Search PubMedSearch

Biomedical subjects

R J Clark

Publications and source records attributed to R J Clark.

At least 19 recordsLinked to original sources

DLCO/Q and diffusion limitation at rest and on exercise in patients with interstitial fibrosis.

Pulmonary diffusing capacity for carbon monoxide (DLCO) and pulmonary capillary blood flow (Qp) were measured on exercise in patients with a low DLCO with the aim of predicting, from the overall DL/Qp ratio, diffusion limitation for oxygen and relating it to the fall in arterial oxygen saturation actually observed. Five patients with cryptogenic fibrosing alveolitis (DLCO ranging from 20-54% predicted normal) exercised for 5 min at a work load equal to 60% of their maximum (45 to 90 watts). At 5 min (and previously at rest) they rebreathed rapidly for 15 sec from a 1.0 L bag containing helium (He), sulphur hexafluoride (SF6) and freon-22, 30% oxygen in argon and less than 1 ppm 11C-labelled carbon monoxide. Pulmonary capillary blood flow (Qp) and diffusing capacity (DLCO) were measured from flow-weighted breath-by-breath concentrations of freon-22 and 11CO, after correction for gas mixing delays (using He and SF6). Oxygen saturation (SaO2) (ear oximetry), MO2 and MCO2 and cardiac frequency were measured. PAO2 (ideal) was derived and mixed venous O2 saturation and content were calculated (Fick); PaO2 and PVO2 were derived from standard dissociation curves. For comparison, DLCO and Qp were measured in a similar fashion in five normal subjects exercising at 60 watts. Mean DLCO in patients with fibrosis was 9.62 (SD 2.88) ml.min-1, mm Hg-1 on exercise and mean Qp was 10.48 (SD 1.79) L.min-1 giving mean DLCO/Q ratios of 0.92 (SD 0.28). At 60 watts mean DLCO/Qp in normal subjects was 2.54 (SD 0.3), 2.76-times greater than in patients. SaO2% fell in patients by 3-15% on exercise. Predictions of alveolar-end capillary PO2 gradients from these overall DL/Q gradients showed that diffusion limitation accounted for 99% of the alveolar-arterial PO2 gradient on exercise in fibrosing alveolitis. Hughes (1991 Respir. Physiol. 83:167-178) [corrected] suggests that this simple approach overestimates the contribution of diffusion limitation by about 30%.

Adult

Coccidioidomycosis during human immunodeficiency virus infection. A review of 77 patients.

Through a retrospective review, we identified 77 previously unreported cases of coccidioidomycosis during HIV infection. Patients were classified into 1 of 6 categories based on their primary clinical presentation: 20 had focal pulmonary disease (Group 1), 31 had diffuse pulmonary disease (Group 2), 4 had cutaneous coccidioidomycosis (Group 3), 9 had meningitis (Group 4), 7 had extrathoracic lymph node or liver involvement (Group 5), and 6 has positive coccidioidal serology without a clinical focus of infection (Group 6). Coccidioidal serologies were positive on initial testing in 83% of the patients in whom such serologic testing was performed. Sera from 39% of patients were positive for TP antibodies while 74% had CF antibodies. Eleven of 12 seronegative patients had pulmonary disease (Group 1 or 2). Serologic results of other patients sent to a single reference laboratory were similar, with 26% positive for immunodiffusion TP antibodies and 79% positive for immunodiffusion CF antibodies. For the 77 patients in this study, the CD4-lymphocyte count was below 0.250 X 10(9) cells/L in 46 of the 55 patients who had this test performed, and a low CD4 count was significantly associated with mortality (p less than 0.01). At the time of follow-up, 32 of the 77 patients (42%) had died. There were significantly more deaths in those with diffuse pulmonary disease (Group 2) than in other groups (p less than 0.001). Amphotericin B, ketoconazole, fluconazole, and itraconazole were all used as antifungal therapies. Outcome could not be related to the therapy used. Of note, 3 patients developed coccidioidomycosis while receiving ketoconazole for other conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Evaluation of N-acetylcysteine and methylprednisolone as therapies for oxygen and acrolein-induced lung damage.

Reactive oxidizing species are implicated in the etiology of a range of inhalational pulmonary injuries. Consequently, various free radical scavengers have been tested as potential prophylactic agents. The sulfydryl compound, N-acetylcysteine (NAC) is the only such compound clinically available for use in realistic dosages, and it is well established as an effective antidote for the hepatic and renal toxicity of paracetamol. Another approach in pulmonary injury prophylaxis is methylprednisolone therapy. We evaluated NAC and methylprednisolone in two rat models of inhalational injury: 40-hr exposure to greater than 97% oxygen at 1.1 bar and 15-min exposure to acrolein vapor (210 ppm). For oxygen toxicity, NAC (80 mg) or methylprednisolone (10 mg) were given IP every 2 or 6 hr, respectively. For acrolein, single doses of NAC (1 g/kg) and methylprednisolone (30 mg/kg) were given intravenously 15 min before exposure. In sham-exposed control animals, neither treatment favorably effected mortality, lung wet/dry weight ratios, or pulmonary histology. The increases in lung wet/dry weight ratios, seen with both oxygen and acrolein toxicity were reduced with both treatments. However, with oxygen, NAC therapy was associated with considerably increased mortality and histological changes. Furthermore, IP NAC administration resulted in large volumes of ascitic fluid. With acrolein, IV, NAC had no significant effect on mortality or pulmonary histological damage. Methylprednisolone had no beneficial effects on either the mortality or histological damage observed in either toxicity model. We caution against the ad hoc use of NAC in the management of inhalational pulmonary injury.

Acrolein

Smoke inhalation.

Deaths from smoke inhalation remain depressingly frequent and most often occur because the victim cannot escape the toxic effects of carbon monoxide. Delayed sequelae of smoke inhalation greatly increase the mortality from cutaneous burns. This article outlines the supportive care of smoke casualties and discusses some of the dilemmas in management which result from the absence of specific therapies.

Carbon Monoxide Poisoning

Immunoglobulins and complement in demyelination induced in mice by Theiler's virus.

Intracerebral inoculation of Theiler's murine encephalomyelitis virus (TMEV) produces chronic demyelination and persistent infection in the central nervous system (CNS) of susceptible SJL mice. This series of experiments examined the contribution of humoral immunity and C to myelin destruction. As in multiple sclerosis, mice persistently infected with TMEV had elevated levels of IgG and oligoclonal bands in the cerebrospinal fluid (CSF). Immunoblot studies revealed that even in animals exhibiting profound demyelination, IgG in the serum and CSF was directed primarily at virus antigen rather than at normal myelin components. Inflammatory cells positive for Ig were distributed mainly around blood vessels, but occasionally they infiltrated the spinal cord parenchyma. Rare examples of myelin sheaths positive for IgG were found by immunoelectron microscopy in spinal cord sections from infected mice; the third component of complement (C3) was commonly found in the walls of CNS blood vessels but not on myelin. Neither serum nor CSF IgG from infected mice bound to myelin sheaths or other CNS components in sections of normal syngeneic spinal cord. There were significantly more demyelinating lesions in infected mice depleted of C components with cobra venom factor. These data do not support a humoral autoimmune basis for the CNS demyelination that occurs in association with persistent TMEV infection. However, the humoral immune response directed at TMEV antigens may either limit virus spread or promote virus persistence.

Animals

Autogenous rib graft-hydroxylapatite augmentation of the severely atrophic mandible: preliminary report.

Traditional transoral rib grafts were combined with particulate hydroxylapatite (HA) for augmentation in four patients who had advanced alveolar atrophy or cortical resection of the mandible. Follow-up evaluation for up to 18 months revealed restoration of mandibular morphology, with good prosthetic function and insignificant resorption. No infection or graft loss was observed, in spite of wound dehiscence in two of the four patients, possibly due to the placement of the HA lateral and superior to the rib grafts.

Aged

Consumption of C3 via the classical and alternative complement pathways by sera and synovial fluids from patients with rheumatoid arthritis.

Five sera and four synovial fluids from patients with rheumatoid arthritis were found to contain substances which consumed hemolytic C3 in normal human serum (NHS) and in normal guinea pig serum (NGPS). These fluids were then tested for ability to activate the alternative pathway by incubating them with NHS containing MgEGTA and C4 deficient GPS. All sera and two synovial fluids depleted C3 in these reagents, indicating direct activation by the alternative pathway. Density gradient ultracentrifugation demonstrated C3 fixing activity in some specimens in the greater than 19s regions. These substances may also activate complement similarly in vivo and participate in the development of inflammatory processes associated with this disease.

Adult

Complement-fixing material in ther sera of patients with rheumatoid arthritis.

We investigated the properties of the complement-fixing material in samples of sera from fifteen patients with rheumatoid arthritis having low levels of C4, in order to determine its possible relationship to the immune complexes and rheumatoid factors. The complement-fixing material in most sera was of high molecular weight, 19s or greater, but in two sera it was also present in an intermediate zone (about 12s--15s). Cryoprecipitation did not remove the complement-fixing material except from serum with a elevated content of cryoglobulin. Analysis of the sera by analytical ultracentrifugation for the content of rheumatoid factor IgG complexes did not show a close relationship between the content of these complexes and the amount of complement-fixing material present in the sera. The responsible material could be absorbed by IgG-Sepharose together with the removal of rheumatoid factor. It was, however, possible to absorb the complement-fixing material from most sera with unconjugated Sepharose without significantly affecting the rheumatoid factor titres. Thus the complement-fixing material in the rheumatoid sera closely resembles an immune complex. It very likely contains rheumatoid factor, but it is not certain whether the material consists entirely of rheumatoid factors complexed to IgG or whether other antigen-antibody systems may also be present.

Antigen-Antibody Complex

An evaluation of silicophosphate as an orthodontic cement.

In a laboratory and clinical evluation, when used for the cementation of orthodontic bands, a zinc silicophosphate cement has proved to be comparable to zinc phosphate cement in its bond strength to enamel. This was demonstrated in laboratory tests by higher values being required to break the mechanical bond and in the clinical study by the slightly smaller percentage of bands which became loose during orthodontic treatment. In both the laboratory and clinical studies it was found that silicophosphate remained attached to the enamel in higher percentages after a band had become loose. It also was found that the remaining cement was often quite difficult to remove from the enamel. Probably the greatest advantage of using silicophosphate is that no decalcification of enamel was found under bands which had become loose during orthodontic treatment. This may be attributable to the higher bond strength and/or the presence of fluoride in the cement. Further clinical studies of this nature appear warranted.

Dental Bonding

Smoke inhalation.

Explore the source record for details and available documents.

Environmental Exposure