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Biomedical subjects

R A Watson

Publications and source records attributed to R A Watson.

At least 19 recordsLinked to original sources
PubMed2006

Effects of intra-gene fitness interactions on the benefit of sexual recombination.

Whereas spontaneous point mutation operates on nucleotides individually, sexual recombination manipulates the set of nucleotides within an allele as an essentially particulate unit. In principle, these two different scales of variation enable selection to follow fitness gradients in two different spaces: in nucleotide sequence space and allele sequence space respectively. Epistasis for fitness at these two scales, between nucleotides and between genes, may be qualitatively different and may significantly influence the advantage of mutation-based and recombination-based evolutionary trajectories respectively. We examine scenarios where the genetic sequence within a gene strongly influences the fitness effect of a mutation in that gene, whereas epistatic interactions between sites in different genes are weak or absent. We find that, in cases where beneficial alleles of a gene differ from one another at several nucleotide sites, sexual populations can exhibit enormous benefit compared with asexual populations: not only discovering fit genotypes faster than asexual populations, but also discovering high-fitness genotypes that are effectively not evolvable in asexual populations.

Animals↗
PubMed2005

Evolution of changes in carbon monoxide transfer factor in men with chronic obstructive pulmonary disease.

Progression of chronic obstructive pulmonary disease (COPD) has been studied predominantly by following change in forced expiratory volume in 1s (FEV1) which reflects both primary airway disease and associated alveolar disease. Carbon monoxide transfer (Tlco) (the product of the transfer coefficient Kco and alveolar volume Va) is the only simple, widely available test of alveolar function, but few studies have followed long-term changes in an individual. Seventeen middle-aged men with moderate chronic airflow obstruction (mean FEV1 56% of predicted values) were observed with yearly measurements of FEV1, Tlco and Kco over a mean of 18.9 yr. At the end of follow-up FEV1 had fallen to 29% of predicted values. Va, measured by single breath dilution, fell in each man. Kco at recruitment ranged from 41% to 110% predicted and remained >75% predicted in eight men at the end of follow-up supporting a phenotype of COPD with predominant airway disease and little emphysema. Fall in FEV1 was faster (2.03% predicted FEV1/yr) in seven men with low initial Kco<75% pred. than in men with initial Kco>75% pred. (1.14% predicted FEV1/yr, P=0.006). Repeated measurements of CO transfer in an individual should increase the present poor knowledge of the contribution of alveolar disease to the progression of chronic airflow obstruction.

Adult↗
PubMed2004

Postural changes in lung volumes and respiratory resistance in subjects with obesity.

Reduced functional residual capacity (FRC) is consistently found in obese subjects. In 10 obese subjects (mean +/- SE age 49.0 +/- 6 yr, weight 128.4 +/- 8 kg, body mass index 44 +/- 3 kg/m2) without respiratory disease, we examined 1) supine changes in total lung capacity (TLC) and subdivisions, 2) whether values of total respiratory resistance (Rrs) are appropriate for mid-tidal lung volume (MTLV), and 3) estimated resistance of the nasopharyngeal airway (Rnp) in both sitting and supine postures. The results were compared with those of 13 control subjects with body mass indexes of <27 kg/m2. Rrs at 6 Hz was measured by applying forced oscillation at the mouth (Rrs,mo) or the nose (Rrs,na); Rnp was estimated from the difference between sequential measurements of Rrs,mo and Rrs,na. All measurements were made when subjects were seated and when supine. Obese subjects when seated had a restrictive defect with low TLC and FRC-to-TLC ratio; when supine, TLC fell 80 ml and FRC fell only 70 ml compared with a mean supine fall of FRC of 730 ml in control subjects. Values of Rrs,mo and Rrs,na at resting MTLV in obese subjects were about twice those in control subjects in both postures. Relating total respiratory conductance (1/Rrs) to MTLV, the increase in Rrs,mo in obese subjects was only partly explained by their reduced MTLV. Rnp was increased in some obese subjects in both postures. Despite the increased extrapulmonary mass load in obese subjects, further falls in TLC and FRC when supine were negligible. Rrs,mo at isovolume was increased. Further studies are needed to examine the causes of reduced TLC and increases in Rrs,mo and sometimes in Rnp in obese subjects.

Adaptation, Physiological↗
PubMed2004

Postural changes in nasal and pulmonary resistance in subjects with asthma.

INTRODUCTION: Subjects with asthma frequently have nasal symptoms and complain of orthopnoea but airflow resistance is usually only assessed during oral breathing and while seated. METHOD: We have used a forced oscillation technique to measure total respiratory resistance (Rrs) at 6Hz during mouth breathing (Rrs,mo) and during nose breathing (Rrs,na) in the sitting and supine postures; resistance of the nasal airway (Rnaw) was estimated as Rrs,na--Rrs,mo. Forced oscillations were applied during normal tidal breathing and the mid-tidal lung volume (MTLV) was determined for each breathing route and posture. SUBJECTS: Three groups of subjects were studied: 10 normal subjects without lung or nasal disease (N; five males, mean age 33.5 [range 23-58] years, mean FEV1 105%pred, FEV1/VC 86%); seven subjects with asthma alone (A; four males, 40.3 [23-57] years, mean FEV1 66%pred, FEV1/VC 74%); 10 asthmatic subjects with nasal obstructive symptoms (AN; six males, 62.8 [38-80] years, mean FEV1 56%pred, FEV1/VC 75%). RESULTS: In all three groups of subjects, mean Rrs,mo and Rrs,na were higher in the supine than sitting posture. In normal subjects the increase in supine Rrs,mo was associated with a 0.6 liter fall in MTLV. In asthma supine Rrs,mo increased despite a much smaller fall in MTLV; supine increases in Rrs,na were particularly large in presence of nasal disease. DISCUSSION: Values of airflow resistance are 2-3 times higher in both normal and asthmatic subjects when breathing via the nose and supine than under normal laboratory conditions of oral breathing and seated.

Adult↗
PubMed2004

Multiphasic helical CT diagnosis of early medullary and papillary necrosis.

PURPOSE: The feasibility of identifying early manifestations of renal papillary necrosis (RPN) and medullary necrosis (RMN) on multiphasic helical CT, leading to prompt treatment for the causative conditions, and its impact on reducing the incidence of late-stage RML and RPN, was investigated. PATIENTS AND METHODS: Sixty-eight patients (35 male, 33 female) aged 19 to 88 years were examined by multiphasic helical CT for complaints of microscopic hematuria (N=49), macroscopic hematuria (N=2), bacteriuria (N=45), pyuria (N=10), fever (N=15), and flank pain (N=27). Preenhancement, arterial corticomedullary, parenchymal, and excretory phase scans generated 1.25 to 7-mm-thick slices. Follow-up CTs were performed at 1 month (N=62) and 3 months (N=58). RESULTS: While the attenuation coefficients of areas suspect for RMN and RPN were similar on preenhancement CT, they differed substantially on the arterial corticomedullary phase (lesions 55 HU mean; normal medulla 120 HU mean) and parenchymal phase (lesions 58 HU mean, normal medulla 210 HU mean). Investigation for predisposing conditions identified diabetes in 18 patients, upper urinary-tract infections in 48, sickle-cell disease or trait in 17, urinary obstruction in 7, and cirrhosis of the liver in 1. On follow-up examinations, enhancement had normalized in 26 compromised areas of 14 patients at 1 month, and 47 areas (23 patients) at 3 months, remained stationary in 28 patients at 1 month and 9 at 3 months, and progressed in 20 at 1 and 26 at 3 months (P<0.001; Fisher's exact test). Patients (N=35) treated for underlying conditions causing ischemia showed reperfusion in 12 cases at 1 month and 20 at 3 months, while of the untreated patients (N=10), none showed reperfusion, and all lesions increased in size. CONCLUSIONS: Multiphasic helical CT is recommended for identification of RMN and RPN at a stage when effective treatment of underlying causative conditions can arrest or reverse the process of devascularization and prevent loss of medullary tissue.

Adult↗
PubMed2004

Multiphasic helical CT criteria for differentiation of recurrent neoplasm and desmoplastic reaction after laparoscopic resection of renal mass lesions.

BACKGROUND AND PURPOSE: Differentiation of recurrent neoplasm and desmoplastic reaction following laparoscopic resection of renal mass lesions poses a problem. The usefulness of multiphasic helical CT-generated criteria based on enhancement and morphologic characteristics was investigated. PATIENTS AND METHODS: The findings in 5 female and 12 male patients aged 29 to 68 years having renal-cell carcinoma (11-38 mm; N = 15) or solitary angiomyolipomas (N = 2) treated by laparoscopic resection (N = 15) or open segmental surgery (N = 2) were analyzed. Multiphasic helical CT was performed in the preenhancement, arterial corticomedullary, parenchymal, and excretory phases generating 2.5- to 7-mm slices. RESULTS: Both recurrent neoplasms showed median postcontrast enhancement of 119 HU in the arterial corticomedullary phase; the median enhancement of desmoplastic masses was 48 HU. In the parenchymal and excretory phase, recurrent neoplasms showed progressive loss of enhancement, whereas desmoplastic lesions sustained enhancement at about the same level. Recurrent neoplasms presented a defined mass with characteristic spiculation, whereas desmoplastic reaction was characterized by an ill-defined mass with spidery projections extending to abutting fat and residual fascial planes. On 2- to 3-month follow-up scans, recurrent neoplasms showed progressive increases in size and desmoplastic reaction a sharp decrease. CONCLUSION: Enhancement of the mass at the operative site on arterial corticomedullary-phase CT to >90 HU strongly suggests recurrent renal-cell carcinoma, while progressive decrease in size on 1- to 3-month follow-up CT suggests a desmoplastic reaction.

Adult↗
PubMed2003

Detection of medullary and papillary necrosis at an early stage by multiphasic helical computerized tomography.

PURPOSE: Multiphasic helical computerized tomography (CT) is advocated to identify early manifestations of papillary and medullary necrosis based on decreased enhancement of circumscribed areas in the medullary pyramid. At this stage the devascularizing process can be reversed if causative conditions such as infections or diabetes mellitus are effectively treated. MATERIALS AND METHODS: Multiphasic helical CTs were performed in 31 male and 26 female patients with complaints of microscopic hematuria (41), macroscopic hematuria (2), bacteriuria (39) and pyuria (9). Pre-enhancement, arterial, early corticomedullary, parenchymal and excretory phase helical CTs generated 1.25 to 5 mm. thick slices. Followup examination included multiphasic helical CT at 1 and 3 months, and excretory urography for some patients at 3 months. RESULTS: Bacteriuria was identified as the probable cause of medullary and papillary necrosis in 39 patients, of whom 28 were treated with effective antibiotic therapy, resulting in normalization and re-perfusion of the initial lesion in 16, no change in 5 and progressive disease in 7 at 3-month followup. Of 8 lesions not treated with specific antibiotic therapy 4 progressed and 4 remained unchanged. CONCLUSIONS: Multiphasic helical CT unlike the excretory urogram can identify medullary and papillary necrosis at an early stage when effective treatment of the underlying cause can reverse the process of devascularization and prevent sloughing of medullary tissues.

Adult↗
PubMed2002

Chemo-ablation of the prostate with dehydrated alcohol for the treatment of prostatic obstruction.

PURPOSE: We confirmed clinically whether chemo-ablation of the prostate with absolute ethanol may be an innovative transurethral approach for the relief of obstructive benign prostatic hyperplasia. METHODS: Using the InjecTx endoscopic device (Injectx Inc., San Jose, California) an initial cohort of 15 patients, including 13 who have now been followed more than 1 year, underwent elective transurethral chemo-ablation of the prostate. RESULTS: Preoperative and postoperative comparisons of the American Urological Association symptom score, maximum urine flow rate and prostatic volume reveal significant improvement with minimal discomfort and no major complication. CONCLUSIONS: The InjecTx technique proved encouragingly successful in this initial small-scale clinical trial.

Aged↗
PubMed2001

IL-6 signaling by STAT3 participates in the change from hyperplasia to neoplasia in NRP-152 and NRP-154 rat prostatic epithelial cells.

BACKGROUND: STAT3 phosphorylation is associated with the neoplastic state in many types of cancer, including prostate cancer. We investigated the role of IL-6 signaling and phosphorylation of STAT3 in 2 rat prostatic epithelial lines. NRP-152 and NRP-154 cells were derived from the same rat prostate, yet the NRP-152 cells are not tumorigenic while the NRP-154 cells are tumorigenic. These lines are believed to represent 2 of the stages in the development of prostate cancer, hyperplasia and neoplasia. Differences in signaling pathways should play a role in the 2 phenotypes, hyperplastic and neoplastic. METHODS: We looked at the phosphorylation state of STAT3 by intracellular flow cytometry, using phospho-specific antibodies to STAT3. We used the same method to examine IL-6 production by the cell lines. We also measured apoptosis by binding of fluorescent annexin V to the cells. RESULTS: Although both cells lines made IL-6 constitutively, phosphorylated-STAT3 was present in untreated NRP-154 cells, but not in NRP-152 cells. Treatment with dexamethasone inhibited the IL-6 production of NRP-152 cells, but enhanced that of NRP-154 cells. Treatment with the JAK2 inhibitor AG490 induced apoptosis in NRP-152, but not NRP-154 cells. CONCLUSIONS: We conclude from these experiments that STAT3 activity plays a role in the phenotype of NRP-154 cell, but not NRP-152 cells. The significance of alternative IL-6 signaling pathways in the different phenotypes of the 2 cell lines is discussed.

Animals↗
PubMed2000

Endourologic management of benign ureteral strictures with and without compromised vascular supply.

OBJECTIVES: To retrospectively assess the efficacy of balloon dilation, endopyelotomy/ureterotomy, and stenting alone in the management of benign ureteral strictures with intact or compromised vascular supply. METHODS: One hundred fourteen patients with benign ureteral strictures were assessed after at least a 2-year follow-up (range 2 to 16 years, mean 6.3). Balloon dilation was performed in 81, endopyelotomy/ureterotomy with temporary stenting in 27, and ureteral stenting alone in 6 patients. Ureteral strictures were divided into strictures with intact or with compromised vascular supply. RESULTS: Balloon dilation was successful in short ureteral strictures with intact vascular supply in 33 of 37 (89.2%), but only in 3 of 8 (37.5%) long ureteral strictures and in 1 of 2 (50%) recurrent ureteropelvic junction strictures. Balloon dilation was less successful when the vascular supply was compromised in 2 (40%) of 5 short strictures, 1 (16.7%) of 6 long strictures, and 2 (33.3%) of 6 recurrent ureteropelvic junction strictures. Endopyelotomy/ureterotomy was successful in 17 (89.5%) of 19 strictures with compromised vascular supply. CONCLUSIONS: Balloon dilation is recommended for management of short strictures with intact vascular supply. Endoureterotomy with stenting is recommended for all long ureteral strictures, for ureteropelvic junction stenoses, and for short ureteral strictures with compromised vascular supply and benign underlying etiology.

Adult↗
PubMed2000

Accuracy of diagnosis by guided biopsy of renal mass lesions classified indeterminate by imaging studies.

OBJECTIVES: To define the accuracy, safety, and impact of percutaneous biopsies of indeterminate mass lesions as an additional diagnostic tool. The vast majority of renal mass lesions are routinely diagnosed by radiographic features alone. However, with the increased use of computed tomography scanning and ultrasound, many smaller renal masses, which are "indeterminate" (refractory to categorization on the basis of imaging alone), are now being discovered. METHODS: We retrospectively reviewed 583 patients (364 male and 219 female) with indeterminate renal mass lesions diagnosed by imaging studies that were further investigated by percutaneous biopsy. Patients were followed up for at least 5 years if the biopsy result demonstrated a benign lesion, or they underwent surgical exploration if the biopsy result demonstrated a malignancy. Biopsy or aspiration material was assessed by histopathologic and cytologic evaluation and, when appropriate, with biochemistry, Gram stain, culture, and sensitivity. The biopsy site was localized by computed tomography, ultrasound, or fluoroscopy. RESULTS: Five hundred eighty-three patients with indeterminate renal mass lesions (representing 7.2% of all renal masses diagnosed from 1967 through 1996) were diagnosed by imaging studies complemented by guided biopsy. Sixty-six patients were lost to follow-up, leaving 517 patients who were analyzed. In 393 cases (76%), the imaging-guided biopsy provided a definitive diagnosis. The incidence of false diagnoses was 1.2% (7 biopsies). In 124 of the cases (21%), imaging-guided biopsy was unable to determine the etiology of the lesion with acceptable confidence; of these, 21 biopsies did not provide enough material to establish the diagnosis (16.9%). CONCLUSIONS: Overall, percutaneous biopsy of the kidney has proved to be a safe and accurate diagnostic procedure, with impact on the management of cystic or solid renal lesions.

Adolescent↗
PubMed2000

Penile Kaposi's sarcoma preceded by chronic penile lymphoedema.

Kaposi's sarcoma localized to the penis with striking lymphoedema is extraordinary. We report a middle-aged Haitian man who was human herpesvirus-8 seropositive, without evidence of immunosuppression or human immunodeficiency virus infection. He was first seen with Kaposi's sarcoma of 6 months duration localized to his penis, preceded by a 3-year history of chronic penile lymphoedema. His tumour regressed completely after radiotherapy. We propose that chronic lymphoedema in this patient predisposed to the development of Kaposi's sarcoma.

Humans↗
PubMed2000

Endourologic management of malignant ureteral strictures.

PURPOSE: This retrospective analysis assessed the efficacy of balloon dilatation, endoureterotomy, percutaneous ureteroneocystostomy with stenting, and insertion of Wallstents in the management of malignant ureteral strictures with an intact or compromised vascular supply. PATIENTS AND METHODS: A series of 127 patients with ureteral strictures secondary to malignancies were assessed after at least 2-year follow-up (range 2-5 years; mean 3.5 years). Balloon dilation (antegrade approach) was applied in 46 patients, endoureterotomy with temporary stenting in 37, percutaneous ureteroneocystostomy with stenting in 34, bougie and stents in 13, and Wallstents in 31. RESULTS: Balloon dilatation was successful in only two of four malignant midureteral stenoses with intact vascular supplies and was even less successful (10%) in midureteral strictures with a compromised vascular supply. Endoureterotomy failed in all cases to prevent ureteral obstruction. Percutaneous ureteroneocystostomy achieved patency in 11 of 34 patients (33%) having a compromised ureteral vascular supply. Wallstents were successful in 18 of 31 patients (58%) with stenoses of the pelvic ureter. CONCLUSIONS: Percutaneous ureteroneocystostomy with stenting meets the requirement for palliation in patients with obstruction secondary to pelvic neoplasms. Wallstents proved to be most successful when used in the pelvic ureter.

Adult↗
PubMed1999

Percutaneous nephrostomy as adjunct management in advanced upper urinary tract infection.

OBJECTIVES: To determine by retrospective review of 315 percutaneous nephrostomies, performed for pyonephrosis, whether this intervention has major clinical advantages. METHODS: From 1977 to 1996, under the direct supervision of the senior author of this report (E.K.L.), at seven hospital sites, 315 patients (181 males, 134 females; 17 to 88 years of age) were treated with percutaneous nephrostomy and antibiotic therapy for infected hydronephrosis. RESULTS: Additional or disparate pathogens were identified in 116 (36.8%) of 315 patients, leading to a clinically significant change in, or addition of, antibiotics and/or antifungal agents in 84 (73%) of 116. Most notably, we often found a clinically important disparity between the results of cultures obtained from the nephrostomy and those obtained from bladder-urine specimens. CONCLUSIONS: This retrospective review confirms previously reported advantages of percutaneous upper urinary tract drainage as a potentially life-saving adjunct in the treatment of pyonephrosis. Several case studies highlight the advantage of this maneuver in difficult cases involving obstruction due to extensive fungus or debris. In particular, our review focuses attention on the clinically important insight that urine cultures from percutaneous nephrostomy drainage often identify pathogens that differ from those detected in concurrent bladder cultures.

Humans↗
PubMed1998

Abdominal compartment syndrome.

BACKGROUND: The abdominal compartment syndrome (ACS) is a newly appreciated and potentially fatal consequence of increased intra-abdominal pressure. It can be due to either trauma or surgery, as well as numerous medical conditions. Prolonged, unrelieved elevation of intra-abdominal pressure can produce pulmonary compromise, renal impairment, cardiac failure, shock, and death. A high index of suspicion is imperative. Measurement of the intravesical pressure provides a urometric window for detecting and monitoring this condition. CONCLUSIONS: Reopening the abdominal incision (decompressive celiotomy) has proven a life-saving intervention. Use of delayed wound closure (staged celiotomy) may prevent development of this condition in high-risk surgical patients. It is urgent that all physicians, and surgeons in particular, be alerted to this potentially lethal complication.

Abdomen↗
PubMed1998

Use of mouth pressure twitches induced by cervical magnetic stimulation to assess voluntary activation of the diaphragm.

There is a need for a simple method to assess the adequacy of diaphragm activation during voluntary inspiratory efforts in patients with suspected respiratory muscle weakness. We have compared mouth (Pmo,t), oesophageal (Poes,t) and transdiaphragmatic (Pdi,t) twitch pressure elicited by cervical magnetic stimulation (CMS) in five normal men (mean (SD) age 32.2 (1.8) yrs) on two separate study days. Single magnetic stimuli were delivered at functional residual capacity during relaxation and during graded voluntary inspiratory efforts against a closed airway. As voluntary-effort transdiaphragmatic and oesophageal pressure increased, Pdi,t and Poes,t decreased linearly (r range, respectively, 0.82-0.98 and 0.87-0.95). During relaxation, Pmo,t was unreliable due to the poor transmission of intrathoracic pressure, but during inspiratory efforts, the relation between voluntary mouth pressure and Pmo,t was also linear (r range 0.84-0.95). On average, our subjects voluntarily generated 99, 100 and 102% of the maximum transdiaphragmatic, oesophageal and mouth pressures predicted by the respective linear regression equations. Pmo,t was correlated to both Poes,t and Pdi,t during inspiratory efforts, but not during relaxation. These studies confirm that twitch pressures induced by CMS during inspiratory efforts can be assessed at the mouth in normal subjects, providing a simple and non-invasive technique for assessing diaphragm activation during voluntary inspiratory efforts. Potentially, this technique could be made more sensitive and accurate and applied to detect submaximal efforts in patients.

Adult↗