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Biomedical subjects

S Neumann

Publications and source records attributed to S Neumann.

At least 73 records · Page 4Linked to original sources
PubMed1997

Metastatic renal cell carcinoma: long-term survival after therapy with high-dose continuous-infusion interleukin-2.

PURPOSE: This article undertakes to define the response rate, long-term survival, and toxicity in patients with metastatic renal cell carcinoma (MRCC) treated with high-dose continuous intravenous infusion (CIV) recombinant interleukin-2 (rIL-2) with or without lymphokine-activated killer (LAK) cells. PATIENTS AND METHODS: One hundred twenty-three consecutive patients received CIV rIL-2 (18-22 MIU/m2/day on days 1-5, and 6-8 MIU/m2/day on days 10-19) on one of five sequential protocols at the University of Washington between 1988 and 1995. The first 76 patients received LAK cells. The median age was 55 years (range, 32-76 years), and 71% had undergone prior nephrectomy. RESULTS: Nine patients achieved a complete response (7.3%) and 14 patients achieved a partial response (11.4%) for an overall response rate of 19% (95% confidence interval, 12%-26%). The median survival was 19 months, and the 5-year survival was 20%. Seven of nine complete responders (78%) remain in continuing complete response at 43+ to 109+ months. Intensive care unit and vasopressor support were required in 42% and 23% of patients, respectively, who received rIL-2 + LAK cells, and in 18% and 4% of those who received rIL-2 alone. There was one treatment-related death. CONCLUSION: We report the largest single-institution experience and the longest survival for patients with MRCC treated with CIV rIL-2. The administration of rIL-2 by CIV is associated with less frequent intensive care unit and vasopressor support than with high-dose intravenous bolus regimens, and hence may enhance the therapeutic index in patients with MRCC.

Adult↗
PubMed1996

Inflammatory pain hypersensitivity mediated by phenotypic switch in myelinated primary sensory neurons.

Pain is normally evoked only by stimuli that are sufficiently intense to activate high-threshold A(delta) and C sensory fibres, which relay the signal to the spinal cord. Peripheral inflammation leads to profoundly increased pain sensitivity: noxious stimuli generate a greater response and stimuli that are normally innocuous elicit pain. Inflammation increases the sensitivity of the peripheral terminals of A(delta) and C fibres at the site of inflammation. It also increases the excitability of spinal cord neurons, which now amplify all sensory inputs including the normally innocuous tactile stimuli that are conveyed by low-threshold A(beta) fibres. This central sensitization has been attributed to the enhanced activity of C fibres, which increase the excitability of their postsynaptic targets by releasing glutamate and the neuropeptide substance P. Here we show that inflammation results in A(beta) fibres also acquiring the capacity to increase the excitability of spinal cord neurons. This is due to a phenotypic switch in a subpopulation of these fibres so that they, like C-fibres, now express substance P. A(beta) fibres thus appear to contribute to inflammatory hypersensitivity by switching their phenotype to one resembling pain fibres, thereby enhancing synaptic transmission in the spinal cord and exaggerating the central response to innocuous stimuli.

Action Potentials↗
PubMed1996

The antitumor agent cisplatin inhibits DNA gyrase and preferentially induces gyrB gene expression in Escherichia coli.

Cisplatin is a widely used anticancer agent that exerts its biological activity principally by damaging DNA. Although detailed knowledge exists concerning mechanisms that lead to cisplatin adducts in DNA, there are few insights into the processes that result in its antitumor action. To explore some of the cellular responses elicited by cisplatin treatment, we studied its influence on DNA supercoiling and DNA gyrase gene expression in E. coli. We found that cisplatin inhibits DNA gyrase in a concentration-dependent manner leading to a transient alteration of DNA supercoiling and to an induction of gyrase gene expression. The induction effect was asymmetrical, affecting gyrB stronger than gyrA. Furthermore, we studied the influence of cisplatin on the supercoiling activity of purified DNA gyrase in vitro and found that cisplatin was an efficient inhibitor of DNA gyrase in the standard assay. However, cisplatin was an excellent inhibitor when added to DNA gyrase before it could interact with its substrate. In this assay GyrB was also more affected by cisplatin than GyrA. This strongly suggests that cisplatin inhibits DNA gyrase primarily by direct interaction with the enzyme. The data from this work present evidence that further cellular responses following cisplatin treatment include DNA gyrase inhibition, altered DNA supercolling and enhanced DNA gyrase gene expression. This suggests an important role of DNA topology in the induction of defense mechanisms against the action of cisplatin in addition to the processes related to DNA damage and repair.

Antibodies↗
PubMed1996

[Spiral computerized tomography of acute abdominal aortic aneurysm with optimal 3-D image reconstruction].

43 of 46 consecutive patients with suspected rupture of abdominal aortic aneurysm could be examined by spiral CT. Rupture of an abdominal vessel was found in 18 patients and proved by surgery. Size and extent of the aneurysm, rupture, dissection and vascular occlusion were demonstrated quickly and precisely by spiral CT, planning of surgical intervention could be optimized. Using spiral CT unnecessary explorative laparotomies could be avoided in 25 patients. In addition spiral CT offers the possibility of multiplanar reconstruction images with spatial visualisation of the vascular system. In 8 patients DSA offered no advantage in comparison with 3-D reconstruction images. Spiral CT meets all requirements for quick and reliable diagnosis in suspected rupture of abdominal vessels. Other imaging modalities like digital subtraction angiography are not necessary for evaluation of abdominal aortic aneurysms.

Aged↗
PubMed1996

[The diagnosis of liver diseases in the dog].

This article shows the possibilities of liver diagnosis in dogs. After a short introduction about metabolism with some aspects in pathophysiology follows the way of investigation from anamnesis, clinical examination, blood work and urinalysis to ultrasound, x-ray and biopsy.

Animals↗
PubMed1995

Mutational analysis of patients with X-linked adrenoleukodystrophy.

Adrenoleukodystrophy (ALD) is an X-linked neurodegenerative disorder characterized by elevated very long chain fatty acid (VLCFA) levels, reduced activity of peroxisomal VLCFA-CoA ligase, and variable phenotypic expression. A putative gene for ALD was recently identified and surprisingly encodes a protein (ALDP) that belongs to a family of transmembrane transporters regulated or activated by ATP (the ABC proteins). We have examined genomic DNA from ALD probands for mutations in the putative ALD gene. We detected large deletions of the carboxyl-terminal portion of the gene in 4 of 112 probands. Twenty-five of the ALD probands whose ALD genes appeared normal by Southern blot analysis were surveyed for mutations by Single Strand Conformation Polymorphism (SSCP) procedures and DNA sequence analysis. SSCP variants were detected in 22 probands and none in 60 X-chromosomes from normal individuals. Mutations were detected in all of the ALD probands. The mutations were distributed throughout the gene and did not correlate with phenotype. Approximately half were non-recurrent missense mutations of which 64% occurred in CpG dinucleotides. There was a cluster of frameshift mutations in a small region of exon 5, including an identical AG deletion in 7 unrelated probands. These data strongly support the supposition that mutations in the putative ALD gene result in ALD.

ATP Binding Cassette Transporter, Subfamily D, Mem↗
PubMed1995

Swallowing therapy of neurologic patients: correlation of outcome with pretreatment variables and therapeutic methods.

The results of swallowing therapy in 58 patients with neurologic disorders are presented. All patients received tube feeding, either partially or exclusively, at admission, and successful outcomes, defined as exclusively oral feeding, were achieved in 67% of patients over a median treatment interval of 15 weeks. A subset of 11 patients who had experienced disease onset 25 weeks or more prior to admission nonetheless had a similar success rate of 64%. No other pretreatment variable, including age, localization of lesion, type or degree of aspiration, or cognitive status, correlated with successful outcome. Indirect therapy methods such as stimulation techniques and exercises to enhance the swallowing reflex, alter muscle tone, and improve voluntary function of the orofacial, lingual, and laryngeal musculature were utilized in all but 1 patient. Direct methods including compensatory strategies such as head and neck positioning, and techniques such as supraglottic swallowing and the Mendelsohn maneuver were additionally employed in nearly one-half of patients. Swallowing therapy is associated with successful outcome, as defined by exclusively oral feeding, among patients with neurogenic dysphagia, regardless of pretreatment variables including time since disease onset. Indirect treatment methods appear to be effective when used either alone or in combination with direct methods. Achievement of oral feeding is not associated with undue risk of pneumonia. Further rigorous scientific studies are needed.

Adult↗
PubMed1995

Influence of physiotherapeutic facilitation techniques on motor evoked potentials in centrally paretic hand extensor muscles.

In the rehabilitation of stroke patients, various facilitation techniques are applied to reduce weakness in centrally paretic muscles and to improve functional motor capacity. The present investigation compared the facilitatory effect of 5 different physiotherapeutic approaches onto the centrally paretic extensor carpi radialis muscle in 30 stroke patients classified into 3 groups according to the individual degree of paresis. In order to quantify the influence of the respective facilitation manoeuvre, single transcranial magnetic stimuli were applied before and during the application of cutaneous/proprioceptive stimuli, a weight bearing task, contraction of the affected and the non-affected extensor carpi radialis muscle and during proximal preinnervation on the affected side. All procedures, indeed, enhanced the frequency of occurrence of muscular response potentials and their amplitudes while diminishing their response latencies. The most prominent effects were observed when the muscle itself was voluntarily activated. A similarly strong facilitation was obtained in the most severely affected patients with cutaneous and proprioceptive stimuli, but such stimuli had inhibitory effects in the healthy control group. The present study illustrates the interaction of cortically evoked motor potentials with peripherally or centrally generated inputs, contributes to the understanding of the neurophysiological mechanisms underlying physiotherapeutic facilitation techniques and helps in providing rational criteria to decide about the most appropriate facilitation method.

Adult↗
PubMed1995

Chimaeric cultures of human marrow stroma and murine leukaemia cells: evidence for abnormalities in the haemopoietic microenvironment in myeloid malignancies and other infiltrating marrow disorders.

PGM-1 is a transplantable C3H/HeJ leukaemia which is not viable in unstimulated in vitro culture, differentiates into mature granulocytes and macrophages in response to soluble cytokines, and undergoes self-renewing cell divisions in coculture with selected human bone marrow stromal cell lines. When PGM-1 cells were cultured on pre-established adherent layers from primary human marrow samples, their fate depended on the source of the human marrow. Adherent layers from healthy marrow donors or patients with reactive marrow alterations had no or very little capacity to maintain PGM-1 cells in an immature colony-forming state. However, in coculture with adherent layers from patients with myeloid leukaemia or, to a lesser extent, lymphoblastic leukaemia or marrow-infiltrating lymphoma the colony-forming potential was retained. There was no correlation between the remission status of the patient and the PGM-1 activity of the adherent layer. Consistent morphological differences between active and inactive stromal layers were not observed. The PGM-1 coculture system enables the detection of a hitherto undescribed regulatory abnormality in bone marrow malignancies. Whether the PGM-1 supporting activity is mediated through differences in the production of a cytokine with close homology to complement factor Bb which has recently been shown to induce self-renewal in immature PGM-1 cells, requires further investigation.

Animals↗
PubMed1994

Influence of sustained stretch on late muscular responses to magnetic brain stimulation in patients with upper motor neuron lesions.

Late muscular responses to transcranial magnetic stimulation occur in healthy subjects only in tonically active muscles with a proportional relationship between the amount of the EMG-response and the voluntary innervation strength. In hemiparetic stroke patients late potentials are elicited in chronically spastic hand flexors without voluntary background muscular activity probably reflecting enhanced excitability of spinal alpha-motoneurons in the spastic state. When spastic muscle hypertonus has been diminished by sustained muscle stretch late EMG-potentials are reduced or have disappeared completely. The relation between spastic muscle hypertonus and the late muscular response potentials as well as the possible mechanisms of sustained muscle stretch on the response characteristics to transcranial magnetic stimulation in spastic flexor muscles of the hand are discussed.

Action Potentials↗