Biomedical subjects
Publications and source records attributed to R Palmer.
A workshop for 18 doctors and managers at the start of their careers revealed considerable differences of opinion about the roles of the two groups. Managers were more firmly convinced than doctors that their role in hospitals was indispensable. Doctors saw managers as being in the pockets of politicians. The workshop did not change doctors' views.
We describe three mutations of the red-cell anion exchangerband 3 (AE1, SLC4A1) gene associated with distalrenal tubular acidosis (dRTA) in families from Malaysia and Papua NewGuinea: Gly(701)-->Asp (G701D), Ala(858)-->Asp(A858D) and deletion of Val(850) (DeltaV850). The mutationsA858D and DeltaV850 are novel; all three mutations seem to berestricted to South-East Asian populations. South-East Asianovalocytosis (SAO), resulting from the band 3 deletion of residues400-408, occurred in many of the families but did not itselfresult in dRTA. Compound heterozygotes of each of the dRTA mutationswith SAO all had dRTA, evidence of haemolytic anaemia and abnormal red-cell properties. The A858D mutation showed dominant inheritance and therecessive DeltaV850 and G701D mutations showed a pseudo-dominantphenotype when the transport-inactive SAO allele was also present. Red-cell and Xenopus oocyte expression studies showed that theDeltaV850 and A858D mutant proteins have greatly decreased aniontransport when present as compound heterozygotes (DeltaV850/A858D,DeltaV850/SAO or A858D/SAO). Red cells with A858D/SAO had only 3% ofthe SO(4)(2-) efflux of normal cells, thelowest anion transport activity so far reported for human red cells. The results suggest dRTA might arise by a different mechanism for eachmutation. We confirm that the G701D mutant protein has an absoluterequirement for glycophorin A for movement to the cell surface. Wesuggest that the dominant A858D mutant protein is possibly mis-targetedto an inappropriate plasma membrane domain in the renal tubular cell,and that the recessive DeltaV850 mutation might give dRTA because ofits decreased anion transport activity.
BACKGROUND: To determine the survival results, patterns of relapse, and organ preservation effects of a targeted chemoradiation protocol for patients with advanced (stage III-IV) carcinoma of the head and neck. METHODS: Analysis of 213 patients with stage III-IV squamous cell carcinoma treated at UT Memphis between June 1993 and March 1998. Treatment included weekly intra-arterial infusions of cisplatin (150 mg/m(2)/ week x 4) rapidly delivered to the tumor bulk, simultaneous intravenous thiosulfate for systemic drug neutralization, and conventional external-beam irradiation (180-200 cGy/fraction) to a total dose of 68-72 Gy. RESULTS: Tumor response, toxicity, disease control above the clavicle, pattern of relapse, and survival. There were 89 events of grade III-IV toxicity and 6 treatment-related deaths (grade V). Complete response in the primary and regional sites was obtained in 171 of 213 (80%) and 92 of 151 (61%), respectively. The rate of clearance of regional disease after neck dissection was 98%. There were 51 of 195 recurrences (26%): 11 local (5.6%), 5 regional (2.6%), and 35 distant (17.9%). The Kaplan Meier plot projections for overall and cancer-related 5-year survival was 38.8% and 53.6%, respectively, whereas disease control above the clavicle was 74.3%. CONCLUSIONS: We believe this chemoradiation protocol represents an effective management scheme for patients with advanced head and neck cancer with a high rate of organ preservation and possibly improved survival.
On radiation safety grounds there is concern about the morbidity attributable to routine radiographs of the spine for the identification of new fractures in large-scale trials of fracture prevention. However, the role of the potentially safer low-radiation-dose technique of vertebral morphometry performed by third generation dual-energy X-ray absorptiometry equipment requires evaluation for use in clinical trials. We have therefore investigated the short-term inter-scan imprecision as well as the imprecision attributable to different-day analyses by the same operator and differences in analyses by different operators. The volunteer subjects were participants in a pilot study for a randomized controlled trial of hormone replacement therapy (Women's International Study of long Duration Oestrogen after Menopause, WISDOM). Each subject had two morphometric X-ray analysis scans separated by 2-4 weeks. Exclusions were women with densitometrically defined osteoporosis, as defined by the WHO criterion, and women with a body mass index exceeding 30.9 kg/m2. On average, the women were 58.7 years of age and had bone mineral density values in the lumbar spine which were about 0.7 SD units higher than a reference US female age-matched population. Scans were assessed from vertebrae T7 through L4. In the study there were no clinically significant differences in performance between the Hologic QDR 4500A and the Lunar Expert XL equipment. Between-scan imprecision was significantly worse than imprecision attributable to reanalysis of the same scan by a different operator or the same operator after an interval. Vertebral level had an effect on measurement uncertainty, especially at the level of the diaphragm and at T7. Coefficients of variation, expressed as percentages of mean values, were better for absolute height measurements than for height ratios, ranging from 1.75% to 3.40% for the three heights measured on three separate machines and from 2.34% to 4.11% for the two height ratios. These results compared favorably with the equivalent figures from a parallel study of morphometry precision undertaken using standard lateral radiographs of the thoracic and lumbar spine (3.1-3.6% and 3.8-3.9%, respectively). We conclude that in trials of prevention therapy in women (or men) selected for not having osteoporosis, low-dose vertebral morphometry using the Hologic 4500A, the Lunar Expert XL or similar equipment is preferable on safety grounds to the classical technique based on standard radiographs, although conventional radiology may still be required in those with prevalent or incident deformities to exclude causes other than osteoporosis. The place of this low-dose technique in trials performed on patients with osteoporosis requires further study.
BACKGROUND: Clarithromycin has an established efficacy and safety profile in the treatment of respiratory tract infections. OBJECTIVE: The purpose of this study was to compare the clinical and bacteriologic efficacy and tolerability of clarithromycin extended-release and immediate-release formulations in patients with acute exacerbation of chronic bronchitis (AECB). METHODS: In a phase III, randomized, double-blind, parallel-group, multicenter study. patients aged > or =12 years with signs and symptoms of AECB and a productive cough with purulent sputum received treatment with extended-release (two 500-mg tablets once daily) or immediate-release (one 500-mg tablet twice daily) clarithromycin for 7 days. Assessments were performed before treatment, within 48 hours after treatment, and at the test-of-cure visit (study days 19-21). Patients who took > or =1 dose of study drug were included in the safety analysis. RESULTS: Of 620 patients randomized and treated, 182 were clinically and bacteriologically assessable (100 in the extended-release group and 82 in the immediate-release group). Treatment groups were well matched with respect to demographic characteristics and medical and social history. At the test-of-cure visit, 83% (83/100) of patients in the extended-release and 82% (67/82) of patients in the immediate-release group achieved clinical cure; 86% (85/99) and 85% (70/82), respectively, demonstrated bacteriologic cure. Overall pathogen eradication rates were 86% (100/116) in the extended-release group and 88% (86/98) in the immediate-release group. The most frequently reported adverse events were diarrhea (6% in extended-release group vs 4% in immediate-release group; no significant difference), taste alterations (4% in each group), and nausea (3% in each group); no clinically meaningful changes in laboratory values or vital signs, as assessed by the investigator, were observed. CONCLUSION: This study suggests that clarithromycin extended-release and immediate-release formulations have equivalent clinical and bacteriologic efficacy and tolerability in patients with AECB.
BACKGROUND: Clarithromycin has an established bacteriologic efficacy and safety profile in the treatment of respiratory tract infections. OBJECTIVE: This study compares the efficacy and tolerability of extended-release and immediate-release formulations of clarithromycin in patients with acute maxillary sinusitis. METHODS: Fourteen days' treatment with once-daily clarithromycin was compared with the immediate-release, twice-daily formulation in a phase III, randomized, double-blind, parallel-group, multicenter study. Patients aged > or =12 years with signs, symptoms, and a radiologically confirmed diagnosis of acute maxillary sinusitis were eligible. Patients were assessed before treatment, within 48 hours after treatment, on study days 16 to 18, and at the test-of-cure visit on study days 24 to 31. Patients who received > or =1 dose of study drug were included in the safety analysis. RESULTS: Of 283 patients treated, 245 were included in the efficacy analysis (122 in the extended-release group, 123 in the immediate-release group). Treatment groups were well matched with respect to demographic characteristics and medical condition and history. At the test-of-cure visit, 85% of patients in the clarithromycin extended-release group and 79% in the immediate-release group were deemed clinical cures; 89% and 91% in the extended-release and immediate-release groups, respectively, demonstrated radiographic success. Overall incidences of study drug-related adverse events were similar in the 2 treatment groups (32% in the extended-release group and 28% in the immediate-release group); however, significantly fewer patients receiving extended-release clarithromycin (2/142 11%]), compared with those receiving the immediate-release formulation (10/141 [7%]: P = 0.02) discontinued therapy because of drug-related gastrointestinal symptoms or abnormal taste. No clinically meaningful changes in laboratory values or vital signs were observed during the study. CONCLUSION: Although the efficacy of the 2 formulations was comparable, once-daily clarithromycin extended-release was better tolerated than the twice-daily immediate-release formulation by patients with acute maxillary sinusitis.
Previous work on in-situ calibration of force platforms has focused primarily on behaviour under static loading conditions. The prototype described in this paper is a dynamic system, designed to approximate the loading profile generated during human gait. The design, construction and performance of an oscillating lead pendulum assembly is described; including three-dimensional visual performance assessment and rigorous multi-component force analysis. No significant difference was found between measured data and a theoretical profile for vertical force and angular displacement. A significant difference was found for the horizontal force component. The authors believe that further development of this prototype model will allow accurate routine dynamic calibration.
We report a 3-year-old girl with a 12-month history of an acquired lipoatrophy that was rapidly progressive. Her karyotype revealed additional material on chromosome 10 at the 10q26 location. The human pancreatic lipase gene maps to chromosome 10q24-26, and we postulate an association. Lipoatrophic panniculitis describes the panniculitides in which atrophy is a feature. The classification of these diseases is confusing in the literature and the precise diagnosis still relies on a combination of clinical and laboratory assessment. Our finding of a chromosomal abnormality on chromosome 10q26 has not been described previously.
OBJECTIVE: Determine whether prehospital advanced life support (ALS) improves the survival of major trauma patients and whether it is associated with longer on-scene times. METHODS: A 36-month retrospective study of all major trauma patients who received either prehospital bag-valve-mask (BVM) or endotracheal intubation (ETI) and were transported by paramedics to our Level I trauma center. Logistic regression analysis determined the association of prehospital ALS with patient survival. RESULTS: Of 9,451 major trauma patients, 496 (5.3%) had either BVM or ETI. Eighty-one percent received BVM, with a mean Injury Severity Score of 29 and a mortality rate of 67%; 93 patients (19%) underwent successful ETI, with a mean Injury Severity Score of 35 and a mortality rate of 93%. Adjusted survival for patients who had BVM was 5.3 times more likely than for patients who had ETI (95% confidence interval, 2.3-14.2, p = 0.00). Survival among patients who received intravenous fluids was 3.9 times more likely than those who did not (p = not significant). Average on-scene times for patients who had ETI or intravenous fluids were not significantly longer than those who had BVM or no intravenous fluids. CONCLUSION: ALS procedures can be performed by paramedics on major trauma patients without prolonging on-scene time, but they do not seem to improve survival.
OBJECTIVE: To determine the prevalence and assess documentation by emergency department (ED) physicians (EPs) of impaired mental status in elderly ED patients. METHODS: Cross-sectional, observational study. Subjects: convenience sampling of ED patients greater than or equal to 70 years of age. Patients were screened for cognitive impairment with the Orientation Memory Concentration exam (OMC), and for delirium with the Confusion. Assessment Method screening tool (CAM). A positive OMC or CAM was considered indicative of impaired mental status. Patients with delirium were excluded from the cognitive impairment screen. EPs were blinded to screening results. Physician documentation, dispositions, and referrals were abstracted from chart review. Proportions and 95% confidence intervals (CIs) are reported. RESULTS: 180 patients were screened. 46 patients (26%; 95% CI = 19% to 32%) had impaired mental status. 22 of these (12%; 95% CI = 7% to 17%) had delirium, and 24 (13%; 95% CI = 8% to 18%) had moderate to severe cognitive impairment. Of all patients with impaired mental status, only 14 (30%; 95% CI = 18% to 46%) had documentation of any impairment by the EP (10 with delirium (46%; 95% CI = 24% to 68%), and 5 with cognitive impairment (21%; 95% CI = 7% to 42%). 7 of 22 (32%; 95% CI = 14% to 55%) patients with delirium were discharged home. Only 2 of 16 patients with impaired mental status (12.5%) were discharged home with plans noted to address the impairment. CONCLUSIONS: Impairment in mental status is highly prevalent among older ED patients. Lack of documentation and referrals by EPs suggests lack of recognition of these problems. Further education of physicians is needed to improve care in these areas.
Published in: Acad Emerg Med. 2000; 7: 563-4.
Explore the source record for details and available documents.
Recombinant human bone morphogenetic protein-2 (rhBMP-2) was biotinated, and the bioactivity of biotinated protein was assessed in vitro (alkaline phosphate induction in limb bud cells) and in vivo (osteoinduction in the rat ectopic assay). Amino-biotinated rhBMP-2 exhibited an increase in bioactivity whereas carboxy-biotinated rhBMP-2 did not exhibit any changes in bioactivity in vitro. Avidin inhibited the bioactivity of amino-biotinated but not carboxyl-biotinated rhBMP-2. Both amino- and carboxy-modified rhBMP-2 induced bone at an equivalent level to that of unmodified rhBMP-2 in vivo. The presence of avidin did not affect the osteoinductive activity of both types of biotinated rhBMP-2. The overall results indicated that binding to a large protein, avidin, might affect rhBMP-2 activity in vitro depending on the binding site; however, in vivo activity was unaffected by the avidin binding.
Autogenous grafts are considered to be the most predictable for replacement of deficient bones to facilitate implant treatment. Augmentation of soft tissue may also be required to improve aesthetics and function.
Implant surgery protocols differ slightly with individual systems. However, basic surgical principles are required to ensure successful osseointegration of the implant in the correct location which allows good aesthetics and loading.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.