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Biomedical subjects

R M Dwyer

Publications and source records attributed to R M Dwyer.

At least 19 recordsLinked to original sources

Sodium iodide symporter-mediated radioiodide imaging and therapy of ovarian tumor xenografts in mice.

Ovarian cancer represents the fifth leading cause of cancer death among women in the United States, with >16 000 deaths expected this year. This study was carried out to investigate the potential of sodium iodide symporter (NIS)-mediated radioiodide therapy as a novel approach for ovarian cancer treatment. Radioiodide is routinely and effectively used for the treatment of benign and malignant thyroid disease as a result of native thyroidal expression of NIS, which mediates iodide uptake. In vitro gene transfer studies in ovarian cancer cells revealed a 12- and five-fold increase in iodide uptake when transduced with Ad/CMV/NIS or Ad/MUC1/NIS, respectively. Western blot/immunohistochemistry confirmed NIS protein expression. In vivo ovarian tumor xenografts were infected with the adenoviral constructs. (123)I imaging revealed a clear image of the CMV/NIS-transduced tumor, with a less intense image apparent following infection with MUC1/NIS. Therapeutic doses of (131)I following CMV/NIS infection caused a mean 53% reduction in tumor volume (P<0.0001). MUC1/NIS-transduced tumors did not regress, although at 8 weeks following therapy, tumor volume was significantly less that of control animals (166 versus 332%, respectively, P<0.05). This study represents a promising first step investigating the potential for NIS-mediated radioiodide imaging and therapy of ovarian tumors.

Adenoviridae↗

Identification of sources of Salmonella organisms in a veterinary teaching hospital and evaluation of the effects of disinfectants on detection of Salmonella organisms on surface materials.

OBJECTIVE: To determine sources of Salmonella organisms in a veterinary teaching hospital, compare bacterial culture with polymerase chain reaction (PCR) testing for detection of Salmonella organisms in environmental samples, and evaluate the effects of various disinfectants on detection of Salmonella organisms on surface materials. DESIGN: Prospective study. SAMPLE POPULATION: Fecal samples from 638 hospitalized horses and 783 environmental samples. PROCEDURE: Standard bacterial culture techniques were used; the PCR test amplified a segment of the Salmonella DNA. Five disinfectants were mixed with Salmonella suspensions, and bacterial culture was performed. Swab samples were collected from 7 surface materials after inoculation of the surfaces with Salmonella Typhimurium, with or without addition of a disinfectant, and submitted for bacterial culture and PCR testing. RESULTS: Salmonella organisms were detected in fecal samples from 35 (5.5%) horses. For environmental samples, the proportion of positive bacterial culture results (1/783) was significantly less than the proportion of positive PCR test results (110/783), probably because of detection of nonviable DNA by the PCR test. Detection of Salmonella organisms varied with the surface material tested, the method of detection (bacterial culture vs PCR testing), and the presence and type of disinfectant. CONCLUSIONS AND CLINICAL RELEVANCE: Results of the present study suggested that Salmonella organisms can be isolated from feces of hospitalized horses and a variety of environmental surfaces in a large animal hospital. Although recovery of Salmonella organisms was affected by surface material and disinfectant, bleach was the most effective disinfectant on the largest number of surfaces tested.

Animals↗

An outbreak of salmonellosis among horses at a veterinary teaching hospital.

Between May 1996 and February 1997, 27 horses and a veterinary student at a veterinary teaching hospital developed apparent nosocomial Salmonella Typhimurium infection. The source of the multiple-drug resistant Salmonella Typhimurium was a neonatal foal admitted for treatment of septicemia. A high infection rate (approx 13% of hospitalized horses) coupled with a high case fatality rate (44%) for the initial 18 horses affected led to a decision to close the hospital for extensive cleaning and disinfection. Despite this effort and modification of hospital policies for infection control, 9 additional horses developed nosocomial Salmonella Typhimurium infection during the 6 months after the hospital reopened. Polymerase chain reaction testing of environmental samples was useful in identifying a potential reservoir of the organism in drains in the isolation facility. Coupled with clinical data, comparison of antimicrobial resistance patterns of Salmonella Typhimurium isolates provided a rapid initial means to support or refute nosocomial infection. Although minor changes in the genome of these isolates developed over the course of the outbreak, pulsed-field gel electrophoresis testing further supported that salmonellosis was nosocomial in all 27 horses.

Animals↗

Field study of the safety, immunogenicity, and efficacy of an inactivated equine rotavirus vaccine.

OBJECTIVE: To determine safety, immunogenicity, and efficacy of an inactivated equine rotavirus vaccine. DESIGN: Prospective randomized controlled trial. ANIMALS: 316 pregnant Thoroughbred mares during the first year of the study and 311 during the second year. PROCEDURE: During the first year, mares received 3 doses of vaccine or placebo, IM, at 8, 9, and 10 months of gestation. Serum neutralizing antibody titers were measured before vaccination and 1 and 35 days after foaling. Antibody titers were measured in foals 1, 7, 35, 60, 90, and 120 days after birth. During the second year, mares that had been vaccinated the previous year received a single booster dose of vaccine approximately 1 month prior to parturition. Mares that had received the placebo the previous year and mares new to the study received 3 doses of vaccine or placebo. Serum neutralizing antibody titers were measured in samples taken from mares approximately 1 day after foaling and from foals approximately 1 and 60 days after birth. RESULTS: Adverse reactions were not observed. Antibody titers were significantly increased at the time of foaling and 35 days after foaling in vaccinated, compared with control, mares and for 90 days after birth in foals born to vaccinated, compared with foals born to control, mares. Incidence of rotaviral diarrhea was lower in foals born to vaccinated, compared with foals born to control, mares, but the difference was not significant. CLINICAL IMPLICATIONS: Results suggest that the equine rotavirus vaccine is safe and immunogenic and that reasonable efficacy under field conditions can be expected.

Analysis of Variance↗

Disinfecting equine facilities.

Disinfection of equine premises provides a challenge to farm managers, in view of the variety of surfaces which may be contaminated and the wide variety of horse pathogens. Of the commonly occurring infectious diseases for which disinfection and disease control are especially important, rotavirus diarrhoea, salmonellosis and strangles are the most difficult to control. Phenolic disinfectants have been scientifically demonstrated to be effective in the presence of organic matter and are also virucidal. When used after thorough cleaning and rinsing of stall surfaces, phenolics have proved effective in controlling outbreaks of disease. In addition, 10% iodophors used for washing hands and cleaning equipment are also virucidal and bactericidal. Quaternary ammonium compounds, chlorhexidine, bleach and pine oil are readily available commercially, but are ineffective disinfectants in the presence of the organic matter encountered on horse farms.

Animal Husbandry↗

Rotaviral diarrhea.

Rotavirus poses a challenge each foaling season to farm managers and veterinarians in intensive horse breeding areas throughout the world. By understanding the epidemiology of the disease as well as characteristics of the virus, veterinarians can make sound recommendations on prevention and control of outbreaks. Even when effective prophylactic products are developed, farm management practices, including quarantine, disinfection, and hygiene, will always need to be in force to prevent any contagious disease outbreak.

Animals↗

Analysis of serotypes and electropherotypes of equine rotaviruses isolated in the United States.

Equine group A rotaviruses isolated over a 10-year period in New York State, New Jersey, Kentucky, and Texas were compared serotypically and electropherotypically. All isolates were determined to be serotype 3 by reaction with hyperimmune antiserum to the serotype 3 H-2 strain of equine rotavirus. All displayed RNA electrophoretic migration patterns related to that of the H-2 strain but distinct from that of serotype 5 strain H-1. A serologic survey of 184 mares in Kentucky, which was done to determine the incidence of H-1 and H-2 infections, showed geometric mean serum neutralizing titers to the H-2 strain of equine rotavirus to be significantly higher than those to the H-1 strain. These data suggest that the serotype 3 H-2 strain is the dominant equine rotavirus in Kentucky and perhaps elsewhere in the United States. We were unable to produce confirmational evidence that the H-1 strain occurs as a natural infection in the United States.

Animals↗

Prograde versus retrograde endoscopic laser therapy for the treatment of malignant esophageal obstruction: a comparison of techniques.

The prograde and retrograde approaches to the treatment of malignant esophageal obstruction with the Nd:YAG, or neodymium: yttrium, aluminum, garnet, laser are compared. With the prograde technique, tumor destruction proceeds from the proximal to the distal tumor margin. In retrograde treatment, the endoscope is passed to the distal tumor margin so that the treatment can proceed in the reverse direction, thereby completing therapy in a single treatment session. This is usually accomplished by passage of a guide wire down the biopsy channel of the endoscope, tumor dilatation, and then passage of the endoscope over the guide wire to the distal tumor margin, where laser destruction is begun. Twenty nonrandomly selected patients with malignant esophageal obstruction were studied. The first ten patients were treated with the prograde technique, the next ten with the retrograde technique. The two groups were similar with respect to age, sex, and tumor histologies. Patients treated retrogradely had narrower pretreatment lumens (average 2.3 vs. 4.1 mm) as well as longer tumor lengths (average 8.9 vs. 4.8 cm). The posttreatment luminal diameters were similar for each group: 18.0 mm for prograde; 16.3 for retrograde. In the retrograde group, therapy was completed in fewer treatments (1.6 vs. 2.9) and over a shorter period of time (3.6 vs. 7.8 days), despite the longer tumor lengths. All patients in both groups were able to tolerate a regular diet at the completion of therapy. The complication rate was low in both groups. It is felt that the retrograde technique (single session therapy) is the preferred method because it allows more-rapid treatment without increased complications and thereby shortens hospital stay and reduces hospital costs.

Adenocarcinoma↗

New laser technique for the treatment of malignant esophageal obstruction.

Endoscopic laser therapy for malignant esophageal obstruction is rapidly gaining widespread acceptance by the medical community. The standard approach utilizing the neodymium: yttrium, aluminum, garnet (Nd: YAG) laser was first described by Fleischer for squamous cell carcinoma of the esophagus and subsequently for adenocarcinoma of the gastroesophageal junction. According to his technique, treatment was begun at the proximal tumor margin and proceeded distally; as many as 13 treatments were necessary to complete therapy and relieve the obstruction. A new technique has been developed utilizing tumor dilatation so that treatment can be started at the distal tumor margin working retrogradely. This new technique has allowed treatment to be completed in a single session in most patients. This rapid completion of therapy has reduced the length of hospitalization and thereby hospital costs. It has also allowed patients to aliment earlier, thereby minimizing the metabolic consequences of prolonged intravenous feedings, has allowed patients to receive other forms of therapy on an outpatient basis, and has obviated the need for the chronic placement of tubes for drainage and feeding. The technique is described and discussed.

Esophageal Neoplasms↗

Large vessel sealing with the argon laser.

This study compared the histology, biochemistry, and tensile strength of laser-welded and sutured canine venotomies, arteriotomies, and arteriovenous fistulas. Twelve animals had bilateral femoral vessels studied, with one repair (control) closed with interrupted 6-0 polypropylene sutures, and the contralateral repair (experimental) welded with the argon laser. Specimens were examined at weekly intervals from 1 to 4 weeks (four animals for each type of repair), and were evaluated histologically by hematoxylin and eosin, elastin, and trichrome stains; biochemically by the formation of [3H]hydroxyproline as an index of collagen synthesis; and mechanically by tensile strength determinations. At removal, all experimental closures were patent without hematomas, aneurysms, or luminal dilatation. Histologic and biochemical examination and tensile strength determinations suggest that laser welding may be an alternative to sutures for repair of large-diameter venotomies, arteriotomies, and arteriovenous fistulas, as healing is comparable to that seen with suture repairs up to 4 weeks postoperatively.

Animals↗

Endoscopic laser therapy for the treatment of malignant esophageal obstruction.

Malignant esophageal obstruction in 24 patients was treated using the neodymium:ytrium, aluminum, garnet laser. There were 15 males and nine females; the average age was 70.9 years. There were 17 adenocarcinomas and seven squamous cell carcinomas, with two of these being recurrent after radiation therapy. Tumor lengths ranged from 2.5-19.0 cm, with an average of 6.7 cm. The average energy delivered per centimeter of tumor was 6,309 joules for the squamous cell carcinomas and 5,598 for the adenocarcinomas. Energy delivered per treatment ranged from 3,152 to 70,527 joules. Total energy delivered per patient depended on the volume of tumor destroyed. Esophageal lumens increased from 3.4 to 16.7 mm, and 23 patients had their diets advanced, 22 to regular and one to soft solids. Reobstruction did not occur in patients who received adjunctive therapy after laser therapy. This consisted of chemotherapy in five, surgery in two, and radiation therapy in one. Complications consisted of aspiration pneumonia in three patients, including one who developed a tracheoesophageal fistula, and one documented and two suspected perforations. Hospital stay averaged 5.4 days overall and 3.5 days in those treated with the single-session technique. This increased to 8.0 days in patients with proven or suspected perforations. Endoscopic laser therapy is a safe and effective method for palliating esophageal cancer.

Adenocarcinoma↗

Preliminary report: a new technique of enterotomy closure using Nd:YAG laser welding compared to suture repair.

This study compared the histology and tensile strength of Nd:YAG laser welded and sutured small bowel enterotomies in Sprague-Dawley rats. Enterotomies (0.5 cm long) were either welded with the Nd:YAG laser (1 W and 10.6 sec pulses) or repaired with interrupted, simple 6-O silk sutures. Group I consisted of seven animals; five with enterotomies repaired by laser welding and two repaired by suturing. Group II consisted of eight animals with each having both laser and suture repairs. Animals were killed and specimens were removed and examined at 1 day, and at 1, 2, and 3 weeks postoperatively to compare the progression of healing. On macroscopic examination the laser welded enterotomies were closed 84% of the time and only 23% had adhesion formation while 90% of sutured repairs were closed and 100% had adhesion formation. Histologic examination of both suture and laser welded enterotomies demonstrated active healing at 1 week with minimal collagen bridging the enterotomies. At 2 and 3 weeks the sutured enterotomies had granulomatous reaction around the sutures while the laser welded enterotomies had minimal inflammatory response and near normal small bowel histology. The tensile strength of the 3-week specimens from both the suture and laser welded enterotomies were 50% of normal bowel. These findings suggest that the laser welding of small bowel enterotomies is comparable in closure and tensile strength to suture repair. The time required to repair the enterotomy is significantly decreased, the procedure is easily performed, and there is a marked decrease in adhesion formation following laser repair.

Animals↗

Biostimulation of wound healing in vivo by a helium-neon laser.

Clinical observations have suggested that low-energy lasers might stimulate wound healing. To understand the mechanism of the biostimulation, we previously examined the effects of low-energy lasers on collagen production by human skin fibroblasts and reported an increase of collagen synthesis in vitro. To examine the effects of low-energy lasers in vivo, hairless mice were experimentally wounded, sutured, and subjected to laser irradiation by a helium-neon laser with a power output of 1.56 mW and an energy fluence of 1.22 Joules/cm2. Experimental wounds were subjected to laser treatment every other day for 2 months; control wounds remained untreated. Specimens from the wounds were then examined for histological findings, tensile strength, and total collagen content. Results demonstrated a considerable improvement in the tensile strength of the laser-irradiated wounds at 1 and 2 weeks. Furthermore, the total collagen content was significantly increased at 2 months when compared with control wounds. These results suggest a beneficial effect of the helium-neon laser on wound healing in vivo.

Animals↗

Demonstration of elevated type I and type III procollagen mRNA levels in cutaneous wounds treated with helium-neon laser. Proposed mechanism for enhanced wound healing.

To assess laser modulation of wound healing, full-thickness cutaneous wounds were produced in the backs of pigs, and subjected to treatment with helium-neon laser. For comparison, some wounds were treated with non-laser energy source (a tungsten light) or left untreated as controls. Type I and type III procollagen mRNA levels were determined in the wounds by molecular hybridization with cDNA probes. The results indicated that type I and type III mRNA levels were markedly increased at days 17 and 28 of the healing in wounds treated with He-Ne laser, when compared to control or tungsten light-treated wounds. The results suggest that helium-neon laser stimulates wound healing by enhancing procollagen gene expression. These observations may have relevance to previous clinical studies suggesting that helium-neon laser stimulates wound healing.

Animals↗

Endoscopic laser therapy of malignant esophageal obstruction.

Malignant esophageal obstruction in patients with carcinoma of the esophagus and adenocarcinoma of the distal esophagus usually indicates far-advanced disease. Palliative therapy with the neodymium-yttrium, aluminum, garnet laser has been proposed as an alternative to more invasive procedures that do little to improve the quality of life or prolong survival. Fifteen patients were treated with endoscopic laser therapy. A previously described technique was used to treat the first ten patients; the remaining five were treated with a single-session therapy method. This new technique allowed more rapid completion of therapy (1.4 treatments over 2.2 days vs 2.9 treatments over 7.8 days) without sacrificing safety. Single session therapy using this laser is recommended as the treatment of choice in patients with carcinoma of the esophagus with obstruction that is surgically or radiotherapeutically incurable.

Adenocarcinoma↗

Laser welding of venotomies.

We investigated the histologic and biochemical effects of carbon dioxide and neodymium (Nd)-YAG laser welding on the healing of venotomies. Ten canine femoral venotomies 2 cm in length were approximated and welded with 10 600-nm wavelength, 1-W power over 20 to 25 s for CO2 laser, and 1060-nm wavelength, 1-W power over 30 to 40 s for Nd-YAG laser. On removal at one to three weeks, all veins (4/4 welded by CO2 and 6/6 by Nd-YAG) were patent without hematomas. Histologic and biochemical analyses of the venous tissues demonstrated active healing at the venotomy sites. We conclude that the CO2 and Nd-YAG lasers can be used successfully to weld venotomies and may provide an alternative to conventional suture techniques for repair of vascular lesions.

Animals↗