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Biomedical subjects

S D Finkelstein

Publications and source records attributed to S D Finkelstein.

88 records · Page 5Linked to original sources

Experimental spinal cord injury: effect of a calcium channel antagonist (nicardipine).

Variable benefits from the use of a number of calcium channel blockers in experimental spinal cord injury have been reported. To our knowledge, these agents have not been previously tested in a contusion model of cord injury in which neurological outcome is one of the critical outcome parameters. We carried out preliminary behavioral toxicity testing to identify a range of low, moderate, and high dosage levels of the calcium channel blocker, nicardipine; these dosage levels were to be used subsequently in formal testing. After laminectomy at T8 under general anesthesia in rats, a 10-g weight was dropped from a height of 5 cm onto the spinal cord. The animals were randomly assigned to four groups: control or one of three nicardipine treatment groups: (a) low dose (1 mg/kg, followed by a continuous 23-hour infusion of 0.5 mg/kg/hour), (b) moderate dose (10 mg/kg, followed by 5 mg/kg/hour for 23 hours, and (c) high dose (20 mg/kg, followed by 23-hour infusion of 10 mg/kg/hour). Functional recovery was tested over the course of 4 weeks with the Tarlov scale, the inclined plane, and a sensory-motor battery of tests (combined behavioral score). After sacrifice at 4 weeks, morphometric analysis of residual gray and white matter was performed at the epicenter of the spinal cord injury. Statistical analysis of the behavioral data failed to reveal any differences among the control or nicardipine treatment groups. The morphometric analysis similarly failed to show differences between the control and any treatment group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

CT-guided stereotactic biopsy of brain tumors: pathologic considerations.

Astrocytic tumors, the most common of the primary intracerebral neoplasms, are a heterogeneous group in terms of clinical behavior and pathologic appearance. Current histopathologic classification emphasizes this aspect; however, its application to tissue specimens removed by means of CT-guided stereotactic brain biopsy requires special considerations. Pertinent aspects of pathology relevant to assessment by CT scan stereotactic needle biopsy are discussed, together with a presentation of early results on the use of this diagnostic technique.

Astrocytoma↗

Propionibacterium acnes cerebral botryomycosis. The role of plastic embedding in the diagnosis of grain-producing infections.

Botryomycosis is a chronic infection in which bacterial colonies, or "grains," occur in purulent exudate associated with draining sinus tracts or abscess formation. This condition usually is caused by Staphylococcus and Streptococcus, but other organisms occasionally have been implicated. This report describes the first case of botryomycosis caused by Propionibacterium acnes, a diphtheroid that has been rarely associated with opportunistic disease. In this case, plastic embedding allowed the observation of the structural details of the organisms composing the grains and permitted their presumptive identification as diphtheroids. The differential diagnosis of infectious agents that produce grains in tissue sections also will be discussed.

Adult↗

Models of spinal cord injury: Part 1. Static load technique.

Testing of potential therapies for spinal cord injury has been significantly hampered by the unavailability of a standardized, reproducible animal model with predictable outcome at a given force of injury (dose-response). The rat was selected in the development of this model in preference to larger animals for economy and availability; this permits use of large numbers of animals to increase statistical validity. In the experiments reported in this article, a static load method (weight placed gently on cord) of inducing cord injury was evaluated. A total of 198 Sprague-Dawley rats were used. Under general anesthesia, a one-level laminectomy was carried out at T-12 with the dura mater intact. Weights varying from 80 to 150 g were lowered onto the dorsal surface of the intact dura mater for durations of 0 to 300 seconds. Recovery of motor function was assessed for up to 8 weeks using two behavioral tests, a modified Tarlov scale and an inclined plane test of hind limb motor function. A statistically significant relationship was found between force of injury and motor recovery as measured by the Tarlov scale, but this did not correlate with inclined plane performance; the duration that the weight rested on the cord did not influence outcome. Pathologically, there was variation in the extent of damage for a given injury load. A semiquantitative pathological assessment of cord injury showed a statistically significant correlation between pathological score and behavioral deficit as measured by the Tarlov scale, but this did not correlate with inclined plane performance. In view of these deficiencies, the static load technique does not seem to be an ideal model for spinal cord injury research.

Animals↗

Naloxone and experimental spinal cord injury: Part 1. High dose administration in a static load compression model.

Previous studies by other investigators using a dynamic weight drop injury model in cats or rats have demonstrated a beneficial effect of naloxone in promoting motor recovery after experimental spinal cord injury. The effective doses ranged from 0.8 mg (total dose) in rats to a high dose of 10 mg/kg in cats. We report here an evaluation of high dose naloxone (10 mg/kg) in a model of cord injury in rats using a static load compression technique. After induction of injury at T-12, naloxone (10 mg/kg) was administered by the intraperitoneal route, followed by five additional bolus injections over the course of the next 2 days. Animals were randomly assigned to this treatment regimen (n = 10) or to a saline control group (n = 10). The animals were observed for 4 weeks, with testing of recovery of hind limb motor function (Tarlov score and on an inclined plane). Although there were slight differences in recovery, the overall evaluation showed no statistically significant difference between the naloxone-treated and control groups. The spinal cords of the sacrificed animals were studied morphometrically; there was no statistically significant difference between the residual gray and white matter at the site of cord injury between the treated and control groups. Naloxone did not seem to promote recovery of motor function in this model of spinal cord injury.

Animals↗

Naloxone and experimental spinal cord injury: Part 2. Megadose treatment in a dynamic load injury model.

We previously reported that high dose naloxone (10 mg/kg) failed to promote recovery of motor function after a static load injury of the spinal cord in rats. In the present experiments, using the more traditional dynamic weight drop model, we tested megadose naloxone administered by the intraperitoneal route in 23 rats, including saline controls (Experiment 1). Thirty minutes after a cord injury at T-12, naloxone was given i.p. in a bolus of 100 mg/kg, followed by a continuous i.p. infusion of 50 mg/kg/hour for 23 hours. Again, no benefit was observed; this raised a question regarding naloxone and its absorption and serum levels. In another study, reported separately, we found that naloxone administered by the subcutaneous route affords higher and more sustained serum levels than by i.p. administration. Consequently, in 20 rats (Experiment 2), we repeated the protocol, using subcutaneous naloxone in a bolus dose of 150 mg/kg, followed by continuous infusion of 75 mg/kg/hour for 23 hours; the result was again negative. Morphometric determination of the residual (normal) cross sectional areas of gray and white matter at the epicenter of the cord lesion showed no statistically significant difference between treated and control animals in either Experiment 1 or Experiment 2. In view of the negative findings at high dose (10 mg/kg) and megadose naloxone, it seems that a reasonable next step would be an evaluation of lower doses using a factorial research design, incorporating a range of doses of naloxone in relation to a variety of intensities of cord injury. This question will be addressed in future experiments.

Animals↗

Alterations in the metabolism of lipids in ischemia of the liver and kidney.

The metabolism of lipids in the ischemic liver has been examined in the attempt to define the cause of the previously described loss of phospholipid and to determine whether additional alterations occur that may be related to the disturbances in membrane function. With 3 hr of ischemia, 30% of the cellular phospholipid was lost when measured either as phosphate in a lipid extract of the whole liver or as fatty acyl esters after separation by thin-layer chromatography of the major lipid classes in the same extracts. All phospholipid species were equally affected, and there was no accumulation of lysophospholipids. The loss of phospholipid acyl chains was not accompanied by an increased number of acyl esters as mono-, di-, or triglycerides. There was no increase in the size of the free fatty acid pool, and the content of long chain acyl CoA esters decreased by 50%. The acyl chain composition of the free fatty acid and neutral lipid pools changed, however, to resemble more closely that of the phospholipids. There was no change in the fatty acid composition of the phospholipids. The incorporation of intraportally injected [3H]arachidonic acid into total phospholipids was decreased upon reperfusion of liver that had been ischemic for only 20 min. These data are consistent with a loss of fatty acyl chains from the phospholipids into the free fatty acid pool. A few of these chains are incorporated into neutral lipids, but most are lost from the liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Multiple malignant astrocytomas in a patient with spontaneous progressive multifocal leukoencephalopathy.

A 67-year-old man with a four-year history of horizontal and vertical nystagmus and progressive cerebellar dysfunction later developed profound dementia and died of bronchopneumonia. Neuropathological examination revealed numerous active and inactive progressive multifocal leukoencephalopathy (PML) lesions in the cerebrum and cerebellum. Active lesions showed marked perivascular lymphocytic cuffing. Papovaviruses were identified ultrastructurally in both oligodendrocytes and astrocytes. Multiple malignant astrocytomas were documented, originating from PML lesions. No viruses could be demonstrated in neoplastic astrocytes. An immune-deficient state was not revealed clinically or at postmortem examination.

Aged↗

An experimental method for rapid growth of liver in spleen. The survival and proliferation of chemically induced preneoplastic hepatocytes in spleen.

Cellular suspensions (2 x 10(6) cells) of isolated preneoplastic liver cells, obtained from carcinogen-treated rats, were injected in the spleens of syngeneic rats divided into groups on the basis of no treatment, partial hepatectomy (PH), and/or feeding regimens including 2-acetylaminofluorene (AAF). Recipient rats undergoing both PH and AAF showed significantly more rapid proliferation of the preneoplastic liver cell implant, compared with other treatment groups and control. The theoretic basis for this observation, supported by a large body of data derived from hepatocarcinogenesis, is as follows: The phenotype of the donor cells has been altered by chemical carcinogens such that the liver cells develop resistance to growth-inhibiting agents such as AAF. The recipient receives PH and AAF, the former creating a strong proliferative stimulus for hepatocytes, while the latter inhibits regeneration of normal liver cells but not those resistant to the mito-inhibitory effect of AAF, ie, the carcinogen-altered donor cells. These manipulations in donors and recipients thus create a selective environment in which the implant undergoes rapid proliferation. This model of resistance induction followed by selective proliferation, built upon the principles of carcinogenesis and applied to isolated liver cell transplantation, provides an experimental basis for achieving rapid liver growth of the splenic implant.

2-Acetylaminofluorene↗

Intrahepatic cholestasis with predominant pericentral deposition in systemic amyloidosis.

Liver involvement in amyloidosis is rarely associated with intrahepatic cholestasis. The cases recorded in the literature indicate that there is a tendency toward periportal deposition, leading to centrilobular cholestasis. Our case was most interesting in that the amyloid deposition was most severe in the centrilobular area. Presumably there was still sufficient compression of canaliculi at the periportal level to produce obstruction of the bile flow. This would appear to be a less common but distinct variant of systemic amyloidosis with associated obstructive jaundice.

Amyloidosis↗

Topographic genotyping of colorectal carcinoma: from a molecular carcinogenesis model to clinical relevance.

BACKGROUND: In recent years, as a result of refinement in molecular biology techniques, significant progress has been made in the understanding of colorectal carcinogenesis. Particular attention has been drawn to identification of genetic mutation that may predispose to colorectal carcinoma (familial syndromes) and may affect tumor behavior and prognosis (sporadic cases). CONCLUSIONS: Our method of topographic genotyping of human colonic carcinomas has shown a correlation between K-ras-2 and p53 mutations and stage at diagnosis as well as long-term survival. Data from other investigators in this field confirm the importance of genetic analysis of human colorectal tumors. These findings are likely to impact management by allowing a more individualized therapeutic approach.

Carcinoma↗

Juvenile laryngeal carcinoma: correlation of computed tomography and magnetic resonance imaging with pathology.

The clinical, radiologic and pathologic features of invasive squamous cell carcinoma of the larynx are reported in a 16-year-old girl. In particular, computerized tomography (CT) and magnetic resonance imaging (MRI) are correlated with histopathological findings. It was found that the combined use of CT and MRI enabled an accurate identification of laryngeal tissue components and a precise delineation of extent of cancer spread. This diagnostic approach is emphasized as well as the need to suspect carcinoma of the larynx in any child unrelenting or recurring hoarseness.

Adolescent↗

Ultrastructural tubular basement membrane lesions in adult polycystic kidney disease.

The pathogenesis of adult polycystic kidney disease (PCKD) remains an enigma. In an attempt to find a defect that might explain the cyst formation, an ultrastructural study was performed on seven fresh bilateral nephrectomies of seven patients suffering from adult PCKD. Marked electron microscopic changes of the tubular basement membranes were detected, including thickening, splitting, fraying, and multilayering of the basement membranes. By contrast, glomerular basement membranes lacked these alterations. The kidneys from two control groups (five donor kidneys harvested for transplantation; 10 patients who suffered from end stage renal disease) showed none of the lesions detected in the polycystic kidneys. The lesions of the tubular basement membrane, the principal support of tubular wall, may be the primary phenotypic expression and cause of the inherited defect.

Basement Membrane↗

Infrasellar craniopharyngioma: CT and MR studies.

A rare case of an infrasellar craniopharyngioma is reported. Pathological proof and CT and magnetic resonance (MR) images of the tumor are presented. This case is thought to demonstrate the first example of MR images of an infrasellar craniopharyngioma. Evidence suggesting that the tumor originated from an infrasellar location is presented.

Brain Neoplasms↗