Search PubMed⌕ Search

Biomedical subjects

S L Brown

Publications and source records attributed to S L Brown.

At least 55 records · Page 3Linked to original sources
PubMed1999

Role of serology in the diagnosis of Lyme disease.

Numerous concerns regarding the potential for misdiagnosis of Lyme disease using commercial assays have been voiced by the US Food and Drug Administration (FDA). We attempted to clarify the clinical value of serologic testing for Lyme disease using the results of commonly marketed assays for detecting antibody to Borrelia burgdorferi, the organism that causes Lyme disease. We reviewed published studies on B burgdorferi test performance published through 1998, package insert labeling from FDA-cleared test kits for B burgdorferi, and Lyme Disease Survey Set LY-A from the College of American Pathologists. We assessed the sensitivity and specificity of commercial serologic tests (enzyme-linked immunosorbent assay [ELISA], immunofluorescence antibody [IFA], and immunodot) for diagnosis of Lyme disease. To reduce this risk of misdiagnosis, it is important that clinicians understand the performance characteristics and limitations of these tests. These tests, in common use in clinical or commercial laboratories, should be used only to support a clinical diagnosis of Lyme disease, not as the primary basis for making diagnostic or treatment decisions. Serologic testing is not useful early in the course of Lyme disease because of the low sensitivity of tests in early disease. Serologic testing may be more useful in later disease, at which time sensitivity and specificity of the test are improved. Positive or equivocal results on an ELISA, IFA, or immunodot assay requires supplemental testing with a Western blot assay. A negative result on the Western blot or ELISA indicates that there is no serologic evidence of infection by B burgdorferi at the time the sample was drawn.

Antibodies, Bacterial↗
PubMed1999

Magnetic resonance imaging of perfusion in rat cerebral 9L tumor after nicotinamide administration.

PURPOSE: To investigate the effect of nicotinamide on normal brain and 9L tumor blood flow in the rat using magnetic resonance imaging (MRI) and arterial spin tagging. METHODS AND MATERIALS: Using MRI at 7 Tesla, measurements of blood perfusion were determined from two-dimensional maps of intracerebral 9L rat tumors and normal Fischer rat brains. The spatial and temporal influence of nicotinamide, 500 mg/kg i.p., on cerebral blood flow (CBF) was studied in normal brain and tumors between 5 and 21 days after tumor implantation. The MRI CBF measurements employed a variable tip-angle-gradient-recalled echo (VTA-GRE-CBF) readout of the magnetization of the tissue slice. The VTA-GRE-CBF required 8 minutes for a blood flow image with inplane resolution of 250 microm x 500 microm x 2 mm. RESULTS: Normal brain blood flow decreased following the administration of nicotinamide. In contrast, tumor blood flow remained unaffected in the time following nicotinamide administration. Consequently, the blood flowing in the tumor relative to that in normal brain demonstrated a significant and selective increase in response to nicotinamide administration. Relative tumor blood flow increased at 10 minutes after nicotinamide injection compared with predrug levels and remained elevated for at least 1 hour. CONCLUSION: The results suggest that nicotinamide will not enhance radiosensitivity of brain tumors. The results support the use of nicotinamide to improve delivery of anticancer therapeutics through its ability to selectively increase tumor blood flow relative to that in normal brain.

Animals↗
PubMed1999

T1 and magnetization transfer at 7 Tesla in acute ischemic infarct in the rat.

T1 and magnetization transfer at a field strength of 7 Tesla were used to discriminate between water accumulation and protein mobilization in tissue undergoing infarction. Twelve rats subjected to acute stroke via intralumenal suture occlusion of the middle cerebral artery, and 19 controls, were studied. In MRI studies to 6 hr post-ictus, serial data acquisition allowed the measurement of cerebral blood flow (CBF), apparent diffusion coefficient of water (ADCw), equilibrium magnetization (M0) and T1, and equilibrium magnetization and T1 under an off-resonance partial saturation of the macromolecular pool (Msat and T1sat). Using these parameters, the apparent forward transfer rate of magnetization between the free water proton pool and the macromolecular proton pool, k(fa), was calculated. Regions of interest (ROIs) were chosen using depressed areas in maps of the ADCw. T1 measurements in bovine serum albumin at 7T were not affected by the mobility of the macromolecular pool (P > 0.2), but magnetization transfer between free water and protein depended strongly on the mobility of the macromolecular pool (P < 0.001). For 6 hr after ictus, k(fa) uniformly and strongly decreased in the region of the infarct (P < 0.0001). Ratios (ischemic/non-ischemic) of parameters M0, Msat, T1, and T1sat all uniformly and strongly increased in the infarct. The ratio T1/T1sat in the region of infarction showed that a progressive accumulation of free water in the region of interest was the major (>80%) contribution to the decrease in k(fa). There also existed a small contribution due to changes at the water-macromolecular interface, possibly due to proteolysis (P = 0.005).

Acute Disease↗
PubMed1999

Penile fracture and testicular rupture.

Traumatic injuries to the penis and testicles are uncommon, likely due to the well-protected location and degree of mobility of these organs. Because of this the management of these injuries has historically been controversial. However, current literature supports immediate evaluation and surgical repair of these traumatic injuries to prevent complications such as erectile dysfunction or testicular loss. Herein the diagnostic and therapeutic options for both traumatic penile fracture and testicular rupture are reviewed with emphasis on immediate evaluation and repair.

Humans↗
PubMed1999

Limitations of routine spiral computerized tomography in the evaluation of bladder trauma.

PURPOSE: We evaluate the accuracy of spiral computerized tomography (CT) in diagnosing traumatic bladder rupture. MATERIALS AND METHODS: Medical records of 24 consecutive patients diagnosed with traumatic bladder rupture at our level 1 trauma center from 1993 to 1998 were retrospectively reviewed. Of the patients 15 underwent retrograde cystography and spiral CT of the abdomen and pelvis. The results of these imaging studies were compared. RESULTS: Retrograde cystography successfully diagnosed all cases of bladder rupture and correctly classified injuries confirmed surgically. Spiral CT successfully diagnosed 9 of 15 bladder ruptures (60%), and correctly classified 4 of 5 intraperitoneal (80%) and 6 of 11 extraperitoneal (55%) ruptures. CONCLUSIONS: Spiral CT is less accurate than retrograde cystography in diagnosing traumatic bladder rupture.

Adolescent↗
PubMed1999

Cocaine associated priapism.

PURPOSE: Cocaine abuse is an ongoing epidemic in the United States. Priapism associated with cocaine use has been reported only twice in the urological literature. To our knowledge we report the first series of priapism associated with cocaine use and the first case associated with the use of this drug in its solid form, known as crack. MATERIALS AND METHODS: We retrospectively reviewed the presentation of 3 patients to our emergency department within the last year. Each patient presented with priapism and no identifiable predisposition other than the use of cocaine within 24 hours, as evident on positive urine toxicology. RESULTS: Each patient delayed seeking treatment, which added to the complexity of therapy. Intracavernosal aspiration and irrigations failed in all 3 cases. Cavernous spongiosal shunting failed in the first 2 cases. Cases 2 and 3 were complicated by the high flow variant of priapism. Case 1 ultimately required partial penectomy for infected, gangrenous, distal penile tissue. CONCLUSIONS: It appears that cocaine can be a cause of refractory priapism and treatment can be challenging. We suggest that urine toxicology screening be considered in such cases. The identification of underlying cocaine abuse is important in preventing priapism recurrence in these patients.

Adult↗
PubMed1999

Expression of plasminogen activator inhibitor type I in genotyped human endothelial cell cultures: genotype-specific regulation by insulin.

Patients with non-insulin-dependent diabetes mellitus frequently have been associated with elevation in plasma levels of PAI-1. Part of the variations in individual plasma PAI-1 levels have been attributed to variations in the PAI-1 gene. In order to determine whether insulin regulates PAI-1 expression in a genotype-specific manner, individual human umbilical vein ECs (HUVECs) were genotyped using a Hind III RFLP and incubated in the absence/presence of insulin. Treatment of 1/1 PAI-1 genotype HUVECs with insulin increased secretion of PAI-1 antigen approximately 1.7 to 2.2-fold and mRNA levels were increased approximately 1.8 to 2.8-fold. Treatment of HUVECs with actinomycin D or puromycin completely abolished the induction of PAI-1 by insulin. The nuclear run-on assays indicated approximately 3-4 fold increase in PAI-1 transcription rates. These in vitro studies with the 1/1 PAI-1 genotyped cultured HUVECs, suggests that hyperinsulinemia may be expected to increase EC PAI-1 synthesis in those patients with the responsive 1/1 genotype.

Cells, Cultured↗
PubMed1999

Medication adherence in patients with HIV infection: a comparison of two measurement methods.

Two measurements of adherence, patient self-report and electronic measurement by the Medication Event Monitoring System (MEMS), were compared in a 3-month adherence study of 44 HIV-infected patients who had been placed on regimens that included protease inhibitors (PIs). The dose percentage and degree of clinically significant dosing time fluctuation were calculated monthly. The mean dose percentage by self-report versus MEMS was 97.5% versus 90.3% during month 1 of adherence monitoring, 96.5 versus 90.1% during month 2, and 98.4% versus 92.8% during month 3. Thirty-two percent of patients taking PIs and 21% of patients taking nucleoside analogues demonstrated clinically significant dosing time fluctuation. Our data confirm that self-reports of adherence overestimate true adherence behavior, and patients' self-reports of dosing times may not accurately reflect their deviation from those times.

Adult↗
PubMed1998

The potentiation of radiation response in human colon carcinoma cells in vitro and murine lymphoma in vivo by AG337 (Thymitaq), a novel thymidylate synthase inhibitor.

PURPOSE: To determine whether the administration of Thymitaq (AG337), a selective inhibitor of thymidylate synthase (TS), enhances radiation-induced cytotoxicity in vitro and increases tumor control rate in vivo. METHODS AND MATERIALS: In vitro studies were carried out with HT-29 human colon carcinoma cells. In vivo studies were carried out using L5178Y(TK-) murine lymphoma implanted in DBA/2 mice. RESULTS: Pretreatment of HT-29 cells to nontoxic concentration of AG337 (<10 microM) for a short period of time (< 24 h) significantly enhanced the radiation induced cell lethality. The radiosensitizing enhancement ratio was 1.7. In contrast, there was no increased cell killing when the drug was exposed immediately after irradiation. In studies using L5178Y(TK-) tumors, the drug alone (50 mg/kg, i.p. x 5) had a minimal tumor growth delay, while a single dose of radiation (17 Gy) resulted in < 10% tumor control at day 30. When radiation and drug (17 Gy + AG337, 50 mg/kg, i.p. x 5) were combined, the tumor control rate reached 90% at Day 30. Using the local tumor control assay (TCD50), the radiation dose modification factor after a single dose of radiation was 2.6. CONCLUSION: The concentration of drug shown to be of radiosensitizing value in the in vivo studies is achievable in humans. The results of the present study further supports the potential utility of AG337 in the treatment of human tumors by radiotherapy.

Animals↗
PubMed1998

Inguinal scrotal incision for penile fracture.

PURPOSE: We report a new incision for repair of penile fracture. MATERIALS AND METHODS: We describe 2 cases in which the inguinal scrotal incision was used for repair of penile fracture. The preoperative evaluation as well as the technical case and rationale for use of this incision are discussed. RESULTS: Preoperative cavernosogram delineated the site of the fracture. Immediate repair of the fracture using the inguinal scrotal incision was successful. CONCLUSIONS: The inguinal scrotal incision should be entertained for cases of penile fracture. It avoids incision into markedly edematous penile skin and allows for excellent visualization of the fracture site.

Adult↗
PubMed1998

Hepatotoxicity related to intracavernous pharmacotherapy with papaverine.

OBJECTIVES: To determine the incidence of hepatotoxicity related to self-administration of intracavernous papaverine or papaverine/phentolamine (bimix). METHODS: From October 1994 through June 1996, we retrospectively reviewed the medical records of 71 consecutive patients diagnosed with organic erectile dysfunction (ED) and receiving intracavernous injection therapy. Inclusion criteria were documentation of normal baseline liver function tests (LFTs), a minimum of 6 months of follow-up that included LFTs, at least one self-injection every 2 weeks, and no other prior or concurrent treatment for ED. Thirty evaluable patients satisfied the inclusion criteria and formed group 1. Mean age was 63 years (range 40 to 77), mean follow-up was 18 months (range 6 to 32), and mean number of injections per month was 5.7 (range 3 to 12). An age-matched population of 20 patients (mean age 69 years, range 46 to 90) without ED but with similar comorbid risk factors formed the control group (group 2). All patients in group 2 had routine long-term follow-up of LFTs (mean 52 months, range 10 to 1 14). RESULTS: Two patients (6.67%) from group 1 had elevated LFTs during treatment: one experienced a mild elevation in alanine aminotransferase and the other developed transient elevations of total bilirubin and aspartate aminotransferase 6 months after beginning therapy. Both patients reported a history of alcohol abuse. Both patients remained asymptomatic. Neither patient required discontinuation of therapy. One patient (5%) from group 2 developed an elevation of total bilirubin at a follow-up of 12 months. CONCLUSIONS: Routine monitoring of LFTs is probably unnecessary during intracavernous pharmacotherapy. Patients with a history of alcohol abuse or liver disease, however, should be followed up more closely when papaverine is selected for intracavernous injection. In these patients, LFTs should be obtained before initiating treatment and at 6-month intervals.

Adult↗
PubMed1998

Ultrasound echogenicity in experimental venous thrombosis.

This study characterizes the echogenicity of experimentally induced venous thrombosis. Venous duplex imaging (Diasonics Spectra) was performed of the rat (n 12) and primate (n 3) inferior vena cava (IVC). Thrombosis was induced by IVC ligation at the level of the renal veins (rat, baboon) or balloon occlusion (baboon) of the IVC at the renal vein and iliac vein bifurcation level. Sham-treated rats served as controls. B-mode images were stored for off-line computer analysis. Fixed depth gain control curves allowed for measuring gain-corrected echogenicity units over the IVC in both a longitudinal and transverse orientation. In rat studies, thrombus was removed at time of euthanasia and dissolved, allowing for fibrin monomer determination using a chromogenic assay. Echogenicity values generally increased over time in both rat and primate studies. Significant differences between ligated and sham-treated rats were noted at each time point measured (6 h, 2 days, and 6 days after IVC ligation) and fibrin monomer values correlated (p < 0.05) with echogenicity units. In primate studies, echogenicity values significantly were different from baseline values at all time points measured (6 h, 2 days, 6 days, and 13 days after thrombus induction). Duplex ultrasound can be used to quantitate thrombus echogenicity, which correlates to fibrin content. Such measurement may potentially allow for improved thrombus age determination and the noninvasive quantitation of thrombus progression/resolution.

Animals↗
PubMed1998

Limitations of routine spiral computerized tomography in the evaluation of blunt renal trauma.

PURPOSE: We have observed that injury to the renal collecting system may be missed during routine abdominal spiral computerized tomography (CT) for trauma. A definitive protocol for spiral CT has been established to identify all cases of renal collecting system injury. MATERIALS AND METHODS: A retrospective review of 35 consecutive cases of blunt renal trauma evaluated with spiral CT between 1994 and 1997 at our Level I trauma center was performed. Each patient received 100 cc intravenous contrast at 2 cc per second. There was a 60-second delay after the start of contrast infusion before scanning was initiated. RESULTS: Of the 35 cases 3 (8.6%) injuries to the renal collecting system were detected on delayed scans obtained after the initial CT failed to demonstrate contrast extravasation. Therefore, at our institution we have modified the protocol for spiral CT for abdominal trauma by repeating scans of the kidneys after the initial scans are completed. CONCLUSIONS: Injury to the renal collecting system may be missed during routine spiral CT, thereby incorrectly under staging renal trauma. In all cases of suspected blunt renal trauma evaluated with spiral CT repeat scans of the kidneys should be performed.

Adolescent↗
PubMed1998

Covalent polymyxin B conjugate with human immunoglobulin G as an antiendotoxin reagent.

Polymyxin B (PMB) is a cyclic decapeptide antibiotic which also binds and neutralizes endotoxin. Unfortunately, PMB can be considerably nephrotoxic at clinically utilized doses, thereby limiting its utility as a therapeutic antiendotoxin reagent. We sought to change the pharmacokinetics and toxicity profile of PMB by covalently linking it to a human immunoglobulin G (IgG) carrier. Conjugates of PMB with IgG were prepared by EDAC [1-ethyl-3-(3-dimethylaminopropyl) carbodiimide]-mediated amide formation. Analysis by dot enzyme-linked immunosorbent assay with an anti-PMB monoclonal antibody showed that the purified conjugate contained bound PMB. The IgG-PMB conjugate reacted with lipid A and J5 lipopolysaccharide in Western blot assays in a manner comparable to that of whole antiserum with anti-lipid A reactivity; unconjugated IgG had no reactivity. The PMB bound in the conjugate retained its endotoxin-neutralizing activity compared to that of unbound PMB as evidenced by its dose-dependent inhibition of tumor necrosis factor release by endotoxin-stimulated human monocytes in vitro; unconjugated IgG had no activity. By this assay, the PMB-IgG conjugate was determined to have approximately 3.0 microg of bound functional PMB per 100 microg of total protein of conjugate (five molecules of PMB per IgG molecule). The PMB-IgG conjugate was also bactericidal against clinical strains of Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae relative to unconjugated IgG with MBCs of <4 microg of conjugate per ml for each of the tested strains. The conjugate appeared to be nontoxic at the highest doses deliverable and provided statistically significant protection from death to galactosamine-sensitized, lipopolysaccharide-challenged mice in a dose-dependent fashion when administered prophylactically 2 h before challenge. However, neither free PMB nor the PMB-IgG conjugate could protect mice challenged with endotoxin 2 h after administration. This suggests that these reagents can play a role in prophylaxis but not in therapy of sepsis. These experiments demonstrated that the PMB-IgG conjugate retains bound yet functional PMB as evidenced by its endotoxin-neutralizing activity both in vitro and in vivo. Further work is required to define the role that this or related conjugate compounds may play in the prophylaxis of endotoxin-mediated disease.

Anti-Bacterial Agents↗
PubMed1998

Silicone breast implants and autoimmune disease.

In 1992, the Food and Drug Administration requested a voluntary moratorium on the scale and implantation of silicone-gel-filled breast implants because of growing concern over the lack of scientific and clinical data supporting their safety and effectiveness. Breast implants had been reported to cause serious local complications, and new questions about breast implants and increased risk for autoimmune disease, including the rare but sometimes fatal connective tissue disease scleroderma, were also raised. Since that time, clinical studies have focused on the adjuvant effect of silicone and of potential autoantibody production. Epidemiologic studies have ruled out a large increased risk for connective tissue disease overall in women with breast implants, but samples were too small to rule out an increase in rare connective tissue diseases. Nor were studies properly designed to address whether an atypical syndrome might develop in women with breast implants. Meta-analyses of these studies cannot remedy their underlying methodologic weaknesses. While the question of whether rare connective tissue disease is associated with breast implants may never be answered definitively, recent progress in identifying new syndromes such as fibromyalgia and chronic fatigue syndrome may provide an insight into methodology for evaluating the existence of a silicone-related syndrome in women with breast implants.

Autoimmune Diseases↗