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Biomedical subjects

M Rosner

Publications and source records attributed to M Rosner.

At least 37 records · Page 2Linked to original sources
PubMed2001

Tuberous sclerosis gene products in proliferation control.

Two genes, TSC1 and TSC2, have been shown to be responsible for tuberous sclerosis (TSC). The detection of loss of heterozygosity of TSC1 or TSC2 in hamartomas, the growths characteristically occurring in TSC patients, suggested a tumor suppressor function for their gene products hamartin and tuberin. Studies analyzing ectopically modulated expression of TSC2 in human and rodent cells together with the finding that a homolog of TSC2 regulates the Drosophila cell cycle suggest that TSC is a disease of proliferation/cell cycle control. We discuss this question including very recent data obtained from analyzing mice expressing a modulated TSC2 transgene, and from studying the effects of deregulated TSC1 expression. Elucidation of the cellular functions of these proteins will form the basis of a better understanding of how mutations in these genes cause the disease and for the development of new therapeutic strategies.

Active Transport, Cell Nucleus↗
PubMed2001

Biased responding: a case series demonstrating a relationship between somatic symptoms and impaired recognition memory performance for traumatic brain injured individuals.

Biased responding on the Sternberg Recognition Memory Test was observed in four patients with traumatic brain injury. None of these individuals met the Diagnostic and Statistical Manual's (DSM-IV) criteria for malingering. Individual recognition memory scores were high shortly after injury, declined to chance or below at the 6- and 12-month evaluations, and then showed substantial recovery by the 24-month evaluation. Recall memory performance actually declined slightly across this same 2-year period. Recognition memory scores were related to the extent to which the patients endorsed somatic items on the Hamilton Rating Scale for Depression (HAM-D). Poor performance was associated with high somatic scores. The relationship between memory and somatic scores on the HAM-D in this case series suggests that unconscious processes can influence memory performance and, because of this, that clinicians should not use such performance as a primary indicator of malingering. More importantly, biased responding and actual memory deficits may coexist. This is indicated in the current cases by the failure of recall memory to improve during the 2 years these patients were followed.

Adult↗
PubMed2001

Cervical sympathetic schwannoma: case report.

OBJECTIVE AND IMPORTANCE: Approximately 20 to 27% of neck masses in the parapharyngeal space may be benign nerve sheath tumors. Cervical sympathetic chain schwannomas or vagal nerve schwannomas are most common. We report a patient with a cervical sympathetic chain schwannoma. CLINICAL PRESENTATION: The patient was a 47-year-old Caucasian man with a 7-month history of a painless, enlarging right neck mass. No hoarseness or Horner's syndrome was found preoperatively. Formal head and neck examination in the otolaryngology department revealed no vocal cord dysfunction. INTERVENTION: By use of a standard right carotid incision, a tumor was identified growing from the cervical sympathetic chain posterior to the carotid bifurcation. A gross total resection was performed and a section of the cervical sympathetic chain was sacrificed. CONCLUSION: Cervical sympathetic chain schwannomas are unusual tumors that require microneurosurgical resection for cure. We discuss the differential diagnosis, evaluation, surgical management, and pathological characteristics of such tumors and review the literature.

Diagnosis, Differential↗
PubMed2000

The TSC1 gene product, hamartin, negatively regulates cell proliferation.

Tuberous sclerosis is an autosomal dominant hereditary disease caused by mutations in either the TSC1 or the TSC2 tumor suppressor gene. The TSC1 gene on chromosome 9q34 encodes a 130 kDa protein named hamartin, and the TSC2 gene on chromosome 16p13.3 codes for tuberin, a 200 kDa protein. Here we show that expression of hamartin, assayed by immunoblot analyses, is high in G(0)-arrested cells and hamartin is expressed throughout the entire ongoing cell cycle. An interaction of hamartin and tuberin can be detected in every phase of the cell cycle. Ectopic expression of high levels of hamartin attenuates cellular proliferation. We provide evidence that this effect could depend on a coiled-coil region earlier proposed to be involved in binding of hamartin to tuberin. Further investigations revealed that hamartin affects cell proliferation via deregulation of G(1) phase. Our data have a clear impact on understanding the role of hamartin during development of this disease.

Animals↗
PubMed2000

Pathological and experimentally induced blindness induces auditory activity in the cat primary visual cortex.

Early blindness in humans and experimental visual deprivation in animal models are known to induce compensatory somatosensory and/or auditory activation of the visual cortex. An abnormal hydrocephalic cat with extreme malformation of the visual system, born in our breeding colony, rendered a good model system for investigating possible cross-modal compensation in such a pathological case. For comparison, we used normal and neonatally enucleated cats. When introduced to a novel environment, the abnormal cat behaved as if it was completely blind, yet it responded normally to auditory stimuli. As anticipated, single cells in the visual cortex of normal cats responded to visual, but not to auditory stimuli. In the visual cortex of enucleated cats, flashes of light did not elicit field-evoked potentials or single-unit responses. However, several cells did respond to various auditory stimuli. In the remnant visual cortex of the abnormal cat, auditory stimuli evoked field potentials and single-cell responses. Unexpectedly, however, unlike the enucleated cats, in the abnormal cat, flashes of light also elicited field-evoked potentials. Judging by its behavior, it is very likely that this deformed cat had completely lost its ability to perceive images, but had probably retained some sensitivity to light.

Abnormalities, Multiple↗
PubMed2000

A critical appraisal of the reporting of the National Acute Spinal Cord Injury Studies (II and III) of methylprednisolone in acute spinal cord injury.

From the beginning, the reporting of the results of National Acute Spinal Cord Injury Studies (NASCIS) II and III has been incomplete, leaving clinicians in the spinal cord injury (SCI) community to use or avoid using methylprednisolone in acute SCI on the basis of faith rather than a publicly developed scientific consensus. NASCIS II was initially reported by National Institutes of Health announcements, National Institutes of Health facsimiles to emergency room physicians, and the news media. The subsequent report in the New England Journal of Medicine implied that there was a positive result in the primary efficacy analysis for the entire 487 patient sample. However, this analysis was in fact negative, and the positive result was found only in a secondary analysis of the subgroup of patients who received treatment within 8 hours. In addition, that subgroup apparently had only 62 patients taking methylprednisolone and 67 receiving placebo. The NASCIS II and III reports embody specific choices of statistical methods that have strongly shaped the reporting of results but have not been adequately challenged or or even explained. These studies show statistical artifacts that call their results into question. In NASCIS II, the placebo group treated before 8 hours did poorly, not only when compared with the methylprednisolone group treated before 8 hours but even when compared with the placebo group treated after 8 hours. Thus, the positive result may have been caused by a weakness in the control group rather than any strength of methylprednisolone. In NASCIS III, a randomization imbalance occurred that allocated a disproportionate number of patients with no motor deficit (and therefore no chance for recovery) to the lower dose control group. When this imbalance is controlled for, much of the superiority of the higher dose group seems to disappear. The NASCIS group's decision to admit persons with minor SCIs with minimal or no motor deficit not only enables statistical artifacts it complicates the interpretation of results from the population actually sampled. Perhaps one half of the NASCIS III sample may have had at most a minor deficit. Thus, we do not know whether the results of these studies reflect the severely injured population to which they have been applied. The numbers, tables, and figures in the published reports are scant and are inconsistently defined, making it impossible even for professional statisticians to duplicate the analyses, to guess the effect of changes in assumptions, or to supply the missing parts of the picture. Nonetheless, even 9 years after NASCIS II, the primary data have not been made public. The reporting of the NASCIS studies has fallen far short of the guidelines of the ICH/FDA and of the Evidence-based Medicine Group. Despite the lucrative "off label" markets for methylprednisolone in SCI, no Food and Drug Association indication has been obtained. There has been no public process of validation. These shortcomings have denied physicians the chance to use confidently a drug that many were enthusiastic about and has left them in an intolerably ambiguous position in their therapeutic choices, in their legal exposure, and in their ability to perform further research to help their patients.

Acute Disease↗
PubMed1999

Pulmonary agenesis, microphthalmia, and diaphragmatic defect (PMD): new syndrome or association?

We present the prenatal diagnosis of a 22-week-gestation fetus with unilateral pulmonary agenesis, diaphragmatic hernia, microphthalmia, pulmonary vessel agenesis, and intrauterine growth retardation. The "association" of pulmonary agenesis, diaphragmatic defect, and microphthalmia was described previously in two patients but the resemblance was not noted by the authors. While each case differs slightly in some of the associated anomalies, it is evident that the mainstay of diagnosis is similar to the case presented here and that this represents a new syndrome or association.

Abnormalities, Multiple↗
PubMed1999

Methylprednisolone therapy for retinal laser injury.

OBJECTIVE: Laser photocoagulation treatment of the posterior pole of the retina is often complicated by immediate visual impairment, which is caused by the unavoidable laser-induced destruction of the normal tissue adjacent to the lesion. A neuroprotective therapy aimed at salvaging this normal tissue might enhance the benefit obtained from treatment and permit safe perifoveal photocoagulation. To determine whether corticosteroids can provide neuroprotection during photocoagulation, we examined the effect of methylprednisolone on laser-induced retinal injury in a rat model. METHODS: Argon laser lesions were inflicted on the retinas of 36 rats and were followed immediately by intraperitoneal injections of high-dose methylprednisolone or saline. The animals were sacrificed after 3, 20, or 60 days, and their retinal lesions were evaluated histologically and morphometrically. RESULTS: No histopathologic differences were observed between the treated and control animals. Methylprednisolone treatment was demonstrated to posses some neuroprotective effect for a short time after laser exposure, but was ineffective in ameliorating the long-term results of retinal laser injury. CONCLUSIONS: On the basis of our results, we suggest that high-dose methylprednisolone treatment is ineffective in ameliorating laser-induced retinal injury. Other drugs should be investigated for their potential role as neuroprotective agents to prevent the spread of retinal laser damage.

Animals↗
PubMed1999

Differential effect of cycloheximide on neuronal and glioma cells treated with chemotherapy and radiation.

Dividing cells and non-dividing cells are distinct in their cell cycle kinetics, and react differently when facing cytotoxic stimuli. A protein synthesis inhibitor, cycloheximide (CHX), has recently been found to protect neuronal cells from oxidative stress. We investigated whether CHX exerts differential effects on dividing and non-dividing cells in the brain under cytotoxic stimuli. Mitotic C6 rat glioma cells and postmitotic neuronal cells were studied with a cytotoxic regimen combining gamma-irradiation (RT) and 1,3-bis,2-chloroethyl-1-nitrosourea (BCNU). Cells were exposed to BCNU (1 g/ml) for 15 h before gamma-irradiation and incubated with CHX (1 g/ml) from 30 min before and until 5 h after irradiation. Clonogenic assay was used to assess cytotoxic effects on C6 glioma cells. LDH assay was used for the viability of H19-7 postmitotic neuronal cells. A 2.27-3.75 fold enhancement of cytotoxicity was noticed with the addition of CHX to BCNU and 2-10 Gy of radiation. Our data demonstrated that CHX enhanced cytotoxicity of RT plus BCNU, while no additional toxicity was incurred to the postmitotic neuronal cells when CHX was added. We further studied whether the inhibition of DNA repair, assayed by single-cell DNA electrophoresis (comet assay), is a contributing factor for the enhanced cytotoxicity on C6 glioma cells. Interestingly, the initial DNA damage after RT plus BCNU was equivalent; whereas DNA repair was significantly less at 5 h after radiation in CHX-treated C6 glioma cells. Protecting non-dividing neuronal cells to avoid excessive functional deficit is an integral part of a successful brain tumor treatment regimen. Taking advantage of the differential effect of CHX on glioma and neuronal cells may improve tumor control without excessive neural toxicity.

Animals↗
PubMed1998

Elevated liver enzymes after nontraumatic intracranial hemorrhages.

OBJECTIVE: To determine the prevalence and possible etiologies of liver enzyme abnormalities in patients with acquired brain injury and to assess the impact of these abnormalities on the rehabilitative process. SETTING: University tertiary care rehabilitation center. DESIGN: Retrospective study. SUBJECTS: Fifty-six consecutive patients admitted to a brain injury unit in a 30-month period who had an intracranial hemorrhage without associated head or abdominal trauma. MAIN OUTCOME MEASURES: Liver function tests, Functional Independence Measure (FIM) scores, exposure to hepatotoxic drugs, antiepileptic medication serum levels, history of alcohol use, medical history, length of stay, and medical costs. RESULTS: There was an increase (from acute hospital admission to inpatient rehabilitation admission) in gamma-glutamyltransferase (GGT) levels from 42 to 147U/L (p=.0012). There was an increase in alkaline phosphatase from 83 to 125U/L (p=.0079). There was a significant relationship between the GGT level on rehabilitation admission and exposure to hepatotoxic drugs, particularly phenytoin (n=55, p=.0007). Similar findings were noted between alkaline phosphatase and phenytoin (n=55, p=.0022) and systemic steroids (n=50, p=.0277). History of alcohol use was not predictive of changes in liver function tests (p > .05). Correlation analysis revealed no detrimental effect of the elevated serum liver enzyme levels on the Rasch-converted FIM cognitive or motor admission or discharge scores or change in the scores while on rehabilitation (p > .05). All radiologic testing and hepatitis profiles were negative, and 10 of the 16 patients with follow-up laboratory tests showed improvement in their serum liver enzyme levels. CONCLUSIONS: After nontraumatic brain injury there is a characteristic pattern of enzyme elevation that statistically relates to phenytoin exposure. No additional etiologic abnormalities were found on further workup, suggesting that further evaluation should be guided by the patient's clinical status, not laboratory value alone.

Activities of Daily Living↗
PubMed1998

Bilateral Kimura's disease with devastating visual outcome.

Kimura's disease is a chronic inflammatory disease involving connective tissues. We treated a patient with bilateral periocular Kimura's disease causing eyelid deformity and exophthalmos for over 20 years. She has been operated on 23 times and biopsies were taken and studied histologically. The disease continued despite the multiple surgical excisions. The consequent exophthalmos and lid changes caused lagophthalmos that resulted in severe visual impairment due to chronic bilateral corneal exposure. Kimura's disease may have a devastating effect on visual function.

Angiolymphoid Hyperplasia with Eosinophilia↗
PubMed1998

Prevention of posterior capsule opacification with the CO2 laser.

BACKGROUND AND OBJECTIVE: Posterior capsule opacification (PCO) is a common complication after cataract extraction, despite the modern surgical techniques and lenses being used for this procedure. Its prevention challenged many investigators, because the current treatment of choice, capsulotomy with Nd:YAG laser, is associated with sight-threatening complications. In the present study, the authors investigated two approaches of preventing PCO using the CO2 laser. MATERIALS AND METHODS: A 15-W CO2 laser with a 17- or 18-gauge hollow probe was used on 20 sheep eyes and 14 rabbit eyes. Lens extraction was done by phacoemulsification. In the equatorial treatment study, the anterior chamber was filled with either air or a viscoelastic substance, and laser burns were applied to the equator of the lens capsule and to the peripheral anterior capsule to destroy the epithelial cells. In the capsulotomy study, a primary posterior capsulotomy was created by delivering 1 to 3 laser shots to the capsule behind an implanted intraocular lens (IOL). RESULTS: The CO2 laser was satisfactory in sheep eyes after filling the anterior chamber with air. In rabbit eyes, however, it was technically impractical to work with air. Using a viscoelastic material to maintain the anterior chamber, the hollow probe of the CO2 laser becomes plugged up and therefore is unable to affect the ocular tissue. However, by combining viscoelastic and air pumping, both the destruction of the lens epithelial cells and the creation of a central posterior opening behind a capsular-fixated IOL was repeatedly achieved. CONCLUSION: Using the CO2 laser for destruction of lens epithelial cells and the creation of controlled posterior capsulotomy is feasible and practical. A different design of the probe (closed gauge) is required to enable it to operate clinically in a fluid or viscoelastic environment.

Animals↗
PubMed1997

Neuroprotective therapy for argon-laser induced retinal injury.

Laser photocoagulation treatment of the central retina is often complicated by an immediate side effect of visual impairment, caused by the unavoidable laser-induced destruction of the normal tissue lying adjacent to the lesion and not affected directly by the laser beam. Furthermore, accidental laser injuries are at present untreatable. A neuroprotective therapy for salvaging the normal tissue might enhance the benefit obtained from treatment and allow safe perifoveal photocoagulation. We have developed a rat model for studying the efficacy of putative neuroprotective compounds in ameliorating laser-induced retinal damage. Four compounds were evaluated: the corticosteroid methylprednisolone, the glutamate-receptor blocker MK-801, the anti-oxidant enzyme superoxide dismutase, and the calcium-overload antagonist flunarizine. The study was carried out in two steps: in the first, the histopathological development of retinal laser injuries was studied. Argon laser lesions were inflicted in the retinas of 18 pigmented rats. The animals were killed after 3, 20 or 60 days and their retinal lesions were evaluated under the light microscope. The laser injury mainly involved the outer layers of the retina, where it destroyed significant numbers of photoreceptor cells. Over time, evidence of two major histopathological processes was observed: traction of adjacent normal retinal cells into the central area of the lesion forming an internal retinal bulging, and a retinal pigmented epithelial proliferative reaction associated with subretinal neovascularization and invasion of the retinal lesion site by phagocytes. The neuroprotective effects of each of the four compounds were verified in a second step of the study. For each drug tested, 12 rats were irradiated with argon laser inflictions: six of them received the tested agent while the other six were treated with the corresponding vehicle. Twenty days after laser exposure, the rats were killed and their lesions were subjected to image-analysis morphometry. The extent of retinal destruction was assessed by measuring the lesion diameter and the amount of photoreceptor cell loss in the outer nuclear layer. Methylprednisolone and MK-801 were shown to ameliorate laser-induced retinal damage, whereas both superoxide dismutase and flunarizine were ineffective. Furthermore, MK-801 diminished the proliferative reaction of the retinal pigment epithelial cells. On the basis of our results we suggest that the pigmented rat model is suitable for studying and screening various compounds for their neuroprotective efficacy in treating retinal laser injury. We further suggest that glutamate might play a key role in mediating retinal injury induced by laser irradiation.

Animals↗
PubMed1997

Correlation between clinical, physical and histopathological characteristics of the cataractous lens.

BACKGROUND: Preoperative evaluation of lens opacity is used to predict surgical qualities of the lens and the expected improvement in visual acuity. The present study was conducted to ascertain whether preoperative clinical examination findings correlate with actual physical hardness of the lens and its histopathologic microstructure. METHODS: Two classification systems for clinical evaluation of lens opacity were compared: simple grading and the Lens Opacities Classification System II (LOCS II). Physical hardness of 65 lens nuclei extracted manually was measured using a specially designed hydrostatic guillotine. Lens material was then studied by low-magnification inspection of stained nuclei and by histologic examination. RESULTS: Multiple observers' simple grading of lens opacities was almost identical to a single observer's LOCS II evaluation. Hardness of the lens demonstrated high correlation with grading of nuclear sclerosis, but not with cortical or subcapsular opacities. Preoperative visual acuity correlated with lens hardness only in eyes with visual acuity less than 6/24. The lamellar structure of the lens is maintained also in dense nuclear cataract. We did not identify microscopic parameters that correlated with clinical appearance or hardness of the lenses. CONCLUSIONS: Preoperative clinical examination of the eye provides reliable information that can be used to predict the physical qualities of the cataractous lens.

Adult↗
PubMed1997

Temperature-controlled CO2 laser tissue welding of ocular tissues.

Lasers can be used for binding tissues by welding, but the clinical application of this method has been limited by the difficulties in defining and maintaining the optimal conditions. Fiberoptic radiometry allows accurate remote temperature measurements for control of laser tissue welding. We evaluated the use of a temperature-controlled tissue welding system to close corneal and corneoscleral wounds. Eighty ex vivo bovine eyes were used for the determination of welding parameters optimal for corneal wound closure. A 4 mm central corneal cut was closed with use of a CO2 laser (600 mw, 0.9 mm spot size), with tissue temperatures ranging from 45-70 degrees C and welding time ranging from 1-30 seconds. Wound strength was measured as burst pressure of the sealed wound. The welding parameters found to cause the strongest wound binding were used to weld a limbal incision of 4 mm in 10 adult albino rabbits. The fellow eye of each animal was used as a control, and the same wound was closed with one 10/0 mersilen suture. Two animals were killed immediately after the procedure, and the eyes were sent for histologic examination. Eight rabbits were followed for 1 month. Clinical examination and refraction were done 1 day, 1 week, 2 weeks, and 1 month after the procedure. Corneal topographic evaluations were done 1 week after the procedure. After 1 month the animals were killed and the eyes were examined histologically. The optimal results of wound binding by laser welding in the enucleated bovine eyes were achieved with 55-60 degrees C and at a welding time of 12-20 seconds. At these parameters the burst pressure of corneal wounds was 70 mm Hg. All laser-welded limbal wounds in the rabbits were tightly closed at the end of procedure and during the follow-up period. The refractive results after laser welding were equal to those of the controlled suture-closed wound. Laser tissue welding combined with tissue temperature monitoring can be used to close corneal wounds.

Animals↗