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Biomedical subjects

H Jäger

Publications and source records attributed to H Jäger.

At least 19 recordsLinked to original sources
PubMed2006

Highly active antiretroviral therapy (HAART) improves survival in HIV-associated Hodgkin's disease: results of a multicenter study.

BACKGROUND: The purpose of the study was to evaluate the outcome of Hodgkin's disease (HD) in patients infected with the human immunodeficiency virus (HIV) with respect to the use of highly active antiretroviral therapy (HAART). MATERIALS AND METHODS: This cohort study included patients with HIV-HD diagnosed from June 1984 to February 2004. Patients treated in the pre-HAART era (1984-1996) were compared with those belonging to the HAART era (1997-2004). RESULTS: Of 66 patients with HIV-HD, 47 (71%) presented with stage III/IV disease and 38 patients (58%) with an AIDS-defining illness. Fifty-nine of 66 patients (89.4%) underwent curative intended chemotherapy. Patients receiving HAART (n = 34) had a significantly better 2-year overall survival (OS) than those not receiving HAART (74% versus 30%, P <0.001). The 2-year OS of HAART-responders was 88% compared with 19% in patients without HAART-response (P = 0.0002). By multivariate analysis patients without HAART had a 5.6-fold higher risk for 3-year mortality [HR 5.6, 95% confidence interval (CI) 2.20-14.26]. Three-year mortality was significantly higher in patients without complete remission (HR 4.40, CI 1.77-10.99), with stage III/IV HD (HR 4.64, CI 1.31-16.49) and with CD4 cells <200/microl (HR 2.69, CI 0.99-7.33). CONCLUSIONS: Use of HAART significantly improved the overall survival in patients with HIV-HD.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Starting or changing therapy - a prospective study exploring antiretroviral decision-making.

BACKGROUND: When to start or change antiretroviral treatment against HIV infection is of major importance. Patients' readiness is considered a major factor influencing such treatment decisions, in particular because no objective, absolute time point when to start antiretroviral therapy exists. We aimed at evaluating patients' readiness to start or change antiretroviral therapy (ART). PATIENTS AND METHODS: HIV-infected patients starting or changing ART between July 2002 and February 2003, treating physicians and nurses participated in this prospective, observational multicenter study. We assessed shared decision-making including qualitative aspects, expected treatment decisions and treatment status after 3 months. RESULTS: 75 patients were included. Of 34 patients for whom starting ART was considered, 27 (79%) indicated that they were willing to start treatment. After 3 months, 21 of 27 (78%) actually started therapy, six did not. Patients with depression were less likely to be ready for ART (p < 0.05). Of 41 patients for whom changing ART was considered, 35 (85%) indicated that they were willing to change treatment. Of the latter 35 patients, 33 (94%) finally changed ART within 3 months. Physicians and nurses were too optimistic in predicting the start or change of ART. The main reason to start or change ART was the sole recommendation of the physician (52% in those starting, 61% in those changing ART). Patients mainly judged the decision as shared and were very satisfied (71%) with the process. Qualitative findings revealed the importance of a dialectic decisionmaking, described with two categories: "dealing with oneself and others"' and "understanding and being understood." CONCLUSION: Patients mainly shared the decision made during consultation. Although physicians have an essential role concerning ART, patients, physicians, and nurses all contribute to the decision. Qualitative findings indicate the importance for health-care providers to include patients' expertise and contributions.

Adult↗
PubMed2004

[Diagnosis and follow-up of HIV/AIDS by the general practitioner].

HIV-infections are often diagnosed in the setting of primary health care. Increased awareness of sexuality and sexually transmissible diseases facilitates identification of patients at risk. Patients with newly diagnosed HIV-infection should be referred to an HIV-specialist for counselling and further evaluation of disease progress. In addition to a regular follow-up in an HIV-priority practice or outpatient clinic, additional as well as HIV-associated diseases should be treated by the general practitioner. He should be informed concerning the patient's treatment situation and discuss therapeutic decisions with the HIV-specialist. Protection of HIV-infected individuals from discrimination and stigmatization remains critically important.

Acquired Immunodeficiency Syndrome↗
PubMed2003

[Entry inhibitors. Ring-free for a new principle of action].

Entry-inhibitors represent a new option in antiretroviral therapy. They prevent infection of HIV target-cells. According to their mechanism of action they can be divided into three groups: attachment-inhibitors, corezeptor-antagonists and fusion-inhibitors. The fusion-inhibitor T-20 (Enfuvirtide) will be the first substance to be licensed in 2003. It has been shown that entry-inhibition is a realistic goal for clinical use. Until now T-20 was mainly added to an optimized background regimen in intensively pretreated patients. To achieve the best efficacy a combination of substances with only slight preexisting resistance seems to be favorable. Further efforts in providing orally applicable drugs with little potential for developing resistance and with synergistic effects are required.

Acquired Immunodeficiency Syndrome↗
PubMed2002

[Saving on drugs, reducing side-effects. Treatment interruptions benefit acute and chronic HIV infected patients].

Patients with new HIV infection have been shown to benefit from therapy interruption. Control of the virus is better, and in some cases, further drug treatment can be obviated over the long term. In the case of deep-salvage patients, opportunistic infections may occur in some cases during the period of interruption. Although patients with chronic HIV infection who have already received lengthy periods of treatment, have no immunologic or virologic benefit from such interruptions, metabolic side effects are reduced, and a 20% to 50% drug-saving effect can be achieved. On the basis of our current knowledge, the question whether treatment interruption may be deleterious, for example, due to the development of resistance, would appear unlikely.

Anti-HIV Agents↗
PubMed2002

Treatment of HIV-associated wasting with recombinant human growth hormone: monitoring of body composition changes by bioelectrical impedance analysis (BIA).

INTRODUCTION: Recombinant human growth hormone (r-hGH) has demonstrated efficacy in treating HIV-associated wasting (HAW), however, HAW has become less prominent since the introduction of highly active antiretroviral therapy (HAART). Recent studies suggest that patients receiving HAART may still experience HAW. We investigated the nature of HAW and the efficacy of r-hGH in these patients. METHODS: We treated 27 HIV-positive patients receiving HAART who had either recent loss of >5% body weight or weight <90% lower limit of normal with 12 weeks of r-hGH (6 mg given either daily or every other day). Body composition changes were monitored using bioelectrical impedance analysis (BIA). RESULTS were assessed for all patients and for a subgroup meeting more stringent definitions of wasting (BIA phase angle a<5.6 degrees, n = 14). - RESULTS: Significant increases from baseline in weight and body cell mass (BCM) occurred in the full population (medians: 2.0 kg weight, 1.5 kg BCM). Patients with phase angle alpha<5.6 degrees also showed increases in weight and BCM (medians: 2.5 kg weight, 1.95 kg BCM), and 10 of 14 showed improvements in the ratio of extracellular mass (ECM) to BCM. At follow-up there was a trend towards loss of the weight and BCM gained on treatment. Treatment was well tolerated. CONCLUSION: Patients receiving HAART continue to experience wasting, and respond well to r-hGH therapy as monitored by BIA.

Adult↗
PubMed2001

Survival of AIDS patients with primary central nervous system lymphoma is dramatically improved by HAART-induced immune recovery.

OBJECTIVE: To evaluate the impact of immune recovery induced by highly active antiretroviral therapy (HAART) on the survival of AIDS patients with primary central nervous system lymphoma (PCNSL). METHODS: In a multicentric retrospective analysis, 29 HIV-infected patients with histologically confirmed PCNSL were identified. To evaluate median survival, Kaplan-Meier statistics were used. To explore the effects of different variables on survival, a Weibull accelerated failure time regression analysis was performed. RESULTS: Median age at manifestation of PCNSL was 39.1 years and median CD4 cell count was 11 x 10(6) cells/l. Seventy per cent of the patients had had a prior AIDS-defining illness. Cranial radiation (CR) was given to 12 out of 29 patients. Six patients were treated with HAART. Survival time of these patients and of the patients treated with CR alone differed significantly from those receiving neither CR nor HAART (median Kaplan-Meier survival estimate: 1093, 132, and 33 days, respectively). In the multivariate regression model, HAART and CR were identified as the only variables independently associated with prolonged survival. HAART versus no HAART and CR versus no CR increased the time to event by a factor of 6.1 (95% confidence interval, 2.4-16.0; P = 0.0002) and 3.1 (95% confidence interval, 1.5-6.3; P = 0.002), respectively. Four out of six patients on HAART showed a marked immune recovery and survived for more than 1.5 years, with two patients still alive. CONCLUSION: Data from this cohort indicate that immune recovery induced by HAART leads to dramatic improvement in survival of patients with AIDS-associated PCNSL. These findings may have important implications for future treatment strategies.

Adult↗
PubMed2001

Drosophila separase is required for sister chromatid separation and binds to PIM and THR.

Drosophila PIM and THR are required for sister chromatid separation in mitosis and associate in vivo. Neither of these two proteins shares significant sequence similarity with known proteins. However, PIM has functional similarities with securin proteins. Like securin, PIM is degraded at the metaphase-to-anaphase transition and this degradation is required for sister chromatid separation. Securin binds and inhibits separase, a conserved cysteine endoprotease. Proteolysis of securin at the metaphase-to-anaphase transition activates separase, which degrades a conserved cohesin subunit, thereby allowing sister chromatid separation. To address whether PIM regulates separase activity or functions with THR in a distinct pathway, we have characterized a Drosophila separase homolog (SSE). SSE is an unusual member of the separase family. SSE is only about one-third the size of other separases and has a diverged endoprotease domain. However, our genetic analyses show that SSE is essential and required for sister chromatid separation during mitosis. Moreover, we show that SSE associates with both PIM and THR. Although our work shows that separase is required for sister chromatid separation in higher eukaryotes, in addition, it also indicates that the regulatory proteins have diverged to a surprising degree, particularly in Drosophila.

Amino Acid Sequence↗
PubMed2001

Expression of sodium pump isoforms and other sodium or calcium ion transporters in the heart of hypertensive patients.

The sodium pump (Na(+),K(+)-ATPase; EC 3.6.1.37) of animal cell membranes is the enzyme responsible for the maintenance of membrane potential, for the function of secondary active transporters, and for osmoregulation of the cell. Since inhibition of the enzyme by cardiac glycosides results in increased contractility of the heart muscle and increased blood pressure, we were interested in whether there is a correlation between hypertension and expression of the various isoforms of the sodium pump. In addition, we also examined the expression of the isoforms of the sarcoplasmic and plasma membrane Ca(2+)-ATPase, the Na(+)/Ca(2+)- and Na(+)/H(+)-exchangers, and Na(+) channel and Ca(2+) channel isoforms. Total mRNA was isolated from 50 mg tissue from the right atrium of hypertensive and normotensive patients who were undergoing cardiac surgery. After reverse transcription and subsequent amplification of ion transporter-specific cDNA fragments by polymerase chain reaction (PCR) in the presence of [alpha-(32)P]dCTP, quantification of the amplified fragments was carried out by the Phosphorimager technique. The data obtained show that the alphal subunit mRNA is expressed similarly in normotensive and hypertensive patients. The amount of alpha2 subunit mRNA, however, is increased 5-fold in hypertensive patients. In the same group, the amount of alpha3 isoform is also significantly increased, although not as dramatically as the alpha2 isoform. Besides the Na(+),K(+)-ATPase isoforms, a significant increase in the expression of mRNA for the Na(+)/Ca(2+)-exchanger and the plasma membrane Ca(2+)-ATPase isoforms was detected. It is possible that the observed changes in mRNA expression for these ion transporters reflect compensatory mechanisms to overcome a defective Na(+) and Ca(2+) metabolism in the tissues of hypertensive patients or reflect defects directly involved in the cause of hypertension. The expression of mRNA for all other transporters investigated was unaltered.

Adult↗
PubMed2001

Endoluminal treatment of internal carotid artery stenosis.

Percutaneous transluminal stent-angioplasty of the carotid artery has indications that are similar but not identical to those for carotid surgery. Certain clinical conditions and morphologic findings, such as myocardial infarction, occlusion of the contralateral carotid artery, or tandem stenoses, favor use of the endoluminal technique. On the other hand, large clots at the site of stenosis, heavily calcified plaques, or elongated, kinked carotid arteries are better suited for carotid endarterectomy. Our experiences with angioplasty of more than 800 carotid stenoses and reports of other groups dealing with carotid angioplasty permit a preliminary evaluation of the method. The technical success rates, complication rates, and the few known long-term results are more or less equal to those of vascular surgery. Therefore further prospectively randomized studies are necessary to determine from which procedure the patient with his or her individual condition can gain the highest benefit.

Angioplasty, Balloon↗
PubMed2001

[New trend in HIV therapy. Later treatment onset and structured pauses].

Clear advantages in HIV therapy can be shown since 5 years. Questions arise concerning possible reductions of drug exposure per unit of time. These questions have become important in the light of possible development of lipodystrophy, hepatotoxicity and other side effects. Eradication at this point is not possible. Control of virus may be possible even when therapy is started later than recommended so far. 200 CD4 cells in asymptomatic patients and 100,000 copies of virus may be new starting points. There is a potential of decreasing drug exposure to 70% or 50% of the actual amount by structured or supervised therapy interruptions. Especially for the largest group of chronically infected patients no clear results concerning immunologic or virologic outcomes can be presented at this moment. If no harm is done, reduced amounts of drug exposure may be considered as an advantage.

Anti-HIV Agents↗
PubMed2001

Regulation of a mammalian Shaker-related potassium channel, hKv1.5, by extracellular potassium and pH.

Using the whole-cell recording mode of the patch-clamp technique we studied the effects of removal of extracellular potassium, [K(+)](o), on a mammalian Shaker-related K(+) channel, hKv1.5. In the absence of [K(+)](o), current through hKv1.5 was similar to currents obtained in the presence of 4.5 mM [K(+)](o). This observation was not expected as earlier results had suggested that either positively charged residues or the presence of a nitrogen-containing residue at the external TEA(+) binding site (R487 in hKv1.5) caused current loss upon removal of [K(+)](o). However, the current loss in hKv1.5 was observed when the extracellular pH, pH(o), was reduced from 7.4 to 6.0, a behavior similar to that observed previously for current through mKv1.3 with a histidine at the equivalent position (H404). These observations suggested that the charge at R487 in hKv1.5 channels was influenced by other amino acids in the vicinity. Replacement of a histidine at position 463 in hKv1.5 by glycine confirmed this hypothesis making this H463G mutant channel sensitive to removal of [K(+)](o) even at pH(o) 7.4. We conclude that the protonation of H463 at pH 7.4 might induce a pK(a) shift of R487 that influences the effective charge at this position leading to a not fully protonated arginine. Furthermore, we assume that the charge at position 487 in hKv1.5 can directly or indirectly disturb the occupation of a K(+) binding site within the channel pore possibly by electrostatic interaction. This in turn might interfere with the concerted transition of K(+) ions resulting in a loss of K(+) conduction.

Amino Acid Sequence↗
PubMed2000

SK2 encodes the apamin-sensitive Ca(2+)-activated K(+) channels in the human leukemic T cell line, Jurkat.

T cells express two different types of voltage-independent Ca(2+)-activated K(+) channels with small (SK) and intermediate (IK) conductance that serve important roles in the activation of T lymphocytes. In contrast to the IK channels from T lymphocytes which are upregulated upon mitogen stimulation, SK channels of Jurkat T cells, a human leukemic T cell line, are constitutively expressed even in the absence of mitogenic stimulation. We have used patch-clamp recordings from transfected or injected mammalian cells to show that the cloned SK2 channel demonstrates the biophysical and pharmacological properties of the majority of K(Ca) channels in Jurkat T cells. The cloned and native channels are voltage-independent, Ca(2+)-activated, apamin-sensitive, show an equivalent voltage-dependent Ba(2+) block and possess a similar ion selectivity. In addition, we used the polymerase chain reaction to demonstrate the presence of SK2 mRNA in Jurkat T cells, whereas SK3 transcripts encoding the other cloned apamin-sensitive SK channel were not detected. These data suggest that the voltage-independent apamin-sensitive K(Ca) channel in Jurkat T cells represents the recently cloned SK2 channel.

Apamin↗
PubMed2000

[Small intestinal transit with radio-opaque markers to localize intermittent small bowel obstruction] .

AIM: In difficult diagnostic cases of partial small bowel obstruction, radiopaque, non-digestible markers were used to challenge and localize the site of obstruction. MATERIAL AND METHOD: 32 patients (19 female, 13 male, 3-80 years) were examined. Each patient received 20 4-mm radiopaque markers orally. Abdominal radiographs were obtained at 4-8 h intervals. Mechanical obstruction was defined as the clustering of at least 3 markers for 4 hours or longer. The transit of radiopaque markers was compared to plain radiography, ultrasound, barium meal, computed tomography, enteroclysis and operative findings. RESULTS: 18 of 32 patients showed small bowel clustering suggestive of obstruction. Diagnostic agreement was found in 12 of 14 cases with ultrasound, in 7 of 13 cases with plain radiography and in 3 of 6 cases with enteroclysis. 13 of the 18 patients with clustering had surgery. All of them (13/13) had adhesions with the need of resection. CONCLUSION: This investigation is an alternative diagnostic method for the decision between conservative and surgical treatment in cases of intermittent partial small bowel obstruction.

Adolescent↗
PubMed2000

[Endoluminal therapy in carotid stenosis].

Stent angioplasty of atherosclerotic carotid artery stenosis has proven its benefit in 912 treated vessels with a success rate of 99% and a rate of permanent neurological deficit of 2.7%. The procedure is indicated in symptomatic patients with a stenosis of > 70% and in asymptomatic patients > 80%. The early and late results are not significantly different from those of carotid surgery. But the endoluminal treatment is more gentle to the patient, requires a shorter hospital stay and reduces the costs of the treatment. Moreover, patients who are no longer surgical candidates for general medical or local reasons or can only be dealt with surgically with a comparably high risk can be treated.

Aged↗