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Biomedical subjects

M Blaivas

Publications and source records attributed to M Blaivas.

At least 19 recordsLinked to original sources

Distinctive molecular profiles of high-grade and low-grade gliomas based on oligonucleotide microarray analysis.

Astrocytomas are heterogeneous intracranial glial neoplasms ranging from the highly aggressive malignant glioblastoma multiforme (GBM) to the indolent, low-grade pilocytic astrocytoma. We have investigated whether DNA microarrays can identify gene expression differences between high-grade and low-grade glial tumors. We compared the transcriptional profile of 45 astrocytic tumors including 21 GBMs and 19 pilocytic astrocytomas using oligonucleotide-based microarrays. Of the approximately 6800 genes that were analyzed, a set of 360 genes provided a molecular signature that distinguished between GBMs and pilocytic astrocytomas. Many transcripts that were increased in GBM were not previously associated with gliomas and were found to encode proteins with properties that suggest their involvement in cell proliferation or cell migration. Microarray-based data for a subset of genes was validated using real-time quantitative reverse transcription-PCR. Immunohistochemical analysis also localized the protein products of specific genes of interest to the neoplastic cells of high-grade astrocytomas. Our study has identified a large number of novel genes with distinct expression patterns in high-grade and low-grade gliomas.

Astrocytoma↗

Unexplained exertional limitation: characterization of patients with a mitochondrial myopathy.

Exercise intolerance is a common complaint, the cause of which often remains elusive after a comprehensive evaluation. In this report, we describe 28 patients with unexplained dyspnea or exertional limitation secondary to biopsy-proven mitochondrial myopathies. Patients were prospectively identified from a multidisciplinary dyspnea clinic at a tertiary referral center. All patients were without underlying pulmonary, cardiac, or other neuromuscular disorders. Patients underwent history, physical examination, complete pulmonary function testing, respiratory muscle testing, cardiopulmonary exercise testing, and muscle biopsy. Results were compared with a group of normal control subjects. The estimated period prevalence was 8.5% (28 of 331). Spirometry, lung volumes, and gas exchange were normal in patients and control subjects. Compared with control subjects, the patient group demonstrated decreased exercise capacity (maximum achieved V O(2) 67 versus 104% predicted; p < 0.0001) and respiratory muscle weakness (PI(max) 77 versus 115% predicted; p = 0.001). These patients have a characteristic exercise response that was hyperventilatory (peak VE/V CO(2); 55 versus 42) and hypercirculatory (maximum heart rate - baseline heart rate/V O(2)max - baseline V O(2)max; 91 versus 41) compared to control subjects. Patients stopping exercise due to dyspnea (n = 16) (as compared with muscle fatigue, n = 11) displayed weaker respiratory muscles (Pdi(max) 61 versus 115 cm H(2)O; p = 0.01) and were more likely to reach mechanical ventilatory limitation (V Emax/ MVV 0.81 versus 0.58; p = 0.02). The sensation of dyspnea was related to indices of respiratory muscle function including respiratory rate and inspiratory flow. We conclude that mitochondrial myopathies are more prevalent than previously reported. The characteristic physiological profile may be useful in the diagnostic evaluation of mitochondrial myopathy.

Adult↗

Proliferation index is related to patient age in glioblastoma.

Younger patients with glioblastomas have a significantly better prognosis than do older patients. To determine whether patient age might be related to proliferation of glioblastoma cells, glioblastomas from patients of different ages were stained with the Molecular Immunology Borstel number 1 antibody to detect proliferating cells. Younger patient age was a significant predictor of a low Molecular Immunology Borstel number 1 proliferation index (p = 0.0001). This previously unreported association favors an intrinsic difference in the type of glioblastomas that afflict younger patients.

Adolescent↗

The gene for the axonal cell adhesion molecule TAX-1 is amplified and aberrantly expressed in malignant gliomas.

The human TAX-1 gene encodes a Mr 135,000 glycoprotein that is transiently expressed on the surface of a subset of neurons during development and is involved in neurite outgrowth. The TAX-1 gene has been mapped to a region on chromosome 1 that has been implicated in microcephaly and the Van der Woude syndrome. Using restriction landmark genome scanning to search for amplified genes in gliomas, we found TAX-1 to be amplified in 2 high-grade gliomas among a group of 26 gliomas investigated. Real-time reverse transcription-quantitative PCR analysis detected high levels of TAX-1 mRNA in glial tumors, even in the absence of TAX-1 gene amplification. Immunohistochemical analysis revealed abundant levels of TAX-1 in neoplastic glial cells of glioblastoma multiforme tumors. Because glial tumors are highly invasive and in view of the role of TAX-1 in neurite outgrowth, we investigated the potential role of TAX-1 in glioma cell migration. Using an in vitro assay, we found that the migration of glioma tumor cells is profoundly reduced in the presence of either an anti-TAX-1 antibody or a TAX-1 antisense oligonucleotide. Our findings suggest that TAX-1 plays a role in glial tumorigenesis and may provide a potential target for therapeutic intervention.

Blotting, Northern↗

Triage in the trauma bay with the focused abdominal sonography for trauma (FAST) examination.

Bedside ultrasonography has been applied to the evaluation of blunt trauma patients for over a decade. The Focused Abdominal Sonography for Trauma (FAST) examination has been used to successfully triage blunt trauma patients. Although not traditionally thought to be as useful in penetrating trauma patients, ultrasound can help determine the extent of injury especially of the heart. We present two cases of multiple-stabbing victims who arrived at our Level I trauma center at the same time, when our trauma system was particularly overburdened by multiple consecutive traumas. The FAST examination helped us to accurately determine which of the two patients required operative intervention first, despite that patient's appearance of relative hemodynamic stability in comparison to the other stabbing victim.

Abdominal Injuries↗

Magnetic resonance imaging of ethyl-nitrosourea-induced rat gliomas: a model for experimental therapeutics of low-grade gliomas.

Human low-grade gliomas represent a population of brain tumors that remain a therapeutic challenge. Preclinical evaluation of agents, to test their preventive or therapeutic efficacy in these tumors, requires the use of animal models. Spontaneous gliomas develop in models of chemically induced carcinogenesis, such as in the transplacental N-ethyl-N-nitrosourea (ENU) rat model. However, without the ability to detect initial tumor formation, multiplicity or to measure growth rates, it is difficult to test compounds for their interventional or preventional capabilities. In this study Fisher-334 rats, treated transplacentally with ENU, underwent magnetic resonance imaging (MRI) examination in order to evaluate this approach for detection of tumor formation and growth. ENU-induced intracranial cerebral tumors were first observable in T2-weighted images beginning at 4 months of age and grew with a mean doubling time of 0.487 +/- 0.112 months. These tumors were found histologically to be predominately mixed gliomas. Two therapeutic interventions were evaluated using MRI, vitamin A (all-trans retinol palmitate, RP), as a chemopreventative agent and the anti-angiogenic drug SU-5416. RP was found to significantly delay the time to first tumor observation by one month (P = 0.05). No differences in rates of tumor formation or growth rates were observed between control and RP-treated groups. MRI studies of rats treated with SU-5416 resulted in reduction in tumor growth rates compared to matched controls. These results show that MRI can be used to provide novel information relating to the therapeutic efficacy of agents against the ENU-induced tumor model.

Angiogenesis Inhibitors↗

Outcome in cardiac arrest patients found to have cardiac standstill on the bedside emergency department echocardiogram.

UNLABELLED: Patients presenting in cardiac arrest frequently have poor outcomes despite heroic resuscitative measures in the field. Many emergency medical systems have protocols in place to stop resuscitative measures in the field; however, further predictors need to be developed for cardiac arrest patients brought to the emergency department (ED). OBJECTIVE: To examine the predictive value of cardiac standstill visualized on bedside ED echocardiograms during the initial presentations of patients receiving cardiopulmonary resuscitation (CPR). METHODS: The study took place in a large urban community hospital with an emergency medicine residency program and a high volume of cardiac arrest patients. As part of routine care, all patients arriving with CPR in progress were subject to immediate and brief subxiphoid or parasternal cardiac ultrasound examination. This was followed by brief repeat ultrasound examination during the resuscitation when pulses were checked. A 2.5-MHz phased-array probe was used for imaging. Investigators filled out standardized data sheets. Examinations were taped for review. Statistical analysis included descriptive statistics, positive and negative predictive values, and likelihood ratios. RESULTS: One hundred sixty-nine patients were enrolled in the study. One hundred thirty-six patients had cardiac standstill on the initial echocardiogram. Of these, 71 patients had an identifiable rhythm on monitor. No patient with sonographically identified cardiac standstill survived to leave the ED regardless of his or her initial electrical rhythm. Cardiac standstill on echocardiogram resulted in a positive predictive value of 100% for death in the ED, with a negative predictive value of 58%. CONCLUSIONS: Patients presenting with cardiac standstill on bedside echocardiogram do not survive to leave the ED regardless of their electrical rhythms. This finding was uniform regardless of downtime. Although larger studies are needed, this may be an additional marker for cessation of resuscitative efforts.

Adult↗

Emergency ultrasonography in the evaluation of the acute scrotum.

Acute scrotal pain accounts for approximately 0.5% of total emergency department (ED) visits. Despite this relatively low percentage, these patients can present a considerable challenge to the treating emergency physician (EP) since the etiologies of acute scrotal pain range from organ-threatening disease to minor idiopathic pain. Few data exist on EP use of bedside ultrasound to evaluate scrotal pain, but there is some suggestion that this may represent a beneficial future application for emergency ultrasonographers. This paper briefly describes the technology and technique involved with the performance of testicular ultrasound examination and briefly discusses its potential application at bedside in the ED.

Acute Disease↗

Emergency evaluation of patients presenting with acute scrotum using bedside ultrasonography.

UNLABELLED: Acute scrotal pain is not a rare emergency department (ED) complaint. Traditional reliance on medical history and physical examination can be precarious as signs and symptoms can overlap in various etiologies of acute scrotal pain. OBJECTIVE: To determine the accuracy with which emergency physicians (EPs) using bedside ultrasonography are able to evaluate patients presenting to the ED with acute scrotal pain. METHODS: The study was performed at an urban community hospital ED with a residency program and an annual census of 70,000. A retrospective chart review identified 36 patients who presented with complaints of acute scrotal pain and were evaluated by EPs using bedside ultrasound. A 5.0- or 7.5-MHz linear-array transducer with color and power Doppler capability was used to scan the scrotum. Patients were seen between July 1998 and September 1999. Diagnoses were verified by radiology or surgery. Sensitivity and specificity with 95% confidence intervals were calculated. RESULTS: The EP ultrasound examinations agreed with confirmatory studies for 35 of 36 patients, resulting in a sensitivity of 95% (95% CI = 0.78 to 0.99) and a specificity of 94% (95% CI = 0.72 to 0.99). Diagnoses included three testicular torsions, six cases of epididymitis, four cases of orchitis, one testicular fracture, three hernias, three hydroceles, and 15 normal examinations. One case of epididymitis was misdiagnosed as an epididymal mass. CONCLUSIONS: This study suggests that EPs using bedside ultrasonography are able to accurately diagnose patients presenting with acute scrotal pain. In addition, they appear able to differentiate between surgical emergencies, such as testicular torsion, and other etiologies.

Acute Disease↗

Incidence of pericardial effusion in patients presenting to the emergency department with unexplained dyspnea.

OBJECTIVE: To evaluate the frequency of pericardial effusion in patients presenting to the emergency department (ED) with unexplained, new onset dyspnea. METHODS: This prospective observational study took place at an urban community hospital ED with a residency program and an annual census of 65,000 visits. Patients presenting between May 1999 and January 2000 with new-onset dyspnea were eligible if they lacked any pulmonary, infectious, hematological, traumatic, psychiatric, cardiovascular, or neuromuscular explanation for their dyspnea after ED evaluation. Patients received a focused echocardiogram by certified emergency physicians. Data were recorded on standardized data sheets and studies were taped for review. Effusions were categorized as small when the fluid stripe measured less than 10 mm. Moderate-sized effusions measured 10 to 15 mm. Large effusions measured more than 15 mm. RESULTS: One hundred three patients were enrolled. Median age was 56 years (IQR 44, 95% CI = 32 to 67). Fourteen patients (13.6%, 95% CI = 8% to 23%) had effusions. Four had large effusions that explained their dyspnea and were admitted to cardiology; two of these effusions were hemorrhagic, and two were viral in origin. Seven patients with small effusions were treated conservatively at home. Three patients had moderate-sized effusions; all were admitted but treated conservatively. CONCLUSIONS: While limited by small numbers, these preliminary data suggest that patients with unexplained dyspnea should be checked for pericardial effusion when bedside ED ultrasound is available.

Adult↗

Ultrasound-guided breast abscess aspiration in a difficult case.

Although ultrasound guidance is occasionally used for abscess detection and aspiration by our radiology colleagues, this is still a very uncommon application in the emergency department (ED). A case is presented of a patient with a difficult-to-drain, recurrent breast abscess. The consulting surgeon was unable to localize the abscess after 15 attempts at aspiration in the ED and requested ultrasound guidance from the attending emergency physician for the procedure. Drainage of the abscess was successfully completed in one attempt with real-time visualization and guidance of the needle. The consulting surgeon requested that ultrasound be available at the patient's follow-up visit to the ED.

Abscess↗

The pathology of REM sleep behavior disorder with comorbid Lewy body dementia.

A patient with REM sleep behavior disorder who subsequently developed probable Lewy body dementia is now reported to have a definite pathologic diagnosis of Lewy body dementia. Examination of brain revealed Lewy bodies as well as marked neuronal loss in brainstem monoaminergic nuclei-particularly locus coeruleus and substantia nigra-that inhibit cholinergic neurons in the pedunculopontine nucleus mediating atonia during REM sleep.

Aged↗

Granulomatous myositis, primary biliary cirrhosis, pancytopenia, and thymoma.

Granulomatous myopathies are rare. Most cases are associated with sarcoidosis. We report a case of granulomatous myopathy associated with primary biliary cirrhosis, pancytopenia, and thymoma. The literature in regard to granulomatous myopathy and its pathogenesis is reviewed. Intermittent pulsed intravenous methylprednisolone may be useful as maintenance therapy for granulomatous myopathy and other neuromuscular syndromes for patients intolerant of oral corticosteroids.

Adult↗

Clinical and pathologic features of focal myositis.

To clarify the nosology of focal myositis (FM), we report the clinical and pathologic features of eight patients presenting with focal enlargement of one muscle. Most patients improved without immunosuppressive therapy, and none developed polymyositis. Pathologic features were those of an inflammatory myopathy, with muscle fiber hypertrophy and moderate to severe inflammation. In most cases, a clustering of tightly packed muscle fibers, enveloped by a thick bundle of fibrosis, was associated with the diagnosis of FM. Immunohistochemistry showed T cell predominance within the interstitial infiltrates in all cases. No evidence of vasculitis was present. Our findings suggest that FM is a benign condition that has certain clinical features separating it from other inflammatory myopathies. Pathologic changes, such as large clusters of nesting muscle fibers surrounded by thick fibrosis, are more characteristic of FM than polymyositis.

Adolescent↗

Experimental gliosarcoma induces chemokine receptor expression in rat brain.

Macrophage/microglial infiltration is a characteristic feature of brain tumors. The functional role(s) of these cells is complex and could include both trophic and suppressive effects on tumors. Information has recently emerged about the molecular signals that regulate the accumulation and function of monocytes in pathological disorders. Recent data indicate that the chemokine, monocyte chemoattractant protein-1 (MCP-1), a potent monocyte activating and chemotactic factor, is a primary regulator of the macrophage response in brain tumors. We hypothesized that if MCP-1 regulates macrophage/microglial infiltration, then expression of the specific MCP-1 receptor, CCR2, will be induced in peritumoral tissue and/or within brain tumors. Identification of a specific receptor that is preferentially expressed in brain tumors could be important both in terms of tumor biology and as a potential therapeutic target. We used an established experimental gliosarcoma model, induced by intracranial transplantation of cultured 9L cells into adult rat brain, to test this hypothesis. RT-PCR analysis showed high levels of both MCP-1 and CCR2 mRNA and Western blot analysis demonstrated increased CCR2 protein in tumor extracts. Immunocytochemistry showed CCR2 immunoreactive microglia in peritumoral tissue and, unexpectedly, that intrinsic tumor cells, rather than monocytes, were the predominant source of CCR2. These results demonstrate that CCR2 expression is markedly upregulated in this brain tumor model.

Animals↗

Quantification of intramuscular nerves within the female striated urogenital sphincter muscle.

OBJECTIVE: To analyze the quantity and distribution of intramuscular nerves within the striated urogenital sphincter and test the hypothesis that decreased nerve density is associated with decreased striated sphincter muscle and cadaver age. METHODS: Thirteen cadaveric urethras (mean age 47 years, range 15-78 years) were selected for study. A sagittal histologic section was stained with S100 stain to identify intramuscular nerves. The number of times that a nerve was seen within the striated urogenital sphincter (nerve number) was counted. The number of axons within each nerve fascicle was also counted. Regression analysis of nerve density against muscle cell number and age was performed. RESULTS: Remarkable variation was found in the quantity of intramuscular nerves in the striated urogenital sphincter of the 13 urethras studied. The number of nerves ranged from 72 to 543, a sevenfold variation (mean 247.1 +/- standard deviation 123.2), and the range of number of axons was 431 to 3523 (2201 +/- 1152.6). The larger nerve fascicles were seen predominantly in the distal (13.1 +/- 5.7 axons per nerve) compared with the proximal part of the striated urogenital sphincter (1.2 +/- 2). Reduced nerve density throughout the striated urogenital sphincter correlated with fewer muscle cells (P =.02). Nerve density also decreased with advancing age (P =.004). CONCLUSION: Remarkable variation in the quantity of intramuscular nerves was found. Women with sparse intramuscular nerves had fewer striated muscle cells. Intramuscular nerve density declined with age.

Adolescent↗

Ultrasonographic diagnosis of testicular torsion by emergency physicians.

Testicular torsion has an incidence of one case per 4,000 men/boys. Most frequently affected are pubescent boys. Average testicular salvage rate is only 50%, and infertility can result Testicular torsion remains problematic for emergency physicians (EPs) as clinical diagnosis can be difficult and other testicular pathology can present similarly. In many institutions there are delays in obtaining Doppler or Scintigraphy studies during off-hours. We report two cases of testicular torsion diagnosed by the treating EPs using power Doppler in the emergency department (ED). Rapid diagnosis of torsion led to successful salvage of the affected testicle in both cases. These represent the first cases for emergency screening ultrasound examinations (ESUEs) of testicular torsion in the literature. Rapid technological advances over the last decade have brought portable equipment with high-resolution capability to the bed-side for EPs, who should consider using it more frequently to evaluate testicular torsion.

Adolescent↗