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Biomedical subjects

J Crawford

Publications and source records attributed to J Crawford.

At least 163 records · Page 9Linked to original sources
PubMed1990

Effects of pentoxifylline administration on blood viscosity and leukocyte cytoskeletal function in patients with intermittent claudication.

We have previously shown that pentoxifylline, a drug used in intermittent claudication, causes depolymerization of actin in leukocytes in vitro. In this study we evaluated several parameters in peripheral blood obtained from 17 patients receiving pentoxifylline, before therapy and at 1 and 2 months after initiation of drug therapy. Total blood viscosity decreased at 1 month and was further reduced at 2 months. The plasma viscosity remained unchanged during the course of the therapy (1.770 +/- 0.147, 1.776 +/- 0.162, and 1.772 +/- 0.164 centipoise at 0, 1, and 2 months, respectively; mean +/- SD, n = 14 to 17). No changes were observed in stimulus-induced actin polymerization in granulocytes, concanavalin A-induced capping in granulocytes and lymphocytes, and anti-IgG-induced caps in lymphocytes, before and after therapy. Similarly, there was no difference in the magnitude of depolymerization caused by pentoxifylline when added in vitro. Thus none of the parameters altered by pentoxifylline treatment in vitro have been observed ex vivo in patients receiving this drug. However, the decrease in total blood viscosity along with unaltered plasma viscosity suggests that the rheology of the cellular elements is being affected by the administered drug. In addition to the direct effects on the cell membrane and the cytoskeleton, pentoxifylline may exert indirect effects through its inhibitory action on cytokine production. Subtle changes in a number of parameters in leukocytes, which taken alone fail to show demonstrable changes, might ultimately be responsible for the therapeutic benefit noted with pentoxifylline.

Actins↗
PubMed1989

Hodgkin's disease presenting as myelofibrosis.

Four patients with Hodgkin's disease and bone marrow fibrosis are presented in whom the clinical presentation was dominated by cytopenias; this was associated with a delayed diagnosis for an average of 20 months. Despite marrow involvement, chemotherapy resulted in complete remissions and two patients appear to have been cured. Marrow fibrosis resolved at least partially after chemotherapy. The medical literature relevant to bone marrow involvement by Hodgkin's disease is reviewed. Hodgkin's disease should be considered in the differential diagnosis of idiopathic myelofibrosis.

Adult↗
PubMed1989

An in vitro analogue of immune dysfunction with altered immunoglobulin production in the aged.

The consequences of aging of the immune system include impaired T-lymphocyte responsiveness and aberrant immunoglobulin production. Although T cells from elderly individuals have a well-described defect in lymphoblastic transformation in response to some polyclonal mitogens, immunoglobulin abnormalities have lacked a clear in vitro model. Peripheral blood mononuclear cells from 13 young and 13 old healthy donors were cultured with phytohemagglutinin (PHA) or pokeweed mitogen (PWM). Old-donor-cell phytohemagglutinin (PHA), but not PWM, cultures had significantly lower lymphoblastic transformation compared with young donor cultures. IgG, IgA, and IgM production tended to be lower in old- versus young-donor PWM cell cultures. By contrast, despite lower lymphoblastic transformation in old-donor PHA cell cultures, immunoglobulin production was higher for old- versus young-donor cell cultures. No significant age differences were present in initial lymphocyte counts, percent B cells, T cells or monocytes, or helper/suppressor ratios to explain this enhancement in immunoglobulin production. PHA-stimulated mononuclear cell cultures in the aged demonstrate not only a defect in proliferation but also increased immunoglobulin production. This in vitro system may be useful to characterize further the pathogenesis of altered immunoglobulin production in the elderly.

Adult↗
PubMed1988

Erythrocyte anisocytosis. Visual inspection of blood films vs automated analysis of red blood cell distribution width.

An improved anemia classification may be available by combining measures of red blood cell size variability with mean corpuscular volume. Visual inspection of the peripheral blood film allows semiquantitative description of anisocytosis while quantitative measures are determined from electronic cell counter analyzers' red blood cell distribution width. We evaluated correlations between semiquantitative and quantitative measures of anisocytosis for different groups of observers. Hematologists', medical students', and medical residents' semiquantitative assessment of anisocytosis correlated with the quantitative red blood cell distribution width. The interobserver variability demonstrated that all observers correlated with each other, while the intraobserver variability of semiquantitative anisocytosis demonstrated that observers were more precise than could be predicted by chance. However, the extreme precision of the red blood cell distribution width strongly suggests that it should be the "gold standard" for measuring red blood cell size variability.

Anemia↗
PubMed1988

Actin depolymerization and inhibition of capping induced by pentoxifylline in human lymphocytes and neutrophils.

Pentoxifylline is used clinically for the treatment of intermittent claudication. It is believed to exert its effect by altering the rheologic properties of blood. The cytoskeleton plays an important role in the maintenance of cell structure and function. In particular, alterations in the state of actin seem to play an important role in cell motility. Therefore, we examined the effect of pentoxifylline on the actin state in human polymorphonuclear leukocytes (PMN) and mononuclear cells. Pentoxifylline (10 mM final concentration) decreased F-actin content in both PMN and mononuclear cells. Pentoxifylline also inhibited concanavalin A-induced capping in PMN and mononuclear cells. Similarly, surface immunoglobulin capping in B lymphocytes was also inhibited. Pretreatment of cells with pertussis toxin did not inhibit pentoxifylline-induced decrease in F-actin, suggesting pentoxifylline does not act through pertussis toxin-sensitive G-proteins. Dibutyryl cyclic AMP failed to show any significant effect on the F-actin content in PMN. Therefore, the effect of pentoxifylline cannot be attributed to changes in cyclic AMP levels. Chemotactic peptide-induced actin polymerization was unaffected in PMN when expressed as percent changes in F-actin. The observations reported here suggest that the rheological effects of pentoxifylline might be due to its effects on the actin state in the cellular elements of the blood. Further studies on the mechanism of action of pentoxifylline on actin state in leukocytes will prove useful in delineating the physiological mechanisms regulating actin state in leukocytes.

Actins↗
PubMed1988

Primary hepatocellular carcinoma in idiopathic hemochromatosis after reversal of cirrhosis.

Previous reports have emphasized the association of primary hepatocellular carcinoma in patients with idiopathic hemochromatosis with cirrhosis. In contrast, patients with idiopathic hemochromatosis without cirrhosis have no increased risk of hepatocellular carcinoma. Phlebotomy therapy, by preventing the accumulation of parenchymal iron and subsequent cirrhosis, is believed to prevent hepatocellular carcinoma in the precirrhotic stage of the disease. We report the case of a 67-yr-old man with a 32-yr history of idiopathic hemochromatosis complicated by cirrhosis, who had reversal of cirrhosis with phlebotomy therapy, yet developed hepatocellular carcinoma. There was no serologic or tissue evidence of hepatitis B infection.

Aged↗
PubMed1988

Cisplatin plus etoposide consolidation following cyclophosphamide, doxorubicin, and vincristine in limited small-cell lung cancer.

From June 1982 through October 1985, the Southeastern Cancer Study Group randomized patients with limited small-cell lung cancer (SCLC) to cyclophosphamide plus doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH) plus vincristine (CAV) for six cycles v CAV plus concomitant thoracic irradiation as induction therapy. Patients achieving either a complete or partial response and remaining in remission after completion of induction therapy were subsequently randomized to consolidation chemotherapy consisting of cisplatin 20 mg/m2 X 4 plus etoposide (VP-16) 100 mg/m2 X 4 every 4 weeks for two courses v no further therapy. There were 160 patients entered on the consolidation phase and 148 were fully evaluable. The median survival for patients randomized to cisplatin plus VP-16 (PVP16) from start of CAV chemotherapy was 97.7 weeks, compared with 68 weeks for the no-consolidation arm (P = .0094). PVP16 consolidation also significantly increased the duration of remission, with median durations of 49 weeks v 28 weeks (P = .0008). The median durations for partial remission were 41 weeks v 23 weeks (P = .013), and for complete remission, 52 weeks v 30.5 weeks (P = .0091). Furthermore, 18 patients on PVP16 consolidation remain in a continuous complete remission for 12+ months and 13 of these are continuously disease free 2+ years. Eight patients randomized to no consolidation remain in a continuous complete remission, with only four patients disease free 2+ years. PVP16 consolidation has significantly improved the duration of remission and overall survival and appears capable of improving the cure rate in limited SCLC.

Adult↗
PubMed1988

Dispharynx nasuta (Nematoda) in California quail (Callipepla californica) in western Oregon.

Seventy-six California quail (Callipepla californica) were collected during a 22-mo period from the E. E. Wilson Wildlife Area near Monmouth, Oregon. Dispharynx nasuta occurred in 38% of the birds with a mean intensity of 4.9 +/- 5.1. In one of 2 yr, host age was significantly associated with prevalence, with immature males showing the highest prevalence (73%). Although C. californica has been the subject of several parasitological surveys, this is the first record of D. nasuta in this host.

Age Factors↗
PubMed1988

Perceptions of drinkers and abstainers in a sample of Scottish adults.

Following Davies and Stacey's investigation (1972, Teenagers and Alcohol, HMSO, London) into perceptions of drinking and abstaining among Scottish teenagers, this study extended their general method to an investigation of the perceptions of 239 Scottish adults. Results showed that the stereotypes of the heavy drinker as 'tough and rebellious' and the abstainer as 'weak and cissy' persist into adulthood. Heavy drinkers were seen as low on 'sociability' and 'sexual attractiveness' and abstainers were seen as less 'sociable' than moderate drinkers. There was also some evidence of a 'double standard' in perceptions of male and female drinking roles. Other findings concerning the effects on perceptions of subjects' sex and drinking behaviour are compared to those reported in the earlier study and implications for the treatment of alcohol problems are discussed. It is concluded that the dimensions described by Davies and Stacey represent a relatively stable structure within future research where fresh initiatives in alcohol education may be located.

Adult↗
PubMed1987

Clinical utility of erythrocyte sedimentation rate and plasma protein analysis in the elderly.

The utilization and interpretation of the erythrocyte sedimentation rate in the elderly have been surrounded by controversy and confusion. To improve the understanding of the erythrocyte sedimentation rate and its determinants in the aged, a defined population of 111 ambulatory, retirement-home residents underwent thorough clinical and laboratory evaluation. Westergren erythrocyte sedimentation rate, Wintrobe erythrocyte sedimentation rate, and plasma viscosity measurements were all significantly correlated with one another as well as with plasma proteins, particularly fibrinogen and globulins. Age per se had no influence on the erythrocyte sedimentation rate in the study population. On the basis of standard upper limits of normal for younger populations, the Wintrobe sedimentation rate was most commonly abnormal and plasma viscosity least commonly abnormal. The "normal" upper limit of 20 mm/hour for Westergren sedimentation rate was also the optimal limit of normal by receiver operating characteristic analysis of the study population. Although the sensitivity of the Westergren sedimentation rate for the presence of an inflammatory condition or monoclonal gammopathy was only 0.55, the specificity was 0.96, and the positive predictive value of an elevated erythrocyte sedimentation rate being associated with a clinical disorder was 0.93. The enhanced clinical utility of the erythrocyte sedimentation rate in this population compared with other elderly populations may be due to a low prevalence of anemia and hypoalbuminemia. In such populations, the erythrocyte sedimentation rate may remain a useful clinical test, regardless of patient age.

Age Factors↗
PubMed1987

Pulmonary hypertension secondary to serum hyperviscosity in a patient with rheumatoid arthritis.

A patient with rheumatoid arthritis who was evaluated for dyspnea of six months' duration is described. Although no primary cardiac or parenchymal lung disease was identified, right heart catheterization revealed marked pulmonary hypertension. The patient was presumed to have pulmonary arteritis. Evaluation of her hyperproteinemia, however, led to the discovery of a polyclonal gammopathy with a marked increase in plasma viscosity. Although the classic clinical findings of the hyperviscosity syndrome were minimal, the patient underwent plasmapheresis, resulting in a marked reduction of pulmonary artery pressures (from 53 +/- 4 mm Hg, mean +/- SD, to 30 +/- 3 mm Hg, p less than 0.05) and pulmonary vascular resistance (from 707 +/- 63 dynes/second/cm5 to 421 +/- 72 dynes/second/cm5, p less than 0.05) concomitant with a return to normal plasma viscosity. Her dyspnea completely resolved. This represents the first successful treatment of pulmonary hypertension by plasmapheresis. Protein evaluation revealed the presence of intermediate complexes of IgG rheumatoid factor. The hyperviscosity syndrome should be considered in the differential diagnosis of pulmonary hypertension in patients with rheumatoid arthritis and other disorders associated with a polyclonal or monoclonal gammopathy. Pulmonary hypertension secondary to the hyperviscosity syndrome is reversible by plasmapheresis. Immunosuppressive therapy that reduces immunoglobulin production may provide a means of long-term treatment.

Arthritis, Rheumatoid↗
PubMed1987

Evaluation of monoclonal gammopathies in the "well" elderly.

The study of monoclonal gammopathies in the elderly provides an opportunity to define immunologic and neoplastic changes with aging. Previous reports using paper and cellulose acetate electrophoresis have documented an age-related increase in monoclonal gammopathies. In this study, the more sensitive techniques of high-resolution agarose gel electrophoresis and immunofixation were used, in conjunction with other protein studies, to further evaluate the prevalence of monoclonal gammopathies in 111 ambulatory residents (aged 62 to 95) of a retirement home. Eleven of the 111 residents (10 percent) were found to have a monoclonal gammopathy, ranging in concentration from 0.2 to 1.8 g/dl. All monoclonal gammopathies were confirmed by immunofixation, which also documented the presence of additional unsuspected monoclonal components in three of the 11 residents. The prevalence of monoclonal gammopathies by age ranged from 6 percent in the group younger than 80 years of age to 14 percent in the group older than 90 years of age. Only one of the 11 residents had any clinical or routine laboratory suggestion of a monoclonal gammopathy. The other 10 had normal ratios of total protein and albumin to globulin. Five of the 11 (45 percent) had an otherwise clinically unexplained erythrocyte sedimentation rate of more than 20 mm/hour, compared with only two of 100 in the group without monoclonal gammopathies. Follow-up studies one to three years after initial evaluation revealed that five of the 11 patients had died, two with evidence of disease progression. In the other six patients, monoclonal protein concentration and other protein values remained stable. An unexplained elevation of the erythrocyte sedimentation rate in the elderly warrants investigation for the presence of a monoclonal gammopathy. Agarose gel electrophoresis and immunofixation identify a higher percent of monoclonal gammopathies in the elderly than has previously been recognized. Identification of monoclonal components in this population is useful for the subsequent study of plasma cell dyscrasias, neoplastic disease, or other immune dysfunction in the aged.

Aged↗