinoma, Squamous Cell↗
PubMed1999

The molecular pathology of Barrett's esophagus.

The incidence of adenocarcinoma of the distal esophagus is rapidly increasing in the Western world. The histopathological sequence of (Barrett's) metaplasia, which develops as a consequence of chronic reflux, to dysplasia and then to carcinoma is well established for these tumors. In Barrett's esophagus a variety of molecular changes have been characterized and correlated with tumor initiation and progression. Among the early changes in premalignant stages of metaplasia are alterations of the transcripts of FHIT, a presumptive tumor suppressor gene which spans the common fragile site FRA3B. Mutations of p53 seem to accumulate mainly in the transition from low to high grade dysplasia. Inactivation of other tumor suppressor genes by mutation (APC, p16) or hypermethylation (p16) as well as amplification of oncogenes such as cerbB2 are relatively late events in the development of adenocarcinoma. Among the phenotypic changes in Barrett's esophagus are an expansion of the Ki67 proliferation compartment which correlates with the degree of dysplasia. Moreover, accumulation of rab11 molecules which are involved in membrane trafficking has been reported to be specific for the loss of polarity seen in low grade dysplasia. Reduced expression of the cadherin/catenin complex as well as increased expression of various proteases develop chiefly in invasive carcinomas. Despite the progress that has been made in the identification of molecular markers in Barrett's carcinoma, to date the histopathological diagnosis of high grade dysplasia in endoscopic biopsies remains the best predictor of invasive cancer. Immunohistochemistry applying a panel of antibodies including p53, Mib-1 or rab11 can be helpful to diagnose regenerative metaplastic epithelium or low and high grade dysplasia.

Barrett Esophagus↗
PubMed1998

Distinct cytogenetic alterations in squamous intraepithelial lesions of the cervix revealed by laser-assisted microdissection and comparative genomic hybridization.

BACKGROUND: It has been established that comparative genomic hybridization (CGH) on Papanicolaou-stained cervical smears can be used to identify chromosomal imbalances. METHODS: In this study, the authors identified normal and dysplastic squamous epithelial cells cytologically, eliminated surrounding bacteria or leukocytes by a ultraviolet laser microbeam under microscopic control, and scraped out the cell groups of interest by a microdissection system. In 3 cases of squamous intraepithelial lesions (SIL), a total of 9 samples of dysplastic (n = 6) and nontumorous cells (n = 3) were investigated, each of them consisting of 3-40 cells. The DNA was amplified by degenerate oligonucleotide primed PCR (DOP-PCR) and used for CGH. RESULTS: Analyses of all nontumorous cell groups resulted in fluorescence ratio profiles that showed no deviation from the normal range, confirming that no methodologic artefacts have been produced. The CGH profiles from dysplastic cells, however, showed various chromosomal imbalances affecting six to nine different chromosomes. The most frequent gains in DNA were observed on chromosomes 1p, 2q, 4, and 5, whereas losses were found on chromosomes 6q and 13q. CONCLUSIONS: The results of this study demonstrate the feasibility and reliability of CGH on microdissected cell samples of routinely processed cervical smears. To the authors' knowledge, this is the first study reporting the use of CGH on cervical routine smears. This approach offers the opportunity to investigate sequence copy number changes in small, morphologically well-defined groups of dysplastic cells. It may, therefore, serve as a cytogenetic screening test for identifying chromosomal aberrations in precancerous lesions that are associated with a high risk for progression to invasive cancer.

Chromosome Aberrations↗
PubMed1998

Genetic heterogeneity in a prostatic carcinoma and associated prostatic intraepithelial neoplasia as demonstrated by combined use of laser-microdissection, degenerate oligonucleotide primed PCR and comparative genomic hybridization.

We combined laser-assisted microdissection from H&E-stained paraffin sections, degenerated oligonucleotide-primed polymerase chain reaction (DOP-PCR), and comparative genomic hybridization (CGH) to analyse chromosomal imbalances in small tumour areas consisting of 50-100 cells. This approach was used to investigate intratumour genetic heterogeneity in a case of metastatic prostatic adenocarcinoma and chromosomal changes in areas of prostatic intraepithelial neoplasia (PIN) adjacent to the invasive tumour. In four microdissected invasive tumour areas with different histological patterns (acinar, cribriform, papillary and solid) marked intratumour heterogeneity was found by CGH. Recurrent chromosomal imbalances detected in at least two microdissected tumour areas were gains on 1p32-->p36, 2p22, 3q21, 7, 8q21-->q24, 11q12-->q13, 16p12-->p13, 17, 19 and loss on 16q23. Additional chromosomal changes were found in only one of the microdissected areas (gains on 16q21-->q23, 20q22 and losses on 8p21-->p23, 12p11-->q12, 12q21-->q26, 13q21-->q34, 16q12, and 18q22). In PIN, gains on chromosomes 8q21-->q24 and 17 were found in both samples investigated (low and high grade PIN), while gains on chromosomes 7, 11q, 12q, 16p, and 20q and losses on 2p, 8p21-->p23, 12q were found only in one PIN area. Controls to ensure reliable CGH results consisted in CGH analyses of (i) approximately 80 microdissected normal epithelial cells, which showed no aberrations after DOP-PCR and (ii) larger cell numbers (approximately 10(5) or 10(7) cells) of the primary tumour investigated without DOP-PCR and partially displaying the chromosomal imbalances (gain on 16p12-->p13, losses on 2p25, 8p21-->p23, 12p11-->p12, 12q21-->q26, 18q22) found in the small microdissected areas. Microsatellite and FISH analyses further confirmed our CGH results from microdissected cells. The combined approach of laser-assisted microdissection, DOP-PCR and CGH is suitable to identify early genetic changes in PIN and chromosomal imbalances associated with the particular histological patterns of invasive prostatic adenocarcinoma.

Adenocarcinoma↗
PubMed1997

An Open Trial of Trimethoprim Alone against Cyclospora Infections.

Cyclospora is a coccidian parasite that infects the upper intestine and causes a prolonged illness consisting of fatigue, anorexia, and diarrhea. Untreated infections can last for several weeks.1 Trimethoprim-sulfamethoxazole (co-trimoxazole) was found to be an effective treatment for Cyclospora infections in a 1994 study performed in Nepal.2 However, people with known allergies to sulfa drugs cannot take co-trimoxazole. A number of antibiotics have been tried against Cyclospora infections without success, including norfloxacin, tinidazole, diloxanide furoate, and quinacrine hydrochloride. Azithromycin was not successful in a small open trial in 1993.3 Trimethoprim is not chemically related to sulfa, and allergy to co-trimoxazole is usually attributed to the sulfamethoxazole component. In order to find a treatment for people infected with Cyclospora who are allergic to sulfa drugs, we undertook an open trial of trimethoprim alone, in a dose of 200 mg twice a day for 7 days.

Journal Article↗
PubMed1996

[Polymer microparticles for right and left heart echocardiography and imaging myocardial perfusion after peripheral vein injection].

It is conceivable that a stable ultrasound contrast agent could be used for reproducible right and left heart echocardiography and myocardial visualization after intravenous injection. Microparticles from different polymers and preparation procedures were screened in six dogs leading to one superior agent with reproducible high quality echo contrast in doses of 1 mg/kg. This special agent is based on condensates of aspartic acid, ethanolamine and decanoic acid. Out of this material particles were formed with an average diameter of 2 micrometers. The easily suspendable particles were used for the following studies in a dose of 1 mg/kg intravenously in eight pigs. Maximal video intensity averaged 116 +/- 42 relative intensity units (IU) in the right, 137 +/- 42 IU in the left ventricle, 42 +/- 7 in the normally perfused and 11 +/- 2 in the hypoperfused myocardium after circumflex ligature. The area under the intensity curve was 1942 +/- 100 IUxs in the right, 2452 +/- 1291 IUxs in the left ventricle, 518 +/- 124 in the normally perfused and 202 +/- 94 in the hypoperfused myocardium after circumflex ligature. There was no change of heart rate, central arterial or pulmonary artery pressure during and after the injections. There was also no loss of echo intensity during the passage of contrast material through the heart due to systolic pressure. The described agent can be used for the opacification and ultrasonic visualization of the right and left heart as well as normally and hypoperfused myocardium without visible side-effects in animal studies.

Animals↗
PubMed1995

Placebo-controlled trial of co-trimoxazole for Cyclospora infections among travellers and foreign residents in Nepal.

Cyclospora is a coccidian (previously referred to as cyanobacterium-like bodies) that has been implicated in cases of prolonged diarrhoea. The average duration of symptoms is more than three weeks, and no specific treatment has been shown to shorten the illness. A case report suggested that co-trimoxazole may be effective. Expatriate persons with gastrointestinal complaints and cyclospora detected on examination of faeces were recruited from two clinics in Kathmandu, Nepal, between May and August, 1994. Participants were assigned in a randomised, double-blinded manner to receive either cotrimoxazole (160 mg trimethoprim, 800 mg sulphamethoxazole) or placebo tablets twice daily for 7 days. Of 40 patients included in the study, 21 received cotrimoxazole and 19 placebo. There were no significant differences between these two groups in age, sex, time in Nepal, duration or severity of illness, or presence of other enteric pathogens. After 3 days, 71% of patients receiving co-trimoxazole still had cyclospora detected, compared with 100% of patients receiving placebo (p = 0.016). After 7 days, cyclospora was detected in 1 (6%) of 16 patients treated with co-trimoxazole who submitted stool specimens compared with 15 (88%) of 17 patients receiving placebo (p < 0.0001). Eradication of the organism was correlated with clinical improvement. There was no evidence of relapse of infection among treated patients followed for an additional 7 days. Treatment with co-trimoxazole for 7 days was effective in curing cyclospora infection among an expatriate population in Nepal.

Adult↗
PubMedDate not supplied

Microdissection of tissue sections: application to the molecular genetic characterisation of premalignant lesions.

The characterisation of the early molecular genetic events of tumor development depends on the selective procurement of histopathologically defined small cell populations from premalignant tissue. In order to obtain high-quality DNA, mRNA and proteins from these small tissue samples and even from single cells, tissue microdissection is one of the most useful techniques, becoming increasingly important for molecular pathologists. Using different microdissection techniques which allow the isolation of morphologically defined cell populations under direct visualisation, it is now feasible to study molecular genetic events that drive the multistep evolution in tumours. This review aims to present the current techniques of tissue microdissection and these techniques are discussed in the light of their ability to isolate premalignant cell populations in particular. Furthermore, we describe the subsequent application of several multiplex molecular analyses for characterising the microdissected premalignant cells. Applying these advanced techniques, alterations in the cellular DNA or the fluctuation of expressed genes that correlate with a particular stage of carcinogenesis can ultimately be compared within or between individual patients. Thus, these new technologies will have an enormous impact on molecular pathology with several diagnostic, prognostic and therapeutic implications.

Cell Separation↗