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Biomedical subjects

J Hahn

Publications and source records attributed to J Hahn.

At least 19 recordsLinked to original sources

Glycoprotein IIb/IIIa inhibitor-induced thrombocytopenia: diagnosis and treatment.

Thrombocyte glycoprotein IIb/IIIa inhibitors prevent fibrinogen binding and thereby thrombocyte aggregation. The inhibition of thrombocyte activation at the damaged coronary plaque is the target of the new therapeutic strategies in treating acute coronary syndrome. This reduces the ischemic complications associated with the non-STelevation myocardial infarction (NSTEMI) and percutaneous coronary intervention (PCI). Thrombocytopenia is a known complication of glycoprotein (GP) IIb/IIIa inhibitors. Although, in general, GP IIb/IIIa inhibitor-induced thrombocytopenia is a harmless side effect which responds readily to thrombocyte transfusion, it can occasionally be a very serious complication associated with serious bleeding. In addition patients developing thrombocytopenia have unfavorable outcome (e.g., death, myocardial infarction, bypass surgery or additional PCI) in comparison to patients without thrombocytopenia. Advanced age (> 65 years), low BMI and a low initial thrombocyte count (<180,000/microl) are independent risk factors of thrombocytopenia. The risk of bleeding is higher with this form of thrombocytopenia not only due to the low thrombocyte count but also to the impaired function of the remaining thrombocytes. It is important to closely monitor platelet count during GP IIb/IIIa antagonist treatment. Platelet count monitoring two, six, twelve and 24 hour after starting the treatment reveals most cases of acute thrombocytopenia. Side effects can be avoided by the early discontinuation of the GP IIb/IIIa antagonist treatment. This article reviews the diagnosis and treatment of glycoprotein IIb/IIIa inhibitor-induced thrombocytopenia and summarizes the differential diagnosis from heparin-induced thrombocytopenia and laboratory-related pseudothrombocytopenia.

Acute Disease↗

Replacement of calcineurin inhibitors with daclizumab in patients with transplantation-associated microangiopathy or renal insufficiency associated with graft-versus-host disease.

Transplantation-associated microangiopathy (TAM) or renal insufficiency (RI) after allogeneic hematopoietic stem cell transplantation is associated with a high mortality. As calcineurin inhibitors (CI) may contribute to TAM or RI, we evaluated the efficacy of replacing CI by daclizumab in patients with graft-versus-host disease (GVHD). Thirteen patients with GVHD-associated TAM and five patients with RI were treated with daclizumab 1 mg/kg intravenous (i.v.)/week, discontinuation of the CI and continuation of the remaining GVHD treatment. All patients had acute GVHD (steroid-sensitive (n=4), steroid-refractory (n=10)) or chronic GVHD (n=4) and were treated with CI before the start of daclizumab. Nine of 13 patients with TAM treated with daclizumab and discontinuation of CI achieved complete remission of TAM, two had stable disease, and one patient did not respond. Patients receiving daclizumab for RI without TAM showed stabilization (2/5) or improvement (3/5) of renal function. Four of 14 patients with acute GVHD achieved CR, two partial remission, eight patients did not respond and 11/14 died at a median of 39 days after start of the daclizumab. Our data demonstrate that replacement of CI by daclizumab can improve TAM and RI. However, mortality remains high in patients with acute GVHD.

Acute Disease↗

Reactivation of resolved hepatitis B virus infection after allogeneic haematopoietic stem cell transplantation.

Hepatitis B virus (HBV) reactivation after allogeneic haematopoietic stem cell transplantation (allo-HSCT) is well known in HBsAg-positive carriers but has only occasionally been reported in patients with resolved HBV infection. We investigated six allo-HSCT recipients with pretransplant anti-HBs and anti-HBc antibodies for serologic markers of HBV infection and for the presence of HBV-DNA in serum. Reverse seroconversion, that is, reappearance of HBsAg after a gradual loss of anti-HBs, but no severe liver damage was observed in three patients at 14, 22 and 12 months after HSCT, respectively. There was an increase in HBV-DNA concentration prior to reverse seroconversion. One patient was repeatedly HBV-DNA positive (10(2)-10(3) copies/ml) without reverse seroconversion. Sequencing of the HBsAg and precore region derived from the four HBV-DNA-positive patients showed no relevant mutations. In conclusion, this study demonstrated a high risk (50%) of reverse seroconversion in allo-HSCT recipients with resolved HBV infection. A highly sensitive HBV-DNA assay (TaqMan-PCR) allowed early identification of the individual patients at risk.

Adolescent↗

[Neuropathological findings after cardiac surgery-retrospective study over 6 years].

Neuropathological studies may contribute to the discovery of central nervous system complications after heart surgery and thus help to reduce the incidence of postoperative neurological or cognitive disturbances. We examined the brains of 262 such patients operated for coronary bypass, valve replacement, or heart transplantation. Circulatory disturbances (macro- and microhemorrhages, infarcts, subarachnoid hemorrhages, and hypoxemic brain damage) were present in 128 cases (49%), as the cause of death in 33 cases (12.6%). The infarcts were caused by local arteriosclerosis of brain arteries, arterial emboli originating from the operative sites or myocardial infarctions, or by fat emboli, foreign body emboli or megakaryocytic capillary emboli in rare cases. Inflammatory disturbances were present in 17 cases and consisted of fungal or bacterial septicopyemic changes (12) or of glial nodules (5) as the substrate of a viral or autoimmunencephalitis (Bickerstaff). An incidental finding was Alzheimer's disease in 37 cases (14% of the material) of elderly patients, often associated with cerebral amyloid angiopathy but not as cause of death or cause of macroscopic brain hemorrhage. Since we have conducted an autopsy study, there is a limitation to transfer the documented changes to the total group of post-cardiac surgery patients with neurologic and cognitive deficits. Contrary to some previous reports, histologically overt microembolic phenomena do not seem to play a major role in our material. On the other hand, careful scrutiny revealed non-fatal white matter microhemorrhages of varying frequency in the different groups, especially after valve operations. These as well as the occasional glial nodules, after resorption and microscarring, could well be the cause of slight neurologic and cognitive impairments.

Aged↗

31P NMR spectroscopy of blood plasma: determination and quantification of phospholipid classes in patients with renal cell carcinoma.

Advanced renal cell carcinoma (RCC) has a poor prognosis and is characterized by an unpredictable clinical course. The aim of this study was to assess the systemic phospholipid distribution as a possible marker of tumor stage and tumor spread beyond the kidney. To this end, the effect of renal cell carcinoma (RCC) on phospholipid concentrations in blood plasma using 31P NMR spectroscopy was studied in: (a) 29 patients with RCC prior to nephrectomy; (b) 19 healthy volunteers; (c) three patients with other renal tumors (renal metastases of bronchial carcinoma and of renal pelvic carcinoma, and a benign renal tumor). Furthermore, the phospholipid concentrations of eight patients of group (a) were determined 6 months after nephrectomy, when they were in remission. We found considerable deviations in the concentrations of the lysophosphatidylcholines (LPC1, LPC2) in both male and female patients with RCC compared to healthy volunteers (male--LPC1 0.217+/-0.062 vs 0.297+/-0.049 mmol/l, LPC2 0.036+/-0.014 vs 0.068+/-0.024 mmol/l; female--LPC1 0.195+/-0.071 vs 0.296+/-0.044 mmol/l, LPC2 0.037+/-0.027 vs 0.044+/-0.014 mmol/l). In addition, female patients with RCC showed lower concentrations of phosphatidylcholines (PC; 1.409+/-0.268 vs 1.947+/-0.259 mmol/l). The low phospholipid concentrations normalized for patients in remission. Phospholipid concentrations were found to depend on tumor stage and metastatic spread. The deviations in phospholipid concentrations (LPC1, LPC2, PC) observed may be attributable to systemic effects caused by the tumor as well as changes in enzyme activities.

Adult↗

Acute pneumatosis cystoides intestinalis following allogeneic transplantation -- the surgeon's dilemma.

Pneumatosis cystoides intestinalis (PCI) is still a poorly understood phenomenon, currently considered to result from primary mucosal insult from varying causes. We report a case of severe PCI in a patient with chronic GVHD after bone marrow transplantation (BMT) performed to treat secondary AML. Post BMT, the patient suffered acute intestinal and cutaneous GVHD, eventually developing intestinal and biopsy-proven cutaneous chronic GVHD, which necessitated continuous steroid therapy. Chronic pancreatitis associated with GVHD was diagnosed by explorative surgery in February 2000 on the basis of increasing epigastric discomfort, tumour marker (CA 125) increase and the CT finding of a suspicious mass in the pancreas. Readmission occurred in April 2000 for rapid onset of inferior abdominal pain with distinct peritoneal signs. Relaparotomy, deemed necessary on the grounds of both clinical and radiological findings, revealed marked PCI of the ascending and transverse colon and attached mesentery in an otherwise intact gastrointestinal tract. Post-operative reconvalescence was uneventful, with no clinical or radiological recurrence of PCI in the following 10 months. In the context of a review of the relevant literature, this case report illustrates the complex underlying pathophysiology, and difficulty in making a differential diagnosis and treating PCI.

Acute Disease↗

Intermediate-term results with 1,019 carbomedics aortic valves.

BACKGROUND: A retrospective study was conducted to evaluate the intermediate-term outcome in patients with the Carbomedics aortic valve prosthesis. METHODS: The study included 1,019 primary valve replacements between 1989 and 1997. Seventy-two percent of patients were men; mean (standard deviation) age was 61 (10) years. The preoperative New York Heart Association functional class was III or IV in 70% of patients. Follow-up at 9 years was 99.6% complete, comprising 2,730 patient-years (mean, 2.7 years). RESULTS: Patient survival, including operative deaths, was 80% at 7 years. The linearized death rate was 2.9%/year. Statistically significant risk factors for mortality were diabetes, pure valve insufficiency, advanced age at operation, and advanced preoperative functional class. Linearized rates were thrombosis, 0.1%/year; thromboembolism, 1.0%/year; hemorrhage, 1.7%/year; endocarditis, 0.1%/year; paravalvular leak, 0.1%/year; reoperation, 0.1%/year; and all events, 3.0%/year. The 7-year estimates of freedom from complications were thrombosis, 99%; thromboembolism, 93%; hemorrhage, 89%; endocarditis, 99%; paravalvular leak, 99.7%; reoperation, 99%; and all events, 82%. No structural valve failure was observed. CONCLUSIONS: The low incidence of valve-related complications favors the continued use of the Carbomedics valve in the aortic position.

Adolescent↗

Construction of recombinant swinepox viruses and expression of the classical swine fever virus E2 protein.

To explore the swinepox virus (SPV) as a potential live vector for immunization, a vector was developed for the construction of a recombinant SPV carrying foreign genes. In this system, a foreign gene placed under the strong vaccinia virus promoter P(11) can be inserted into the viral thymidine kinase (TK) gene, and the recombinant virus can be isolated in a non-selective medium by the co-expression of E. coli lacZ gene. Compared with the wild type virus, the TK(-)recombinant SPV showed a modest level of attenuation in porcine cells while more attenuation was observed in monkey or human cells. Using this system, a recombinant virus expressing the E2 glycoprotein of classical swine fever virus (CSFV) was produced. Engineered with the gX signal sequence of the pseudorabies virus, and transmembrane domain of E2, the E2 protein was expressed as a dimeric form in the cytoplasm of the infected cells.

Animals↗

A ComGA-dependent checkpoint limits growth during the escape from competence.

In Bacillus subtilis, competence for transformation develops in 5-10% of the cells in a stationary phase culture. These cells exhibit a prolonged lag in the resumption of growth and cell division during the escape from competence. To better understand the basis of this lag, we have characterized competent cultures microscopically. To distinguish the minority of competent cells, a translational fusion between ComK, the competence transcription factor, and the green fluorescent protein (GFP) was used as a marker. Only 5-10% of the cells in a competent culture were fluorescent, indicating that ComK synthesis is an all or nothing event. To validate the identification of competent cells, we demonstrated the coincident expression of comEA, a late competence gene, and comK-gfp. Competent cells resemble stationary phase cells; the majority are single (not in chains), contain single nucleoids, and rarely contain FtsZ rings. Upon dilution into fresh medium, competent cells maintain this appearance for about 2 h. In contrast, the majority of non-competent cells rapidly resume growth, exhibiting chaining, nuclear division and FtsZ-ring formation. The late competence protein ComGA is required for the competence-related block in chromosome replication and cell division. In the competent cells of a comGA mutant culture, chromosomal replication and FtsZ-ring formation were no longer blocked, although competent comGA mutant cells were abnormal in appearance. It is likely that one role for ComGA is to prevent growth, chromosome replication and cell division until ComK can be eliminated by degradation. A mutation in the ATP-binding site of comGA inactivated the protein for transformation but did not prevent it from inhibiting DNA replication and cell division. The buoyant density difference between competent and non-competent cells depends on the competence-specific growth arrest.

Bacillus subtilis↗

Roles of the two ClpC ATP binding sites in the regulation of competence and the stress response.

MecA targets the competence transcription factor ComK to ClpC. As a consequence, this factor is degraded by the ClpC/ClpP protease. ClpC is a member of the Clp/HSP100 family of ATPases and possesses two ATP binding sites. We have individually modified the Walker A motifs of these two sites and have also deleted a putative substrate recognition domain of ClpC at the C-terminus. The effects of these mutations were studied in vitro and in vivo. Deletion of the C-terminal domain resulted in a decreased binding affinity for MecA, a decreased ATPase activity in response to MecA addition and decreased degradative activity in vitro. In vivo, this deletion resulted in a failure to degrade ComK and in a decrease in thermal resistance for growth. Mutation of the N-terminal Walker A box (K214Q) caused a drastically decreased ATPase activity in vitro, but did not interfere with MecA binding. In vivo, this mutation had no effect on thermal resistance, but had a clpC null phenotype with respect to competence. Mutation of the C-terminal Walker A motif (K551Q) caused essentially the reverse phenotype both in vivo and in vitro. Although binding to MecA was only moderately impaired with 2 mM ATP, this mutant protein displayed no response to 0.2 mM ATP, unlike the wild-type ClpC and the K214Q mutant protein. The ATPase activity of the K551Q mutant protein, induced by the addition of MecA plus ComS, was decreased about 10-fold but was not eliminated. In vivo, the K551Q mutation showed a partial defect with respect to competence and a profound loss of thermal resistance. Sporulation was reduced drastically by the K551Q and less so by the K214Q mutation, but remained unaffected by deletion of the C-terminal domain. Although the evidence suggests that the functions of the two ATP-binding domains overlap, it appears that the N-terminal nucleotide-binding domain of ClpC is particularly concerned with MecA-related functions, whereas the C-terminal domain plays a more general role in the activities of ClpC.

Adenosine Triphosphatases↗

Sedation of children for electroencephalograms.

OBJECTIVE: Sedation sometimes is necessary to perform an electroencephalogram (EEG) on a child. A dramatic decline in the need to use conscious sedation in our EEG laboratory prompted this review of our sedation experience. The purpose of this review was to determine the incidence of adverse sedation effects and to determine why the need for sedation had declined. METHODS: All 513 attempts to administer sedation to children who were undergoing EEG studies during a 4-year period were reviewed retrospectively. Parameters studied included type and amount of the sedative agents, need for repeated dosing, successful completion of the EEG, and complications attributed to the sedative. RESULTS: Sedation was attempted in 513 (18%) of 2855 EEGs performed during the 4-year period. Ninety-one percent of the EEGs performed with sedation were completed successfully. Chloral hydrate was the most frequently administered sedative. Complications (transient oxygen desaturation) occurred in 3 children, all of whom had recognized risk factors for airway compromise. The proportion of children who required sedation decreased from 32% to just 2% during that time period. CONCLUSION: Sedation of children who are undergoing EEG examinations is effective and safe. Complications are infrequent. The need for sedation can be decreased greatly by adequate preparation and by creating a less-threatening, child-friendly environment in which to perform the study.

Adolescent↗

Dysregulated L-selectin expression on lymphocytes in patients with chronic venous insufficiency.

In this study we analysed blood samples taken from the dorsalis pedis vein and a brachial vein of 11 healthy test persons and 8 patients with venous leg ulcer under experimental venous hypertension in order to examine changes in the expression of leukocyte adhesion molecules (LFA-1 (CD11a), Mac-1 (CD11b), p150,95 (CD11c), CD18, VLA-4 (CD49d) and L-selectin (CD62L)) which are involved in the adhesion steps of leukocytes to endothelial cells for transmigration into tissues. Under orthostatic stress, lymphocytes in controls collected at the foot level showed a significant reduction in the expression of L-selectin (p=0.002), compared to those of patients. This finding suggests that venous stasis negatively influences the expression of L-selectin on leukocytes only in healthy volunteers. Patients with chronic venous insufficiency seem to suffer from a specific defect in the regulation of L-selectin shedding under orthostatic stress.

Adult↗

Job exposures as correlates of recovery in population-based rehabilitation intervention for work-related low back disorders.

PURPOSE: Evaluating the impact of population-based rehabilitation interventions for work-related low back disorders (WR-LBD) requires job exposure factors to be considered as time-varying covariates. The role of job factors in recovery has not been well-established as most studies are based upon clinic samples, not working populations. This report represents the initial exploration of variables to be included in modeling job exposures as time-varying covariates of a study of work-place based rehabilitation intervention.METHODS: The study sample consisted of 162 hourly production employees from two automotive plants with work-related low back disorder not due to external trauma. Data reported herein were collected at baseline from an on-going large randomized clinical trial of rehabilitation for WR-LBD. Low back pain as measured by the North American Spine Society Baseline Form was examined in relation to: self-reported job factors from the Job Content Questionnaire and job risk category for low back disorder determined by the Lumbar Motion Monitor (LMM), an electronic goniometer which transmits back motion signals to a computer for analysis.RESULTS: Low back pain, with and without leg pain, was not found to be associated with hours worked in the previous week, job shift, perceptions of the pace of the job, or job risk of low back disorder as measured by the LMM. Low back pain was significantly (p < 0.05) correlated with perceptions of: how hard the work was, how much physical effort was required, how hectic the job was, whether or not there was sufficient time to do the job, and how much concentration and physical effort were required for the job.CONCLUSIONS: Self-report of perceptions of job strain may be as important, if not more important, than current quantitative factors thought to influence recovery from work-related low back pain.

Journal Article↗

Ginsenosides inhibit capsaicin-activated channel in rat sensory neurons.

Ginsenosides isolated from ginseng are biologically active components. In this study, whole-cell and inside-out configurations of patch clamp technique had been used to test the effect of ginsenosides on the capsaicin-activated channels in cultured small diameter sensory neurons of young rat. Ginsenosides (100 microg/ml) decreased the amplitude of capsaicin-activated currents by 78.2% in whole cell mode. Similarly, ginsenosides decreased capsaicin-activated single-channel activities in a dose-dependent manner in inside-out patches. These results indicate that ginsenosides might directly block capsaicin-activated channels, resulting in attenuation of the currents in rat sensory neurons.

Animals↗