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Biomedical subjects

D Welch

Publications and source records attributed to D Welch.

At least 19 recordsLinked to original sources

How we do it: tympanoplasty: are different three- and four-frequency averages comparable?

The results of tympanoplasty may be reported in a variety of ways. Pure-tone audiometry underpins reporting, yet there is no constancy in the pure-tone threshold average used. We examine the relationship between the 0.5, 1, 2 kHz, 0.5, 1, 2, 3 kHz and 0.5, 1, 2, 4 kHz pure-tone audiometry averages. Using audiometric data collected for 77 patients, we have compared hearing threshold using three different frequency averages derived from pure-tone audiometry. The 0.5, 1, 2 kHz, 0.5, 1, 2, 3 kHz and 0.5, 1, 2, 4 kHz three- and four-frequency averages are significantly different, this difference being primarily determined by the changes in the 4-kHz threshold. Using an average including 4 kHz results in 8% few patients achieving an ABG closure to within either 10 dB or 20 dB. When comparing surgical results with others, surgeons should use reports employing comparable audiometric measures of analysis.

Adolescent↗

All-optical hydrogen-sensing materials based on tailored palladium alloy thin films.

Optical reflectance measurements were performed to determine the hydrogen response characteristics of 20-nm-thick Pd-Au (Ag) films. The response characteristics displayed a strong dependence on alpha, mixed alpha/beta, and beta Pd-hydride phases formed in the films. The response time peaks in the alpha --> beta phase transition region (1625 s at 0.4% H(2) for Pd(0.94)Ag(0.06) and 405 s at 1% H(2) for Pd(0.94)Au(0.06)), consistent with critical slowing down phenomena. The alpha --> beta phase transition region was shifted and inhibited by changing the alloy element to Au and increasing its corresponding content to 40 atom %, respectively. Initial hydrogen uptake rate measurements determined that, due to the adsorption of ambient background gases, the rate-limiting step for alpha or beta phase PdH formation is dissociative chemisorption of hydrogen for each palladium alloy film. By tuning the alloy content and composition of the palladium films, the surface properties of the film become more receptive toward the rapid detection of hydrogen and a novel hydrogen-sensing material using Pd alloyed with 40 atom % Au is presented.

Journal Article↗

Clinical findings in 111 ex-Porton Down volunteers.

OBJECTIVE: To determine whether the health of Porton Down volunteers (PDV) has suffered as a result of their participation in medical trials, during which they were exposed to single low dose concentrations of chemical warfare agents. METHODS: Data were obtained from a self-selected series of ex-Porton Down volunteers who attended the MOD's Porton Down Volunteers' Medical Assessment Programme (PDVMAP). One hundred and eleven men attended with a mean age of 62 (range 37-81) years. Information obtained was analysed to determine whether clinical diagnoses and symptoms reported had any relationship to chemical exposures. RESULTS: The diagnoses were not unusual for UK nationals with a mean age of 62 years. The majority of volunteers went to Porton Down in the 1950s and then had a mean age of 19. The mean time between volunteers attending Porton Down and coming to MAP was 42 years. We found no correlation between chemical exposures and later development of established diagnoses, a latent period of 30 years. CONCLUSION: On a clinical basis, no evidence was found to support the hypothesis that participation in Porton Down trials produced any long-term adverse health effects or unusual patterns of disease compared to those of the general population of the same age.

Adult↗

Adult and pediatric liver transplantation for autoimmune hepatitis.

BACKGROUND: Due to the early age that pediatric patients with autoimmune hepatitis (AIH) are transplanted, it is theorized that older AIH patients may have different outcomes than pediatric patients following liver transplantation. METHODS: This is a retrospective review of both the adult and pediatric liver transplant programs consisting of 56 patients. Rejection and recurrence of AIH were determined by biopsy. RESULTS: The autoimmune patient having rejection episodes had a 1.76-fold increase in relative risk to develop autoimmune recurrence when compared to patients without rejection [RR = 1.76; 95% CIRR (1.08, 2.86)]. The pediatric group had a 6.62-fold increase in relative risk to develop colitis following liver transplantation [RR = 6.62; 95% C.I.R.R. (1.36, 32.13); P =.02]. Mean days to recurrence of AIH were similar in both groups (1364 +/- 1074 vs 936; P = NS). There were more hospitalized days in the pediatric group compared to the adults (20.5 +/- 13.3 days vs 51.7 +/- 22.2 days, P =.039). OKT-3 was rarely used (n = 5) in either group (9.3% vs 7.7%, P = NS) and was not correlated with which patients would be weaned from steroids or recurrence. CONCLUSIONS: Based on this review, pediatric patients were more likely to develop ulcerative colitis following liver transplantation and they incurred longer hospital stays than adults. The adult group was more likely to be weaned from steroids, with AIH recurrence unrelated to weaning.

Adult↗

Hepatic artery thrombosis in pediatric liver transplantation.

PURPOSE: Children have been reported to be at greater risk for hepatic artery thrombosis when compared to adults due to small arterial size, nonuse of intraoperative microscope, and postoperative hypercoagulable state. METHODS: We evaluated arterial anastomosis type, intraoperative field magnification, and hepatic artery complications and how they were managed. All patients underwent ultrasound, anticoagulation consisted of 41 mg aspirin once a day, and 35 patients received alprostadil (PGE) for the first 7 days after transplantation. No patients were administered intravenous heparin following liver transplantation. RESULTS: Of the 74 livers transplanted, 36 grafts (48.6%) were whole organ transplants and 38 grafts (51.4%) were partial livers. We observed HAT in 1 of 74 (1.35%) transplants in our pediatric liver transplant population. The only patient with HAT was a young girl with a history of biliary atresia. The occurrence of a hepatic artery thrombosis on day 7 was caused by the migration of an intimal plaque dissection within the artery graft. She was emergently taken back into the operating room for graft revision. This individual currently has a survival time of 426 days following her last transplant. CONCLUSIONS: Hepatic artery thrombosis may be minimized in pediatric liver transplantation without the use of microsurgery. Anticoagulation utilizing ASA and alprostadil is sufficient to avoid HAT. Accurate use of ultrasound is crucial to avoid this complication. Graft and patient salvage is possible with expedient surgical treatment; microsurgery, anticoagulant therapy, site of arterial inflow, and recipient size and weight.

Anastomosis, Surgical↗

Biliary complications after pediatric liver transplantation revisited.

BACKGROUND: Biliary complications in pediatric liver transplantation (PLT) are associated with increased morbidity and mortality. METHODS: Prospectively, data was collected on 89 consecutive liver transplants performed in 82 children. Eighty-nine consecutive PLTs were tracked for transplant type (partial versus whole), recipient age/weight, duct anastomosis type, surgical technique, and biliary complications. Treatments of biliary complications (surgical versus interventional radiology) were also evaluated. RESULTS: Forty-six children (51.7%) received partial transplants and 43 (48.3%) children received whole organs. The average age for whole liver transplanted children was 8.95 +/- 6.62 years and average weight was 36.2 +/- 28.7 kg; for those receiving partial livers, 3.19 +/- 3.52 years and 14.1 +/- 13.0 kg. Duct-to-duct anastomosis was performed for 26 grafts and Roux-en-Y choledochojejunostomy for 63 grafts. Biliary complications occurred in 10 of 89 (11.2%) grafts. Complications included anastomotic strictures in four (40%), bile leak in five (50%), intraparenchymal biloma in one (10%). The complication rate for whole organs was 1/43 (2.3%) and 9/46 (19.6%) for partial organ (P =. 015). No difference in complication rates were seen in type of ductal anastomosis (7.7% vs 12.7%, P = NS). Reoperation for biliary complication was necessary in only 2/10 (20%) of grafts. CONCLUSIONS: Technical advances have reduced the incidence of biliary complications in PLT. Partial liver grafts have a statistically higher risk of biliary complication than whole grafts. Most biliary complications can be managed with radiological intervention without surgical exploration. Pediatric biliary complications are not associated with graft loss.

Anastomosis, Roux-en-Y↗

Direct detection of a microlens in the Milky Way.

The nature of dark matter remains mysterious, with luminous material accounting for at most approximately 25 per cent of the baryons in the Universe. We accordingly undertook a survey looking for the microlensing of stars in the Large Magellanic Cloud (LMC) to determine the fraction of Galactic dark matter contained in massive compact halo objects (MACHOs). The presence of the dark matter would be revealed by gravitational lensing of the light from an LMC star as the foreground dark matter moves across the line of sight. The duration of the lensing event is the key observable parameter, but gives non-unique solutions when attempting to estimate the mass, distance and transverse velocity of the lens. The survey results to date indicate that between 8 and 50 per cent of the baryonic mass of the Galactic halo is in the form of MACHOs (ref. 3), but removing the degeneracy by identifying a lensing object would tighten the constraints on the mass in MACHOs. Here we report a direct image of a microlens, revealing it to be a nearby low-mass star in the disk of the Milky Way. This is consistent with the expected frequency of nearby stars acting as lenses, and demonstrates a direct determination of a lens mass from a microlensing event. Complete solutions such as this for halo microlensing events will probe directly the nature of the MACHOs.

Journal Article↗

Sleep disorders in regional sleep centers: a national cooperative study. Coleman II Study Investigators.

STUDY OBJECTIVE: In the last two decades there has been an increase in the awareness of and professional expertise in sleep disorders. The objective of this study was to determine the spectrum of sleep-related disorders diagnosed in regional sleep centers and compare this to a previous survey published in 1982. DESIGN: A two-month prospective point-prevalence survey SETTING: Nineteen accredited regional sleep centers in the United States. PARTICIPANTS: Patients evaluated at regional sleep centers during a two-month period. INTERVENTIONS: NA. RESULTS: Obstructive sleep apnea, narcolepsy, and restless legs syndrome were the top three reported primary diagnoses with a prevalence of 67.8%, 4.9%, and 3.2%, respectively. The entire range of sleep disorders, however, was represented in the study sample. Nearly a third of patients had either a primary or secondary diagnosis of a non-respiratory sleep disorder. Referral physicians were most likely to be from internal medicine, pulmonary medicine, and otolaryngology. Compared to the previous survey from 1982, there has been an absolute increase in patient referrals/center with a two- to four-fold increase in the number of patients/center with a final diagnosis of a non-respiratory sleep-related problem. Moreover, there has been a greater than twenty-fold increase in the diagnosis of obstructive sleep apnea. CONCLUSION: Regional sleep centers are encountering increasing patient referrals and a broad range of sleep-related disorders. The predominant reasons for referral are related to obstructive sleep apnea, narcolepsy, and restless legs syndrome.

Adult↗

An outbreak of multidrug-resistant pneumococcal pneumonia and bacteremia among unvaccinated nursing home residents.

BACKGROUND: Outbreaks of pneumococcal disease are uncommon and have occurred mainly in institutional settings. Epidemic, invasive, drug-resistant pneumococcal disease has not been seen among adults in the United States. In February 1996, there was an outbreak of multidrug-resistant pneumococcal pneumonia among the residents of a nursing home in rural Oklahoma. METHODS: We obtained nasopharyngeal swabs for culture from residents and employees. Streptococcus pneumoniae isolates were serotyped and compared by pulsed-field gel electrophoresis. A retrospective cohort study was conducted to identify factors associated with colonization and disease. RESULTS: Pneumonia developed in 11 of 84 residents (13 percent), 3 of whom died. Multidrug-resistant S. pneumoniae, serotype 23F, was isolated from blood and sputum from 7 of the 11 residents with pneumonia (64 percent) and from nasopharygeal specimens from 17 of the 74 residents tested (23 percent) and 2 of the 69 employees tested (3 percent). All the serotype 23F isolates were identical according to pulsed-field gel electrophoresis. Recent use of antibiotics was associated with both colonization (relative risk, 2.3; 95 percent confidence interval, 1.3 to 4.2) and disease (relative risk, 3.6; 95 percent confidence interval, 1.2 to 10.8). Only three residents (4 percent) had undergone pneumococcal vaccination. After residents received pneumococcal vaccine and prophylactic antibiotics, there were no additional cases of pneumonia, and the rates of carriage decreased substantially. CONCLUSIONS: In this outbreak a single pneumococcal strain was disseminated among the residents and employees of a nursing home. The high prevalence of colonization with a virulent organism in an unvaccinated population contributed to the high attack rate. Clusters of pneumococcal disease may be underrecognized in nursing homes, and wider use of pneumococcal vaccine is important to prevent institutional outbreaks of drug-resistant S. pneumoniae infection.

Adult↗

Phase Ib trial of bryostatin 1 in patients with refractory malignancies.

A Phase Ib trial of bryostatin 1, a macrocyclic lactone and protein kinase C (PKC) activator, was conducted in patients with refractory nonhematological malignancies with the primary goal of determining whether down-regulation of peripheral blood mononuclear cell (PBMNC) PKC activity could be achieved in vivo in humans. Patients (four patients/cohort) received bryostatin 1 (25 microg/m2) as a 1-h infusion weekly three times every 4 weeks, but to study the schedule dependence of pharmacokinetics and pharmacodynamics, the first dose was administered according to one of three schedules: (a) a 1-h infusion; (b) a 24-h infusion; or (c) a split course (12.5 microg/m2 as a 30-min infusion) on days 1 and 4. Conventional toxicities (grades I-III) included myalgias, fever, anemia, fatigue, phlebitis, and headache; in addition, two patients in cohort 3 experienced transient elevations in liver function tests, although these patients had preexisting liver metastases. No objective clinical responses were encountered. Effects on PBMNC PKC activity were heterogeneous. Several patients in cohorts 1 and 2 experienced significant declines in activity (approximately 50%) that were sustained in some cases for periods of > or = 72 h. Comparison of 72-h with baseline values for all three patient cohorts combined revealed a trend toward PKC down-regulation (P = 0.06; signed rank test). For each schedule, plasma bryostatin 1 levels were below the level of detection of a platelet aggregation-based bioassay (3-4 nm). Bryostatin 1 administration failed to produce consistent alterations in lymphocyte immunophenotypic profiles, interleukin 2-induced proliferation, or cytotoxicity, although two of three samples from patients in cohort 3 did show significant posttreatment increases in proliferation. Moreover, in some patients, bryostatin 1 treatment increased lymphokine-activated killer cell activity. These findings indicate that bryostatin 1 doses of 25 microg/m2 can induce in vivo PBMNC PKC down-regulation in at least a subset of patients and raise the possibility that higher bryostatin 1 doses may be more effective in achieving this effect.

Adult↗

Discriminability of electrocutaneous stimuli after topical anesthesia: detection-theory measurement of sensitivity to painful stimuli.

In three experiments on the psychophysical measurement of pain, electrocutaneous currents were applied to the volar surface of the forearm. In the first experiment, a conventional category scaling method was compared with the rating method of signal detection. The results of both methods were analyzed in detection-theory terms to derive receiver operating characteristic curves and measures of the discriminability of adjacent currents. The rating method yielded larger discriminability values than the category scale did, and that method was therefore used in the subsequent experiments to examine the effect of a topical anesthetic on discriminability. When the stimuli were applied through surface electrodes, no effect of the topical anesthetic on discriminability was found, but when the stimuli were applied to a more localized area by intradermal needle electrodes, a dose-dependent effect of the anesthetic on discriminability occurred. For this experiment, the slope of the cumulative sensitivity function increased with increasing elapsed time since the removal of the anesthetic. This result is congruent with the theory that discriminability can serve as a measure of sensitivity to painful stimuli.

Anesthesia↗

Quantitative analysis of endoneurial T-cells in human sural nerve biopsies.

We used immunocytochemical methods on sural nerve biopsies from 42 patients with peripheral neuropathy to identify mononuclear cells, determine whether lymphocytic infiltration occurs in a variety of neuropathies, and identify the subtypes of lymphocytes. Immunostained cells were present in 76% of nerve biopsies. CD3+ cells (T lymphocytes) were greatest in density (cells/mm2). In patients whose CD4:CD8 T cell ratio was measured also in blood and cerebrospinal fluid, the CD4:CD8 T cell ratio was similar in all three compartments. These findings suggest that T lymphocytes are frequently present in nerves obtained from patients with various types of neuropathies and raise questions about factors that attract T lymphocytes into nerve that may be important in pathogenesis.

Biopsy↗

Detection of plasmid DNA from all Chlamydia trachomatis serovars with a two-step polymerase chain reaction.

A polymerase chain reaction was used to amplify a 137-base-pair sequence of DNA from a Chlamydia trachomatis plasmid. Various parameters of the polymerase chain reaction were explored, and it was found that two short steps per reaction cycle were sufficient to achieve 10(12)-fold amplification in less than 1 h. By use of this procedure, 10(-18) g of a sequence of plasmid DNA, representing the amount of that sequence found in one C. trachomatis bacterium, was amplified to the point where it was clearly visible on an ethidium bromide-stained polyacrylamide gel under UV light. DNA from intact cells from each of the 15 serovars of C. trachomatis could also be amplified for visualization. With this procedure, the presence or absence of C. trachomatis DNA in a sample could be established in less than 1.5 h. The speed and extreme sensitivity of this detection procedure may make it a useful method for the detection of C. trachomatis, and similar techniques should be possible for any type of bacteria.

Base Sequence↗