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Biomedical subjects

M S Cohen

Publications and source records attributed to M S Cohen.

At least 19 recordsLinked to original sources

Genotypic analysis of the protease and reverse transcriptase of HIV type 1 subtype C isolates from antiretroviral drug-naive adults in Malawi.

The protease (PR) and reverse transcriptase (RT) regions of HIV-1 isolates from 21 antiretroviral (ARV)-naive Malawian adults were sequenced and analyzed to determine the prevalence of drug resistance-associated mutations in this population. Phylogenetic analysis confirmed that all isolates grouped with HIV-1 subtype C, the predominant subtype in Malawi. No major mutations associated with resistance to PR inhibitors (PIs), nucleoside RT inhibitors (NRTIs), or nonnucleoside RT inhibitors (NNRTIs) were found. In contrast, accessory mutations were found in the protease region at positions 10, 20, 36, 63, 77, and 93, and in the RT region at positions 118, 211, and 214. Further studies will be needed to determine the clinical impact of these polymorphisms on viral susceptibility to existing antiretroviral drugs.

Adult↗

Trichomoniasis: clinical manifestations, diagnosis and management.

Trichomonas vaginalis was originally considered a commensal organism until the 1950s when the understanding of its role as a sexually transmitted infection (STI) began to evolve. Trichomoniasis has been associated with vaginitis, cervicitis, urethritis, pelvic inflammatory disease (PID), and adverse birth outcomes. Infection with T vaginalis could have an important role in transmission and acquisition of HIV. T vaginalis is site specific for the genitourinary tract and has been isolated from virtually all genitourinary structures. Asymptomatic disease is common in both men and women, thus screening for disease is important. Various sociodemographic factors have been correlated with presence of T vaginalis, and may be used to predict infection. Diagnosis is usually made from wet mount microscopy and direct visualisation, which are insensitive. DNA amplification techniques perform with good sensitivity, but are not yet approved for diagnostic purposes. In areas where diagnostic methods are limited, management of trichomoniasis is usually as part of a clinical syndrome; vaginal discharge for women and urethral discharge for men. A single dose of metronidazole is effective in the majority of cases. Outside of the United States, other nitroimidazoles may be used and are as effective as metronidazole. Metronidazole resistance is an emerging problem, but its clinical importance is not yet clear. Concomitant treatment of sexual partners is recommended.

Animals↗

Surgical treatment of medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) is a malignancy of the parafollicular C cells of the thyroid gland. It occurs sporadically or as part of the multiple endocrine neoplasia type 2 (MEN 2) syndromes. Patients who have inherited a mutation in the RET proto-oncogene should have thyroidectomy early in life to prevent formation and spread of this cancer. Most patients with sporadic disease present with a palpable neck mass. The diagnosis is made by fine needle aspiration biopsy and by measuring calcitonin levels in the blood. Primary treatment consists of surgical resection including a total thyroidectomy, central neck nodal dissection and functional lateral neck nodal dissections. Most patients with a palpable primary tumour have nodal disease present at the time of operation, and nodal involvement is often bilateral. Adequate resection of the primary tumour and cervical lymph nodes is important to optimize outcome and minimize the risk of recurrent disease. Proper handling of the parathyroid glands prevents hypoparathyroidism. Following primary surgical resection, more than half of the patients will have recurrent disease with persistent elevation of calcitonin levels. Currently, there is no adequate systemic therapy for treating recurrent disease. Surgical reoperation or conservative observation are the best available options. Diagnostic laparoscopy for liver evaluation is the most sensitive diagnostic test to detect the presence of distant metastases.

Calcitonin↗

Maintenance and manipulation in spatial working memory: dissociations in the prefrontal cortex.

Two experiments were conducted to compare thec ries of the functional organization of spatial working memory within the human prefrontal cortex. In Experiment I, memory set size for locations was parametrically varied, allowing for the assessment of BOLD signal across maintenance requirements. In the sec ond experiment, manipulation of spatial information held in working memory was contrasted with simple maintenance of that information. Both experiment evoked significant activity in a distributed spatia working memory network. Although dorsolateral prefrontal activation increased monotonically with memory set size, this region was differentially engaged in task conditions involving explicit manipulation of in ternal representations. Activation in the superior frontal sulcal region was associated with maintenance of spatial information, increasing with memory se size. In contrast, ventrolateral prefrontal activation was present only at the highest memory set size, possibly due to the differential use of organizational strategies with more complex stimuli. These results sup port claims that the dorsolateral prefrontal cortex is involved in the manipulation of internal representa tions and that the superior frontal sulcal region is involved in the maintenance of spatial information but they suggest a complex role for the ventrolatera prefrontal region.

Algorithms↗

Laboratory diagnosis of sexually transmitted infections in women with genital discharge in Madagascar: implications for primary care.

Women seeking care in Madagascar for genital discharge (n = 1,066) were evaluated for syphilis seroreactivity; bacterial vaginosis (BV) and trichomoniasis. Chlamydial infection was assessed by ligase chain reaction (LCR) and by direct immunofluorescence (IF); gonorrhoea by direct microscopy, culture and LCR. Leucocytes were determined in endocervical smears and in urine using leucocyte esterase dipstick (LED). Gonococcal isolates were tested for minimal inhibitory concentrations. BV was found in 56%, trichomoniasis in 25%, and syphilis in 6% of the women. LCR detected gonorrhoea in 13% and chlamydial infection in 11% of the women. Detection of Gram(-) intracellular diplococci in endocervical smears, and gonococcal culture were respectively 23% and 57% sensitive and 98% and 100% specific compared to LCR. Chlamydia antigen detection by IF was 75% sensitive and 77% specific compared to LCR. Leucocytes in endocervical smears and LED testing lacked precision to detect gonococcal and chlamydial infections. Of 67 gonococcal strains evaluated, 19% were fully susceptible to penicillin, 33% to tetracycline; all were susceptible to ciprofloxacin, ceftriaxone, and spectinomycin. Patients who present with genital discharge in Madagascar should be treated syndromically for gonococcal and chlamydial infections and screened for syphilis. Gonorrhoea should be treated with ciprofloxacin.

Animals↗

Antiretroviral therapy effects on genetic and morphologic end points in lymphocytes and sperm of men with human immunodeficiency virus infection.

Many human immunodeficiency virus (HIV)-infected persons receive prolonged treatment with DNA-reactive antiretroviral drugs. A prospective study was conducted of 26 HIV-infected men who provided samples before treatment and at multiple times after beginning treatment, to investigate effects of antiretrovirals on lymphocyte and sperm chromosomes and semen quality. Several antiretroviral regimens, all including a nucleoside component, were used. Lymphocyte metaphase analysis and sperm fluorescence in situ hybridization were used for cytogenetic studies. Semen analyses included conventional parameters (volume, concentration, viability, motility, and morphology). No significant effects on cytogenetic parameters, semen volume, or sperm concentration were detected. However, there were significant improvements in sperm motility for men with study entry CD4 cell counts >200 cells/mm(3), sperm morphology for men with entry CD4 cell counts < or =200 cells/mm(3), and the percentage of viable sperm in both groups. These findings suggest that nucleoside-containing antiretrovirals administered via recommended protocols do not induce chromosomal changes in lymphocytes or sperm but may produce improvements in semen quality.

Adult↗

Viral burden in genital secretions determines male-to-female sexual transmission of HIV-1: a probabilistic empiric model.

OBJECTIVE: To develop a model to predict transmission of HIV-1 from men to women. DESIGN: HIV-1 in seminal plasma, and endocervical CCR5 receptors were correlated with epidemiological studies of HIV-1 transmission to develop a probabilistic model. SETTINGS: Semen samples were collected from patient subjects in Seattle Washington, Chapel Hill, North Carolina, and St. Gallen, Switzerland. Endocervical biopsy specimens were obtained from women in Chicago, Illinois. PARTICIPANTS: Eighty-six men (not receiving antiretroviral therapy) in whom CD4 cell count and semen volume were available, and 24 women in whom the number of endocervical CCR5 receptors were determined. MAIN OUTCOME MEASURES: Prediction of transmission of HIV-1 from men to women per episode of vaginal intercourse based on the absolute burden of HIV (volume x HIV RNA copies/ml seminal plasma). RESULTS: The model suggests efficient heterosexual transmission of HIV-1 when semen viral burden is high. When semen contains 100 000 copies of non-syncytium-inducing (NSI) HIV RNA the probability of HIV-1 transmission is 1 per 100 episodes of intercourse; conversely, with 1000 copies NSI HIV RNA in semen, transmission probability is 3 per 10 000 episodes of intercourse. CONCLUSIONS: This model links biological and epidemiological data related to heterosexual HIV-1 transmission. The model can be used to estimate transmission of HIV from men with high semen viral burden from inflammation, or reduced burden after antiretroviral therapy. The results offer a biological explanation for the magnitude of the HIV epidemic in places where earlier studies have shown men have high semen viral burden, such as in sub-Saharan Africa. The model can be used to develop and test HIV-1 prevention strategies.

Cervix Uteri↗

Adequacy of fellowship training: results of a survey of recently graduated fellows.

The adequacy of fellowship training in the field of infectious diseases was assessed by means of a survey of recently graduated fellows. Surveys were mailed to all individuals who had passed the American Board of Internal Medicine's board certification examination in infectious diseases since 1992. A total of 666 completed surveys were returned by the deadline (response rate, 36%). Although most recent graduates thought that training in the standard components of clinical infectious diseases was adequate, only 50% thought that training in infection control was adequate. Fewer than 1 in 3 believed that they had received adequate training in the business aspects of infectious diseases practice. The adequacy and duration of research training were linked to ultimate career choice. These results form the basis for the Infectious Diseases Society of America's new initiatives to assist with more-diversified and relevant fellowship training.

Data Collection↗

Real-time functional magnetic resonance imaging.

Magnetic resonance imaging (MRI) has been shown to be useful in the detection of brain activity via the relatively indirect coupling of neural activity to cerebral blood flow and subsequently to magnetic resonance signal intensity. Recent technical advances have made possible the continuous collection of successive images at a rate rapid compared with such signal changes and in the statistical processing of these image time series to produce tomographic maps of brain activity in real time, with updates of 10 frames/s or better. We describe here our preferred method of real-time functional MRI and some of the early results we have obtained with its use.

Brain↗

Qualitative and quantitative evaluation of six algorithms for correcting intensity nonuniformity effects.

The desire to correct intensity nonuniformity in magnetic resonance images has led to the proliferation of nonuniformity-correction (NUC) algorithms with different theoretical underpinnings. In order to provide end users with a rational basis for selecting a given algorithm for a specific neuroscientific application, we evaluated the performance of six NUC algorithms. We used simulated and real MRI data volumes, including six repeat scans of the same subject, in order to rank the accuracy, precision, and stability of the nonuniformity corrections. We also compared algorithms using data volumes from different subjects and different (1.5T and 3.0T) MRI scanners in order to relate differences in algorithmic performance to intersubject variability and/or differences in scanner performance. In phantom studies, the correlation of the extracted with the applied nonuniformity was highest in the transaxial (left-to-right) direction and lowest in the axial (top-to-bottom) direction. Two of the six algorithms demonstrated a high degree of stability, as measured by the iterative application of the algorithm to its corrected output. While none of the algorithms performed ideally under all circumstances, locally adaptive methods generally outperformed nonadaptive methods.

Algorithms↗

Atrioventricular valve regurgitation in patients with single ventricle: impact of the bidirectional cavopulmonary anastomosis.

BACKGROUND: It is not known whether atrioventricular valve regurgitation (AVVR) can improve in some patients after the bidirectional cavopulmonary anastomosis (BCPA) without undertaking concomitant valvuloplasty. METHODS: We retrospectively reviewed our experience with patients who underwent the BCPA between June 1989 and June 2000 with specific attention to those patients with moderate or severe AVVR. The degree of AVVR was determined by color Doppler echocardiography. During the study period there were 576 patients who underwent BCPA at a median age of 6.8 months (range, 1.3 months to 4.8 years). The majority of subjects (66%) had a tricuspid valve as the systemic atrioventricular valve. Significant (moderate or severe) AVVR before BCPA was noted in 36 of 576 patients (6%) and was significantly more prevalent (8 of 52 patients, 15%; p = 0.01) in patients with a common atrioventricular canal. RESULTS: Of the 36 subjects with moderate or severe AVVR, 8 had interventions (6 valvuloplasty, 2 aortic arch dilation) at BCPA. There was 1 hospital death (2.8%). Of the remaining 27 survivors who did not undergo additional interventions at BCPA, improvement in AVVR (mild or none) was noted in 6 (22%) at intermediate follow-up (median, 2 years; range, 0.5 to 3.1 years). The presence of significant AVVR before BCPA was not significantly associated with hospital survival or intermediate-term freedom from death or transplantation. CONCLUSIONS: We conclude that AVVR improves in some patients after BCPA and that valvuloplasty is not justified in all patients with moderate preoperative AVVR.

Anastomosis, Surgical↗

Fetal diagnosis and management of congenital heart disease.

Fetal echocardiography has had a significant impact on the diagnosis and management of congenital heart disease. Although the fetal circulation is quite forgiving for many heart lesions, other flow abnormalities gravely affect fetal physiology. Serial studies have given us a window to observe the natural history of many lesions that progress during gestation. Although fetal cardiac surgery is not yet a viable alternative to neonatal repair, fetal intervention on noncardiac disorders has had limited success and the field is growing. Fetal diagnosis remains an integral part of the management of children with cardiac lesions.

Disease Progression↗

The accessory posterior portal for shoulder arthroscopy: Description of technique and cadaveric study.

As the indications for shoulder arthroscopy continue to expand, so too does the need for complete access to the glenohumeral joint. Specific regions of the joint, including the axillary recess, are often times difficult to access using traditionally described posterior and anterior portals. In this article, we describe a technique for the placement of an accessory posterior portal into the inferior hemisphere of the glenohumeral joint, effectively in the 8 o'clock or 4 o'clock position. To demonstrate the safety and effectiveness of this portal, 6 cadaveric specimens were dissected after the placement of a standard and accessory posterior portal. The proximity of the posterior portals to the axillary and suprascapular nerves was analyzed. Measurements were made in simulated beach-chair and lateral decubitus positions. The authors show that the accessory posterior portal is safe to use and may prove useful to the surgeon who wishes to gain access to the inferior recesses of the glenohumeral joint.

Arthroscopy↗

Degenerative arthritis of the wrist: proximal row carpectomy versus scaphoid excision and four-corner arthrodesis.

Two cohort populations of 19 patients from separate institutions performing exclusively either a scaphoid excision and 4-corner arthrodesis (lunate, capitate, hamate, and triquetrum) or proximal row carpectomy (PRC) for scapholunate advanced collapse arthritis were compared. There were no preoperative differences with respect to age, gender, dominance, stage of arthritis, or preoperative measures of pain and function. The length of the follow-up period averaged 28 months for the 4-corner arthrodesis group compared with 19 months for the PRC patients. At the follow-up examination wrist motion revealed no significant differences in the flexion-extension arc, averaging 81 degrees in the PRC patients and 80 degrees following 4-corner arthrodesis, which was 62% and 58%, respectively, of the opposite wrist. The 4-corner arthrodesis patients maintained greater radial deviation and total percent radial-ulnar deviation of the wrist. Grip strength averaged 71% for the PRC group compared with 79% for the 4-corner arthrodesis patients. Pain relief was similar using a variety of measures and patient satisfaction was equivalent. Function was similar except that the 4-corner arthrodesis patients scored significantly higher on the mental health component of the short form-36 health status survey. No differences were seen on the physical health component or an outcome scale specifically designed for the wrist. Both PRC and scaphoid excision and 4-corner arthrodesis are motion-preserving options for the treatment of scapholunate advanced collapse arthritis with minimal subjective or objective differences in short-term follow-up evaluations.

Adult↗

Bone graft harvesting from the distal radius, olecranon, and iliac crest: a quantitative analysis.

The purpose of this study was to quantify the volume and density of cancellous bone available from 3 commonly used bone graft sites in upper extremity surgery: the distal radius, olecranon process, and anterior iliac crest. Sixteen cadavers (age range, 59-98 years) with no prior history of bone harvest or metabolic conditions affecting bone were used. Cancellous graft was obtained using standardized techniques designed to simulate the clinical setting. Packed cancellous bone volume was determined as the volume occupied by the harvested bone after compression packing with a uniform load. Defect volume was determined by measuring the volume of the site from which bone was harvested. The distal radius and olecranon provided similar volumes of packed cancellous bone (2.7 and 2.8 cc, respectively). The anterior iliac crest provided approximately twice this amount (5.3 cc). The packed cancellous bone volume/defect volume ratio was not different between the 3 sites studied. Male gender was associated with a significantly greater amount of packed cancellous bone volume for all sites. We believe the olecranon to be an alternative to the distal radius as a source of bone graft for upper extremity procedures. We suggest using the anterior iliac crest when a large volume of cancellous bone is required.

Aged↗