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Publications and source records attributed to R Smith.
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The enzyme 11 beta-hydroxysteroid dehydrogenase (11-HSD) is thought to confer specificity on the nonselective Type I adrenocorticoid receptor by converting glucocorticoids to receptor-inactive metabolites in mineralocorticoid target tissues. S1 nuclease analyses using a rat liver 11-HSD probe demonstrated tissue-specific expression of the 5' region of the 11-HSD gene in the liver, lung, and kidney not evident in previous studies. Renal tissue contained a unique protected species which mapped to a position within the coding region, consistent with a divergence in liver and kidney protein sequences. Screening of a rat kidney cDNA library resulted in the isolation of several clones (11-HSD1B) noncolinear in their 5' regions with the liver sequence (11-HSD1A). Nucleic acid sequence analysis showed that the divergent clones code for a protein lacking a 26-amino acid NH2-terminal putative membrane-spanning signal peptide. The deletion of the leader sequence from the microsomal 11-HSD1A protein may result in a nuclear localization of the 11-HSD1B isoform. The renal 11-HSD1A and 11-HSD1B species increased coordinately during ontogeny and in parallel with the developmental surge in glucocorticoids. At least three alternate sites of polyadenylation were found to be utilized by the 11-HSD gene. Southern blot analysis showed the presence of a single gene in the rat. This study shows the expression of a kidney-specific 11-HSD isoform which may protect the Type I adrenocorticoid receptor from occupation by glucocorticoids in the nucleus of a mineralocorticoid target cell.
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OBJECTIVE: To determine the short-term and long-term results of percutaneous aortic valvuloplasty. DESIGN: A retrospective follow-up study. SETTING: The Cardiac Catheterisation Laboratory and Cardiovascular Medicine Unit of a teaching hospital. PATIENTS: Eighteen patients with severe aortic stenosis who were not accepted for surgery; there were 11 men and 7 women, mean age 79 +/- 4.5 years. INTERVENTIONS: Percutaneous transluminal aortic valvuloplasty (PTAV) by means of balloon catheter techniques. MAIN OUTCOME MEASURES: Patient survival and symptomatic status. RESULTS: PTAV resulted in a significant decrease in the aortic valve pressure gradient from 64.8 +/- 23.2 mmHg to 38 +/- 14.7 mmHg (mean +/- SD) (P less than 0.00001) in the 18 patients and a significant increase in the mean aortic valve area from 0.4 +/- 0.16 cm2 to 0.6 +/- 0.18 cm2 (P less than 0.0001) in 14 patients. Complications occurred in seven patients; two of them, who had been in terminal heart failure with a low output state before PTAV, died. Fifteen patients improved in at least one New York Heart Association functional class early after PTAV and one patient had an aortic valve replacement. In follow-up of between 5 and 32 months (mean, 13.3 +/- 7.7 months) six patients are in a better functional class than before PTAV, one patient is in Class IV, one patient had an aortic valve replacement and seven patients died (three died of cardiac failure and four of non-cardiac causes). CONCLUSIONS: PTAV has a place as a palliative procedure in selected patients with aortic stenosis in whom another condition precludes aortic valve replacement.
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To assess the efficacy and safety of twice-daily administration of nedocromil sodium 2% ophthalmic solution, we performed a multicenter study involving 140 patients with seasonal allergic conjunctivitis. Subjects had a history of seasonal allergic conjunctivitis and positive results of a skin test to ragweed. The trial coincided with the peak ragweed pollen season at five treatment centers. Patients treated with nedocromil sodium had improvements in symptoms with statistically significant reductions recorded for eye itching (P less than or equal to .04), conjunctival injection (P less than or equal to .001), and overall disease severity (P less than or equal to .001) as compared to the placebo-treated group. Adverse events were minor and transient. We concluded that nedocromil sodium 2% ophthalmic solution administered twice daily is effective in relieving major symptoms associated with seasonal allergic conjunctivitis.
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A prospective, randomized trial of inpatient vs. outpatient bowel preparation for elective colorectal surgery was performed in 100 consecutive patients. Bowel preparation was standardized for both groups and consisted of 4 liters of Colyte (Reed & Carnrick, Piscataway, NJ) and oral neomycin and Flagyl (G. D. Searle & Co., Skokie, IL) the day before surgery. Patients were randomized into four subcategories: ileocolostomy, colocolostomy, abdominal perineal resection, and other. Tap water enemas were administered on the morning of surgery to ensure and adequate mechanical preparation. Ninety-six percent of the inpatient group and 97 percent of the outpatient group were able to drink three-fourths or more of the oral lavage preparation (P = 0.789, Fisher's exact text). A mean of 2.26 tap water enemas was required to achieve clear returns for the inpatient group, compared with 2.28 tap water enemas for the outpatient group (P = 0.221, Fisher's exact test). The adequacy of the bowel preparation as graded by the primary surgeon was good (84 percent), fair (12 percent), and poor (4 percent) in the outpatient group (P = 0.673, Fisher's exact test). Wound infection developed in 4 percent of the inpatient group and 4 percent of the outpatient group (P = 1.0, Fisher's exact test). Anastomotic leak of intra-abdominal abscess was seen in one patient in each group (P = 1.0, Fisher's exact test). We conclude that outpatient bowel preparation is as effective as inpatient bowel preparation for elective colorectal surgery and offers the advantage of cost savings and shorter hospitalization.
Appropriate care of a patient with primary lymphoma of the penis requires consideration of the diagnoses, thorough evaluation, and knowledge of the various therapeutic approaches. A patient is presented with brief review of similar cases together with the rationale for the use of radiation therapy and chemotherapy rather than surgery.
The polymerization shrinkage of light-cured dental composite resins has been reported to cause a marginal gap between the cavity wall and the restoration, leading to the premature and/or tensile stress failure of the composite restoration. This study measured the volumetric shrinkage of six light-cured posterior composites by measuring specific gravity differences between uncured and cured composite test specimens, using a modified version of ASTM method D792 "Specific Gravity and Density of Plastics by Displacement." The measured volumetric shrinkage ranged from 1.35% to 3.22%.
Three-dimensional (3-D) treatment planning is a labor-intensive process with contouring of the target volume and critical normal tissues being a significant time-consuming component. The use of 3-D treatment planning on a routine basis may be limited by the time required to complete treatment plans. Despite the need to increase the efficiency of the process, there is little literature addressing the speed and accuracy of contouring systems. In an attempt to initiate systematic analysis of the contouring process, data sets consisting of 10 CT images each were developed on two patients with esophageal carcinoma. Nine different operators manually contoured structures (target volume, spinal canal, lungs) on the data sets using four different contouring systems present in our department. These included both commercially available systems and those developed by the authors. There was a wide variation in the hardware and software characteristics of these systems. The time required to contour the CT data sets was recorded and analyzed. The contouring accuracy was assessed by comparison with a standard template derived from the CT data set for each image. The contouring time was found to be dependent on the system design, previous contouring experience, and the type of drawing instrument (lightpen vs mouse). The mean contouring time ranged from 26 minutes per patient for the fastest system to 41 minutes for the slowest. Potential clinically significant errors in contouring were rare for the spinal canal and lungs but present at a greater rate for the target volume (30.3%). The implications of this finding are discussed.
The d.c. electrical conductivity of dry phospholipid films is increased by some 8-11 orders of magnitude by the adsorption of iodine vapor. The conductivity of these films has been found to increase as a function of iodine 'vapor pressure' and the quantitative relationship between electrical conductivity and the adsorbed iodine has been determined. Films composed of phospholipids with unsaturated hydrocarbon chains are some three orders of magnitude more electrically conductive than are films of phospholipids containing saturated hydrocarbon chains. Optical spectroscopic measurements show the development of absorption bands centered near 294 nm and 365 nm, upon iodine adsorption. These bands are much more intense for unsaturated phospholipids than for saturated ones. X-ray diffraction studies show that exposure to iodine decreases the thickness of phospholipid bilayers containing unsaturated hydrocarbon chains but does not change the thickness of bilayers containing only saturated chains. The electrical response of the lipid films, upon exposure to iodine, suggests their possible use as iodine sensors.
High-dose prochlorperazine 0.8 mg/kg administered intravenously 30 min pre and 7 h 30 min post the initial dose of emetogenic chemotherapy was compared to high-dose metoclopramide 2 mg/kg over 20 min every 2 h for five doses starting 30 min prior to chemotherapy in a randomised, double-blind, parallel subjects design study. On the prochlorperazine arm intravenous dextrose placebos every 2 h maintained blinding. Complete suppression of vomiting occurred in 42% on metoclopramide (53% with non-cisplatin regimens) and 36% on prochlorperazine (52% with non-cisplatin-containing regimens) while major responses (2 or less vomits) occurred in 58% on metoclopramide and 54% on prochlorperazine. In patients who vomited after cisplatin, prochlorperazine achieved a significantly shorter duration of vomiting, a median of 5 h compared to 15 h on metoclopramide (P = 0.03). The response rate to prochlorperazine for cisplatin-induced emesis between 12 and 24 h was significantly better than for metoclopramide (prochlorperazine = 0.02). Toxicities were equivalent except for significantly greater sedation and dry mouth on prochlorperazine. Extrapyramidal reactions were recorded equally on both arms but were only severe enough to stop treatment on metoclopramide. The metoclopramide regimen was five times as expensive as prochlorperazine. High-dose prochlorperazine is an active and cost-effective antiemetic.
We performed a quantitative assessment of the risk of lung cancer from exposure to cadmium based on a retrospective cohort mortality study of cadmium-exposed workers. The study population consisted of white male workers who were employed for at least 6 months at a cadmium smelter between January 1, 1940, and December 31, 1969, and who were first employed at the facility on or after January 1, 1926. The study findings were analyzed using a modified life-table analysis to estimate standardized mortality ratios (SMRs), and various functional forms (i.e., exponential, power, additive relative rate, and linear) of Poisson and Cox proportional hazards models to examine the dose-response relationship. Estimates of working lifetime risk (45 years) were developed using an approach that corrects for competing causes of death. An excess in mortality from lung cancer was observed for the entire cohort (SMR = 149, 95% confidence interval (CI) = 95, 222). Mortality from lung cancer was greatest among non-Hispanic workers (SMR = 211, 95% CI = 131, 323), among workers in the highest cadmium exposure group (SMR = 272, 95% CI = 123, 513), and among workers with 20 or more years since the first exposure (SMR = 161, 95% CI = 100, 248). A statistically significant dose-response relationship was evident in nearly all of the regression models evaluated. Based on our analyses, the lifetime excess lung cancer risk at the current Occupational Safety and Health Administration standard for cadmium fumes of 100 micrograms/m3 is approximately 50 to 111 lung cancer deaths per 1000 workers exposed to cadmium for 45 years.
Acute cholecystitis, morbid obesity, and previous upper abdominal surgery have been reported as relative contraindications to laparoscopic cholecystectomy. An analysis of 706 laparoscopic cholecystectomies performed at our institution was undertaken to determine if these relative contraindications led to increased morbidity, an increased rate of conversion to the open technique, or longer operating time. One hundred ninety-seven patients demonstrated one or more relative contraindications to laparoscopic cholecystectomy. Morbidity was not increased in patients with these risk factors, but conversion to open cholecystectomy was required in a greater percentage of patients with acute cholecystitis. We favor an attempt at laparoscopic cholecystectomy in patients with these risk factors; however, they should be counseled as to the increased risk of conversion to open cholecystectomy in the presence of acute cholecystitis.
Solid-state 1H, 13C, 14N, and 31P NMR spectroscopy was used to study the effects of the bee venom peptide, melittin, on aligned multilayers of dimyristoyl-, dilauryl- and ditetradecyl-phosphatidylcholines above the gel to liquid-crystalline transition temperature, Tc. Both 31P spectra from the lipid headgroups and 1H resonances from the lipid acyl chain methylene groups indicate that the peptide does not affect the mosaic spread of the lipid molecules at lipid:peptide molar ratios of 10:1, or higher. None of the samples prepared above Tc showed any evidence of the formation of hexagonal or isotropic phases. Melittin-induced changes in the chemical shift anisotropy of the headgroup phosphate and the lipid carbonyl groups, and in the choline 14N quadrupole splittings, show that the peptide has effects on the headgroup order and on the molecular organization in the sections of the acyl chains nearest to the bilayer surface. The spin-lattice relaxation time for the lipid acyl chain methylene protons was found to increase and the rotating-frame longitudinal relaxation time to markedly decrease with the addition of melittin, suggesting that motions on the nanosecond time scale are restricted, whereas the slower, collective motions are enhanced in the presence of the peptide.
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Serious complications resulting from the use of fast neutrons to treat head and neck malignancies are reported in 38 patients. The average interval between treatment and onset of complications was 5.5 years. Significant airways obstruction, requiring a tracheostomy, occurred in two patients, and a gastrostomy or pharyngostomy was performed for intractable dysphagia in six. Eight patients developed osteoradionecrosis: carotid artery rupture occurred in three patients following surgery for residual or recurrent disease. Our experience suggests that complications following fast neutron therapy for head and neck tumours are more severe, more common and occur after a longer time interval than those seen following conventional radiotherapy. Subsequent surgery in the irradiated area is compromised by severely impaired wound healing. When radical surgery is necessary for residual or recurrent disease the entire volume of irradiated tissue must be removed if healing is to be achieved.