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Biomedical subjects

B Koehler

Publications and source records attributed to B Koehler.

At least 19 recordsLinked to original sources

[Knowledge and use of Pap-smear among HIV-positive women].

AIM: HIV-positive women are at increased risk for preneoplastic lesions and invasive cervical cancer (ICC). The occurrence of these lesions can be substantially reduced by appropriate cervico-vaginal screening protocols (i.e., Pap-test). The aim of study was to assess: 1) awareness of Pap-smear and 2) the association between awareness of Pap-smear and screening attitudes of HIV-positive women. METHODS: Three-hundred and ninety HIV-positive women who attended the HIV outpatient gynecological unit of the National Institute for Infectious Diseases, Rome, from January 2003 to April 2005 were included in this investigation. These 390 women were interviewed to assess whether they were aware that Pap-test was a preventive tool against cervical cancer. In addition, past history of Pap-test, socioeconomic condition, history of HIV infection, and sexual habits were investigated. Odds ratios (OR) and 95% confidence intervals (CI) were used to assess the association between knowledge of Pap-test and covariates. RESULTS: Of these 390 HIV-positive women, 54.6% were not aware that Pap-test could prevent ICC. Women with a low educational level (OR = 6.6) or women who originated from Africa (OR = 6.5) were more likely to be unaware of Pap-test. Lack of Pap-test awareness was strongly associated with negative history for lifetime Pap-test (OR = 4.7). CONCLUSIONS: We showed that a large proportion of HIV-infected women are not aware that ICC could be prevented through Pap-test screening, and that lack of Pap-test screening is strongly associated with lack of awareness. The need for Pap-test counseling targeted to HIV-infected women clearly emerges from our findings.

Adult↗

Valsartan versus ACE inhibition after bare metal stent implantation--results of the VALVACE trial.

The use of ACE inhibitors (ACE-i) represents an Ia recommendation in the treatment of patients with STEMI and NSTEMI. However, results of smaller studies suggest an increase of in-stent-restenosis under ACE-i administration. The effects of ACE-i and valsartan after bare metal stent implantation of the culprit type B2/C lesion should be compared. Seven hundred patients were treated either by ACE-i in cases of LVEF<50% or 80 mg valsartan in cases of LVEF> or =50%. Restenosis rates after 6 months were analysed in 399 patients under valsartan and 224 patients under ACE-i with control angiography and major adverse cardiac events (death, infarction, reintervention) in a follow-up of up to 4 (mean 2.6) years in all patients. In-stent-restenosis was found in 19.5% under valsartan and in 34% under ACE-i (p<0.005). In diabetic patients, restenosis occurred in 24% under valsartan and in 43% under ACE-i (p<0.01). In initial acute coronary syndrome (ACS), restenosis rate was 14% under valsartan and 43% under ACE-i (p<0.0001). In stable angina, restenosis rates were 26.5% and 27.5%, respectively. Total MACE rates revealed significant differences in ACS due to reintervention rates of 22% and 7% under ACE-i and valsartan (p<0.0001). The administration of 80 mg valsartan after bare metal stent implantation leads to a reduction of in-stent-restenosis compared to ACE-i. This effect is mainly due to beneficial effects of valsartan in cases with initial ACS. Major differences between ACE-i and valsartan are discussed including inflammation, activation of neutrophils, mode of bradykinin activation, AT2 receptor stimulation and apoptosis of smooth muscle cells.

Aged↗

Successful recanalization of an occluded coronary artery by percutaneous coronary intervention, systemic administration of tirofiban, a glycoprotein IIb/IIIa inhibitor, and intracoronary thrombolysis with alteplase.

A 51 year-old male was admitted to our institution with subacute inferior myocardial infarction. Coronary angiography showed thrombotic occlusion of the right coronary artery. Percutaneous coronary intervention including the delivery of 3 stents was unsuccessful (TIMI grade 0 flow). In addition to an ongoing systemic administration of tirofiban, a glycoprotein IIb/IIIa inhibitor, the patient received intracoronary thrombolysis (ICT) with alteplase (recombinant tissue type plasminogen activator, rt-PA). There was complete reperfusion on control angiography the following day (TIMI grade 3 flow); 7 months later, there was still TIMI grade 3 flow. To our knowledge, this is the first report on systemic administration of tirofiban combined with ICT.

Angioplasty, Balloon, Coronary↗

Drug-resistant tuberculosis in HIV-infected persons: Italy 1999-2000.

BACKGROUND: Patients with HIV infection may be a valuable target for assessing the impact of drug-resistant tuberculosis (TB). PATIENTS AND METHODS: An observational, prospective study was conducted in 96 infectious disease hospital units in Italy during 1999-2000. A total of 140 HIV-infected patients with diagnosis of TB and with an isolate tested for drug susceptibility entered the analysis. Drug resistance (DR) was defined as resistance to either isoniazid (INH) or rifampin (RIF), while multidrug resistance (MDR) was defined as resistance to INH and RIF. RESULTS: A total of 117 (83.6%) episodes of TB were classified as new cases and 23 (16.4%) as previously treated cases. Prevalence of resistance to INH or RIF was 12.8% and 4.3% among new cases, and 17.4% and 26.1% among previously treated cases, respectively. Prevalence rates of DR and MDR were 14.5% and 2.6% among new cases and 30.4% and 12.5% among previously treated cases, respectively. No statistically significant risk factors associated with DR or MDR TB emerged in this analysis. CONCLUSION: High prevalence rates of DR and MDR are present among HIV-infected TB patients in Italy, in particular among previously treated cases.

Adult↗

Effects of recombinant growth hormone therapy on thyroid hormone concentrations.

BACKGROUND AND OBJECTIVE: There are numerous, often contradictory reports on the effects of growth hormone (GH) therapy on thyroid function. The aim of this study was to assess the effect of such therapy on serum concentrations of thyroid hormones in GH-deficient children euthyroid prior to the treatment, and to determine the necessity of thyroid hormone administration in these patients. MATERIAL AND METHODS: The study included 32 GH-deficient patients in the first stage of sexual development, in whom disorders of thyroid function could be excluded. The inclusion criteria were based on clinical examination and levels of thyroxine (T4), triiodothyronine (T3), free thyroxine (fT4), free triiodothyronine (fT3), reverse triiodothyronine (rT3), thyrotropin (TSH) before and after stimulation with thyrotropin-releasing hormone (TRH). Recombinant growth hormone (rGH) (Genotropin 16U, Pharmacia) was administered at a dose of 0.7 U/kg/week. Fasting blood samples were drawn before treatment and after 3, 6, 9 and 12 months of therapy. Thyroid hormones were measured using RIA and IRMA methods. RESULTS: There were no physical signs of hypothyroidism in the patients examined during 12 months of rGH administration, and the satisfactory growth rate was achieved. T4 levels decreased in the first 3 months but remained within the normal range, and then returned to the values prior to the treatment. A similar trend was observed for fF4, with 28.5% of patients exhibiting fF4 levels below the normal in the 3rd month. An increase during the first 3 months of therapy was observed in the cases of T3 (statistically non-significant) and fT3, and these values then fell to levels within the normal range of patients' age. During treatment, TSH levels decreased but remained within the normal range. CONCLUSIONS: A transient decrease in T4 concentrations in the 3rd month with unchanged T3 and an increase in fT3 concentrations probably result from the effect of rGH on the peripheral metabolism of thyroid hormones. The results obtained do not support the use of thyroid hormone therapy with levothyroxine during the first year of rGH therapy in patients who are initially euthyroid.

Adolescent↗

Contralateral suppression of TEOAE in diabetic children. Effects of 1.0 kHz and 2.0 kHz pure tone stimulation--preliminary study.

The medial efferent system and its regulating outer hair cell function have not been previously studied in diabetic children. In this study, the group comprised 32 diabetic children, aged 6.0-16.0 years, with diabetes lasting 2.0-9.0 years, with normal tonal and impedance audiometry. A control group consisted of 30 healthy children with similar age and sex distribution. Contralateral stimulation (CS) was performed using 1.0 and 2.0 kHz pure tones on the level of 30 and 50 dB SL. Effects of CS on transient evoked otoacoustic emissions (TEOAE) elicited by click of a level equal to 70 and 60 dB SPL were investigated. Analysis included assessment of TEOAE amplitude and 0.8 kHz frequency bandwidth (0.8-FBW) amplitudes (signal/noise) centred at 1.0; 2.0; 3.0; 4.0; 5.0 kHz. TEOAE-RA recorded for stimulus 80, 70 and 60 dB SPL without CS were decreasing: average values respectively 7.3, 4.7 and 3.9 dB SPL. In the group of diabetic children TEOAE amplitudes, recorded for different click levels without CS, were similar to these recorded in healthy children. It suggested that normal function of the cochlea was preserved, mostly outer hair cells. However, the obtained effects of CS, in comparison with healthy children, were weaker and not so regular. Statistical analysis revealed that the reduction of TEOAE amplitudes for adequate 0.8-FBW in the control group was significantly higher, for both 1.0 kHz and 2.0 kHz CPTs of 30 dB SL and 50dB SL, in comparison with diabetic children. It is concluded that the suppressive effect on OAE in diabetic children is rather weak and seems to be associated with pathological changes in medial olivo-cochlear myelinated fibres.

Adolescent↗

Energy requirement for eating in cattle.

We determined the energy requirement for the activity associated with eating in an experiment with four adult Hinterwälder steers weighing 640+/-25 kg BW (mean+/-SD), using indirect calorimetry in respiration chambers. Heat production was measured during 3 h with and 3 h without ad libitum access to wheat straw, and the energy cost of eating was calculated as the difference, which was on average 27+/-13 J/(min x kg BW) (mean+/-SD). Straw intake, the time spent for eating, and the number of jaw movements were recorded. Values for the energy cost of eating reported in the literature are similar to those in this study, and values for ruminating amount to approximately 27% of those for eating. The energy cost of eating (literature values) varies greatly between feeds and feed treatments, when related to the amount of feed ingested, but it was relatively constant when related to time spent eating and was similar for cattle, sheep, and horses, when related to BW or metabolic BW (35 J/[min x kg BW] or 124 J/ [min x kg BW.75]). Calculations indicated that in high-quality roughage 10% of the ME and in untreated straw approximately 30% of the ME provided by the feed are used for eating and ruminating. This might be the main reason for the lower efficiency of ME utilization in roughages. The energy requirement for eating and ruminating should therefore be considered as a distinct proportion of the total ME requirement.

Animal Feed↗

Cyclopent[a]anthraquinones as DNA intercalating agents with covalent bond formation potential: synthesis and biological activity.

A series of mitomycin C (MMC) analogues, namely cyclopentanthraquinone derivatives, were synthesized via Diels-Alder cyclization of naphthoquinone with 1-vinylcyclopent-1-enes. These new compounds are planar structures, like MMC, and bear an aziridine ring and a methyl carbamate side chain. After bioreduction, they are anticipated to be capable of intercalating into double-stranded DNA and bind covalently. Structure-activity relationships were studied. Of these compounds, 2,3-aziridino-4-[[(methylamino)carbonyl]methyl] cyclopent[alpha]anthracene-6,11-dione (4) was shown to have inhibitory activity against several leukemic and solid tumor cell lines. Mice (BDF1) bearing Lewis lung adenocarcinoma were treated with 4 and MMC (i.p., QD x 5). At a dose of 30.0 mg/kg, compound 4 was as effective as MMC (0.8 mg/kg). Compound 4 appears to be less toxic than MMC. DNA unwinding assay indicated that 4 is able to intercalate into DNA double strands and is also a topoisomerase II inhibitor.

Animals↗

[Efficacy and safety of dexfenfluramine treatment in obese adolescents].

To assess the effect of dexfenfluramine on weight loss in obese adolescents, a group of 19 obese girls and boys was treated with a low calorie diet, supplemented with dexfenfluramine. The control group comprising the same number of patients was treated with diet only. Three weeks of hospitalization were followed by three weeks of treatment on an outpatient basis. An insignificantly larger weight loss in the dexfenfluramine-treated group was noted during the outpatient treatment. Dexfenfluramine therapy also resulted in a significant reduction of the serum triglycerides level. No serious side effects of dexfenfluramine therapy were noted.

Adolescent↗

Recombinant human interleukin 4 has antiproliferative activity on human tumor cell lines derived from epithelial and nonepithelial histologies.

Interleukin 4, a T cell-derived 20-kDa glycoprotein, plays an important role in regulating the immune response of B cells, T cells, and macrophages against infections and malignant cells. For this reason recombinant human interleukin 4 (rhIL-4) has entered early clinical trials in cancer patients. In the present study we report that rhIL-4 has an antiproliferative effect on five of nine cell lines derived from human colon tumors, head and neck tumors, and glioblastomas as measured by a decrease of colony formation in human tumor cloning assays. All of the cell lines with in vitro responsiveness express at least 100 high-affinity receptors for human interleukin 4 per cell on their cell surface, whereas the nonresponsive tumor cell lines lack expression of high-affinity receptors for human interleukin 4 on their cell surface. In the next series of experiments we have xenotransplanted some of the responsive cell lines into athymic nude mice. Subsequently, the animals were treated s.c. twice daily with 0.5 mg/m2 rhIL-4 or control vehicle for at least 12 days. There was a clear growth inhibition of these xenotransplanted tumors in the mice treated with rhIL-4. Histology of the tumors in both groups revealed no marked infiltration with murine hematopoietic and lymphocytic cells as evaluated by staining with a rat anti-mouse CD45 antibody. We conclude that rhIL-4 has a direct therapeutic activity on the growth of some human epithelial and nonepithelial tumor cell lines which, along with its regulatory function on hematolymphopoietic cells, makes this cytokine an interesting candidate for experimental tumor therapy.

Animals↗

Antiproliferative effect of human interleukin-4 in human cancer cell lines: studies on the mechanism.

Interleukin-4 (IL-4) plays an important role in activating the immune system against malignant cells. The human interleukin-4 receptor (hIL-4R) is not only expressed by hematopoietic cells but also on a large number of tissue specimens which include colon, breast and lung carcinomas. In this study we report that rhIL-4 has an antiproliferative effect on 2 out of 3 non-small cell lung carcinoma (NSCLC) cell lines in vitro as measured by human tumor cloning assays (HTCA). In comparison, rhIL-4 had no effect on the growth of small cell lung carcinoma cell lines (SCLC) in vitro. The response towards the cytokine is correlated with expression of at least 1500 high affinity receptors/cell for hIL-4 on the responsive cell lines. Xenotransplanting the human lung tumor cell lines into nude mice followed by 12 days of systemic treatment of the mice with rhIL-4 revealed a significant growth retardation of the IL-4R positive NSCLC cell lines when compared with the controls, whereas the growth of the IL-4R negative SCLC cell lines was unaffected also in vivo. Studies of possible mechanisms involved in the antiproliferative effect of rhIL-4 showed that rhIL-4 does not induce apoptosis or modulation of the transcription factor c myc in the responsive NSCLC cell lines. Additionally, the expression of the epidermal growth factor receptor (EGFR), which is discussed as mediating autocrine/paracrine growth stimulation of NSCLC, is unaffected by rhIL-4. However, we have observed that rhIL-4 inhibited G1-S-phase cell cycle progression. We conclude that rhIL-4 has an antiproliferative effect on the growth of some NSCLC in vitro and in vivo. The mechanisms involved remain to be further elucidated.

Animals↗

[Levels of cholesterol, HDL-cholesterol, LDL cholesterol and triglycerides in blood serum of children from Silesia].

In order to estimate the mean and borderline total cholesterol, HDL-cholesterol, LDL-cholesterol and triglyceride levels, a group of 1151 children aged 7 to 15 years was examined. They were randomly chosen from elementary schools in Katowice, the capital city of Silesia. Significantly lower total cholesterol levels were found in 14-15 year old boys and girls than in children from the younger age groups. The highest borderline total cholesterol level was found in children aged 10 years. Older children had the lowest borderline HDL-cholesterol values. As the prevention of coronary disease should already start in childhood, it is necessary to assess the mean and borderline lipoprotein levels in school children. The present work, together with the previously published papers from different parts of Poland, may contribute to establishing normal values for our country.

Adolescent↗

[Atherosclerosis risk factors in school children from Silesia].

Hypercholesterolemia, hypertriglyceridemia, elevated LDL-cholesterol levels, lowered HDL-cholesterol levels, obesity and elevated blood pressure incidence were studied among 1151 school children from the Silesian region. Children whose parents had a positive history for cardiovascular disease were also analyzed. In 20.8% subjects at least one risk factor was found, in 5.6% subjects--two, in 1.6% subjects--three and in 0.8% subjects--four risk factors were present. Obesity was the most common risk factor and obese children were the most likely to be hypertensive or have dyslipoproteinemia.

Adolescent↗

Goiter incidence in region of Katowice in relation to iodine deficiency and iodine prophylaxis (Katowice coordinating center).

Geographical region of Katowice is situated in an upland built of carbonate rocks, often with predominance of loss. A randomized trial was carried out in the urban population of this area. 1080 children aged 7-13 were examined. In 505 urine iodine was measured. 17.5% of the examined children had enlarged thyroid glands (Ib, II, III) in palpation, 82.3% did not have goiter (O, Ia). Interviews with patients revealed that 48.8% of the examined children used iodized salt, while 51.2% did not. Mean urine iodine concentration was 70.6 micrograms/l. No correlation between use of iodized salt, urine iodine concentration, and goiter was found. However, prevalence of goiter and low urine concentration suggested deficiency of this microelement in the examined industrial region. Therefore there is need for further investigations and for a profound change of the existing ineffective iodine prophylaxis.

Adolescent↗

[Evaluation of glucose and cholesterol levels in the mother and newborn infant in the perinatal period].

In 30 live born newborns the connections were assessed between glucose and cholesterol levels in umbilical cord blood after birth, and also in maternal blood before and two days after birth. Statistically significant differences of glucose and cholesterol levels were found between mothers and newborns in the perinatal period. Attention is called to greater independence of cholesterol (total, free and esterified) levels in newborn and mother in perinatal period.

Adult↗

Identification and quantification of Bence-Jones proteinuria by automated nephelometric screening.

A two-step screening of urine samples for Bence-Jones proteins is described. The proposed method is fast and fully mechanized; quantitative results are obtained within minutes. As a first step alpha 1-microglobulin, albumin, transferrin and IgG are measured immunonephelometrically. Then the cumulative concentration of the four markers is compared with that of total protein, which is determined by nephelometry during trichloroacetic acid protein precipitation. Bence-Jones proteinuria is indicated by large concentrational differences (greater than 31%) between the four markers and total protein. As a second step, Bence-Jones proteins are assessed directly if they are present. Immunoglobulin light-chains are measured immunonephelometrically and the kappa:lambda ratio is used to discriminate between monoclonal and polyclonal forms. Using this strategy, urine samples from 84 patients with monoclonal gammopathia or multiple myeloma were screened. Bence-Jones proteinuria was detected in 40 cases. In a reference collective (69 patients with different types of renal proteinuria) Bence-Jones proteinuria was not observed. Comparing the results with those obtained by immunofixation, the nephelometric method has a sensitivity of 100% and a specificity of 97%, differing only in a single false-positive result. Additional information about renal forms of proteinuria is supplied by the first screening step. This permits an assessment of the renal involvement in Bence-Jones proteinuria, and the method can also be used for nephrological diagnosis.

Adult↗