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D J Williams

Publications and source records attributed to D J Williams.

At least 73 records · Page 4Linked to original sources
PubMed1999

Unrestrained stochastic dynamics simulations of the UUCG tetraloop using an implicit solvation model.

Three unrestrained stochastic dynamics simulations have been carried out on the RNA hairpin GGAC[UUCG] GUCC, using the AMBER94 force field (Cornell et al., 1995. J. Am. Chem. Soc. 117:5179-5197) in MacroModel 5.5 (Mohamadi et al., 1990. J. Comp. Chem. 11:440-467) and either the GB/SA continuum solvation model (Still et al., 1990. J. Am. Chem. Soc. 112:6127-6129) or a linear distance-dependent dielectric (1/R) treatment. The linear distance-dependent treatment results in severe distortion of the nucleic acid structure, restriction of all hydroxyl dihedrals, and collapse of the counterion atmosphere over the course of a 5-ns simulation. An additional vacuum simulation without counterions shows somewhat improved behavior. In contrast, the two GB/SA simulations (1.149 and 3.060 ns in length) give average structures within 1.2 A of the initial NMR structure and in excellent agreement with results of an earlier explicit solvent simulation (Miller and Kollman, 1997. J. Mol. Biol. 270:436-450). In a 3-ns GB/SA simulation starting with the incorrect UUCG tetraloop structure (Cheong et al., 1990. Nature. 346:680-682), this loop conformation converts to the correct loop geometry (Allain and Varani, 1995. J. Mol. Biol. 250:333-353), suggesting enhanced sampling relative to the previous explicit solvent simulation. Thermodynamic effects of 2'-deoxyribose substitutions of loop nucleotides were experimentally determined and are found to correlate with the fraction of time the ribose 2'-OH is hydrogen bonded and the distribution of the hydroxyl dihedral is observed in the GB/SA simulations. The GB/SA simulations thus appear to faithfully represent structural features of the RNA without the computational expense of explicit solvent.

Base Sequence↗
PubMed1999

Experience with heparin-bonded collagen-coated grafts for infrainguinal bypass.

The perfect conduit for infrainguinal reconstructive surgery does not exist. When autologous vein is not available, then a prosthetic graft must be used. The use of a heparin-bonded graft has the theoretical advantage of reducing smooth muscle cell proliferation and thrombus formation, thereby reducing occlusion rates. The application of a collagen layer to the external surface of the graft serves to reduce transfabric haemorrhage. Forty-six patients underwent 47 infrainguinal reconstructions using heparin-bonded collagen-coated Dacron grafts over a 4-year period. Twenty grafts were for disabling claudication and 27 for critical ischaemia. Twenty-two grafts were to the above knee popliteal artery (47%), 10 to the below knee popliteal (21%) and 15 to one of the crural vessels (32%). There was a cumulative patency at 4 years of 69% for the above knee grafts, and 30-month patency of 58% and 45% for the below knee and crural grafts, respectively. There were three deaths over the study period and eight patients required major amputations.

Aged↗
PubMed1999

Experimental assessment of proximal stent-graft (InterVascular) fixation in human cadaveric infrarenal aortas.

OBJECTIVES: This paper investigates the radial deformation load of an aortic endoluminal prosthesis and determines the longitudinal load required to cause migration in a human cadaveric aorta of the endoprosthesis. DESIGN AND METHODS: The endovascular prosthesis under investigation was a 24 mm diameter, nitinol, self-expanding aortoaortic device (InterVascular, Clearwater, Florida, U.S.A.). Initially, a motorised digital force gauge developed an incremental load which was applied to the ends of five stent-grafts, to a maximum of 10 mm (42%) compression. Secondly, using a simple bench model, each ends of four stent-grafts were deployed into 10 cadaveric experimental aneurysm necks and a longitudinal load applied to effect distraction. RESULTS: Increasing load produced increasing percentage deformation of the stent-grafts. The mean longitudinal distraction load for an aneurysm neck of 20 mm was 409 g (200-480 g), for 15 mm was 277 g (130-410 g) and for 10 mm was 218 g (130-340 g). The aneurysm diameter and aortic calcification had p values of 0.002 and 0.047, respectively, while the p value for aneurysm neck length was less than 0.00001. CONCLUSIONS: These results suggest that there is a theoretical advantage of oversizing an aortic prosthesis and that sufficient anchorage is achieved in an aortic neck of 10 mm to prevent migration when fully deployed.

Aorta, Abdominal↗
PubMed1999

The history of Werner Spalteholz's Handatlas der Anatomie des Menschen.

Werner Spalteholz's Handatlas der Anatomie des Menschen is one of the most elegantly illustrated anatomical atlases of all time. Originally published in Leipzig as three volumes from 1895 to 1903, the atlas is still widely used and remains highly regarded by many. The atlas was remarkably popular during the first half of the 20th century, especially the English version in North America and the UK. Unfortunately, the original illustrations and printing plates for the work disappeared following the Second World War and their fate remains a mystery. And, in spite of the atlas's popularity, little is known to the men who prepared the artwork for Spalteholz. It is commonly believed that Max Brödel contributed illustrations to the atlas, but a close examination of the work does not confirm this. A century after its inception, Spalteholz's atlas remains a classic milestone in the history of anatomical illustration.

Anatomy, Artistic↗
PubMed1999

Azithromycin as treatment for disseminated Mycobacterium avium complex in AIDS patients.

This multicenter, randomized, dose-ranging study was performed to determine the safety and efficacy of two different doses of azithromycin for treating disseminated Mycobacterium avium complex (MAC) in patients with AIDS. Eighty-eight AIDS patients with symptoms and blood cultures consistent with disseminated MAC were treated with 600 or 1,200 mg of azithromycin daily for 6 weeks; 62 patients completed the entire 6 weeks of study. Of note, this study was done prior to the time when combination antiretroviral or anti-MAC regimens were the standard of care. Over the 6-week study period, symptomatic improvement was noted in both dose groups. Microbiological responses were comparable, with mean decreases of 1. 5 and 2.0 log CFU/ml in the high- and low-dose groups, respectively. Sterilization of blood cultures occurred in 54% of samples; patients with lower baseline colony counts were more likely to achieve culture negativity. Resistance developed in one patient. Gastrointestinal symptoms were the most common side effects and were more frequent in patients receiving 1,200 mg. Azithromycin is a useful alternative treatment for disseminated MAC infection in AIDS patients. Symptomatic improvement correlates with measurable decreases in mycobacterial load.

AIDS-Related Opportunistic Infections↗
PubMed1999

Questionnaire survey of interpreter use in accident and emergency departments in the UK.

OBJECTIVE: To determine the support for a national telephone interpreter service from accident and emergency (A&E) departments across the UK, and the factors that may influence that support. To determine the nature of interpreter needs for these departments. METHODS: Postal questionnaire survey of 255 A&E departments in the UK. RESULTS: A total of 197 replies were received, a response rate of 77.3%. Altogether 186 respondents answered the question on support for a national telephone interpreter service and 124 (66.7%) would support one. Those departments in favour were no more likely to have required an interpreter in the last seven days (chi 2 = 0.16, df = 1, p = 0.69), be in the inner city (Fisher's exact test, two sided probability, p = 1), have predominantly local population needs compared with tourist needs (chi 2 = 0.65, df = 1, p = 0.42), or be current users of a telephone interpreter service (chi 2 = 0.01, df = 1, p = 0.93). Seventy-nine of 180 (42.9%) departments had used some form of interpreter in the seven days preceding completion of the survey. Seventy-six of 86 (88.4%) of those departments using face to face interpreters had experienced difficulty obtaining an interpreter out of hours. Nationally, the following proportion of all A&E departments listed the named language as occurring among the three most common languages requiring interpretation: French 0.46 (95% confidence interval 0.42 to 0.50), Urdu 0.30 (0.26 to 0.34), and German 0.24 (0.21 to 0.27). CONCLUSIONS: There is widespread need and support for a national telephone interpreter service that would match the requirements of 24 hour emergency health care provision.

Communication Barriers↗
PubMed1998

Review of US medical school finances, 1996-1997.

Based on data from the Annual Medical School Questionnaire of the Liaison Committee on Medical Education, to which 100% of schools responded, the revenues that supported the programs and activities of the 125 accredited medical schools in the United States totaled $34897 million in 1996-1997. A large proportion (78.9%) of these revenues was derived from 3 sources: practice plans, grants and contracts, and hospital support. Both public and private medical schools, in aggregate, have continued to experience growth throughout the last decade but at a progressively slower rate, primarily because of a slowing in the growth of practice plan revenues. Federal revenues supporting research in public and private medical schools since 1992-1993 have grown at annualized, constant-dollar rates of 5.6% and 4%, respectively. Growth in state and local appropriations to public medical schools has tended to lag behind inflation. Growth in reported revenues from endowments that are used to support programs at private medical schools is on the rise. The aggregate numbers mask considerable variation among schools with regard to changes in financing. A small, but appreciable, number of schools have witnessed a constant-dollar decline in their total practice plan revenues since 1992-1993. The financial data reviewed in this report demonstrate the continued dependence of medical schools on faculty-generated sources of revenue and confirm the perception that medical schools, as a group, are experiencing constraints on the growth of their enterprises.

Data Collection↗
PubMed1998

Safety and tolerability of intravenous-to-oral treatment and single-dose intravenous or oral prophylaxis with trovafloxacin.

BACKGROUND: The new fourth-generation fluoroquinolone, trovafloxacin, is active in vitro against gram-positive and gram-negative organisms, atypical pathogens, and anaerobes, and has pharmacokinetics permitting once-daily intravenous or oral dosing. Safety/tolerability data from phase II/III clinical trials of sequential intravenous alatrofloxacin to oral trovafloxacin and single-dose intravenous or oral prophylaxis are summarized. METHODS: All trials were double-blind, randomized, and multicenter. In multidose trials with alatrofloxacin, 1,257 patients requiring initial intravenous therapy received once-daily alatrofloxacin (trovafloxacin prodrug, 200 or 300 mg/day) followed by oral 200 mg/day trovafloxacin. An additional 444 patients received a single alatrofloxacin or trovafloxacin dose prophylactically for surgical procedures. RESULTS: Therapy with alatrofloxacin was well tolerated. The most common treatment-related adverse events in studies of intravenous alatrofloxacin followed by oral trovafloxacin were nausea, headache, insertion site reaction, and dizziness. In single-dose intravenous or oral prophylaxis studies, insertion-site reaction, pruritus, and insertion-site pain were the most common treatment-related adverse events. No serious quinolone toxicity or drug interactions were reported. The incidence of serious treatment-related adverse events was < 1% in both the alatrofloxacin and comparator groups. In comparative trials, mortality due to all causes after trovafloxacin was similar to that after comparative agents; there was no mortality related to trovafloxacin administration. CONCLUSION: In this large patient sample, intravenous alatrofloxacin followed by oral trovafloxacin was safe and well tolerated. Serious adverse events, such as phototoxicity, cardiovascular toxicity, and hemolytic anemia associated with older fluoroquinolones, were not noted with trovafloxacin. No interactions of trovafloxacin with other drugs were reported. The safety and tolerability of trovafloxacin, along with in vitro activity against key pathogens and pharmacokinetics permitting once-daily administration, support its oral and intravenous use in patients with obstetric, gynecologic, and intra-abdominal infections as well as for prophylaxis of surgical infection.

Administration, Oral↗
PubMed1998

The scope and limitations of the reaction of delta 5-steroids with mercury(II) trifluoroacetate.

The effect of the C-3 substituent on the reaction of androst-5-enes with mercury(II) trifluoroacetate in dichloromethane (modified Treibs oxidation) was investigated. 3 beta-Acyloxyandrost-5-en-17-ones gave 3 beta-acyloxy-6 beta-hydroxyandrost-4-en-17-ones accompanied by 3 beta-acyloxy-6-chloromercuriandrost-5-en-17-ones. 3 beta-Acetoxy-6 beta-trifluoroacetoxyandrost-4-en-17-one and 3 beta-acetoxy-4 beta-trifluoroacetoxyandrost-5-en-17-one were revealed to be intermediates in the reaction. The formation of the chloromercury steroids indicated participation in the reaction by the solvent. With 3 alpha-acetoxyandrost-5-en-17-one as substrate, a complete reversal in the product distribution was observed. 3 beta-Haloandrost-5-en-17-ones gave mainly products that reflected SN1 substitution of the halide. 3 beta-Hydroxy- and 3 beta-trifluoroacetoxyandrost-5-en-17-ones were formed. 3 beta-Methoxyandrost-5-en-17-one afforded in nearly identical yields androst-4-ene-3,17-dione, 3 beta-methoxy-6 beta-hydroxyandrost-4-en-17-one, 3 beta-methoxy-6-chloromercuriandrost-5-en-17-one and 6 beta-hydroxyandrost-4-ene-3,17-dione while androst-5-en-17-one yielded 3 beta,6 beta-dihydroxyandrost-4-en-17-one, androst-5-ene-7,17-dione and androst-4-ene-3,17-dione. The effects of solvent and other mercury salts on the reaction were also studied. Treibs oxidation was successful in chloroform, carbon tetrachloride, and dibromomethane, but not in other solvents tested. 3 beta-Acetoxy-6-bromomercuriandrost-5-en-17-one was obtained in dibromomethane. Replacement of the reagent by mercury(II) trichloroacetate altered the intermediates formed but not the products. Mercury(II) tribromoacetate was unreactive, however.

Androstenes↗
PubMed1998

Presentation, pathology, and outcome of HIV associated renal disease in a specialist centre for HIV/AIDS.

OBJECTIVES: To describe the presentation, pathology, and outcome of biopsy proved renal disease in HIV infected patients at a central London HIV unit from 1992 to 1996. METHODS: Retrospective review of a computerised database and case notes to identify patients with renal disease confirmed by antemortem percutaneous renal biopsy or necropsy. RESULTS: 17 patients were identified, 13 had biopsy and four necropsy confirmed renal disease. Abnormalities included HIV associated nephropathy (HIVAN) in seven (41%) patients, membranous glomerulonephritis (GN) in four (23%), haemolytic uraemic syndrome (HUS) in two (12%), and interstitial nephritis, rhabdomyolysis, IgA nephropathy, and membranoproliferative GN in one patient each. Although renal disease was the first presentation of HIV disease in six (35%) patients the majority had advanced HIV disease (median CD4 count 40 x 10(6)/l). The commonest presentation was acute renal failure (ARF) in 10 (59%) patients, chronic renal failure (CRF) in five (29%), and proteinuria alone in two (12%). Although the majority of patients died during the study period (9/13) only three deaths were attributable to their renal disease. Survival ranged in those with HIVAN from 0 to 31 (median 10) months and, in those with membraneous GN from 1 to 46 (median 29) months. CONCLUSIONS: HIVAN was the commonest renal disease found in this group of patients; however, a variety of other pathologies were seen with variable outcomes. All cases of HIVAN were in patients of African or Afro-Caribbean origin and for the majority this was their first presentation of HIV disease. Nephrologists need to be aware of the possibility of HIV infection in patients presenting with renal disease.

AIDS-Associated Nephropathy↗
PubMed1997

Novel ELISA for detection of Neospora-specific antibodies in cattle.

An enzyme-linked immunosorbent assay (ELISA) to detect antibodies to Neospora species in cattle was developed. Whole formalin-fixed Neospora caninum (NC-Liverpool) tachyzoites were used as antigen and a monoclonal antibody to bovine immunoglobulin light chain and an anti-mouse horseradish peroxidase conjugate were used to reveal bound antibody. A panel of 46 sera, negative by the immunofluorescent antibody test (IFAT), were used in the ELISA at a serum dilution of 1:500 to calculate the negative cut-off value of OD405 = 0.77. There was a 95 per cent agreement between the results of the ELISA and the IFAT with 104 serum samples. The specificity and sensitivity of the ELISA were 96 per cent and 95 per cent, respectively, when compared with the IFAT. No significant cross-reaction was observed with the sera from cattle infected experimentally with Toxoplasma gondii, Cryptosporidium parvum, Babesia divergens, Sarcocystis cruzi, Eimeria alabamensis or E bovis. A significantly modified version of the test is now commercially available.

Animals↗
PubMed1997

Hemolytic uremic syndrome following taipan envenomation with response to plasmapheresis.

We report a case of hemolytic uremic syndrome (HUS) in a 33 year old male who was bitten by a taipan, with apparent massive envenomation. The microangiopathic hemolytic anemia (MAHA) and thrombocytopenic aspects of his HUS appeared to respond to plasmapheresis, but his anuric renal failure persisted. He also had prolonged severe muscular paralysis which gradually began to resolve over the course of two weeks. At this point he suffered a cardiac arrest sustaining severe and subsequently fatal hypoxic brain injury. This case raises the possibility that the taipan venom may have induced HUS by damaging the renal endothelium. His cardiac arrest was not apparently related to his HUS.

Adult↗
PubMed1997

Nitric oxide-mediated vasodilation in human pregnancy.

The maternal circulation vasodilates during pregnancy. We investigated the contribution of nitric oxide to this vasodilatation. Using venous occlusion plethysmography, we measured the effect of nitric oxide synthase inhibition on hand blood flow during human pregnancy. We compared the response to a brachial artery infusion of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) with the response to norepinephrine in three groups of women: nonpregnant, early pregnant (9-15 wk), and late pregnant (36-41 wk). Basal hand blood flow increased significantly during late pregnancy compared with nonpregnant and early pregnant subjects (P = 0.007). L-NMMA produced a greater reduction in hand blood flow in both pregnant groups compared with nonpregnant controls (P = 0.0003). Norepinephrine produced an attenuated response in late pregnancy compared with nonpregnant and early pregnant women (P = 0.0029). If other vascular beds respond in the same way as the hand, the gestational increase in vasoconstrictor response to L-NMMA that we observed implicates increased generation of nitric oxide in the fall of peripheral vascular resistance during healthy human pregnancy.

Enzyme Inhibitors↗