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Biomedical subjects

M Horn

Publications and source records attributed to M Horn.

At least 19 recordsLinked to original sources

Direct measurement of spin-lattice relaxation times of phosphorus metabolites in human myocardium.

T1 values of phosphorus metabolites visible in human cardiac 31P-MR spectra were determined in 12 volunteers at 1.5 T. Consecutive spectra were acquired with varying pulse repetition time (TR) from 1.6 to 24 s; volume selection was achieved with ISIS. T1's of creatine phosphate (CP), [gamma-P], [alpha-P], and [beta-P]ATP, 2-3 diphosphoglycerate, and phosphodiesters were 6.1 +/- 0.5, 5.4 +/- 0.5, 5.5 +/- 0.5, 5.8 +/- 1.0, 7.6 +/- 1.0, and 5.0 +/- 1.0 s, respectively. CP/ATP ratios showed little change with varying TR; linear regression of CP/ATP vs TR was of borderline significance (r = 0.28, P = 0.06). T1's for CP and ATP were also determined in standard solution (20 mM CP, 10 mM ATP) yielding T1CP of 8.7 +/- 0.2 and T1[gamma-P]-ATP of 9.9 +/- 0.7 s. Thus, T1's for CP and ATP were similar at 1.5 T in both human heart and standard solution. In human cardiac 31P-MR spectra, CP/ATP ratios may need little correction for partial saturation.

2,3-Diphosphoglycerate

Deletions in exon 5 of the human rhodopsin gene causing a shift in the reading frame and autosomal dominant retinitis pigmentosa.

By screening patients with autosomal dominant retinitis pigmentosa for mutations in the rhodopsin gene, two deletions (8 bp and 1 bp) have been identified in exon 5; these deletions cause a shift in the reading frame. The predicted proteins should be radically altered with translation continuing past the normal stop signal and resulting in a rhodopsin molecule that is, respectively, 1 and 10 amino acids longer. The clinical phenotype of the patients is described and is compared with that associated with other mutations in the same region of the gene.

Adult

Delayed neuronal death and delayed neuronal recovery in the human brain following global ischemia.

The understanding of delayed hippocampal death as a therapeutic window for post-ischemic treatment of the brain has led to numerous investigations focusing upon underlying cellular mechanisms and pharmacological potentials in gerbils and rats. Nevertheless, studies on the occurrence of delayed neuronal death in the human brain have been singular and dealt with only small files of patients. To complement these limited data, in the present study 26 adult patients with a history of a single cardiac arrest were included. Following successful resuscitation, individual survival ranged from less than 1 h to 186 days (mean = 11 days). The severity of the resultant ischemic injury in hippocampus CA1, among Purkinje cells, or in frontal neocortex, respectively, was quantified by direct counting of necrotic neurons. Additionally, hippocampal specimens were immunostained for neuron-specific enolase. The data obtained demonstrate the occurrence of delayed neuronal death in human hippocampus and, in a minor form, in cerebellar Purkinje cells. This is in contrasts to the immediate manifestation of ischemic neuronal necrosis in the neocortex. Unlike previous findings in experimental animals and in humans, the delay of CA1 cell death could be defined as lasting about 7 days following cardiac arrest. Moreover, the immunohistochemical results indicate delayed neuronal recovery in CA1, which in the time course reciprocally corresponds to delayed manifestation of hippocampal neuronal death. Interpretation of the results must consider the lack of information about the exact individual duration of cardiac arrest and resuscitation, as well as missing data concerning pre-ischemic physiological variables.

Adult

Malignant rhabdoid tumor: primary intracranial manifestation in an adult.

Clinical, histopathological, and ultrastructural features of an extended intracranial malignant neoplasm are presented. Following incomplete extirpation of a large epidural tumor at the temporal base of the skull, the 21-year-old male patient suffered from several local recurrences and died at the age of 27. The neoplasm was defined by its histopathological and ultrastructural characteristics and by the pattern of its antigenicity as a malignant rhabdoid tumor (MRT). Considering previous publications on MRT, this case may be the first of primary intracranial MRT appearing in an adult.

Adult

Does ND-YAG laser extend the indications for resection of pulmonary metastases?

Surgery forms part of a combined oncological concept in the management of pulmonary metastases. The following questions are relevant for its role: Does survival depend on the type of primary tumor? Are there any prognostic factors? What are the limits on radical resection? We analyzed retrospectively 657 patients who had undergone 759 resections of pulmonary metastases between 1973 and 1990. After conducting in vitro and in vivo experiments with the non-contact neodymium aluminum garnet (Nd-YAG) laser with a generating and delivery power of 10-120 W at the site of operation for 0.1-9.9 s, we have treated 65 patients by laser resection and/or vaporization since January 1990. Our preferred surgical approach was median or transverse thoracotomy. The 5-year survival of all resected patients was 30%, ranging from 21% (soft tissue sarcoma) to 60% (testicular carcinoma). Statistically significant differences in prognosis were seen related to the type of primary tumor, the disease-free interval, the caval or portal type of metastatic spread, the number of metastases and the potential degree of radical resection. The potential degree of conventional radical resections (wedge, anatomical sub-/segmental) was negatively influenced by the number of metastases (n > 9: 79% "radical" surgery = 38% 5-year survival). Laser treatment allowed parenchyma-preserving resection in cases of metastases of more than 0.5 cm in diameter, and vaporization in smaller ones. Resection with the intention of achieving complete remission was possible in up to 72 unilateral metastases. The complication rate was comparable to conventional resections.

Female

[The direct measurement of the spin-grid-relaxation times of phosphorus metabolites in the human myocardium].

The T1 relaxation times of the phosphorus metabolites in human heart muscle measurable by 31P-MR spectra were determined in 12 individuals using a 1.5 Tesla system. Several spectra were recorded consecutively with a pulse repetition time of 1.6 s to 24 s. The T1 times of creatine phosphate (CP), of gamma-, alpha-, beta-adenosintriphosphate (ATP), 2,3-diphosphoglycerate (2,3-DPG) together with anorganic phosphate) and phosphodiester (PDE) showed mean measurements of 6.1 +/- 0.5, 5.4 +/- 0.5, 5.0 +/- 0.5, 5.8 +/- 1.0, 7.6 +/- 1.0, and 5.0 +/- 1.0 s (M +/- SE). The accuracy of the ISIS technique was tested with a special phantom. T1 times were also measured in standard solutions (20 mM CP, 10 mM ATP); CP was 8.7 +/- 0.2 s and gamma-ATP was 9.9 +/- 0.7 s. Corrections for partially saturated 31P-MR spectra--at least for CP/ATP ratios--are relatively small.

2,3-Diphosphoglycerate

Continued remission in children with neuroblastoma despite elevations of urinary catecholamine metabolites.

Our experience at the Children's Hospital of Pittsburgh with a patient with neuroblastoma suggested that renewed elevations of urinary catecholamine metabolites may not necessarily be an indication of progressive disease. To test this possibility, we reviewed the courses of children with neuroblastoma who achieved a clinical status of "no evidence of disease" (NED), and in whom homovanillic acid (HVA) and/or vanillylmandelic acid (VMA) levels were subsequently noted to exceed normal limits initially in the presence of normal restaging studies. Five patients were identified. Of these, one had stage I, one had stage II, two had stage III, and one had stage IV disease at diagnosis. Elevations of their HVA and/or VMA levels following achievement of NED status ranged from 1 1/2 to 4 times maximal normal levels for age, and abnormalities persisted for 17 to 47 months. Only one patient relapsed, while the other four remain disease-free 8-12 years following diagnosis. These results confirm that in patients with neuroblastoma, mild elevations of HVA and/or VMA may be compatible with continuous remission.

Child, Preschool

31P magnetic resonance spectroscopy in dilated cardiomyopathy and coronary artery disease. Altered cardiac high-energy phosphate metabolism in heart failure.

BACKGROUND: The purpose of this work was to further define the value of cardiac 31P magnetic resonance (MR) spectroscopy for patients with coronary artery disease and dilated cardiomyopathy. METHODS AND RESULTS: Blood-corrected and T1-corrected 31P MR spectra of anteroseptal myocardium were obtained at rest using image-selected in vivo spectroscopy localization, a selected volume of 85 +/- 12 cm3, and a field strength of 1.5 T. Nineteen volunteers had a creatine phosphate (CP)/ATP ratio of 1.95 +/- 0.45 (mean +/- SD) and a PDE/ATP ratio of 1.06 +/- 0.53; in four patients with left anterior descending coronary artery (LAD) stenosis, six patients with chronic anterior wall infarction, and four patients with chronic posterior wall infarction, CP/ATP and phosphodiester (PDE)/ATP ratios did not differ from those in volunteers. Twenty-five measurements of 19 patients with dilated cardiomyopathy yielded a CP/ATP of 1.78 +/- 0.51 and a PDE/ATP of 0.98 +/- 0.56 (p = NS versus volunteers). When these patients were grouped according to the severity of heart failure, however, CP/ATP was 1.94 +/- 0.43 in mild (p = NS versus volunteers) and 1.44 +/- 0.52 in severe DCM (p < 0.05), respectively. No correlation was found between CP/ATP and left ventricular ejection fraction or fractional shortening, but correlation of CP/ATP with the New York Heart Association (NYHA) class was significant (r = 0.60, p < 0.005). Six patients with dilated cardiomyopathy were studied repeatedly before and after 12 +/- 6 weeks of drug treatment leading to clinical recompensation with improvement of the NYHA status by 0.8 +/- 0.3 classes. Concomitantly, CP/ATP increased from 1.51 +/- 0.32 to 2.15 +/- 0.27 (p < 0.01), whereas PDE/ATP did not change significantly. CONCLUSIONS: Cardiac high-energy phosphate metabolism at rest is normal in LAD stenosis and chronic myocardial infarction in the absence of heart failure. The CP/ATP ratio has low specificity for the diagnosis of dilated cardiomyopathy. However, CP/ATP correlated with the clinical severity of heart failure and may improve during clinical recompensation.

Adult

[Surgical emergency interventions in acute diseases of the large intestine].

Emergency operations due to acute colonic disease between 1. 1. 1984 and 31. 12. 1991 were retrospectively analyzed with regard to causality, surgical procedure, complications and mortality. 55 of 1105 colonic operations were emergency cases requiring immediate surgical intervention. Primary continuity preserving resections were carried out whenever possible, attending not only to the acute situation but also to the primary disease. The mean age of the 26 females and 29 males was 69 [1, 9] years. 29 patients had a colonic ileus, 21 a diffuse peritonitis and 5 patients had an uncontrolled haemorrhage. Colorectal carcinomas were initially diagnosed in 20 of the 50 patients; 14 of these patients (70%) could be operated for potential cure and primary continuity preserving resections were also possible for 14 patients (70%). Continuity preserving resections were possible for 18 of 21 patients with peritonitis and 3 colonic perforations were oversutured. In the 5 patients with acute haemorrhage, 4 resections and one transanal intervention were performed. Postoperative complications were observed in 19 patients (35%). Postoperative mortality was 16% (9/55), 5% for operations due to peritonitis, 24% for operations due to colonic ileus and 20% for operations due to haemorrhage. Primary continuity preserving resections were possible for 39 of 55 patients (71%).

Abdomen, Acute

Immunocytochemical characterization of cytomegalovirus (CMV) infected giant cells in perinatal acquired human immunodeficiency virus (HIV) infection.

In a pediatric case of necrotizing CMV myelitis after perinatal HIV infection characteristic cytomegalic cells, which could not be attached to a particular cell line by cell morphology, were studied after immunostaining with monoclonal and polyclonal antibodies raised against GFAP, S100 protein, NSE, synaptophysin, factor VIII, vimentin, macrophages, leukocytes, CMV, HSV I + II, toxoplasma, and HIV 1 gp41. Astrocytes, oligodendrocytes, neurons, ependymal and endothelial cells, macrophages, and Schwann cells stained positively with CMV antiserum. With regard to their immunological features the majority of cytomegalic cells ("owl eye cells") was identified as astrocytes, and in decreasing frequency, the remainder was characterized as macrophages, mesenchymal, and endothelial cells. It is concluded that CMV giant cells represent one phase of virus induced cell transformation, not only one single, but numerous cell types are exposed to after CMV infection.

Acquired Immunodeficiency Syndrome

Diffuse loss of rod function in autosomal dominant retinitis pigmentosa with pro-347-leu mutation of rhodopsin.

There is considerable variety among the clinical features of autosomal dominant retinitis pigmentosa (ADRP). This is probably at least in part due to genetic heterogeneity. Recently, various mutations of the rhodopsin gene have been detected in some ADRP families. We report on six patients from two families with ADRP who were investigated by means of psychophysical and electrophysiological methods. All displayed the same rhodopsin gene mutation at codon 347, which exchanges the amino acid proline for leucine (pro-347-leu). The patients had early-onset night blindness and impaired side vision as of the end of their second life decade. They produced monophasic dark-adaptation curves, showing a lack of rod function and elevated cone thresholds. Dark-adapted two-color threshold perimetry using 500- and 650-nm stimuli revealed a diffuse loss of rod function and centrally preserved cone function. The electroretinogram was nonrecordable at the age of about 30 years. A certain variability of visual function loss was noted among patients in the overall severe course of the disease, but the clinical findings of this genotype corresponded to type 1 ADRP of Massof and Finkelstein in all cases.

Adult

[Cerebral resuscitation].

The present paper illustrates the physiological basis of brain function as well as the pathophysiological and neurochemical cascades during cerebral ischemia and subsequent reperfusion. It is emphasized that brain resuscitation preferably focuses upon those cerebral functions or structures, respectively, which are not definitely damaged until the early period of recirculation. Finally, current experimental considerations and already clinically established concepts in treatment of ischemic brain injury are pointed out. Their principles of action and their therapeutical value in cerebral resuscitation following cardiocirculatory arrest are discussed.

Cerebrovascular Circulation

Global cerebral ischemia and subsequent selective hypothermia. A neuropathological and morphometrical study on ischemic neuronal damage in cat.

A new method of external selective brain cooling is described, showing its effectiveness in reducing neuronal damage following global cerebral ischemia in cat. The cooling apparatus consists of a specially fitted kind of water jacket in which the animal's head was laid. In a preliminary study it was verified that the device effectively reduces brain temperature without the risk of cardiac arrhythmias due to lowering of core temperature. In the main study cardiac arrest was induced in 23 adult cats, followed after 15 min by cardiopulmonary resuscitation (CPR). Eight cats could not be revived; of the 15 remaining animals, 7 were assigned to the control group (normothermia) and 8 to the treatment group (cerebral hypothermia). The latter received external brain cooling for 30 min, starting as soon as CPR was begun. Four hours after cardiac arrest all animals were transcardiacally perfused with glutardialdehyde. The brains were stored in fixative and subsequently processed for histopathological and morphometrical evaluation by light microscopy. Analysis of the resulting data showed that animals in the treatment group had a significantly higher percentage of undamaged neurons than animals in the control group, both in the cingulate gyrus (38% vs 10%) and in the parietal cortex (39% vs 14%). The treatment group also had more undamaged neurons in the hippocampus and fewer severely damaged neurons in all three regions, but these differences, though suggestive, were not statistically significant.

Analysis of Variance

Intravascular large cell lymphoma: diagnosis on renal biopsy.

The case is reported of a woman aged 60 yrs who presented with systemic symptoms and who was found to have proteinuria of 3.5 g per day. A renal biopsy revealed numerous neoplastic cells filling many of the glomerular capillary lumina. Immunoperoxidase stains revealed that the phenotype of the malignant cells was LCA+, L26+, MB2+, UCHL1-, CD43-, CAM5.2- and S100-, indicating that they were of lymphoid origin and B-cell lineage. The diagnosis of intravascular large cell lymphoma was therefore made. Remission was induced by chemotherapy with CAVP (cyclophosphamide, adriamycin, vincristine and prednisone). A subsequent relapse was treated with cyclophosphamide, VP16 and prednisone, and again remission occurred. This is the first case known to the authors in which the diagnosis of intravascular large cell lymphoma was made on renal biopsy. We confirm the experience of others that chemotherapy with regimens utilized in other varieties of large cell lymphoma may also be appropriate for this unusual neoplasm.

Antineoplastic Combined Chemotherapy Protocols

[Selective cerebral hypothermia following cardiac arrest in the cat].

The aim of the present study was to introduce a new method of external selective brain cooling in cats. By means of this device, which mainly consisted of a head-sized, closely fitting copper basin, it was possible to reduce brain temperature rapidly. The resultant difference between core and cerebral temperatures amounted to mean values of about 10 degrees C after a 20-min cooling period. Ventricular fibrillation lasting for 15 min was induced in 23 healthy adult cats by internal cardiac electrical overpacing and followed by cardiopulmonary resuscitation (CPR). In several animals (n = 8) CPR efforts failed completely or they died without any indication of sufficient spontaneous circulation. In the initial postischemic period the remaining animals stayed normothermic and served as controls (n = 7) or received external brain cooling (n = 8), which was started simultaneously with CPR and continued for 30 min. During a survival time of 4 h cardiocirculatory function was stabilized pharmacologically and artificial respiration was performed, followed by transcardiac perfusion fixation. After removal from the skull, the brains were processed for histopathological evaluation of ischemic neuronal damage by light microscopy and morphometry. The clinical data obtained indicate that the described method provides a means for efficient heat exchange from within the intracranial space. Rapid, selective brain cooling could be achieved without any critical reduction of the core temperature and therefore, cardiac arrhythmias, a usual consequence of generalized hypothermia, could be avoided. The histopathological evaluation of ischemic neuronal damage showed a significantly higher percentage of unaffected cells in some areas of the cerebral cortex in animals treated with postischemic cerebral hypothermia than in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals