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R W Lewis

Publications and source records attributed to R W Lewis.

At least 37 records · Page 2Linked to original sources
PubMed1999

Androgenic maintenance of the erectile response in the rat.

Ongoing studies in this laboratory have used the castrated rat, with and without testosterone replacement, to investigate how androgens maintain the erectile response. The high intracavernosal pressures during erection depend on both an increase in the rate at which blood flows into the sinuses of the corpus cavernosum and a decrease in the rate at which blood flows out (veno-occlusion). Accordingly, our studies investigated androgenic regulation of the arterioles that regulate inflow and of the intracavernosal muscle that regulates the veno-occlusive mechanism controlling outflow. The results of these studies show that castration causes a decline in the rate of inflow and that androgen replacement reverses this decline. The decline in inflow in the castrated rats is also reversed by the administration of a nitric oxide donor drug, suggesting that the androgen may regulate inflow by increasing the synthesis of nitric oxide. Testosterone also appears to regulate outflow by controlling the sensitivity of the erectile mechanisms to norepinephrine, considered to be the principle vaso-constrictor neurotransmitter in the erectile response. Taken together, the results of these studies suggest that androgens control the erectile response by altering the synthesis and action of the neurotransmitters that normally alter the state of contraction and relaxation of smooth muscle in the erectile tissue.

Androgens↗
PubMed1998

Androgenic maintenance of inflow and veno-occlusion during erection in the rat.

Ongoing studies in this laboratory are designed to determine the role of androgens in the maintenance of the erectile response in the rat. Testosterone-treated castrated rats (TESTO) and untreated castrated rats (CASTRATE) were used for measurement of the rate at which blood flows into the cavernous sinuses by timed collections of blood after partial amputation of the penis. A laser Doppler flow meter was employed to determine whether androgens also regulate the veno-occlusive mechanism that controls the rate of blood flow out of the sinuses. Erection was induced by direct electrical stimulation of the autonomic ganglion that controls cavernosal blood flow in the erectile response. The results of these studies showed that blood flow into the sinuses was approximately twice as great in the TESTO animals as the CASTRATE rats. Furthermore, during ganglionic stimulation, veno-occlusion occurred in the TESTO rats but failed to occur in the CASTRATE rats. The dependence of these responses on nitric oxide (NO) was demonstrated by showing that injection of sodium nitroprusside (SNP) enhances the intracavernosal pressure response in TESTO rats but not CASTRATE animals. However, when SNP injection was combined with ganglionic stimulation, veno-occlusion did occur in the CASTRATE animals. Taken together, these studies show that both the rate of blood flow into the cavernous sinuses and the blood flow out are under androgenic regulation and may involve the actions of NO.

Androgens↗
PubMed1997

The oral administration of polysorbate 80 to the immature female rat does not increase uterine weight.

Some xenobiotics display estrogenic activity in in vitro and/or in vivo systems. Previous studies by Gajdova et al. have shown that polysorbate 80 (also known as Tween 80) administered by intraperitoneal injection to neonatal female rats on days 4-7 after birth produced estrogenic effects including earlier vaginal opening, prolongation of the estrus cycle and persistent vaginal estrus. Some of these effects were evident many weeks after cessation of administration of polysorbate 80. The present study has evaluated the estrogenic properties of polysorbate 80 following oral administration, a route of exposure which is more relevant for the consideration of human health hazard. The effects of polysorbate 80 at oral gavage doses of up to 5 g/kg/day for 3 consecutive days on uterine growth of immature female rats, a commonly used in vivo mammalian assay for estrogenic activity, have been determined. Estradiol benzoate administered subcutaneously was used as a positive control and significantly increased uterine weight in this age and strain of female rat (21-23 days, Alpk:APfSD Wistar derived) by up to 4.5-fold above vehicle control values. Polysorbate 80 administered orally to rats had no effect on uterine weight. Thus, intrinsic estrogenic effects of polysorbate 80 reported following its intraperitoneal injection to neonatal 4-day-old female rats are not manifest when it is administered by oral gavage to immature 20- to 22-day-old female rats. This latter route of exposure is of more relevance to human exposure scenarios and these data are, therefore, important in assessing hazard/risk of polysorbate 80 to man.

Administration, Oral↗
PubMed1997

External vacuum therapy for erectile dysfunction: use and results.

This review assesses the continuing role of noninvasive vacuum therapy as treatment for erectile dysfunction and discusses the action of negative pressure in producing assisted erection. Through recent research in this area has centered on the development of pharmaceutical therapies, vacuum-therapy programs appear to be a consistent long-term option for patients experiencing either chronic or occasional impotence of any etiology. Very little testing is required before the initiation of vacuum treatment, and the overall; clinical success rate is approximately 90%. Significant success has been reported in more difficult patient populations, including those with veno-occlusive disorders and explanted penile prostheses. Vacuum therapy may also be used in conjunction with other therapies to enhance results. Contraindications to the use of vacuum therapy are few and primarily include patients with unexplained intermittent priapism and bleeding disorders. Side effects such as occasional numbness, pain, penile bruising, or petechiae have a low incidence. A recently reported survey of 5,847 vacuum users showed that 83.5% of patients continue to use the device for intercourse as desired. Patients should receive individual instruction in the use of these devices and should expect a learning or practice period to achieve optimal results. As newer treatments for erectile dysfunction gain increasing attention, it should be kept in mind that nearly every patient showing impotence of any degree or duration as well as patients who have failed other therapeutic choices are candidates for vacuum therapy.

Erectile Dysfunction↗
PubMed1997

IRAG working group 4. Cell cytotoxicity assays. Interagency Regulatory Alternatives Group.

Twenty-seven data sets from 12 cellular cytotoxicity assays, intended to predict ocular irritation, were submitted to the Interagency Regulatory Alternatives Group (IRAG) for review. These data consisted of paired in vivo (Draize) and in vitro responses to individual chemicals and formulations. In vivo data consisted of individual tissue scores so that the predictive value of the in vitro assay could be assessed for each tissue response normally measured in the standard Draize assay. Data were compiled and evaluated according to the IRAG Guidelines Document. The Pearson's linear correlation coefficient was used as the first step in assessing the relationship between the in vitro and in vivo responses. The majority of the data sets represented the study of surfactant-based materials. In many cases, there was good correlation between the in vitro scores and the in vivo tissue responses. Most pronounced were the particularly good correlations between the in vitro scores and conjunctival redness scores across most of the assays. Based on the data submitted, a number of the cell cytotoxicity assays show considerable promise as screens for ocular irritancy. None of the submitters recommended that their cell cytotoxicity assay be used as a sole replacement for in vivo assessment. For almost all of these assays, the materials being tested should be water-soluble/miscible. The toxicity of products with reserve acidity or alkalinity or with high reactivity may be underestimated. A given user may prefer certain assays depending on the types of materials to be tested, the expected range of toxicities and the resources available. The cell cytotoxicity assays can serve as a valuable component of a tiered or battery testing program. As with any assay, a sufficient number of replicate values, concurrent positive and negative controls, and a strict adherence to assay acceptance criteria are essential to produce credible data.

Animal Testing Alternatives↗
PubMed1997

Modified Nesbit procedure for the treatment of Peyronie's disease: a comparative outcome analysis.

PURPOSE: We describe a surgical modification of the Nesbit procedure to correct Peyronie's disease, and compare the results of this procedure with those of 2 other surgical techniques. MATERIALS AND METHODS: In 30 patients a vertical incision in the tunica albuginea was closed in a horizontal fashion with permanent suture knots buried beneath the tunica in a running looped fashion, resulting in watertight closure with no exposed suture material. A standard Nesbit procedure and plaque excision with a polyethylene terephthalate mesh reinforced silicone sheet patch graft were done in 28 cases each. RESULTS: Elimination of penile curvature, patient satisfaction and postoperative impotence rates were not statistically different for standard and modified Nesbit procedures. However, plaque excision and synthetic patch grafting resulted in less elimination of curvature (61%, p = 0.004), a lower rate of satisfaction (30%, p = 0.00002) and a higher incidence of impotence after surgery (18%, p = 0.04). The modified Nesbit procedure achieved an overall higher rate of correction of curvature than the standard approach (93 versus 79%). CONCLUSIONS: A modified Nesbit procedure achieves the greatest functional success for Peyronie's disease with an acceptably low complication rate.

Adolescent↗
PubMed1996

Cadaver skin allografts and transmission of human cytomegalovirus to burn patients.

BACKGROUND: The potential role of cadaver skin as a vehicle for CMV transmission to burn patients has never been clearly defined. We sought to determine if a cytomegalovirus (CMV)-positive cadaver allograft transmits CMV infections to CMV-seronegative burn patients. STUDY DESIGN: All patients in this study were CMV seronegative on admission. They received CMV-seronegative blood products, and cadaver allografts for temporary wound closure and management without regard to the donor's CMV serum status (positive or negative). RESULTS: Of 493 patients admitted from 1989 to 1993, 22 were CMV seronegative on admission and required cadaver allografts for their burn wounds. Five (22.7 percent) of 22 patients seroconverted during hospitalization: one of five had CMV pneumonia develop, two had CMV viruria develop, and three had persistent fever, abnormal liver enzymes, and diarrhea not ascribable to bacterial or other viral agents. CONCLUSIONS: Cytomegalovirus infections result from using CMV-seropositive cadaver allografts on seronegative burn patients.

Adolescent↗
PubMed1995

Asymmetry of the planum temporale: methodological considerations and clinical associations.

Asymmetry of the planum temporale, a region on the posterosuperior surface of the temporal lobe involved in the production and comprehension of language, is a notable feature of the normal human brain. Several attempts have been made to measure it using both post-mortem and magnetic resonance imaging (MRI) methods, but previous approaches made inadequate allowance for the convoluted nature of the structure. The current study used rigorous criteria to define the planum and examined three separate approaches for its measurement on MRI scans. A method involving triangulation of the surface consistently gave larger values for the surface area of the planum, suggesting that this method takes account of the convoluted nature of the structure.

Adult↗
PubMed1995

Analysis of changes in coagulation factors after postoperative blood loss in burn and non-burn patients.

A prospective study of the postoperative kinetics of coagulation factors was undertaken in 23 burn patients and in six non-burn patients. All procedures resulted in a large volume blood loss. Fibrinogen, platelets and factors V, VIII and IX were measured serially. Burn patients returned all parameters to preoperative levels by 48 h postoperation, while non-burn patients showed a slower rate of return of platelets and factor V. This study suggests that burn patients may safely undergo re-operation at 48 h intervals for successive wound debridements if clinically necessary.

Adolescent↗
PubMed1995

Immediate impotence after penetrating perineal trauma: restoration of erections with penile artery revascularization, corpus cavernosum aneurysm repair, and deep penile venous ligation.

Erectile dysfunction can result from blunt or penetrating pelvic or perineal trauma. Rupture of the corpora cavernosa leading to loss of the veno-occlusive mechanism and penile artery occlusion have been found in these patients. We present a case of immediate loss of erectile function after penetrating perineal trauma resulting in corpus cavernosum rupture and traumatic occlusion of multiple arteries in the hypogastric-cavernous bed. Conservative management of the corpus injury resulted in post-traumatic aneurysmal dilation at the site of injury with venous leakage from aberrant veins. Penile arterial revascularization and aneurysm repair with deep penile venous ligation resulted in near-complete return of normal erectile function.

Adolescent↗
PubMed1995

Prospective comparison of two management strategies of central venous catheters in burn patients.

OBJECTIVE: Central venous catheters (CVCs) are associated with sepsis in burn patients. This study was undertaken to compare two strategies of CVC management in patients with major burn injuries. DESIGN: Forty-two burn patients with major burn injuries were randomly assigned to undergo site change every 48 hours of the CVC or to undergo wire guide exchange of the CVC every 48 hours at the same site. MATERIALS AND METHODS: Catheter insertion site, distance from the burn wound, cultures of catheter tips, and blood cultures were obtained from all patients in a prospective manner. MEASUREMENTS AND MAIN RESULTS: There was no difference in the incidence of CVC sepsis between the two groups studied. CVCs inserted less than 5 cm from the burn wound developed bacterial contamination at an earlier time than CVCs inserted more than 5 cm from the burn wound. CONCLUSIONS: There was no advantage to changing the CVC insertion site every 48 hours. Changing the CVC using the wire guide technique did not prevent, nor predict, CVC bacterial contamination.

Bacteria↗
PubMed1995

Reversal of asymmetry of the planum temporale in schizophrenia.

OBJECTIVE: The planum temporale is intimately involved in the generation and understanding of language and has been suggested to be a key area affected in schizophrenia. To explore temporal lobe abnormalities in schizophrenia, the authors measured the planum temporale, a normally asymmetric area lying on the superior part of the temporal lobe, in schizophrenic patients. METHOD: High-resolution magnetic resonance imaging (MRI) scans were obtained for 14 right-handed schizophrenic patients and 14 healthy comparison subjects individually matched for age, sex, handedness, race, and parental socioeconomic status. The surface area of the planum temporale was measured by using MRI reconstruction techniques. RESULTS: There was striking reversal of the normal asymmetry (left larger than right) in planum temporale surface area in 13 of the schizophrenic patients but in only two of the comparison subjects. However, Heschl's gyrus (primary sensory cortex), which served as an anatomically contiguous nonheteromodal cortical comparison region, showed no difference between the left and right sides in either group. Severity of thought disorder in the patients was related to asymmetry. CONCLUSIONS: This is a clear demonstration of a reversal of expected symmetry in the brains of right-handed schizophrenic patients, which involves a region of key importance in normal human behavior. The nature of the abnormality strongly suggests that schizophrenia is a neurodevelopmental disorder.

Adult↗