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Biomedical subjects

M A Vickers

Publications and source records attributed to M A Vickers.

At least 37 records · Page 2Linked to original sources
PubMed1995

Conservation of position and sequence of a novel, widely expressed gene containing the major human alpha-globin regulatory element.

We have determined the cDNA and genomic structure of a gene (-14 gene) that lies adjacent to the human alpha-globin cluster. Although it is expressed in a wide range of cell lines and tissues, a previously described erythroid-specific regulatory element that controls expression of the alpha-globin genes lies within intron 5 of this gene. Analysis of the -14 gene promoter shows that it is GC rich and associated with a constitutively expressed DNase 1 hypersensitive site; unlike the alpha-globin promoter, it does not contain a TATA or CCAAT box. These and other differences in promoter structure may explain why the erythroid regulatory element interacts specifically with the alpha-globin promoters and not the -14 gene promoter, which lies between the alpha promoters and their regulatory element. Interspecies comparisons demonstrate that the sequence and location of the -14 gene adjacent to the alpha cluster have been maintained since the bird/mammal divergence, 270 million years ago.

Amino Acid Sequence↗
PubMed1995

Assessment and modeling of the physical components of human corporovenous function.

To understand and quantify specific causes of venoocclusive dysfunction, an analog model of penile hemodynamics, including a mechanism of flow limitation by subtunical veins, was developed and a detailed analytic study was conducted in patients with erectile dysfunction. Computer simulations for steady-state and transient intracavernosal conditions were carried out to study graded changes in cavernosal smooth muscle tone, subtunical venular resistance, and cavernosal and tunical compliances. The model predicted a steady-state cavernosal pressure (Pca)-infusion flow relationship with two phases: an initial phase characterized by a gradual slope up to a critical flow and a second phase characterized by a much steeper slope after limitation of subtunical venular flow. Model predictions were compared with clinical data obtained during incremental saline cavernosometry (SaC) and pharmacocavernosometry (PhC) in 13 patients with erectile dysfunction with use of a computer-controlled infusion system that automatically changed from constant-flow to constant-pressure feedback control when Pca reached the threshold of 80 mmHg. Steady-state pressure-flow and pressure-circumference relationships of the penis were analyzed and interpreted in terms of specific components of the electrical analog model. These clinical studies demonstrated that patients with a functional venoocclusive mechanism (i.e., those able to achieve 100 mmHg Pca with infusion flow rates < 60 ml/min during PhC) had a steeper initial slope of the pressure-flow relationship during SaC and a greater increase in penile circumference and Pca after intracavernosal injection of papaverine-phentolamine than those with an impaired venoocclusive mechanism. From the electrical analog model, initial steepness of the pressure-flow relationship (slope) during SaC mainly represented subtunical venular resistance, whereas maintenance of flow during PhC depended on overall function of the different components, i.e., subtunical venular resistance, cavernosal and subtunical compliances, and full relaxation of cavernosal smooth muscle. We conclude that the proposed analog model can be used to interpret and characterize clinical penile hemodynamic data and may provide guidelines for more successful management of patients with erectile dysfunction.

Adult↗
PubMed1995

Correlation of American Urological Association symptom index with obstructive and nonobstructive prostatism.

The precise role of the American Urological Association (AUA) symptom index in the management of benign prostatic hyperplasia (BPH) is not well established. The AUA symptom index has been recommended only for quantifying the symptoms of BPH but not for its diagnosis. However, to our knowledge the ability to discriminate obstructive from nonobstructive BPH using the AUA symptom index has never been investigated. To establish the relationship between the AUA symptom index and prostatic obstruction 125 men (mean age 67.7 +/- 8.4 years) with voiding dysfunction presumably related to BPH were analyzed. Patients were given the AUA symptom questionnaire, following which video urodynamic studies were done, including micturitional urethral pressure profilometry for specifically diagnosing outlet obstruction. The patients were divided into 2 groups: group 1-78 with primary BPH dysfunction and group 2-47 with prostatism of ambiguous etiology. The mean AUA symptom index in group 1 (15.5 +/- 7.1) was not statistically different from that in group 2 (14.8 +/- 7.9). In both groups the mean AUA symptom index in the patients with obstruction (15.3 +/- 7.2 for group 1 and 13.9 +/- 7.9 for group 2) was not statistically different from that in the nonobstructed group (17.0 +/- 5.4 and 16.1 +/- 7.9, respectively). Of the severely symptomatic patients 22% did not have obstruction whereas all mildly symptomatic patients did. No significant correlations were found between the severity of obstruction and the AUA symptom index in either group. These observations indicate that the AUA symptom index cannot discriminate obstructed from nonobstructed BPH cases, not all severely symptomatic BPH patients will have outlet obstruction, a significant proportion of mildly symptomatic BPH patients can have outlet obstruction and voiding dysfunctions in elderly men, regardless of the etiology, produce similar symptoms.

Aged↗
PubMed1994

Prostate cancer screening: role of the digital rectal examination and prostate-specific antigen.

BACKGROUND: This study was designed to determine the efficacy of digital rectal examination (DRE) and serum prostate-specific antigen (PSA) for early detection of prostate cancer in men > or = 50 years of age. METHODS: A prospective single-center clinical trial was conducted to screen 644 asymptomatic men, who were elicited by newspaper and radio advertisements, with DRE and PSA. Quadrant biopsy examinations of the prostate were performed if PSA > 4 ng/ml or if DRE was suspicious. RESULTS: Thirty-seven percent of the men (n = 241) had an abnormality of DRE or elevated PSA. Of the 163 patients who underwent transrectal ultrasound and quadrant biopsies of the prostate, 77% had normal biopsies, 14 (8%) had prostatic intraepithelial neoplasia, and 24 (15%) had carcinoma of the prostate. PSAs ranged from 0.3 to 65.5 ng/ml, with a mean of 2.35 and a median of 1.6. Ninety-five patients had a PSA > 4 ng/ml, of whom 17 had a PSA > 10 ng/ml. Sensitivity of PSA was 75% and specificity 87%; for DRE the sensitivity was 75% and the specificity 69%. Clinical stage of patients who underwent radical prostatectomy was B1 in 15 and B2 in five. Fifteen of 20 patients (75%) had organ-confined disease; the other five had specimen-confined disease. No patient was found to have nodal involvement. CONCLUSION: The combination of PSA and DRE seems to improve the stage of diagnosis of patients with prostate cancer. Larger, randomized studies will be necessary to evaluate the effect of screening on overall survival.

Aged↗
PubMed1993

Structure of the human 3-methyladenine DNA glycosylase gene and localization close to the 16p telomere.

We recently reported the presence of four genes lying between the human alpha-globin gene cluster and the telomere of the short arm of chromosome 16 (16p). We now report that one of these genes encodes 3-methyladenine DNA glycosylase, an enzyme important in the repair of DNA after damage by alkylating agents. The gene comprises five exons, representation of which differs in independently isolated cDNA clones. Although the gene is widely expressed, the abundance of its mRNA is considerably higher in a colon adenocarcinoma cell line (HT29) than in other cell lines that were tested. The major positive erythroid-specific regulatory element controlling alpha-globin gene expression lies equidistant between the promoters of the alpha-globin genes and the 3-methyladenine DNA glycosylase gene. Interestingly, in contrast to the alpha-globin genes, expression of the 3-methyladenine DNA glycosylase gene is not influenced by the regulatory element in the human erythroleukemia cell line K562.

Amino Acid Sequence↗
PubMed1993

Diagnosis and treatment of psychogenic erectile dysfunction in a urological setting: outcomes of 18 consecutive patients.

The diagnostic criteria and treatment outcomes of 18 consecutive patients with psychogenic erectile dysfunction were examined. Average patient age was 38 years, and all patients had either awakening penile or masturbatory rigidity. Each patient was studied with home monitoring (ART-1000) on 2 consecutive nights. The average number of maximum erectile episodes, the event during which the maximum rigidity was maintained for at least 5 minutes, was 1.6. The maximum sleep erectile episodes averaged 11.2 minutes during which penile rigidity averaged 572 gm. The main predictor for remission of erectile dysfunction in this study was whether the dysfunction was primary or secondary. Of 14 patients with secondary psychogenic erectile dysfunction, that is history of being able to achieve and maintain penile rigidity sufficient for at least 5 minutes of vaginal intercourse, 10 (71%) experienced remission. Three patients noticed spontaneous remission during the initial evaluation and another 3 experienced remission within 3 months of completion of the evaluation and reassurance that they had normal erectile capacity. Two patients had remission while considering penile vascular surgery and in 2 normal erectile function returned during injection therapy. Only 2 of 3 patients referred for sex therapy actually received it (Freudian theory), and neither noticed improvement in erectile function. One patient received yohimbine without benefit. None of the patients elected treatment with the vacuum constriction device. All 4 patients with primary psychogenic erectile dysfunction, that is never able to achieve and/or maintain penile rigidity sufficient to achieve vaginal intercourse, failed to respond to physician reassurance and time. Of 2 patients who received sex therapy (1 Freudian and 1 behavioral) without improvement in erectile function 1 has entered the pharmacological erection program and has achieved vaginal penetration, and the other is considering the pharmacological erection program. The remaining 2 patients have deferred all therapy. Based on this experience, we currently reassure patients with secondary psychogenic erectile dysfunction that they have erectile capacity for sustained vaginal intercourse and schedule a followup visit in 3 months. Additional individualized therapy (pharmacological erection program, vacuum constriction device, sensate focus/psychodynamic specific therapy or penile prosthesis) is offered as needed and requested. Patients with primary psychogenic erectile dysfunction are initially offered the pharmacological erection program or the vacuum constriction device and sex sensate focus/psychodynamic specific therapy. The penile prosthesis is considered for treatment failures.

Adult↗
PubMed1993

Correlation of duplex sonography with arteriography in patients with erectile dysfunction.

OBJECTIVE: Our objective was to assess the accuracy of using measurements of peak systolic velocity in the cavernosal artery for the diagnosis of arteriogenic impotence. MATERIALS AND METHODS: Twenty consecutive men with erectile dysfunction had duplex sonography after intracavernosal injection of papaverine to induce an erection. Peak systolic velocities in the right and left cavernosal arteries were measured by using Doppler sonography. Right and left selective penile arteriography was performed with low-osmolality contrast media after intracavernosal injection of papverine and intraarterial tolazoline. On the basis of the angiographic findings, penile arterial function was classified as normal, moderately insufficient, or severely insufficient. Doppler measurements of peak systolic velocity were correlated with arteriographic results. RESULTS: All 11 cavernosal arteries with peak velocities less than 25 cm/sec were associated with arterial disease, nine severe and two moderate. Thirteen of 17 carvernosal arteries with peak systolic velocities 25-34 cm/sec were associated with arterial disease, five severe and eight moderate. Only one of the 12 cavernosal arteries with peak velocity at or greater than 35 cm/sec was associated with arterial disease. CONCLUSION: We conclude that peak systolic velocity in the cavernosal artery as measured on duplex sonography is an accurate predictor of arterial disease in patients with erectile dysfunction. A peak systolic velocity of at least 35 cm/sec indicates normal arterial supply. At peak systolic velocities less than 35 cm/sec, the likelihood and severity of arterial disease increase as the peak systolic velocity decreases, with a peak velocity less than 25 cm/sec indicating a high likelihood of severe arterial disease.

Adult↗
PubMed1992

Cis-acting sequences regulating expression of the human alpha-globin cluster lie within constitutively open chromatin.

Current models suggest that tissue-specific genes are arranged in discrete, independently controlled segments of chromatin referred to as regulatory domains. Transition from a closed to open chromatin structure may be an important step in the regulation of gene expression. To determine whether the human alpha-globin cluster, like the beta-globin cluster, lies within a discrete, erythroid-specific domain, we have examined the long-range genomic organization and chromatin structure around this region. The alpha genes lie adjacent to at least four widely expressed genes. The major alpha-globin regulatory element lies 40 kb away from the cluster within an intron of one of these genes. Therefore, unlike the beta cluster, cis-acting sequences controlling alpha gene expression are dispersed within a region of chromatin that is open in both erythroid and nonerythroid cells. This implies a difference in the hierarchical control of alpha- and beta-globin expression.

Animals↗
PubMed1992

Microsurgical nerve graft repair of the ablated cavernosal nerves in the rat.

Erectile dysfunction is a significant complication of radical pelvic surgery in men. Using the rat as an experimental model, we investigated the feasibility of repairing surgically ablated cavernosal nerves. Known fertile male Sprague-Dawley rats were randomly divided into three surgical groups of 30 animals (60 study nerves) per group consisting of nerve ablation, immediate nerve reconstruction, and control groups. The nerve ablation group had 5-mm sections of the cavernosal nerve excised bilaterally. The nerve graft group had 5-mm sections of the cavernosal nerve excised bilaterally, followed by immediate microsurgical reconstruction with an autologous interposition nerve graft utilizing the ipsilateral genitofemoral nerve bilaterally. The anastomoses were performed with 10-O nylon sutures at 16 to 25x magnification. The control group underwent sham operations with the cavernosal nerves being exposed only. Erectile function was evaluated at 1, 2, 4, and 6 months postoperatively. Return of erectile function was defined as tumescence of the corporal bodies with application of direct electrical stimulation (3 V of 5 msec pulses at 20 Hertz) to the proximal cavernosal nerves. The 4- and 6-month electrical stimulation studies resulted in tumescence from 65 and 75% of the grafted nerves, which represented a significant difference compared to the ablated group 11 and 5%, respectively (P less than 0.001 at 4 and 6 months). Behavioral copulatory studies, performed prior to electrical stimulation testing, corresponded closely with the results of electrically induced tumescence. We conclude that in this experimental model immediate nerve graft repair appears to be a successful method of salvaging erectile function when the cavernosal nerves have been divided.

Animals↗
PubMed1992

Entubulization repair of severed cavernous nerves in the rat resulting in return of erectile function.

Erectile dysfunction is a significant complication of radical pelvic surgery in men. Using the rat as an experimental model, we investigated the feasibility of repairing surgically ablated cavernous nerves utilizing silastic tube nerve growth conduits filled with nerve growth enhancing media. Known fertile male Sprague-Dawley rats were randomly divided into four surgical groups consisting of nerve ablation, immediate nerve reconstruction utilizing the entubulization technique (two groups) and control. The nerve ablation group had five mm. sections of the cavernosal nerve excised bilaterally. The entubulization nerve graft group had five mm. sections of the cavernous nerve excised bilaterally, followed by immediate microsurgical reconstruction with a silastic nerve tube conduit filled with either Matrigel and heparin (MA) or Matrigel and heparin plus acidic fibroblast growth factor (MA/aFGF), interposed between the severed cavernous nerve stumps bilaterally. The control group underwent sham operations with the cavernous nerves being exposed only. Erectile function was evaluated at one, two, and four months postoperatively. Return of erectile function was defined as tumescence of the corporal bodies with application of direct electrical stimulation (four volts of five millisecond pulses at 20 Hertz) to the proximal cavernous nerves. The two and four month electrical stimulation studies resulted in tumescence from 50% and 58% of the entubulization nerve reconstructed nerves with MA/aFGF versus 29% and 30% for the MA only group and only 5% and 11% for the ablated group, respectively. We conclude that in this experimental model immediate nerve graft repair utilizing entubulization techniques with the addition of nerve growth enhancing media appears to be a successful method of salvaging erectile function when the cavernous nerves have been divided.

Animals↗
PubMed1992

The current cavernosometric criteria for corporovenous dysfunction are too strict.

In an attempt to define the hemodynamic and radiographic parameters of normal erectile function 6 patients 20 to 41 years old (mean age 30.3 years) with erectile dysfunction that spontaneously resolved after a comprehensive evaluation were reviewed. The results included normal hormonal assays, normal penile biothesiometry and normal penile brachial index. The sleep tumescence and rigidity tracings were abnormal according to the criteria that sleep erections occur every 90 minutes, are associated with penile rigidity of greater than 550 gm. plus an increase in penile circumference of greater than 1.5 cm. and last longer than 15 minutes. High resolution ultrasonography, pulse wave Doppler ultrasound, dynamic pharmacocavernosometry and dynamic cavernosography were performed. After testing the patients were informed that no organic abnormalities had been detected. No medical or surgical treatment was given. The hemodynamic values are presented as suggested normal parameters: maintenance rate (mean 11 +/- 3 cc per minute), initial decompression rate (mean 59 +/- 17 mm. Hg/30 seconds) and radiographic findings (visualization of the cavernous, external pudendal and deep dorsal veins during pharmacocavernosography, performed at intracorporeal pressures of 100 mm. Hg). All 6 patients had maintenance rates of greater than 5 cc per minute. Of these 6 patients 5 had initial decompression rates of greater than 48 mm. Hg/30 seconds and 4 had 5-minute, post-infusion steady state values of less than 50 mm. Hg, criteria that have been used to define corporovenous dysfunction.

Adult↗
PubMed1992

A PCR-based strategy to detect the common severe determinants of alpha thalassaemia.

A rapid and inexpensive polymerase chain reaction (PCR) based strategy is described which detects the three common, severe alpha thalassaemia determinants observed in southeast Asia (--SEA) and the Mediterranean (--MED and -(alpha)20.5). Oligonucleotide primers have been chosen which allow specific identification of both normal (alpha alpha) and abnormal (--) chromosomes using identical conditions in either the same or parallel PCR reactions. This strategy should be useful in the development of screening programmes to identify carriers of alpha thalassaemia (--/alpha alpha) and prenatal diagnosis of the Hb Bart's hydrops fetalis syndrome (--/--) for those populations in which this represents a major cause of perinatal death.

Base Sequence↗
PubMed1992

Cystic testicular mass caused by dilated rete testis: sonographic findings in 31 cases.

We reviewed the scrotal sonograms of 31 patients who had a testicular mass consisting of multiple small spherical or tubular anechoic structures in the region of the mediastinum testis. The median age of the patients was 62 years (range, 31-76 years). The abnormality was unilateral in 22 patients and bilateral in nine. Thirty-four (85%) of the 40 involved testicles had coexisting epididymal abnormalities: 32 with epididymal cysts and two with epididymitis. Follow-up sonograms were available in five patients and showed no change up to 4.5 years after the initial diagnosis. Surgical and histologic findings were available in one other patient and showed dilatation of the rete testis. The sonographic appearance and location of the lesions, the frequent presence of an epididymal abnormality, and the surgical and histologic findings in one case suggest that the lesion is due to dilatation of the rete testis, probably associated with obstruction in the epididymis. Recognition of this entity on sonograms may prevent unnecessary orchiectomy.

Adult↗
PubMed1991

Acute urinary retention secondary to Herpes simplex meningitis.

We report a case of acute urinary retention in a 24-year-old man with Herpes simplex meningitis without genital lesions. Since the differential diagnosis in young patients who present with acute urinary retention also includes multiple sclerosis, lumbosacral disk herniation, rheumatological disorders and drug intoxication, a thorough history and careful neurological examination are of paramount importance in distinguishing these syndromes. As part of a directed neurological evaluation prompt performance of lumbar puncture is indicated; a lymphocytic pleocytosis is suggestive of herpetic meningitis. Culture of Herpes simplex virus from the cerebrospinal fluid should be attempted. We recommend conservative management only, typically with intermittent catheterization, since bladder function usually normalizes within 10 to 14 days.

Acute Disease↗
PubMed1990

Alpha-thalassemia caused by a large (62 kb) deletion upstream of the human alpha globin gene cluster.

We describe a family in which alpha-thalassemia occurs in association with a deletion of 62 kilobases from a region upstream of the alpha globin genes. DNA sequence analysis has shown that the transcription units of both alpha genes downstream of this deletion are normal. Nevertheless, they fail to direct alpha globin synthesis in an interspecific hybrid containing the abnormal (alpha alpha)RA chromosome. It seems probable that previously unidentified positive regulatory sequences analogous to those detected in a corresponding position of the human beta globin cluster are removed by this deletion.

Animals↗
PubMed1990

High resolution ultrasonography and pulsed wave Doppler for detection of corporovenous incompetence in erectile dysfunction.

Cavernosometry and cavernosography have been the primary modalities available for detection and mapping of corporovenous incompetence in patients with erectile dysfunction. These procedures are expensive, time-consuming and associated with some morbidity, prompting us to study a less invasive method, high resolution ultrasonography and pulsed wave Doppler ultrasound. We evaluated 13 patients with nonendocrinological, nonneurological erectile dysfunction by high resolution and Doppler ultrasound for flow in the dorsal and cavernosal veins after intracorporeal papaverine. All patients had a nonrigid response to papaverine and a mean maximum cavernous arterial systolic velocity of greater than 25 cm. per second. The 13 patients were subsequently studied by dynamic cavernosometry and cavernosography, which revealed evidence of venous incompetence (12 with dorsal venous leaks and 11 with cavernous venous leaks). Only 5 of the 12 patients with dorsal venous incompetence had flow detected in the dorsal vein by ultrasound and Doppler studies. High resolution and Doppler ultrasound was unable to detect leakage in the cavernous veins. Among the 2 groups of patients with dorsal venous leaks (those with and without flow detectable by Doppler ultrasound) there was no significant difference in mean cavernous artery diameter or mean cavernous arterial maximum velocity. Similarly, there was no significant difference between the 2 groups in induction, maintenance or initial decompression rates on cavernosometry. We conclude that high resolution and Doppler ultrasound cannot replace dynamic cavernosometry and cavernosography as the diagnostic modality for venous incompetence.

Blood Flow Velocity↗