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Biomedical subjects

G Arnold

Publications and source records attributed to G Arnold.

At least 73 records · Page 4Linked to original sources

CO2 laser surgery for verrucous carcinoma of the larynx.

BACKGROUND: The verrucous carcinoma (VC) is a low grade malignant tumor. Treatment strategies of VC of the larynx are topics of the ongoing discussion, and the role of the carbon dioxide laser therapy in the management remains unclear to date. STUDY DESIGN/MATERIALS AND METHODS: From 1986 to 1995, 21 patients with glottic VC were treated with transoral carbon dioxide laser surgery. Follow-up ranged from 6 to 122 months (mean 52). RESULTS: In T1 lesions, a complete removal of the tumor was possible with laser-cordectomy in ten cases and with extended laser cordectomy in four cases. In seven patients suffering from T2 carcinoma, a partial laser laryngectomy was performed. There was no tumor-related death in this series. No patient required laryngectomy or radiotherapy. CONCLUSION: The results presented here are superior to those previously reported with radiotherapy. They add further support to the observation that surgery is the better treatment option for VC of the larynx. Based on the results of this study, recommended treatment for T1 and T2 VC is oncologic CO2 laser surgery in combination with a meticulous follow up for early recognition of local recurrence.

Adult↗

[123]IBZM binding predicts dopaminergic responsiveness in patients with parkinsonism and previous dopaminomimetic therapy.

We investigated the cases of 55 patients with parkinsonism and prior dopaminomimetic therapy in whom the response to this treatment was questionable or reported to be negative. None of these patients had shown motor fluctuations prior to this study. We compared the results of imaging of dopamine-D2 receptors by using [123I]iodobenzamide-single-photon-emission computed tomography (IBZM-SPECT) with the improvement in motor signs following a subcutaneous injection of apomorphine and a subsequent increase in oral dopaminomimetic therapy. IBZM-SPECT accurately predicted a positive or negative response to apomorphine in 37 (84%) of 44 patients. The sensitivity/specificity was calculated as 96.3%/ 64.7%. The sensitivity/specificity of IBZM-SPECT for the response to oral treatment with levodopa (L-dopa) was calculated as 100%/75%. After a follow-up period of 2-4 years, 25 patients developed motor fluctuations. All of these patients had normal IBZM binding. Nine developed clinical signs indicating a basal ganglia disorder other than Parkinson's disease. Eight of these nine patients had reduced, and one patient had normal, IBZM binding. We conclude that normal IBZM binding is a useful predictor of a good response to dopaminergic drugs in patients with parkinsonism and a questionable response to previous dopaminomimetic therapy. Reduced IBZM binding seems to exclude a diagnosis of Parkinson's disease, because none of the latter patients clearly benefited from L-dopa and 66.7% developed clinical signs indicating another disorder of the basal ganglia.

Adult↗

Different responses of non-ischemic and post-ischemic myocardium towards Ca2+ sensitization.

We tested whether decreased Ca2+ sensitivity is a major cause for dysfunctional stunned myocardium. The experiments employed a novel Ca2+ sensitizing agent: the thiadiazinone derivative EMD 60 263. Experiments were done on 14 isolated, blood-perfused rabbit hearts. After control, seven hearts were subjected to 20 min no-flow ischemia, and then allowed to recover during 30 min reperfusion. Thereafter, EMD 60 263 was administered (3, 10 and 30 microm). For comparison, the effect of the same doses was investigated in seven non-ischemic hearts. At the low dose, the agent improved ventricular systolic function in the post-ischemic group significantly (LVPmax: 65+/-13 v 91+/-17 mmHg; dP/dtmax: 845+/-235 v 1300+/-350 mmHg/s), and non-significantly in the non-ischemic group (LVPmax: 115+/-35 v 132+/-39 mmHg; dP/dtmax: 1415+/-545 v 1885+/-720 mmHg/s). Early relaxation (dP/dtmin) was slightly improved in both groups (800+/-225 v 1050+/-220 mmHg/s post-ischemic; 1120+/-315 v 1205+/-285 mmHg/s non-ischemic). Heart rate was increased (151+/-35 v 175+/-45 beats/min) in the post-ischemic group and was unaffected in the non-ischemic group. At the higher dose, systolic ventricular function in the post-ischemic group was further improved (LVPmax: 109+/-17 mmHg, dP/dtmax: 1330+/-180 mmHg/s), but tended to decrease in the non-ischemic group (LVPmax: 121+/-40 mmHg, dP/dtmax: 1605+/-680 mmHg/s). This dose decreased heart rate in both groups (133+/-34 and 134+/-23 beats/min). 30 microm EMD 60 263 had deleterious effects in both groups. The different responses towards Ca2+ sensitization suggest that a decrease in Ca2+ sensitivity might play a role in dysfunctional stunned myocardium. Therefore, Ca2+ sensitizing agents of the thiadiazinone type could be useful to recruit a positive inotropic reserve in stunned myocardium.

Action Potentials↗

Management of fibrous histiocytoma of the corneoscleral limbus: report of a case and review of the literature.

BACKGROUND: Fibrous histiocytomas of the corneoscleral limbus are rare tumors. We present an additional case and review the treatment approaches in the literature. So far, only light and electron microscopic studies have been performed. We used immunohistochemical stains to further characterize the cellular composition. METHODS: The excised lesion was routinely fixed and processed for light microscopy and immunohistochemical studies. For comparison, three dermal fibrous histiocytomas were also examined and processed similarly. RESULTS: The corneolimbal tumor was mainly composed of fibroblasts and histiocytes with a large amount of interstitial collagen, arranged in a storiform pattern. Immunohistochemical stains were positive for histiocytes, fibroblasts, and a marker for mesenchymal cells. The staining pattern of the dermal lesions was similar. CONCLUSION: Fibrous histiocytomas of the corneolimbal region are morphologically benign, slowly growing and infiltrative tumors. Complete resection, especially of the deep margin, is suggested. The immunohistochemical staining pattern is similar to that of dermal fibrous histiocytomas, which behave in a benign manner.

Adult↗

Ultrastructural study of human herpesvirus-7 replication in tissue culture.

Human herpesvirus 7 (HHV-7) was grown in a CD4+ lymphoblastic cell line (SupT1) and in cord blood mononuclear cells (CBMC). Virus infection was demonstrated by immunohistology with positive control sera, with monoclonal antibodies and by in situ hybridization for viral DNA. Cytopathic effects following HHV-7 infection generally resemble those after HHV-6 infection but are less pronounced. The ultrastructural appearance of HHV-7 and the replicative stages were similar to those described by Kramarsky and Sander for HHV-6. There were some minor discrepancies, including quite an extensive and space-filling tegument, a slightly different structure of the nucleoid, the frequent finding of nucleocapsids without any visible core and apparently scarce or delicate spikes on the envelope. These differences may suggest HHV-7 rather than HHV-6, but this finding needs confirmation. Mature HHV-7 particles measured 170 nm in diameter, with nucleocapsids of 90-95 nm and a tegument of about 30 nm.

CD4-Positive T-Lymphocytes↗

Spatial distribution of field potential profiles in the cat cerebellar cortex evoked by peripheral and central inputs.

The present study was designed to characterize the spread of excitation within the frontal plane of the cat cerebellar cortex following different types of stimuli. In particular, experiments were performed to determine whether the spread of excitation evoked by mossy fibre inputs proceeds primarily along the parallel fibres ("beam-like" spread) or whether these inputs activate non-propagated foci ("patches") in the cerebellar cortex. Field potentials were recorded within a frontal plane as a medial to lateral array at different depths in parallel tracks. The recordings were made following electrical stimulation of different forelimb nerves and functionally related areas of the sensorimotor cortex as well as during passive paw movements. The resulting spatial grid of responses provides discrete spatio-temporal information reflecting the activation of specific cerebellar afferents and the neuronal interactions they evoke. The method employed demonstrates the spatial distribution of the temporal sequence of excitability changes throughout all the cerebellar cortical layers. In general, the characteristics of the responses in the intermediate cerebellar cortex depended on the source of the signals. Activity patterns evoked by peripheral nerve stimulation showed more clustered foci compared with those following electrical stimulation of functionally related areas of the sensorimotor cortex. The centrally evoked profiles were generally more homogeneous. The largest number of foci were observed following passive movements around the wrist joint. The spread of excitation in the vertical direction was evaluated by the spatial shift of the line of reversal of the N3/P2-potential (zero-isopotential line). Lines of reversal for peripherally-evoked activity patterns were approximately 90 microns closer to the molecular layer than those evoked by central stimulation in animals in which recordings have been performed in lobule Vc. The opposite was found for recordings in lobule Vb, where potential reversals following peripheral stimulation were located 40 microns deeper than those evoked following central stimulation. Cortical inputs resulted in a more proximal activation of lobule Vc Purkinje cell dendrites than in lobule Vb. This type of input processing thus seems to be lobule dependent. A beam-like spread of excitation could not be demonstrated. For both climbing fibre and mossy fibre afferent systems multiple foci were found in the frontal plane. The foci due to mossy fibre activation arose from the granular layer and expanded vertically to the molecular layer. For the climbing fibre system the foci were restricted to the molecular layer, where they merged to form a superficial band of activation. Although the data presented in this paper favour a focal distribution of activity, they do not exclude beam-like propagation along the parallel fibres, because of the difficulty of detecting this pattern in response to the stimuli. The "beam"- and "patch"-like hypotheses need not be mutually exclusive. Each could contribute to a specific stage of the temporal-spatial processing in the cerebellar cortex in a functional and task-specific manner.

Animals↗

[Drug treatment of invasive aspergillosis of the paranasal sinuses].

Aspergillosis belongs to the group of mycotic diseases of the paranasal sinuses. The invasive forms, and particularly the fulminant forms, are potentially fatal. Primary surgical intervention with complete removal of the mycotic mass should be performed. Additionally an antimycotic drug therapy with amphotericin B must be started. In a review of the literature, there is no case surviving an extended invasive aspergillosis after failure of the operative therapy and after failure of the postoperative amphotericin B treatment. We report an interesting case of a complete remission of an invasive, partially fulminant aspergillosis of the paranasal sinuses and frontal and basal regions. After incomplete removal of the mycotic mass by an endo- and extranasal approach, we started postoperative drug therapy with amphotericin B. Under this treatment the mycosis progressed. Additionally the patient developed severe renal side effects requiring suspension of the treatment. At this time, we started a combined antimycotic drug therapy with liposomal amphotericin B (AmBisome) and itraconazol. Within 10 weeks there was complete clinical and radiologic remission. The patient died 63 weeks after this treatment because of a fulminant bacterial pneumonia. Post mortem examination showed no aspergillosis in the skull base, the paranasal sinuses, or in the lung. The question arises as to whether this drug combination of liposomal amphotericin B (AmBisome) and itraconazol is a real alternative to high-risk surgical interventions in this region.

Amphotericin B↗

Invasive amoebiasis in two patients with AIDS and cytomegalovirus colitis.

Homosexual persons or human immunodeficiency virus (HIV)-infected patients frequently excrete cysts of nonpathogenic strains of Entamoeba histolytica ("Entamoeba dispar"). However, invasive amoebiasis is rare. We report two patients with AIDS and cytomegalovirus colitis in whom invasive amoebiasis was histologically diagnosed. It is concluded that E. histolytica has to be considered in HIV-infected patients with colitis.

AIDS-Related Opportunistic Infections↗

The antiretrovirus drug 3'-azido-3'-deoxythymidine increases the retrovirus mutation rate.

It was previously observed that the nucleoside analog 5-azacytidine increased the spleen necrosis virus (SNV) mutation rate 13-fold in one cycle of retrovirus replication (V. K. Pathak and H. M. Temin, J. Virol. 66:3093-3100, 1992). Based on this observation, we hypothesized that nucleoside analogs used as antiviral drugs may also increase retrovirus mutation rates. We sought to determine if 3'-azido-3'-deoxythymidine (AZT), the primary treatment for human immunodeficiency virus type 1 (HIV-1) infection, increases the retrovirus mutation rate. Two assays were used to determine the effects of AZT on retrovirus mutation rates. The strategy of the first assay involved measuring the in vivo rate of inactivation of the lacZ gene in one replication cycle of SNV- and murine leukemia virus-based retroviral vectors. We observed 7- and 10-fold increases in the SNV mutant frequency following treatment of target cells with 0.1 and 0.5 microM AZT, respectively. The murine leukemia virus mutant frequency increased two- and threefold following treatment of target cells with 0.5 and 1.0 microM AZT, respectively. The second assay used an SNV-based shuttle vector containing the lacZ alpha gene. Proviruses were recovered as plasmids in Escherichia coli, and the rate of inactivation of lacZ alpha was measured. The results indicated that treatment of target cells increased the overall mutation rate two- to threefold. DNA sequence analysis of mutant proviruses indicated that AZT increased both the deletion and substitution rates. These results suggest that AZT treatment of HIV-1 infection may increase the degree of viral variation and alter virus evolution or pathogenesis.

Antiviral Agents↗

Contractile systolic and diastolic dysfunction in renin-induced hypertensive cardiomyopathy.

The present study investigated whether functional, molecular, and biochemical alterations occurring in chronic heart failure can already be detected in compensated hypertensive cardiac hypertrophy. Force of contraction (isolated papillary muscle strip preparations), sarcoplasmic reticulum (SR) protein and myosin heavy chain isoform expression (Northern and Western blot analysis), myocardial fibrosis (collagen stains, hydroxyproline quantification), myocardial renin mRNA (RT-PCR), and angiotensin II levels and plasma aldosterone concentrations (radioimmunoassay) were studied in hypertrophied myocardium from transgenic rats harboring the mouse Ren-2d gene. Contraction and relaxation velocities of isolated papillary muscle strips were significantly reduced in cardiac hypertrophy. The beta-/alpha-myosin heavy chain ratio was significantly increased in the hypertrophied left ventricles, whereas SR Ca2+-ATPase (SERCA 2a) and phospholamban mRNA and protein levels were significantly decreased. The decrease in SERCA 2a was more pronounced than the decrease in phospholamban levels. There was no increased myocardial fibrosis. Left ventricular myocardial renin mRNA and angiotensin II concentrations, as well as plasma aldosterone levels, were higher in transgenic than in control rats. In hypertensive cardiac hypertrophy, myosin heavy chain isoform shift and reduction of SR protein levels are related to systolic and diastolic dysfunction, respectively. These alterations precede the development of myocardial fibrosis. Increased myocardial renin mRNA and angiotensin II concentrations suggest that an activated tissue renin-angiotensin system might contribute to these alterations. Since the alterations in compensated cardiac hypertrophy apparently precede those in chronic heart failure, they might accelerate the transition from hypertrophy to failure and could therefore be targets for pharmacological interventions.

Angiotensin II↗

Evidence for functional relevance of an enhanced expression of the Na(+)-Ca2+ exchanger in failing human myocardium.

BACKGROUND: The present study aimed at investigating the expression of the Na(+)-Ca2+ exchanger and its functional role in human failing myocardium. METHODS AND RESULTS: Na(+)-Ca2+ exchanger mRNA and protein levels were examined in nonfailing (NF, n = 8) and failing human myocardium (New York Heart Association functional class IV) with idiopathic dilated cardiomyopathy (DCM, n = 8) or ischemic heart disease (ICM, n = 6). The inotropic effect of the Na+ channel activator BDF 9148 was determined in electrically driven left ventricular papillary muscle strip preparations (1 Hz, 37 degrees C) from nonfailing (n = 8) and failing (n = 8) human hearts. Na(+)-Ca2+ exchanger mRNA levels were significantly increased, by 79% (P < .001) in DCM and by 58% (P < .01) in ICM compared with NF; protein levels increased by 36% (P < .001) and by 20% (P < .05), respectively. BDF 9148 increased the force of contraction concentration dependently, with a similar maximal effect in NYHA class IV and NF, but was more potent in NYHA class IV as demonstrated by a significantly smaller (P < .01) EC50 value (NYHA class IV, 0.18 [0.16 to 0.22] mumol/L; NF, 1.65 [1.3 to 3.0] mumol/L). In NYHA class IV, BDF 9148 (0.1 mumol/L) restored the positive force-frequency relationship and reduced the frequency-dependent increase in diastolic tension in relation to force of contraction. CONCLUSIONS: The increased expression of the Na(+)-Ca2+ exchanger is a possible explanation for the increased inotropic potency of the Na+ channel activator BDF 9148 in failing human myocardium. The increase in exchanger molecules could be of functional relevance for the modulation of cardiac contractility by agents that increase the intracellular Na+ concentration. Enhancement of Na(+)-Ca2+ exchanger activity might be a powerful mechanism for increasing cardiac contractility in chronic heart failure.

Adult↗

Computational analysis of open loop handwriting movements in Parkinson's disease: a rapid method to detect dopamimetic effects.

We used a computational analysis of open loop handwriting movements and a clinical rating scale for monitoring the effect of apomorphine in 16 patients with early untreated parkinsonism [subsequently L-DOPA responsive, probable Parkinson's disease (PD)], six patients with long-standing PD with L-DOPA associated motor fluctuations, and seven patients with known L-DOPA unresponsive parkinsonism. Subjects were instructed to write fluently concentric circles of approximately 12 mm in diameter. Movements were recorded for two periods of 3 s each, using a digitizing tablet. Mean peak velocity (Vmax) and mean peak acceleration (Amax) were determined. In addition, two sensitive indices describing the degree of automation of handwriting were derived: (a) NCV, calculated as the mean Number of Changes in direction of Velocity per half circle, and (b) NCA, the mean Number of Changes in the direction of Acceleration. Clinical rating was performed according to the Unified Parkinson's Disease Rating Scale part III (UPDRS III). After apomorphine injection, the patients with early untreated probable PD showed significant improvement of Vmax, Amax, NCV, NCA, and UPDRS III scores. Likewise, the patients with long-standing PD improved significantly in all kinematic parameters and UPDRS III scores. Patients with L-DOPA unresponsive parkinsonism failed to change significantly in any of the parameters tested. These observations suggest that the computer-assisted analysis of automated handwriting movements can be used as an objective quick method for quantifying dopamimetic effects on the kinematics of handwriting movements in parkinsonian patients.

Adult↗

Geometric properties of the fractured tibia stabilized by unreamed interlocking nail: development of a three-dimensional finite element model.

Based upon magnetic resonance scans of five human tibiae a three-dimensional finite element model using eight nodal isoparametric elements was developed to analyze the biomechanical properties of fracture fixation by an unreamed interlocking nail. Tension phenomena and bone implant translations occurring in the borderlines of the fracture zone, bone-implant interface, and the fixation site of the interlocking screws were analyzed with the help of link elements. The proximal fracture segment was fixed with a link element so as to produce exclusively translatory shifts corresponding to the vector of the load applied. Under condition of static load F = 500 N or axial torsion MT = 15 Nm the biomechanical properties of a nailed horizontal fracture (42-A3), a three fragment lesion (42-B2), and a comminuted midshaft fracture (42-C3) were evaluated. On condition of axial load maximum dislocations of 0.1549 mm are induced in the direction of the x-axis due to the asymmetric geometry of the human tibia which promotes medially directed translations. Independent from the fracture type present a homogenous tension profile was calculated for the whole tibia diaphysis with a sigmaEQV ranging from 24.18 to 121.14 MPa due to the relative low elastic modulus of the cortical bone compared to material characteristics of the implant. However, application of a torsional moment MT = 15 Nm induces significantly increased tension maxima in the nail-interlocking screw interface with a sigmaEQV = 7, 626 MPa. Maximum translatory movements ux = 12.59 mm and uy = 23.53 mm in the x and y plane indicate that these load conditions bear a high risk of an implant failure.

Biomechanical Phenomena↗

Histopathology of episcleral fibrosis after trabeculectomy with and without mitomycin C.

BACKGROUND: The aim of the study was to investigate the histopathologic features of scar tissue which have proliferated at the site of trabeculectomy of surgical failures after procedures with and without the use of the antimetabolite mitomycin C (MMC). METHODS: We obtained seven surgical specimens after trabeculectomy without MMC and five specimens after trabeculectomy with MMC, which were compared with 23 controls. Sections were stained with hematoxylin and eosin, Verhoeff-van Gieson, Grocott methenamine silver, and alcian blue. An immunohistochemical stain was performed for alpha-smooth muscle actin. RESULTS: Specimens from eyes operated without MMC showed dense scar tissue with many fibroblasts, much ground substance, parallel-oriented collagen fibers, and contractile intracellular proteins within the fibroblasts. Specimens from eyes operated with MMC consisted of tissue with only few fibroblasts which did not exhibit contractile proteins. Collagen fibers were arranged randomly with less ground substance. CONCLUSION: Even after 1-10 months, the scar tissue was distinctly different in the two groups. These results suggest that the use of MMC has long-term effects in vivo. Surgical failures related to scar formation are possible and not reduced to zero.

Actins↗

Pyogenic granuloma of the cornea: report of a case and review of the literature.

BACKGROUND: Pyogenic granulomas are ulcerated vascular proliferations, often accompanied by inflammatory infiltrates, which rarely affect the eye. Only few reports on pyogenic granulomas of the cornea have been presented. METHODS: The enucleated globe containing the corneal tumor was examined histopathologically, and special immunohistochemical stains were performed. RESULTS: The lesion had a yellowish appearance with marked vascularization. The inflammatory infiltrate was mainly composed of mononuclear cells, with no multinucleated giant cells, and was located anterior to Bowman's layer, leaving the corneal stroma unaffected. Immunohistochemical studies outlined the high vascular content, even in dense cellular areas, and confirmed the inflammatory nature of the mononuclear infiltrates. CONCLUSIONS: Pyogenic granuloma of the cornea represents a clinical and morphological entity developing in a traumatized eye with corneal vascularization. Although the origin of these lesions remains obscure, there have been no signs of malignancy. Therefore, enucleation of an eye with a pyogenic granuloma should be avoided.

Aged↗

Multiplex PCR assay for the routine detection of Listeria in food.

The development and validation of a multiplex PCR assay for the detection of Listeria that can be employed in routine investigation of food samples are described. The assay, which employs a short culture enrichment step followed by isolation of bacterial cells and detection by multiplex PCR reaction, is highly sensitive and specific for the detection of Listeria monocytogenes and all other Listeria species. Over 350 food samples were tested in parallel by standard cultural procedures and the PCR assay, with no false-positive or false-negative results obtained with the PCR assay. Compared to the standard cultural methods the PCR assay is highly sensitive, cost effective and extremely rapid with results obtained within 48 h from sample receipt.

Food Microbiology↗