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Biomedical subjects

M D Smith

Publications and source records attributed to M D Smith.

At least 181 records · Page 10Linked to original sources

Efficacy and safety of oral sildenafil (Viagra) in men with erectile dysfunction caused by spinal cord injury.

OBJECTIVE: To evaluate the efficacy and safety of 50-mg doses of sildenafil during a 28-day period in patients with erectile dysfunction caused by spinal cord injury (cord level range, T6 through L5). BACKGROUND: Sildenafil is an orally active, potent, and selective inhibitor of phosphodiesterase type 5, an important regulator of cyclic guanosine monophosphate in the human corpus cavernosum. METHODS: To be included in this double-blind, placebo-controlled study, all patients had to be able to achieve at least a partial reflexogenic erectile response to penile vibratory stimulation. The study utilized a single triangular sequential trial design. A total of 27 patients were randomized to receive 50 mg of sildenafil or placebo, taken orally as required (not more than once daily) approximately 1 hour before sexual activity. RESULTS: After 28 days of treatment, nine of 12 patients (75%) on sildenafil and one of 14 patients (7%) on placebo reported that treatment had improved their erections (p=0.0043). Furthermore, eight of 12 patients (67%) on sildenafil and two of 13 patients (15%) on placebo indicated that they wished to continue treatment (p=0.018). A significant improvement in satisfaction with their sex life was reported by patients taking sildenafil (p=0.012). No patients discontinued treatment due to adverse events. CONCLUSION: Oral sildenafil, taken as required (not more than once daily), significantly improves the quality of erections and satisfaction with sex life in men with erectile dysfunction caused by a spinal cord injury between T6 and L5.

Administration, Oral↗

Assessment of left ventricular diastolic function after single lung transplantation in patients with severe pulmonary hypertension.

OBJECTIVES: This study was designed to observe left ventricular filling by Doppler echocardiography before and after single lung transplantation in patients with severe pulmonary hypertension. BACKGROUND: Right ventricular pressure overload causes the deformation of the left ventricle by septal flattening toward its cavity, which may result in impaired left ventricular early filling. Recent studies have demonstrated the ability of single lung transplantation to restore right ventricular function in patients with severe pulmonary hypertension. However, changes in left ventricular filling after single lung transplantation have not been well studied. METHODS: We performed Doppler echocardiography in nine patients with severe pulmonary hypertension before, early (<3 months), and late (>1 year) after single lung transplantation. The study group consisted of eight female patients and one male patient with mean age of 32 years (range, 15 to 48 years). Six patients were diagnosed as having primary pulmonary hypertension and three as having secondary pulmonary hypertension. Nine age-matched normal subjects served as a control group. Doppler measurements included the following: transmitral flow early (E) and atrial (A) velocities, integrals (Ei and Ai), and left ventricular isovolumic relaxation time. The ratio of E/A and atrial filling fraction (Ai/Ei+Ai, AFF) were also determined. Left ventricular geometry was assessed from mid-short axis view with a circular shape factor (CSF). RESULTS: Early after lung transplantation, the left ventricular geometry became more circular with CSF (mean+/-SD) increasing from 0.63+/-0.09 to 0.88+/-0.05 (p<0.05). However, impaired early filling persisted in the patient group (E/A 0.7+/-0.1 vs preoperative 0.6+/-0.1, AFF 0.61+/-0.1 vs 0.64+/-0.1; both p=not significant). One year later, the left ventricular filling had returned to normal range with E/A 1.4+/-0.6 and AFF 0.35+/-0.1. CONCLUSIONS: This study observed that the impaired left ventricular early filling persisted shortly after single lung transplantation in patients with severe pulmonary hypertension, despite findings that left ventricular geometry was restored earlier after reversal of pulmonary hypertension. The abnormal filling pattern appeared to be resolved 1 year later. The findings suggest the impaired early filling may be caused by intrinsic left ventricular abnormalities other than ventricular interaction in these patients.

Adolescent↗

Accuracy of SPECT scanning in diagnosing pseudoarthrosis: a prospective study.

The present study attempted to analyze the efficacy of single photon emission computed tomography (SPECT) in diagnosing pseudoarthrosis after fusion using surgical exploration as the gold standard. This study examined the SPECT scans of 38 patients before they underwent surgical exploration of their fusion mass for suspected pseudoarthrosis or in conjunction with instrumentation removal. Surgical findings were compared with the radiologists' findings to determine the efficacy of SPECT in diagnosing pseudoarthrosis. Radiographic determination of pseudoarthrosis has been difficult after attempted fusion of the spine. Multiple radiographic modalities have been touted as accurate depicters of the failure of spinal fusion. However, no method has been found to be highly accurate in the clinical setting. Thirty-eight patients (mean age = 42.8, 21 males/17 females, 35 of 38 with instrumentation) underwent SPECT scans before surgical exploration of their fusion mass for suspected pseudoarthrosis or in conjunction with instrumentation removal as part of this prospective study. The average interval from their fusion procedure until their SPECT scan was 23.9 months (range, 9-120 months). All surgical findings were recorded with regard to solidity of the fusion and the level of the possible pseudoarthrosis. All SPECT scans were read at a time after surgery by an independent nuclear radiologist who had not read their SPECT scans before surgery and who did not know the results of exploration. Results of the radiologist's reading were then compared with surgical exploration findings, and sensitivity and specificity was calculated. There were 24 solid fusions and 14 pseudoarthroses. SPECT scans correctly identified 7 of the 14 pseudoarthroses and 14 of the 24 solid fusions. This represents a sensitivity of 0.50 and a specificity of 0.58. SPECT scanning correctly diagnosed the one solid fusion and two pseudoarthrosis patients in the three patients who had no instrumentation. This study demonstrates that SPECT scanning alone is inaccurate in diagnosing pseudoarthrosis when using surgical exploration as the gold standard. Given recent pressures for cost containment, we cannot recommend SPECT scanning as a routine modality for use in the diagnosis of pseudoarthrosis. We cannot define the accuracy of SPECT scanning used together with computed tomography scans, plain films, or other radiographic modalities in the diagnosis of pseudoarthrosis.

Adult↗

Cell detachment during sinusoidal reperfusion after liver preservation: an in vitro model.

BACKGROUND: Sinusoidal endothelial cells (SEC) are significantly more vulnerable to cold storage and reperfusion than hepatocytes. Swelling and disruption of the sinusoidal lining induce the microcirculatory disturbances seen after reperfusion. In this article, the investigation of a method to assess the adhesion and morphology of SEC in vitro during reperfusion after preservation is described. METHODS: Time-lapse video microscopy analysis was performed and cell detachment rates and cell lengths were determined. Preservation intervals between 6 and 24 hr and flow rates ranging from 3 L/min to 9 L/min (resulting in shear stresses between 5.1 and 15.3 dynes/cm2 on the monolayer surface) during reperfusion period were compared. SEC that were stored for 6 hr in University of Wisconsin solution and nonpreserved control cultures were compared. RESULTS: Varying the preservation intervals from 6 hr to 24 hr during reperfusion at a flow rate of 3 L/min led to increased cell erosion rates (6 hr, 35.5+/-15.2%; 12 hr, 38.0+/-7.6%; 18 hr, 54.3+/-5.7%; 24 hr, 76.7+/-6.7%; nonpreserved cells, 3.4+/-3.4%). Storage periods from 12 hr to 24 hr led to significantly higher cell detachment rates than occurred in nonpreserved cells. CONCLUSIONS: This method allows the investigation of the adhesion capability and morphology of individual cells in vitro. Indications of the kind of preservation/reperfusion injury that occurs after treatment with several preservation solutions and the resultant repair behavior can be obtained.

Adenosine↗

Coordinate induction of the three neurofilament genes by the Brn-3a transcription factor.

The POU domain transcription factor Brn-3a is able to stimulate neurite outgrowth when overexpressed in the neuronal ND7 cell line, whereas the closely related Brn-3b factor does not have this effect. We show that Brn-3a overexpression also enhances the expression of the three neurofilament genes at both the mRNA and protein levels, whereas Brn-3b overexpression has no effect. In addition Brn-3a activates the three neurofilament gene promoters in co-transfection assays in both neuronal and non-neuronal cells. As observed for enhanced neurite outgrowth, the stimulation of neurofilament gene expression and activation of the neurofilament gene promoters is observed with the isolated POU domain of Brn-3a. A single amino acid change in the POU homeodomain of Brn-3a to the equivalent amino acid in Brn-3b abolishes its ability to activate the neurofilament promoters, whereas the reciprocal change converts Brn-3b to an activator of these promoters.

Animals↗

The long-term follow-up of patients with Klippel-Feil syndrome and congenital scoliosis.

STUDY DESIGN: This study evaluated the long-term results of Klippel-Feil syndrome in patients with congenital scoliosis. OBJECTIVES: To determine the incidence of cervical and cervical-related symptoms of patients who have Klippel-Feil syndrome associated with congenital scoliosis. SUMMARY OF BACKGROUND DATA: Many authors have described the association of Klippel-Feil syndrome and congenital scoliosis. In this population of patients, cervical lesions often are discovered incidentally. The significance of these lesions is unknown. METHODS: Thirty-two patients with congenital scoliosis and Klippel-Feil syndrome were observed for more than 10 years. They were questioned specifically about cervical and cervical-related symptoms. All patients had sequential cervical radiographs and physical examinations. RESULTS: Despite rather dramatic radiographic appearances, only seven (22%) of the 32 patients had cervical or cervical-related symptoms, with two patients requiring surgery for their cervical lesions. The extent of the deformities and the average number of cervical vertebrae fused and cervical fusion-patterns were statistically similar between the symptomatic and asymptomatic groups. Patients fused to the cervicothoracic junction for management of their deformities had a significantly increased incidence of cervical symptoms. Also, patients with congenital stenosis had a significantly greater incidence of upper extremity pain. CONCLUSIONS: Only a small number of patients with Klippel-Feil syndrome and congenital scoliosis developed cervical symptoms. No fusion pattern that placed the patient at greater risk for developing symptoms could be identified. Factors that did lead to a greater incidence of cervical symptoms were fusion to the cervicothoracic junction and congenital cervical stenosis.

Adult↗

Inhibition of neuronal process outgrowth and neuronal specific gene activation by the Brn-3b transcription factor.

The differentiation of the ND7 neuronal cell line to a nondividing phenotype bearing numerous neurite processes is accompanied by a dramatic increase in the levels of the activating POU family transcription factor Brn-3a and a corresponding fall in the levels of the closely related inhibitory factor Brn-3b. We have previously shown that the artificial overexpression of Brn-3a in these cells can induce neurite outgrowth and the activation of genes encoding synaptic vesicle proteins in the absence of a differentiation-inducing stimulus. Here we show that overexpression of Brn-3b can reduce process outgrowth and synaptic vesicle gene expression following exposure to a stimulus which would normally induce differentiation. These inhibitory effects are abolished by altering a single amino acid in the POU homeodomain of Brn-3b to its equivalent in Brn-3a. The converse mutation in Brn-3a allows it to inhibit process outgrowth in response to a differentiation-inducing stimulus. Hence a single amino acid difference results in these closely related factors having opposite effects and allows the balance between them to regulate differentiation.

Animals↗

Effects of pulse methylprednisolone on inflammatory mediators in peripheral blood, synovial fluid, and synovial membrane in rheumatoid arthritis.

OBJECTIVE: To establish whether the clinical efficacy of pulse methylprednisolone (MP; 1,000 mg intravenously) is related to the modulation of proinflammatory cytokines within the peripheral blood, synovial membrane, or synovial fluid compartments. METHODS: Eighteen patients with active rheumatoid arthritis (RA) were studied. Peripheral blood (11 patients) and knee synovial fluid (9 patients, 10 knees) were obtained before and at 4 and 24 hours after MP therapy. Interleukin-1beta (IL-1beta), IL-8, and tumor necrosis factor alpha (TNFalpha) were measured by enzyme-linked immunosorbent assay and biologic assays; prostaglandin E2 (PGE2) was measured by competitive radioimmunoassay. In 10 patients, arthroscopically directed synovial biopsies were obtained before and at 24 hours after treatment, at disease relapse (4 patients), and after retreatment (1 patient). Membranes were stained by immunohistochemical techniques with monoclonal antibodies against TNFalpha, IL-8, IL-1beta, and the IL-1 receptor antagonist protein (IL-1Ra). RESULTS: MP therapy was associated with a rapid (within 24 hours) and substantial decrease in the expression of TNFalpha in the lining and sublining regions of the synovial membrane, as well as substantial decreases in the levels of TNFalpha in serum and synovial fluid. There was also reduced IL-8 expression in the synovial lining, as well as reduced synovial fluid IL-8 levels. No effect on synovial membrane IL-1beta and IL-1Ra or synovial fluid IL-1beta and PGE2 was found. CONCLUSION: MP therapy rapidly reduces IL-8 and TNFalpha levels in the synovial compartment, with cytokine changes in the serum and synovial fluid reflecting the changes in the synovial membrane. Alterations in TNFalpha expression in the synovial membrane correlated with clinical response to, and subsequent relapse after, MP therapy.

Aged↗

Systemic liberation of interleukin-8 in the perioperative phase of liver transplantation.

Serum levels of interleukin-8 (IL-8) were investigated in the perioperative phase of liver transplantation (LTx) in order to help determine whether this cytokine might serve as a parameter for preservation injury. In a study of 45 patients undergoing LTx, systemic IL-8 was estimated at the end of the anhepatic phase, at 30, 60, and 120 min after reperfusion of the graft, and 24 h and 7 days after LTx. A maximum mean concentration of 665 +/- 135 pg/ml was seen 60 min after LTx. The minimum was found on the 1st postoperative day (POD 1): 328 +/- 33 pg/ml. Significant changes were found between 60 min and PODs 1 and 7, as well as between 120 min and POD 1. Differences in cold ischemia time were not found to be significant. We conclude that monitoring of systemic IL-8 levels is not useful in the development of new liver preservation concepts.

Adult↗

Little knowledge and limited practice: emergency contraceptive pills, the public, and the obstetrician-gynecologist.

OBJECTIVE: To assess Americans' knowledge and attitudes about emergency contraceptive pills and the knowledge, attitudes, and practices of obstetrician-gynecologists with respect to emergency contraceptive pills. METHODS: A random sample of a national cross-section of 2002 Americans, age 18 and older, including 1000 women and 1002 men, was surveyed by telephone between October 12 and November 13, 1994. A nationally representative sample of 307 obstetrician-gynecologists, whose names were drawn from the American Medical Association Physicians' Masterfile, was surveyed by telephone between February 1 and March 21, 1995. Both Surveys addressed knowledge and attitudes about unplanned pregnancy and contraception options, including emergency contraception. Despite response rates of 50 and 77%, respectively, both unweighted samples closely mirror the populations from which they were drawn. RESULTS: Americans are not well informed about emergency contraceptive pills. Only 36% of respondents indicated that they knew "anything could be done" within a few days after unprotected sex to prevent pregnancy. Fifty-five percent said they had "heard of" emergency contraceptive pills, and only 1% had ever used them. Ninety-nine percent of obstetrician-gynecologists reported being "familiar" with emergency contraceptive pills. Twenty-two percent were "somewhat familiar." Among those who said they were "very familiar" with the method (77%), the majority considered emergency contraceptive pills to be "very safe" (88%) and "very effective" (85%). Overall, 70% of obstetrician-gynecologists surveyed said they had prescribed emergency contraceptive pills within the last year, but on an infrequent basis; 77% of those who prescribed emergency contraceptive pills did so five or fewer times. CONCLUSION: Public knowledge about the availability and use of emergency contraceptive pills is limited, as is the practice of prescribing the pills among obstetrician-gynecologists. Because patients rely on health care providers for information on birth control, health care providers can improve knowledge about the availability of emergency contraceptive pills among their patients.

Adult↗

Polymerase chain reaction for the detection of Burkholderia pseudomallei.

Melioidosis is a potentially lethal infection of humans and animals in Southeast Asia and northern Australia. Current methods for detection of the causative organism, Burkholderia pseudomallei, lack both speed and sensitivity. We report the development of a highly sensitive polymerase chain reaction-based method that can detect as few as 35 colony-forming units of B. pseudomallei/mL in saline suspensions. This polymerase chain reaction test also detected the presence of B. pseudomallei DNA in culture-negative splenic tissue obtained from mice infected with the organism, but without clinical evidence of disease. Specificity has been confirmed using a variety of pathogenic and nonpathogenic organisms, including B. mallei, B. cepacia, and Pseudomonas species. The clinical usefulness of this test should be assessed prospectively and compared with conventional diagnostic techniques.

Animals↗

Musculoskeletal pain in cardiac ultrasonographers: results of a random survey.

Myalgias and arthralgias are common among workers whose jobs require repetitive isometric maneuvers or malalignment of body position. However, few systematic studies have been performed to evaluate the frequency of these complaints among cardiac ultrasonographers. Therefore the purpose of this study was to determine the prevalence of musculoskeletal pain (MSP) among ultrasonographers and to identify risk factors related to their occurrence. Two hundred twenty ultrasonographers randomly chosen from a list of more than 1600 active members of the American Society of Echocardiography were mailed surveys consisting of 22 questions. Included were questions regarding height, age, years of experience, frequency and type of physical exercise, and job-related parameters such as a number of scans per day, scanning from right or left side of bed, number of hours, bed type, type of equipment, and manual or self-propelled machines. Respondents were asked whether they had had back, neck, or shoulder pain related to their profession and to describe treatment rendered and its effectiveness. One hundred thirteen (51%) of 220 ultrasonographers responded to the survey. Ninety (80%) of 113 respondents reported new pain that was not present before they began scanning, with 42 of this group (46%) requiring either physiotherapy (n = 17) or medication (n = 23). Treatment was believed to be helpful in 63% of cases. Factors found to have a positive relationship to MSP included ultrasonographer height less than 63 inches, performing 100 or more scans per month, average scan time of 25 minutes or more per patient, and use of manually propelled machines (each p < 0.05). Factors found to have no relationship to MSP included age, type of equipment, right or left scan position, physical conditioning, bed type, and time between patients. Musculoskeletal pain is prevalent among cardiac ultrasonographers, and may have specific work-related factors for its occurrence.

Adult↗