Management of chronic obstructive pulmonary disease: the Swiss guidelines. Official Guidelines of the Swiss Respiratory Society.
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Chronic Disease↗
Biomedical subjects
J Wacker
Publications and source records attributed to J Wacker.
Glutathione levels and antioxidative status in pre-eclampsia.
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Antioxidants↗
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↗
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↗
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↗
Mutations of the activation-associated phosphorylation sites at codons 308 and 473 of protein kinase B are absent in human melanoma.
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Adult↗
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↗
[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↗
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↗
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↗
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↗
Alteration of the activity of the 11beta-hydroxysteroid dehydrogenase in pregnancy: relevance for the development of pregnancy-induced hypertension?
In this study we evaluated the activity of renal 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) in patients with pregnancy-induced hypertension (PIH). A reduction of the activity of 11beta-HSD2 leads to pseudohyperaldosteronism due to insufficient interconversion of cortisol to its inactive 11-oxo-metabolite cortisone in the renal tubulus cell. We measured urinary free cortisol and cortisone in patients with and without PIH and calculated the urinary free cortisol to free cortisone ratio, which is well accepted as a correlate of the activity of renal 11beta-HSD2. One hundred twenty-six pregnant women were included. Fifty-nine patients had PIH (mean age 31.5 +/- 4.4 yr, blood pressure 158.7 +/- 16.0/100.8 +/- 9.5 mm Hg), and 67 were normotensive (mean age 29.4 +/- 4.6, blood pressure 112.6 +/- 8.9/68.8 +/- 8.6 mm Hg). The excretion rate of cortisol was increased in the PIH group (138.8 +/- 93.0 vs. 106.5 +/- 65.4 nmol/d, P = 0.027), whereas excretion rate of cortisone was similar (362.9 +/- 254.1 vs. 366.5 +/- 221.7 nmol/d, P = 0.933). The free cortisol to free cortisone ratio was significantly higher in the PIH group (0.47 +/- 0.25 vs. 0.31 +/- 0.12, P < 0.00002). Within this group, the patients with blood pressure in the uppermost quartile had a significantly higher free cortisol to free cortisone ratio than those in the lowest quartile [0.61 +/- 0.31 vs. 0.38 +/- 0.15 (P = 0.019) for diastolic, 0.60 +/- 0.29 vs. 0.35 +/- 0.13 (P = 0.012) for systolic, and 0.62 +/- 0.32 vs. 0.39 +/- 0.16 (P = 0.023) for mean blood pressure, respectively]. We conclude that a reduction of the activity of the 11beta-HSD2 is a relevant factor for the development of PIH. Whether the ratio of urinary free cortisol to free cortisone is a useful risk factor for the development of PIH must be investigated in further prospective studies.
11-beta-Hydroxysteroid Dehydrogenases↗
Down-regulation of insulin-like growth factor-I receptor and insulin receptor substrate-1 expression in advanced human breast cancer.
The ligands, receptors and related signaling proteins of the insulin-like growth factor family are involved in the regulation of breast-cancer cell growth. We investigated the expression pattern of insulin-like growth factor-I receptor (IGF-IR), insulin receptor (IR) and insulin receptor substrate-1 (IRS-1), a core downstream signaling protein, in 69 primary breast-cancer specimens of different grades and in 21 control tissues by immunohistochemistry. In addition, cell proliferation (percentage of Ki67(+) nuclei) and estrogen receptor (ER) expression were determined. IGF-IR, IRS-1 and IR were expressed mainly in epithelial cells. IRS-1 and IGF-IR were expressed at high levels in control tissues and in well and moderately differentiated carcinomas but at low levels in poorly differentiated breast cancers. IR expression did not show a significant correlation with the differentiation grade of the tissues investigated. Statistical analysis (ROC analysis for tumor grade) demonstrated that down-regulation of IGF-IR and IRS-1 correlated better with tumor progression than reduction of ER expression or increase in cell proliferation, IGF-IR showing the best correlation, followed by IRS-1 and, less significant, ER and Ki67. Our findings clearly show that progression of breast cancer is accompanied by a reduction of IGF-IR/IRS-1 expression and that IGF-IR/IRS-1 expression inversely correlates with high proliferation rate in dedifferentiated breast cancers. The strong correlation of IGF-IR and IRS-1 down-regulation with tumor progression suggests the use of IGF-IR and IRS-1 as a novel set of marker proteins for tumor grading.
Adult↗
Riboflavin deficiency and preeclampsia.
OBJECTIVE: To examine in a prospective study riboflavin deficiency as a predisposing factor for preeclampsia in a high-risk collective of pregnant women in Zimbabwe. METHODS: At an antenatal clinic in Bulawayo, Zimbabwe, 154 women at increased risk for preeclampsia were observed prospectively until delivery. Riboflavin status was determined using the erythrocyte glutathione reductase activation coefficient test on the day of antenatal booking. Riboflavin deficiency was expressed by erythrocyte glutathione reductase activation coefficient of 1.4 or greater. RESULTS: Riboflavin deficiency was frequently found among the study population (33.8%). Incidence rose toward the end of pregnancy (27.3% at 29-36 weeks' gestation compared with 53.3% at over 36 weeks). In the riboflavin-deficient group, mothers were more likely to develop preeclampsia (28.8%) than in the riboflavin-adequate group (7.8%; P <.001, odds ratio [OR] 4.7, 95% confidence interval [CI] 1.8-12.2). The calculated concentrations of intracellular free flavin adenine dinucleotide were significantly lower in patients who developed preeclampsia than in normal pregnancies (P <.05). CONCLUSION: Riboflavin deficiency should be considered a possible risk factor for preeclampsia. Insufficient concentrations of the riboflavin-derived cofactors flavin adenine dinucleotide and flavin adenine mononucleotide could contribute to the established pathophysiologic changes including mitochondrial dysfunction, enhanced oxidative stress, and disturbances in nitric oxide release.
Adult↗
No correlation of tyrosinase mRNA in bone marrow with prognosis of metastatic melanoma.
BACKGROUND: 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. OBJECTIVE: We addressed the question, whether patients with metastatic melanoma and with RT-PCR-detectable tyrosinase mRNA in blood or bone marrow have a different prognosis compared to tyrosinase mRNA-negative patients. METHODS: 20 melanoma patients with widespread clinical metastases were enrolled and the survival time after first diagnosis of visceral metastases was correlated to tyrosinase mRNA presence in blood and bone marrow samples. RESULTS: The time of survival of 8 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. CONCLUSION: Although based on a limited number of patients our results suggest that 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. For this purpose, 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↗
Delayed sequential ruptures of the index and thumb flexor tendons due to an occult scaphoid nonunion.
A case of sequential spontaneous loss of flexion in the thumb and index finger over a 10 year period is reported. Previously unrecognized carpal collapse as a consequence of a longstanding scaphoid nonunion was identified as the cause. Fusion of the interphalangeal joint of the thumb and suture of the index profundus tendon to the middle profundus tendon resulted in a good outcome.
Aged↗
[Significance of the renin-angiotensin-aldosterone system for pathogenesis and early diagnosis of pregnancy-induced hypertension with special reference to mineralocorticoid receptors].
OBJECTIVE: In women with pregnancy-induced hypertension (PIH) the density of mineralocorticoid receptors (MR) in human mononuclear leukocytes (HML) is reduced compared with healthy pregnant women. The same applies to plasma levels of aldosterone and 18-hydroxycorticosterone. In this study, we investigated whether alterations of these parameters preceded the development of clinical symptoms and, therefore, might be potential predictors of PIH involved in the pathogenesis. PATIENTS AND METHODS: In eighty-four women belonging to the risk-group for PIH but not showing any symptoms neither of PIH nor preeclampsia (PE) we characterized prospectively before the onset of disease in the second trimester of pregnancy mineralocorticoid receptor status in HML and steroid plasma levels of aldosterone and its precursors as well as cortisol through radioimmunoassay. RESULTS: 15 women developed PIH, three of which developed PE. Neither in the density of MR nor in the affinity the women that developed PIH showed any difference from healthy women. Steroid plasma levels were identical as well. CONCLUSION: We conclude that a reduction of mineralocorticoid receptors does not precede PIH within the peripheral blood. But still one can assume that the RAAS may be involved in the pathogenesis of PIH, possibly on a local level within the placenta or as a secondary change, initiated by still unknown factors.
Adult↗
[Doppler ultrasound findings in therapy with urapidil].
OBJECTIVE: In a prospective study we investigated, whether changes in fetal or maternal circulation can be found by Doppler sonography under therapy with urapidil. PATIENTS AND METHODS: We investigated in 11 patients with severe pregnancy-induced hypertension (PIH) or superimposed preeclampsia in the third trimester. Doppler flow results of maternal and fetal vessels before and during therapy with urapidil. Hemodynamic parameters, like maternal blood pressure, and heart rate as well as other clinical parameters were assessed. RESULTS: Whereas the antihypertensive effects in the systolic and diastolic blood pressure were significant, we couldn't find changes in the resistance indices of fetal circulation. In contrast we found a decrease in the resistance indices in maternal vessels after an average of six days of urapidil therapy. These changes were significant in the uterine artery on the side of placental insertion. CONCLUSIONS: Because of only few side effects and a safe lowering of blood pressure, therapy with urapidil seems preferable to other well known drugs. Although Doppler flow velocimetry of uteroplacental vessels has no diagnostic benefit in monitoring PIH, the findings with this method under prolonged antihypertensive therapy are a chance for a better understanding of hemodynamic changes. The decrease in the resistance indices is another argument for the use of urapidil.
Adult↗