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Biomedical subjects

A Kofler

Publications and source records attributed to A Kofler.

At least 19 recordsLinked to original sources
PubMed2007

[Importance of intrathecal pain therapy].

Intraspinal drug infusion using implantable pumps and catheter systems is a safe and effective therapy for selected pain patients with severe chronic pain. It improves pain relief, reduces drug-related side effects, decreases the need for oral analgesia and enhances quality of life in a segment of chronic pain patients whose pain has not been controlled with more conservative therapies. Intrathecal drug therapy has therefore established its role in the treatment of malignant pain, benign pain and severe spasticity.Careful patient selection and management as well as a multidisciplinary approach are determinants of successful treatment. Current practices for patient selection and management, screening, drug selection, dosing and implantation for intrathecal drug delivery systems are discussed.

Analgesia, Epidural↗
PubMed2006

Hepatitis C virus and non-Hodgkin's lymphoma: Findings from the Swiss HIV Cohort Study.

Infections with hepatitis C virus (HCV) and, possibly, hepatitis B virus (HBV) are associated with an increased risk of non-Hodgkin's lymphoma (NHL) in the general population, but little information is available on the relationship between hepatitis viruses and NHL among people with HIV (PHIV). We conducted a matched case-control study nested in the Swiss HIV Cohort Study (SHCS). Two hundred and ninety-eight NHL cases and 889 control subjects were matched by SHCS centre, gender, age group, CD4+ count at enrollment, and length of follow-up. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were computed using logistic regression to evaluate the association between NHL and seropositivity for antibodies against HCV (anti-HCV) and hepatitis B core antigen (anti-HBc), and for hepatitis B surface antigen (HBsAg). Anti-HCV was not associated with increased NHL risk overall (OR = 1.05; 95% CI: 0.63-1.75), or in different strata of CD4+ count, age or gender. Only among men having sex with men was an association with anti-HCV found (OR = 2.37; 95% CI: 1.03-5.43). No relationships between NHL risk and anti-HBc or HBsAg emerged. Coinfection with HIV and HCV or HBV did not increase NHL risk compared to HIV alone in the SHCS.

Adult↗
PubMed2003

Resistance to glucocorticoid-induced apoptosis in lymphoblastic leukemia.

Glucocorticoid (GC) resistance is a phenomenon of major significance in a number of clinical situations, including the therapy of lymphoid malignancies. Resistance may concern all, or just selected, GC effects, it may be absolute or just reflect a state of reduced sensitivity and, clinically relevant, be reversible or irreversible. Numerous molecular mechanisms can be envisaged acting either 'upstream' in the GC-triggered signaling pathway, i.e. at the level of the GC receptor (GR), or 'downstream' at the level of the GC-regulated genes responsible for individual GC effects. In lymphoid malignancies, GCs have anti-leukemic effects through the induction of apoptosis and/or cell cycle arrest. In this condition evidence for only a small number of mechanisms for GC resistance has been provided, mostly at the level of the GR. Herein, we review reports and hypotheses regarding 'upstream' and 'downstream' mechanisms for GC resistance in lymphoblastic leukemia and present an in vitro GC resistance model that might allow identification of resistance mechanisms.

Apoptosis↗
PubMed2001

Craniectomy in severe, life-threatening encephalitis: a report on outcome and long-term prognosis of four cases.

OBJECTIVE: To report the feasibility of craniectomy with duraplasty in four patients with life-threatening encephalitis and, in particular, their long-term outcome. DESIGN: Report of four cases, analysis of the acute clinical course and neurological long-term sequelae. RESULTS: Generous craniectomy with duraplasty was performed in four patients with life-threatening encephalitis leading to decortication and decerebration. This treatment approach reduced intracranial pressure. The long-term sequelae (1.5-8 years after craniectomy) confirmed its appropriateness, having led to full neurological (cerebral) function, resocialization, and reintegration into their professional life in all four patients. CONCLUSION: Craniectomy with dural augmentation is a treatment approach in cases of severe space-occupying encephalitis, not only saving the patient's life but also leading to favorable long-term outcome.

Adolescent↗
PubMed2001

Deep wound infection after vagus nerve stimulator implantation: treatment without removal of the device.

Effective treatment of deep wound infection without removal of a previously implanted foreign body is difficult. The Neurocybernetic Prosthesis (NCP) System (Cyberonics Inc., Webster, TX, U.S.A.), implanted for vagus nerve stimulation in patients with medically refractory epilepsy, uses coil-like electrodes placed around the left vagus nerve after exposure of the nerve in the carotid sheath. Infection within this compartment endangers the contained structures and makes removal of the system hazardous. We report the case of one patient implanted with the NCP who underwent successful open wound treatment without removal of the system. A 35-year-old man had local signs of wound infection 5 weeks after implantation of a vagus nerve stimulator. Systemic signs of infection were absent. C-reactive protein was slightly elevated, but all other laboratory values were normal. After open wound debridement and thorough rinsing with bacitracin-containing solution, the wound was packed with 3% iodoformized gauze. The NCP was left in place. Systemic antibiotic therapy with fosfomycin and cefmenoxim was started. Cultures confirmed an infection with Staphylococcus aureus. The wound was rinsed daily with 3% hydrogen peroxide solution and 5% saline until cultures were sterile and granulation tissue started to fill the wound. Delayed primary closure was performed 2 weeks later. Wound healing was accomplished without removal of the device. No signs of recurrent infection were observed during a follow-up of 1 year. Open wound treatment without removal of the implanted vagus nerve stimulator is feasible in cases of deep cervical wound infection and can be an alternative if removal of the device appears hazardous.

Adult↗
PubMed2001

Clinical and objective data on spinal cord stimulation for the treatment of severe Raynaud's phenomenon.

Ischemic vascular disease of the upper extremity represents a difficult therapeutic problem wherein medical treatment often fails. Epidural spinal cord stimulation has been shown to be an effective alternative in severe peripheral arterial disease. Although this method has been used for nearly two decades only limited experience exists in Raynaud's phenomenon of the upper limbs. In addition objective parameters to prove therapeutic success are not well defined. Herein we describe a patient with severe primary Raynaud's phenomenon over several years who had significant pain relief and complete healing of ischemic digital ulcerations after spinal cord stimulation. Pain level was evaluated using a visual rating scale before and after surgery. Microcirculatory parameters were assessed before and after spinal cord stimulation by capillary microscopy and laser Doppler anemometry. Significant improvement of red blood cell velocity, capillary density, and capillary permeability was demonstrated. At follow-up 18 months after surgery the patient had no complaints and all ulcerations of her fingertips had healed. Spinal cord stimulation appears to be an effective treatment in severe cases of Raynaud's phenomenon and we recommend its use in the case of failed medical therapy. Pain rating and capillary microscopy enable one to assess and visualize the effects of spinal cord stimulation.

Aged↗
PubMed1999

[Implementing limited therapy methods in intensive care units: discontinuing therapy, reducing therapy and withholding therapy in intensive care units of the Innsbruck University Clinics].

INTRODUCTION: The intensive care physician is frequently confronted with the decision to withhold or withdraw therapy in patients with a poor prognosis. Apart from the legal implications, the practical management of withholding or withdrawing intensive care treatment continues to be indistinct. The subject has not been investigated in Austria or Germany. The aim of the study was to examine the different points of view of intensive care physicians and the various procedures to limit therapy in patients with a poor prognosis. METHODS: We interviewed physicians working at different intensive care departments of the University Hospital of Innsbruck from March to April 1998. RESULTS: Withholding treatment was given preference over withdrawing treatment. In regard of withdrawing treatment, 64% of the interviewed physicians felt more uncertain. In the decision making process the potential reversibility of disease was estimated to be more important than the wish of the patient. Hemofiltration and antibiotics were mentioned as the first measures the physicians would withdraw. The last measure that would be withheld was ventilatory support. Sixty-three per cent of the physicians felt that sedation and analgesia should be continued. In regard of withholding or withdrawing treatment 83% voted for an obligatory DNR order. CONCLUSION: Before withholding or withdrawing intensive care therapy, a medical specialist must determine and document the futile prognosis of the patient. If the patient's wish is unknown, all further decisions should be made in agreement with all participants. The goal of the therapy is to provide the patient maximum comfort under minimal intensive care treatment.

Attitude of Health Personnel↗
PubMed1999

[On the topic of do not resuscitate (DNR) orders on intensive care units: an evaluation of the present status on intensive care units of the Innsbruck University clinics].

INTRODUCTION: Intensive care physicians are frequently called upon to decide whether intensive care treatment is justified. Critically ill patients with a poor prognosis receive "Do Not Resuscitate (DNR) Orders", which entitles the physician in charge to withhold cardiopulmonary resuscitation in case of cardiac arrest. Guidelines concerning the implementation of DNR orders do not exist for Austrian intensive care units. The aim of this study was to evaluate the different practices of issuing a DNR order in the departments of intensive care medicine at the University Hospital of Innsbruck. METHODS: Forty-nine physicians working in intensive care units were interviewed about the different procedures in the management of a DNR order. Furthermore, the various answers of senior physicians and assistant physicians were evaluated. RESULTS: Thirty-nine per cent of the interviewed physicians reported that DNR orders were always issued in writing. According to the answers of 63% of intensive care physicians, the decision to issue a DNR order is usually made by senior physicians. Twenty-nine per cent mentioned that nurses are never included in the decision making process and 6%, that the family is not included in the decision making process. According to 29%, the family is regularly informed about a written DNR order. Twenty per cent of the interviewed physicians reported that the quality of the administration of a written DNR order is very good, 6% that the quality is poor. CONCLUSION: We believe that the unsatisfactory situation in regard of DNR orders is not due to inactivity on the part of physicians, but is more likely a result of the inconclusive and, in part, contradictory legal situation. The physician is compelled to take a major decision within a poorly defined legal situation.

Adult↗
PubMed1999

DOTA-lanreotide: a novel somatostatin analog for tumor diagnosis and therapy.

Long acting somatostatin-14 (SST) analogs are used clinically to inhibit tumor growth and proliferation of various tumor types via binding to specific receptors (R). We have developed a 111In-/90Y-labeled SST analog, DOTA-(D)betaNal1-lanreotide (DOTALAN), for tumor diagnosis and therapy. 111In-/90Y-DOTALAN bound with high affinity (dissociation constant, Kd, 1-12 nM) to a number of primary human tumors (n = 31) such as intestinal adenocarcinoma (n = 17; 150-4000 fmol/mg protein) or breast cancer (n = 4; 250-9000 fmol/mg protein). 111In-/90Y-DOTALAN exhibited a similar high binding affinity (Kd, 1-15 nM) for the human breast cancer cell lines T47D and ZR75-1, the prostate cancer cell lines PC3 and DU145, the colonic adenocarcinoma cell line HT29, the pancreatic adenocarcinoma cell line PANC1, and the melanoma cell line 518A2. When expressed in COS7 cells, 111In-DOTALAN bound with high affinity to hsst2 (Kd, 4.3 nM), hsst3 (Kd, 5.1 nM), hsst4 (Kd, 3.8 nM), and hsst5 (Kd, 10 nM) and with lower affinity to hsst1 (Kd, approximately 200 nM). The rank order of displacement of [125I]Tyr11-SST binding to hsst1 was: SST (IC50, 0.5 nM) >> DOTALAN (IC50, 154 nM) > lanreotide (LAN) approximate to Tyr3-octreotide (TOCT) approximate to DOTA-Tyr3-octreotide (DOTATOCT) approximate to DOTA-vapreotide (DOTAVAP; IC50, >1000 nM); that to hsst2 was: DOTATOCT approximate to TOCT approximate to DOTALAN approximate to SST approximately LAN approximate to DOTAVAP (IC50, 1.4 nM); that to hsst3 was: SST (IC50, 1.2 nM) > DOTALAN = LAN (IC50, 15 nM) approximate to TOCT (IC50, 20 nM) approximate to DOTAVAP (IC50, 28 nM) > DOTATOCT (IC50, 73 nM); that to hsst4 was: SST (IC50, 1.8 nM) approximate to DOTALAN (IC50, 2.5 nM) > LAN (IC50, 22 nM) >> DOTATOCT approximate to DOTAVAP approximate to TOCT (IC50, >500 nM); and that to hsst5 was: DOTALAN (IC50, 0.45 nM) > SST (IC50, 0.9 nM) > TOCT (IC50, 1.5 nM) > DOTAVAP (IC50, 5.4 nM) >> LAN (IC50, 21 nM) > DOTATOCT (IC50 260 nM). In Sprague Dawley rats (n = 10), 90Y-DOTALAN was rapidly cleared from the circulation and concentrated in hsst-positive tissues such as pancreas or pituitary. Taken together, our results indicate that 111In-/90Y-DOTALAN binds to a broad range of primary human tumors and tumor cell lines, probably via binding to hsst2-5. We conclude that this radiolabeled peptide can be used for hsst-mediated diagnosis (111In-DOTALAN) as well as systemic radiotherapy (90Y-DOTALAN) of human tumors.

Adenocarcinoma↗
PubMed1998

Epileptic seizure associated with intracerebroventricular and intrathecal morphine bolus.

We report on two patients with morphine-related seizures associated with either intrathecal or intracerebroventricular administration. Both patients had a history of malignant tumor and both experienced the seizures following bolus application of morphine, while even higher dosages were well tolerated when continuously infused. Seizures occurred without signs of intoxication. Initiation of intrathecal morphine therapy and bolus application should be performed carefully and only when constant monitoring is provided for at least 12 h. Animal data and possible mechanisms for morphine-related seizures are discussed.

Adult↗
PubMed1997

Evidence for the existence of galanin receptors on cultured astrocytes of rat CNS: colocalization with cholinergic receptors.

The cellular localization of binding sites for [125I]galanin was studied in explant cultures of rat neocortex, cerebellum, locus coeruleus and spinal cord by means by of autoradiography. Binding sites for the peptide were observed on a great number of astrocytes in all CNS regions studied. In addition to astrocytes, many neurones were intensely labelled by [125I]galanin. Binding of [125I]galanin (10(-8) M) to both astrocytes and neurones was markedly reduced or inhibited by the unlabelled peptide at high concentration (10(-6) M), suggesting 'specific' binding of the radioligand. Evidence for the colocalization of galanin and cholinergic receptors on astrocytes was provided by combined autoradiographic and immunohistochemical studies. Many astrocytes were labelled by [125I]galanin and immunostained with antibodies to either muscarinic or nicotinic receptors. Electrophysiological studies revealed that addition of galanin (10(-9) to 10(-7) M) to the bathing fluid caused a dose-dependent hyperpolarization of the majority of astrocytes studied. When galanin (10(-8) M) and the cholinergic agonists muscarine and nicotine (10(-6) M) were tested on the same astrocyte, all three compounds induced a hyperpolarization, suggesting a colocalization of functional galanin and cholinergic receptors on the glial membrane.

Animals↗
PubMed1997

Effects of normo- and hypocapnic nitrous-oxide-inhalation on cerebral blood flow velocity in patients with brain tumors.

Nitrous oxide (N2O) use during anesthesia for intracranial procedures has been a subject of controversy in the past. To date, the isolated influence of N2O on mean cerebral blood flow velocity in the middle cerebral artery (VMCA) has not been investigated during hypocapnia in patients with brain tumors. We compared VMCA during normocapnic (ETCO2: 40 mm Hg) and hypnocapnic (ETCO2: 25 mm Hg) inhalation of air and 50% nitrous oxide in oxygen N2O/O2 in eight patients with unilateral brain tumors on both the tumor side and the healthy side. Six patients completed the study. Mean VMCA increased during normocapnic inhalation of N2O/O2 (tumor side: 86 +/- 16 cm sec-1; healthy side: 74 +/- 17 cm sec-1) when compared with air (tumor side: 72 +/- 18 cm sec-1; healthy side: 62 +/- 14 cm sec-1, p < 0.01), whereas during hyperventilation VMCA decreased on both sides (p < 0.001). Mean VMCA values were quite similar during hypocapnic inhalation of 50% N2O/O2 (tumor side: 50 +/- 12 cm sec-1; healthy side: 45 +/- 13 cm sec-1) and air (tumor side: 51 +/- 14 cm sec-1; healthy side: 45 +/- 12 cm sec-1). The data of our study suggest that in patients with cerebral tumors the N2O-induced increase in mean VMCA can be completely reversed by hyperventilation.

Adult↗
PubMed1996

[Intraventricular morphine administration as a treatment possibility for patients with intractable pain].

The treatment of intractable pain, especially in cancer patients, often sets problems to patient and therapist. While epidural and intrathecal spinal administration of opiates is a routine treatment in pain with a sub-diaphragmatic topography it is almost ineffective in cervicocephalic or thoracic cancer. An alternative here is the administration of morphine into the lateral or third ventricle by a catheter-reservoir system. We report on our experience in the treatment of twenty patients, mostly suffering from cancer (18 cases), from 1990 to 1993. It is shown to be an effective, non-destructive method with minimal side effects in the treatment of nociceptive pain. Analgesia takes effect within a few minutes and the necessary doses are low. Our results agree with those of other authors describing good to excellent results in 95% of patients with somatogenic pain. However, no or only minimal effect is achieved in the treatment of neurogenic pain by intracerebroventricular morphine therapy.

Brain↗
PubMed1995

Characterization of mutants of the vitamin D-binding protein/group-specific component: molecular evolution of GC*1A2 and GC*1A3, common in some Asian populations.

A well defined polymorphism of vitamin D-binding/group-specific component (GC) residues in exon 11. To characterize the molecular basis of GC*1A2 and GC*1A3, common in some Asian populations, we analyzed all coding exons amplified by the polymerase chain reaction. GC*1F was divided into GC*1FC and GC*1FT by a C-T transition in the third nucleotide of the codon (TGC/T) for cysteine283 in exon 8. The sequencing of exons 8 and 11 showed that GC*1A2 and GC*1A3 had occurred on a GC*1FC genetic background. They also shared a substitution of cysteine (TGC) for arginine (CGC) at position 429 in exon 11. GC*1A2 was characterized by having glycine (GGC) instead of serine (AGC) at position 335 in exon 9. GC*1A2 evolved from GC*1FT by three mutational events, i.e. GC*1FT-->GC*1FC-->GC*1A3-->GC*1A2. No evidence was obtained for the existence of the duplicated gene GC*1F.1A2 suggested by isoelectric focusing (IEF) of serum samples. The idea that the characteristic banding pattern of GC*1F.1A2 after IEF results from partial formation of a disulfide bond in the additional cysteine at position 429 is discussed.

Alleles↗
PubMed1995

A novel sequence polymorphism in exon 8 of the human vitamin D-binding protein (GC) gene in an African population.

A novel sequence polymorphism due to a T to C transition at the third nucleotide of the codon for Cys283 of the vitamin D-binding protein (GC) gene assigned to chromosome 4q13-4q21.1 was revealed by sequence analysis. Population studies by single strand conformation polymorphism (SSCP) analysis showed this GC-283.3 site was polymorphic in a Black African population but monomorphic in a European population.

Base Sequence↗
PubMed1995

Characterization of mutants of the vitamin-D-binding protein/group specific component: GC aborigine (1A1) from Australian aborigines and South African blacks, and 2A9 from south Germany.

The structure and organization of the human vitamin-D-binding protein gene (DBP, group-specific component, GC) have recently been determined. Each exon may now be amplified by the PCR method using oligonucleotide primers deduced from the intron sequences near their 5' ends and 3' ends. In this study we examined the anodal GC variants 1A1 and 2A9. Genomic DNA of the variant 1A1 was obtained from Australian Aborigines and from South African Bantu-speaking Blacks. Amplification and sequencing of exon 11 of 1A1 revealed a point mutation in codon 429 at the second position. It is remarkable that this mutation was found in the Australian 1A1 variant and in the African 1A1 variant, and raises the question whether the mutation in these two ethnic groups has a common origin. Genomic DNA of the 2A variant called 2A9 was obtained from South Germany and a point mutation also concerning position 429 in exon 11 was found. The nucleotide exchange in this case, however, was at the first position of the codon. The widely distributed genetic polymorphism of DBP/GC is located in exon 11 and is characterized by substitution at amino acid positions 416 and 420. Variant 1A1 is due to a second site mutation of the allele GC*1F; variant 2A9 is due to a mutation in the GC*2 allele.

Australia↗
PubMed1993

Sequence and organization of the human vitamin D-binding protein gene.

The structure and organization of the human vitamin D-binding protein (DBP) gene has been determined. The gene is composed of 13 exons and 12 intervening sequences. With the help of the polymerase chain reaction (PCR) introns were amplified using exon-specific oligonucleotide primers, and were sequenced after subcloning; the exon/intron borders were determined. The introns 2, 5, 7, 9 and 10 were sequenced completely; the introns 1, 3, 4, 6, 8, 11 and 12 were sequenced in part. We designed intron-specific primers for the amplification of each exon by the PCR-method. This permits the analysis of mutational and function-related sites. By comparison with the genes for human albumin and alpha-fetoprotein the gene for DBP/GC is confirmed as a member of this multigene family. The location of the introns in the coding region of the human DBP-gene is identical with the position of the introns in the rat DBP-gene.

Amino Acid Sequence↗