Search PubMed⌕ Search

Biomedical subjects

J Wacker

Publications and source records attributed to J Wacker.

At least 19 recordsLinked to original sources
PubMed2005

[Strategies for perioperative sympatho-modulation].

Despite the growing evidence for the efficacy of different sympatho-modulatory therapies to lower perioperative cardiac morbidity and mortality, such therapeutic strategies are rather infrequently used in daily clinical practice. Most physicians involved in perioperative medicine are aware of the increasing literature related to this topic, but only few comply with current clinical practice guidelines even in the absence of contraindications. This review discusses possible explanations for this reluctance and again summarizes the basic and clinical principles of current sympatho-modulatory therapies including alpha(2)-agonism, beta-adrenergic antagonism, and regional anesthetic techniques in modern anesthetic practice. In addition, the emerging perioperative concept of a patient-tailored individualized pharmacotherapy based on "gene profiling", particularly the adrenergic polymorphisms, is discussed.

Adrenergic alpha-Agonists↗
PubMed2005

High hepatotoxicity of pyrazinamide and ethambutol for treatment of latent tuberculosis.

Pyrazinamide (PZA) combined with either ethambutol (EMB) or a fluoroquinolone for 6-12 months is one of the treatments recommended for latent tuberculosis infection (LTBI) in contacts exposed to multidrug-resistant tuberculosis (MDR-TB). The aim of the present study was to describe the side effects related to combined PZA and EMB treatment given for LTBI, in contacts previously exposed to MDR-TB. In total, 12 consecutive contacts, all of African origin and aged 38+/-5 yrs, were treated with daily PZA (23+/-4 mg.kg(-1)) and EMB (17+/-4 mg.kg(-1)) at Geneva University Hospital outpatient clinic (Switzerland), as a result of contact-tracing procedures for two patients with contagious MDR-TB. Clinical status and liver function tests (aspartate aminotransferase (ALAT) and alanine aminotransferase (ASAT)) were monitored monthly. In seven cases (58%) treatment was discontinued after a median of 119 days, due to hepatic toxicity in six cases (ALAT or ASAT elevation more than four times the upper normal limit), and gastrointestinal symptoms in one case. In conclusion, combined pyrazinamide and ethambutol for latent tuberculosis infection may be associated with a high risk of hepatic toxicity, and warrants close monitoring. There is clearly a need for alternative preventive treatments for contacts exposed to multidrug-resistant tuberculosis.

Adult↗
PubMed2004

Diagnosing melanoma patients entering American Joint Committee on Cancer stage IV, C-reactive protein in serum is superior to lactate dehydrogenase.

Lactate dehydrogenase (LDH) in serum has recently been introduced into the American Joint Committee on Cancer (AJCC) staging system for cutaneous melanoma because of its prognostic value. We hypothesised LDH to be of value in discriminating melanoma patients entering AJCC stage IV from patients staying in AJCC stages I, II or III. Lactate dehydrogenase was compared to the acute phase protein C-reactive protein (CRP), which we observed to reflect the course of melanoma metastasis in a previous report. In this prospective study, we measured LDH and CRP in the serum of 91 consecutive melanoma patients progressing into AJCC stage IV in comparison to 125 patients staying in AJCC stages I, II or III. Comparing distributions of the parameters by median values and quartiles by Mann-Whitney test, LDH was not significantly elevated in patients entering AJCC stage IV melanoma (P=0.785), whereas CRP was (P<0.001). Analysing the sensitivity and the specificity jointly by the areas under the receiver operating characteristics curves (ROC-AUC), LDH did not discriminate between the defined groups of patients (AUC=0.491; 95% confidence interval, 0.410, 0.581), whereas CRP did (AUC=0.933; 95% confidence interval, 0.900, 0.966; P<0.001). Upon logistic regression analysis to calculate the ROC-AUC values upon the predictive probabilities, LDH provided no additional information to CRP. Choosing a cutoff point of 3.0 mg l(-1), CRP yielded a sensitivity of 0.769 together with a specificity of 0.904 in diagnosing AJCC stage IV entry. Altogether, for first diagnosing AJCC stage IV melanoma, CRP is the superior serum marker when compared to the conventional LDH.

Aged↗
PubMed2004

[Differential diagnosis of chronic perianal dermatitis. Premalignant and malignant disorders].

Several premalignant and malignant neoplasms clinically appear as chronic eczematous lesions of the perianal region and have to be distinguished from benign processes. Anal intraepithelial neoplasia (AIN) presenting as bowenoid papulosis and perianal Bowen disease is a precursor lesion for invasive squamous cell carcinoma. When AIN is widespread, persistent or progressive, an underlying immunosuppression should get excluded. Verrucous carcinoma of the perianal region is a highly differentiated variant of squamous cell carcinoma characterized as a slowly growing but locally invasive tumor. Extramammary Paget disease (EMP) is an intraepithelial adenocarcinoma of the skin with apocrine differentiation. Along with EMP, basal cell carcinoma, Langerhans cell histiocytosis and cutaneous T-cell lymphoma should be included in the differential diagnosis for lesions simulating chronic perianal dermatitis. In such situations, biopsies and histopathologic examination are imperative to avoid delayed diagnosis and assure prompt therapy.

Adult↗
PubMed2004

Bizarre annular lesion emerging as tinea incognito.

Tinea incognito has first been described in 1968. The term describes a tinea infection whose clinical morphology has been modified by the application of topical corticosteroids. The clinical manifestation can masquerade a number of other dermatoses and leads to misdiagnosis of annular eruptions. We describe a patient who showed a bizarre appearance of annular, inflammatory skin lesions at the umbilical region. Mycological culture yielded Microsporum canis.

Administration, Topical↗
PubMed2002

Female genital cutting in southern urban and peri-urban Nigeria: self-reported validity, social determinants and secular decline.

Despite growing public resistance to the practice of female genital cutting (FGC), documentation of its prevalence, social correlates or trends in practice are extremely limited, and most available data are based on self-reporting. In three antenatal and three family planning clinics in South-west Nigeria we studied the prevalence, social determinants, and validity of self-reporting for FGC among 1709 women. Women were interviewed on social and demographic history, and whether or not they had undergone FGC. Interviews were followed by clinical examination to affirm the occurrence and extent of circumcision. In total, 45.9% had undergone some form of cutting. Based on WHO classifications by type, 32.6% had Type I cuts, 11.5% Type II, and 1.9% Type III or IV. Self-reported FGC status was valid in 79% of women; 14% were unsure of their status, and 7% reported their status incorrectly. Women are more likely to be unsure of their status if they were not cut, or come from social groups with a lower prevalence of cutting. Ethnicity was the most significant social predictor of FGC, followed by age, religious affiliation and education. Prevalence of FGC was highest among the Bini and Urhobo, among those with the least education, and particularly high among adherents to Pentecostal churches; this was independent of related social factors. There is evidence of a steady and steep secular decline in the prevalence of FGC in this region over the past 25 years, with age-specific prevalence rates of 75.4% among women aged 45-49 years, 48.6% among 30-34-year olds, and 14.5% among girls aged 15-19. Despite wide disparities in FGC prevalence across ethnic, religious and educational groups, the secular decline is evident among all social subgroups.

Adolescent↗
PubMed2002

Absence of mutations in the pleckstrin homology (PH) domain of protein kinase B (PKB/Akt) in malignant melanoma.

During recent years it has become evident that protein kinase B (PKB)/Akt plays an important role in oncogenic transformation. The gene for PKB/Akt has been found to be overexpressed in certain human tumours and a viral fusion protein gains transforming capacity. Recruitment to the plasma membrane is mandatory for the physiological activation of PKB/Akt; this shift from cytoplasm to the membrane is achieved by the N-terminal pleckstrin homology (PH) domain. We attempted to find out whether mutations of this domain were present in human malignant melanoma. RNA from 18 primary melanoma lesions of different sizes and histological subtypes and two melanoma metastases from 20 Caucasian patients were used for reverse transcription and subsequent polymerase chain reaction (PCR) amplification of the PH domain of PKB/Akt alpha. Cycle sequencing of the purified PCR products showed that mutations of the PH domain of PKB/Akt were absent in all 20 melanoma specimens. In virtual Northern hybridizations PKB/Akt showed a low expression in both melanomas and acquired melanocytic naevi; however, no overexpression of PKB/Akt was detected. Thus in human melanoma PH domain mutations of PKB/Akt do not play a major role in melanoma carcinogenesis.

Adult↗
PubMed2001

Prognosis of metastatic melanoma: no correlation of tyrosinase mRNA in bone marrow and survival time.

Recent publications suggest that tyrosinase mRNA in blood as well as in bone marrow is detectable only in a subgroup of patients with metastatic melanoma. This would imply that tyrosinase mRNA is of limited value as a tumor marker. We addressed the question of whether patients with metastatic melanoma and RT-PCR-detectable tyrosinase mRNA in blood or bone marrow have a different prognosis than tyrosinase mRNA-negative patients. Twenty melanoma patients with widespread clinical metastases were enrolled; the survival time after first diagnosis of visceral metastases was correlated to tyrosinase mRNA presence in blood and bone marrow samples. The time of survival of eight patients with metastatic melanoma and detectable tyrosinase mRNA in either blood or bone marrow was not different from the prognosis of 12 patients without detectable tyrosinase mRNA in either blood or bone marrow. Detection of tyrosinase mRNA in blood or bone marrow samples of melanoma patients with advanced disease seems to have no substantial relevance for survival time and outcome of disease. In this constellation, detection of tyrosinase mRNA by RT-PCR is not a valid tumor marker. Nevertheless, tyrosinase positivity in bone marrow in earlier tumor stages might indicate increased risk for the development of distant metastases. This should be addressed in further studies.

Bone Marrow↗
PubMed2001

Sedative and anxiolytic effects of zopiclone's enantiomers and metabolite.

We evaluated racemic zopiclone, its (S)- and (R)-enantiomers and a metabolite, (S)-desmethylzopiclone, for their actions on locomotor activity, rotarod performance, the elevated plus maze and the Vogel conflict test of anxiety, and electroconvulsive shock-induced seizures duration. Zopiclone and its (R)- and (S)-enantiomers reduced locomotor activity, and zopiclone and its (S)-enantiomer disrupted rotarod performance at 10 mg/kg. (S)-desmethylzopiclone did not alter these measures at doses of less than 200 mg/kg. (S)-desmethylzopiclone altered plus maze performance at the lowest dose of all the zopiclone derivatives tested, caused a dose-related effect on the Vogel conflict test and caused a dose-related reduction of electroconvulsive shock-induced seizure durations. The data indicate that (S)-desmethylzopiclone can bring about an anxiolytic effect without a substantial degree of central nervous system depression, and suggest that the agent may be particularly useful clinically in the treatment of anxiety.

Alprazolam↗
PubMed2001

[Effect of Urapidil in antihypertensive therapy of preeclampsia on newborns].

OBJECTIVE: For the therapy of preeclamptic patients is Urapidil besides Dihydralazine another possible option for iv-therapy with good results in first clinical studies. Effects of both drugs on the newborns were observed. - METHODS: The maternal and fetal Urapidil plasma-concentrations and cardiovascular parameters of the newborns were observed in a randomised comparative therapy-study. - RESULTS: We found low fetal Urapidil plasma-concentrations as well as a less influence on cardiovascular parameters compared to dihydralazine. - DISCUSSION: With Urapaidil we have another therapeutic option in preeclampsia where we could not show any negative side-effects on the newborns.

Adult↗
PubMed2001

Are responses to therapy of metastasized malignant melanoma reflected by decreasing serum values of S100beta or melanoma inhibitory activity (MIA)?

In metastatic melanoma S100beta as well as melanoma inhibitory activity (MIA) are elevated in the serum in the majority of patients. Elevation has been found to correlate with shorter survival, and changes in these parameters in the serum during therapy were recently reported to predict therapeutic outcome in advanced disease. However, the value of these markers with respect to other possible markers by multivariate analysis has not yet been proven for individual patients. In this prospective study, S100beta and MIA were measured in the serum of 67 consecutive patients before and following treatment. Analysing both the sensitivity and the specificity of the serum parameters by the areas under the receiver operating characteristics (ROC) curves, decreases in S100beta and MIA during therapy were associated with response to therapy, while increases indicated progressive disease. Unexpectedly, the individual diagnostic value of changes in tumour markers during therapy was not superior to one-point measurements at restaging. Moreover, S100beta and MIA were not superior to the conventional parameters lactate dehydrogenase and C-reactive protein (CRP) on multiple logistic regression analysis. Applying classification and regression trees (CARTs), one-point measurements of CRP was shown to be the most relevant overall parameter.

Adult↗
PubMed2001

The protein phosphatase 2A subunit Bgamma gene is identified to be differentially expressed in malignant melanomas by subtractive suppression hybridization.

Several genes implicated in the development of various malignancies appear to be of minor relevance in melanoma. We therefore aimed to find a tumour suppressor candidate involved in this malignancy by comparing gene expression in uncultured primary melanoma specimens with those in acquired melanocytic naevi, from which quite often melanomas are known to arise. Applying the subtractive suppression hybridization technique, we generated a subtracted library of candidate genes downregulated in melanoma. Among the cDNA fragments identical to known genes, this library included a cDNA fragment 630 bp in length that is identical to the gene for the human protein phosphatase 2A (PP2A) regulatory subunit B (B56) gamma isoform (PP2A-Bgamma, PPP2R5C). On further evaluation of 15 primary melanoma and 16 acquired melanocytic naevus tissue specimens from independent patients using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis, expression of this gene was found to be suppressed in melanomas compared with naevi; the difference was statistically significant. As PP2A is known to be a major cellular serine-threonine phosphatase, and has been implicated not only in the regulation of cell growth and division but also in the control of gene transcription and growth factor signal transduction, alterations in the pattern of the regulatory subunits may affect substrate specificity and subcellular localization of the PP2A holoenzyme in melanoma cells.

DNA Primers↗
PubMed2001

Mutations of the PH domain of protein kinase B (PKB/AKT) are absent in human epidermal skin tumors.

BACKGROUND: While for most human solid tumors genetic alterations of few distinct genetic regions have been found, studies on basal cell carcinomas (BCC) have shown the prevalence of several abnormalities including alterations of the three ras genes, GAP (GTPase activating protein), p53, PTCH (the human homologue of Drosophila patched) and SMOH (the human homologue of Drosophila smoothened). On the other hand, during the last decade, a new oncogene, protein kinase B (PKB/AKT), has been characterized and found to be overexpressed in certain human tumors. In vivo activation of PKB/AKT necessitates its recruitment to the cell membrane mediated by the N-terminal pleckstrin homology (PH) domain. OBJECTIVE: We investigated whether mutations of this mandatory domain are present in a subset of human epidermal skin tumors. METHODS: RNA of 19 human skin tumors including 13 BCC, 4 squamous cell carcinomas (SCC; including 1 keratoacanthoma) and 2 neurofibromas of different size and tumor stage were used for reverse transcription and subsequent PCR amplification of the PH domain of PKB/AKT. RESULTS: Cycle sequencing of the purified PCR products did not reveal any mutation of the PH domain of PKB/AKT. CONCLUSION: In human BCC and SCC, mutations of the PH domain of PKT/AKT do not play a major role during the carcinogenesis of these tumors.

Adult↗