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Biomedical subjects

D M Williams

Publications and source records attributed to D M Williams.

At least 271 records · Page 15Linked to original sources

Accuracy of tobramycin delivery by four i.v. infusion methods.

The accuracy of tobramycin delivery by four methods of intermittent intravenous infusion was studied in 11 healthy male volunteers. Subjects received intravenous tobramycin (as the sulfate salt) 1.5 mg/kg by each of four infusion methods in a nonblinded, randomized, four-way crossover design. The methods used for intravenous infusion were (1) minibag via gravity flow (MG), (2) minibag with the secondary infusion tubing inserted below a volumetric infusion pump (MP), (3) metered chamber via volumetric infusion pump (MC), and (4) syringe pump (SP). Doses were diluted to a volume of 50 mL, except for the two minibag methods, for which the dilution was necessarily greater because of manufacturer overfill. Intravenous flow rates for both primary fluid and drug administration were set at 100 mL/hr, and the duration of drug infusion was documented by observation for each administered dose. The fluid volume of 12 minibags was measured to assess manufacturer overfill. Fluid remaining in the secondary i.v. tubing for the minibag methods was collected after the infusion. Seventeen blood samples were obtained before and at various time intervals after each dose and analyzed in duplicate for tobramycin content by fluorescence polarization immunoassay. A mean of 10% of each dose remained in the secondary i.v. tubing at the completion of the infusion for the minibag methods, whereas less than 1% of each dose remained in the secondary tubing for the SP method.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of four intravenous infusion methods on tobramycin pharmacokinetics.

The influence of four intermittent intravenous infusion methods on the determination of tobramycin pharmacokinetic values and predicted doses was evaluated in 11 healthy adult volunteers. Each subject received tobramycin (as the sulfate salt) 1.5 mg/kg by each of four i.v. infusion methods: (1) minibag via gravity flow (MG), (2) minibag with the secondary infusion tubing inserted below a volumetric pump (MP), (3) metered chamber via volumetric pump (MC), and (4) syringe pump (SP). Infusion rates were initially set to administer each dose over a 30-minute period. Sixteen blood samples were obtained over an eight-hour period before and at various time intervals after each dose and were analyzed for tobramycin content by fluorescence polarization immunoassay. Area under the serum concentration-time curve from time zero to infinity (AUC0-infinity) was calculated by the trapezoidal rule. Serum tobramycin concentration data for each subject were fitted to a biexponential decay model with zero-order input. beta and V beta were calculated from fitted data. One-compartment pharmacokinetic values, elimination rate constant (kappa), apparent volume of distribution (V), and predicted doses to achieve steady-state peak concentrations of 6 micrograms/mL were calculated by the method of Sawchuk and Zaske. There were no significant differences in either beta or kappa among the infusion methods. V beta values (mean +/- S.D.) for the methods were 0.240 +/- 0.025 (MG), 0.257 +/- 0.025 (MP), 0.221 +/- 0.027 (MC), and 0.231 +/- 0.032 (SP) L/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

An approach to the stereoselective synthesis of Sp-dinucleoside phosphorothioates using phosphotriester chemistry.

An approach to the stereoselective synthesis of Sp- dinucleoside phosphorothioates has been investigated which utilizes phosphotriester chemistry. The stereoselectivity of internucleotide bond formation between N4-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-deoxycytidine-3'-O-(S2-cyano-e thyl) phosphorothioate (3) and 3'-O-acetylthymidine has been studied using either mesitylenesulphonyl-5-(pyridin-2-yl)tetrazole (MSPy) or 1-mesitylenesulphonyl-3-nitro-1,2,4-triazole (MSNT) as the activating agent. The removal of the cyanoethyl group from the protected dinucleoside phosphorothioate has been studied, and conditions are reported which provide rapid deprotection without concomittant desulphurisation.

Benzene Derivatives↗

Presentation and perioperative management of arterioportal fistulas.

Arterioportal fistulas (APFs) are usually traumatic in origin and may result in portal hypertension and its complications. Over six years, six patients (aged 20 to 59 years) presented with APFs. Two APFs developed after percutaneous liver biopsy, but only one was complicated (hemobilia). Neither patient was treated operatively. Four APFs occurred two days to three years after gunshot wounds. Three patients presented with gastrointestinal tract hemorrhage. All patients had abdominal bruits. Two patients underwent primary repair. One patient underwent APF resection and replacement of the superior mesenteric artery with autogenous vein. Another patient underwent APF and bowel resection. Three patients survived. One patient died of liver failure. The development of an abdominal bruit in a patient with penetrating abdominal trauma suggests APF and should prompt angiography. Elective repair is recommended before complications of portal hypertension develop.

Adult↗

Dual expression of the cell-surface antigens HLA-DR and CD1 (T6) by Langerhans cells in human buccal mucosa and skin.

The expression of HLA-DR and CD1 (T6) by Langerhans cells (LC) in human buccal mucosa and skin was investigated with the monoclonal antibodies YE2/36HLK (HLA-DR) and HTA1-C1 (CD1). A five-stage sequential double immunofluorescent-labelling technique, with rhodamine and fluorescein as the fluorochromes, was used to visualize the two surface antigens in the same microscope field. The majority of LC in cryostat sections of buccal mucosa and skin expressed both HLA-DR and CD1.

Antibodies, Monoclonal↗

The sequential demonstration of non-specific esterase reactivity Ia antigen and Thy-1 antigen in murine epidermal sheets.

Immunofluorescence demonstrating Ia and Thy-1 antigens and non-specific esterase (NSE) enzyme histochemistry were performed sequentially on sheets of ear epidermis from CBA, C3H.OH, A/J, and Balb/c mice. The same areas of epidermis were photographed after each reaction and individual cells identified and compared. Thy-1+ dendritic cells expressed neither Ia antigen nor NSE reactivity. No cell was found to express Ia antigen or NSE alone: thus all Langerhans cells (LC) in normal murine epidermis appeared to co-express Ia antigen and NSE reactivity. LC expressing greatly increased amounts of Ia antigen were occasionally seen apposed to Thy-1+ cells suggesting that these cells may be immunologically active--perhaps involved in antigen presentation.

Animals↗

Digital subtraction venography of the upper extremity.

Seventy four digital subtraction venograms of the upper extremity and mediastinum were performed in 69 patients. The indications included idiopathic arm and shoulder swelling, difficulties with a central venous catheter, chronic venous access device, or dialysis fistula, superior vena cava syndrome, or pre-operative anatomical mapping. Clinically useful information was obtained in all studies. The digital subtraction technique allows the simple and rapid performance of venography, especially in patients with limited venous access.

Adult↗

Closing forces of the bovine teat canal.

The magnitude of the forces causing closure of the bovine teat canal was estimated by measuring the pressure required to cause retrograde flow of milk into the canal from a manometer attached to the external teat orifice. Before milking, the hydrostatic pressure required to cause retrograde flow was 12 kPa or greater. Retrograde flow occurred at a pressure of 4-6 kPa once the teat canal surface had been wetted. This 2- or 3-fold fall in the closing forces presumably resulted from the combined effects of fracturing the teat canal epithelium and loss of initial resting tension in the smooth muscle fibres surrounding the teat canal. After milking, retrograde flow into any teat canal occurred at a pressure approximately 1 kPa lower than the wetted, pre-milking value. This small drop, and subsequent recovery approximately 30 min after milking, reflects the change in tonicity of the smooth muscle fibres which are stretched during milking. At hydrostatic pressures below 7-9 kPa, retrograde flow could be arrested momentarily by the occurrence of a teat contraction. At 4-7 kPa, the wave of contraction was also capable of expelling 4-14 microliters milk from the teat canal indicating the outwardly directed, peristaltic nature of the phasic muscular activity.

Animals↗

Compressive load applied by the teatcup liner to the bovine teat.

The magnitude of the cyclic load applied to the teat apex by the collapsed liner during milking was estimated by measuring the pressure required to cause retrograde flow of milk into the teat canal from a manometer attached to the external teat orifice. The study was extended by observation of the milk flow cycle within a transparent teatcup assembly and by pressure recordings within the teat canal using a catheter-tip transducer. The source of the force compressing the teat is the small airspace, within the collapsed liner, directly below the teat apex. The total force generated is determined mainly by the size of this airspace and the pressure difference (PD) acting across the opposing liner walls. When the PD reached 80-90% of the liner vacuum, the load was just sufficient to occlude the teat canal. Further increase in PD provided the compressive load capable of offsetting vascular congestion of the teat apex. Increasing liner tension increased the load applied. The narrow range of compressive loads applied by conventional liners (5-12 kPa above atmospheric pressure) may be sufficient to offset congestion and oedema in the teat. Loads greater than the mean arterial pressure within the teat apex might serve only to expose the tissues to non-productive compression.

Animals↗

Flow effects in multislice, spin-echo magnetic resonance imaging. Model, experimental verification, and clinical examples.

Flowing blood is responsible for a number of complex effects on clinical magnetic resonance (MR) images. To help elucidate these effects, a computer model of a conventional multislice spin-echo pulse sequence was developed. Using TR, TE, and direction of slice acquisition, the model calculates and plots a profile of MR signal intensity vs. z-axis velocity. The model predicts complex profiles with multiple segments of MR signal loss depending on TR, TE, direction of flow, sequence and timing of slice excitation, and slice location relative to adjacent slices. Model predictions were verified by imaging a bulk-flow phantom, consisting of a rotating cylinder filled with a manganese chloride solution with T1 = 840 msec and characterized by a velocity-gradient resolution of 0.23 cm/sec/pixel. In conventional spin-echo MRI of medium and large vessels using body coils, in which the velocity gradients exceed 2-5 cm/sec/pixel, most of the flow artifacts are averaged and are difficult to appreciate. However, bright crescents or rings of MR signal occasionally are seen in the inferior vena cava and portal vein, which the model is invoked to explain. The bulk-flow phantom will find use as a tool for calibrating flow-sensitive pulse sequences when these become widely available.

Blood Circulation↗

Role of natural killer cells in infection with the mouse pneumonitis agent (murine Chlamydia trachomatis).

Natural killer (NK) activity is increased in both spleen and lung early in pulmonary infection by murine Chlamydia trachomatis in both susceptible nude and resistant heterozygous (nu/+) mice. Ablation of the rise in NK activity by giving the mice antiasialo GM-1 antibody or stimulation of NK activity by immunomodulators did not affect quantitative tissue counts of the mouse pneumonitis biovar of C. trachomatis or significantly affect survival. Studies are needed to further define the role of NK cells in host defense, immunoregulation, and immunopathology during chlamydial infection.

Animals↗

Primary murine Chlamydia trachomatis pneumonia in B-cell-deficient mice.

Mice were rendered deficient in B-cell activity by treatment with anti-mu antibody from birth. These animals were then infected intranasally with murine Chlamydia trachomatis (murine pneumonitis agent [MoPn]). They produced neither local nor systemic antibody to MoPn but had intact delayed-type hypersensitivity to MoPn. Anti-mu-treated mice were not significantly more susceptible to primary invasive infection with MoPn than were control mice, and unrestricted multiplication with MoPn did not occur. The dominant immune response controlling this type of infection is not likely to be antibody.

Animals↗

Porta hepatis: duplex Doppler US with angiographic correlation.

Duplex Doppler ultrasonography (US) and panhepatic angiography were performed and interpreted independently in 20 patients with suspected portal hypertension to assess the accuracy of duplex US in the porta hepatis. Hepatic arterial resistive indexes were correlated with corrected sinusoidal pressures. The results of duplex US agreed with those of angiography in 16 patients with a normal portal vein (including three with hepatofugal flow) and two with total thrombosis. One angiographically normal portal vein appeared thrombosed on an initial sonogram, but a second scan was normal. One case of partial thrombosis was not diagnosed with duplex US. Sensitivity and specificity for main portal vein disorders were 83% and 93%, respectively. Two patients had portal vein branch occlusions that were found by angiography but not by US. Portal vein echogenicity was neither sensitive nor specific for thrombosis. The resistive index of the hepatic artery was specific for portal hypertension when above .78, but it was not sensitive. Duplex US is accurate in prospectively assessing the direction of flow and the presence of total thrombosis in the portal vein, but partial thrombosis may not be detected on sonograms.

Adolescent↗

Unilateral hypertrophic osteoarthropathy in a patient with an infected axillary-axillary bypass graft.

Hypertrophic osteoarthropathy (HO) is a specific clinicoradiologic entity, the most common cause of which is the presence of pulmonary lesions. Eight cases of aortic graft infection and aortoenteric fistulae in association with HO have been recognized. A case of an infected axillary-axillary graft presenting as unilateral HO of the upper limb is reported, and its unusual features are used to postulate a mechanism underlying HO.

Aged↗

Effectiveness of improved targeting efforts for influenza immunization in an ambulatory care setting.

Annual vaccination programs against influenza are aimed at decreasing the morbidity and mortality associated with an infection. Recent epidemics have resulted in 40,000 excess deaths reported. The success of an immunization program depends both on the composition of the annual vaccine and the targeting efficacy of the program. National estimates of targeting efficacy are reported at 20%. An evaluation performed in the author's ambulatory care practice in the spring of 1984 yielded an overall efficacy of 24% in targeting activities. Efforts to improve the targeting practices included enhanced practitioner and patient education about the vaccine, flagging of medication records for patients at risk, and adoption of CDC guidelines for categorizing patients based on the degree of risk. A subsequent evaluation in 1986 showed a significant improvement in targeting efficacy (40%; P less than .001). Subgroup analysis indicated that the targeting efficacy of the program was greatest for the high-risk patients (P less than .025). An overall immunization rate of at least 80% of patients at risk is our desired goal.

Adolescent↗

Chlamydia trachomatis pneumonia in the immune, athymic and normal BALB mouse.

This paper compares the histopathology of pneumonia due to murine Chlamydia trachomatis (MoPn, mouse pneumonitis agent) in susceptible athymic nude mice (nu/nu), resistant heterozygous littermates (nu/+) and very resistant immunized nu/+ mice. While all groups had an early heterophil response, successful host defence correlated with the presence of large numbers of plasma cells, lymphocytes, monocytes, and lipid laden macrophages. Reticulate bodies were seen in all groups, predominantly in type I alveolar epithelial cells. By 24 h in the immune nu/+ group, no intact organisms were visible. Optimal control of infection was thus rapid and not clearly related to heterophils. These studies show that the histopathology of chlamydial infection may be quite atypical in the immunocompromised host, mononuclear cells seem critical in host defence, and B cell activation with plasma cell infiltration is dependent on intact T cell function in this model.

Animals↗