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Biomedical subjects

P Froom

Publications and source records attributed to P Froom.

At least 91 records · Page 5Linked to original sources

Factors associated with leukocyturia in asymptomatic pilots.

We attempted to relate the prevalence of leukocyturia during annual examinations to recent activities and history data in 923 pilots. Urinary analysis was done and the results cross-tabulated with answers from a questionnaire and with a past history of leukocyturia obtained from the pilot's chart. The prevalence of 4 to 6 or more white blood cells (WBCs) in the urinary sediment was 5.3%. Leukocyturia was 35.7 times more common (odds ratio) in those with a previous history of leukocyturia and a concomitant history of urethritis (p less than 0.0001). Yet, a history of leukocyturia accounted for only 18.1% of the cases of leukocyturia. There was a trend for an association between jogging and leukocyturia. The prevalence of leukocyturia was not affected by smoking, other physical exercise, a history of nephrolithiasis, air duty in the preceding 24 h or a history of transient illness during the last 2 weeks. We conclude that there is an association between a history of both leukocyturia and urethritis and leukocyturia. In most cases, however none of the variables tested were found to be associated with leukocyturia.

Aerospace Medicine↗

Multiple myeloma in the geriatric patient.

Consecutive patients with multiple myeloma were studied. The clinical characteristics and survival of 17 patients aged 75 years or more were compared to 42 patients younger than 75 years of age. Of the patients older than 75 years, 14/17 (82%) died in less than 12 months compared to only 11/42 (26%) of those under 75 years old (P less than 0.001). Multivariate analysis showed that both age and hemoglobin were significant predictors of survival (P less than 0.012 and P less than 0.002, respectively) explaining 34.6% of the variance (r = 0.588, P less than 0.000), whereas the extent of bone lesions, the presence of more than 50% plasma cells in the bone marrow, the amount of serum monoclonal protein, functional class, and the Salmon and Durie staging system did not significantly add to the analysis. We conclude that the factors that best predict prognosis are hemoglobin levels and age at presentation. Different approaches including more appropriate chemotherapeutic regimes and comprehensive geriatric assessment with improved supportive treatment need to be developed for the geriatric patient with multiple myeloma.

Age Factors↗

Effect of adherent cells on the regulation of BFU-E in patients with myeloproliferative disease.

The interaction between adherent cells and red cell progenitors from peripheral blood of patients with polycythemia vera (PV), essential thrombocytosis (ET), and healthy controls was studied. Various combinations of adherent and nonadherent cells were co-cultured in a semisolid system. Adherent cells from controls, when added at low concentrations, stimulated BFU-E proliferation, whereas high concentrations (40% of total cells in the culture) caused a significant decrease in the number of BFU-E colonies in 6/8 PV patients, 4/4 ET patients, and 8/12 controls. On the other hand, low and high concentrations of adherent cells from both patients with PV and ET caused a significant increase in BFU-E from either patients or controls. Moreover, adherent cells from these patients induced endogenous BFU-E proliferation (independent of erythropoietin) in nonadherent cells of 12/12 normal controls. The results show that BFU-E from patients with PV and ET are sensitive to suppression by normal adherent cells. On the other hand, adherent cells from these patients possess stimulatory activity on BFU-E from peripheral blood at all concentrations and are devoid of the inhibitory activity. This suggests a possible defect in the functioning of adherent cells in PV and ET patients which may contribute to the abnormal regulation of hematopoiesis in these disorders.

Cell Adhesion↗

Concomitant effect of 2'-deoxycoformycin on natural killer cell activity and tumour cell sensitivity to lysis in hairy cell leukaemia--discordant effects of alpha interferon.

The effects of 2'-deoxycoformycin (dCF) and alpha interferon (IFN-alpha) on natural killer (NK) cell-enriched fractions and hairy cell (HC) targets from three patients with HC leukaemia (HCL) were investigated. There was no significant increase in NK activity when either the HC targets or NK-enriched cells were preincubated with dCF. However, preincubation of both HC and NK cells with dCF resulted in increased NK activity. Culture of enriched NK cells with IFN-alpha enhanced their activity. However, preincubation of HC targets with this drug in the presence or absence of dCF resulted in a protective effect. Maximal NK activity towards HCL was obtained when the target tumour cells were separately precultured with dCF and the NK-enriched effectors precultured with dCF + IFN-alpha. The effect of dCF and IFN-alpha was also measured using the standard K562 cells as targets for NK activity. dCF enhanced NK activity following preculture of both effector and target K562 cells, but IFN-alpha did not reduce K562 cell susceptibility to NK lysis as it did for HC cells. Our findings suggest that (a) dCF and IFN-alpha, which are used to treat HC, could function via activation of NK cells, (b) effects on both effector and tumour target cells should be taken into account, and (c) caution should be exercised in extrapolating the effects of NK-cell activity against K562 cells to those on HC targets.

Cytotoxicity, Immunologic↗

The effect of desmopressin on massive gastrointestinal bleeding in hereditary telangiectasia unresponsive to treatment with cryoprecipitate.

A patient with hereditary hemorrhagic telangiectasia and reduced levels of von Willebrand factor had severe recurrent gastrointestinal bleeding. Treatment with either desmopressin acetate or cryoprecipitate normalized both bleeding time and kaolin-activated partial thromboplastin time. Hematochezia (five episodes) continued, however, for a week despite daily treatment with cryoprecipitate, whereas treatment with desmopressin at the onset of three later episodes of hematochezia resulted in the prompt cessation of bleeding. After an episode of life-threatening gastrointestinal bleeding, desmopressin administration allowed a total colectomy without excessive bleeding. During the 3 years after colectomy, no further gastrointestinal bleeding occurred. In the past year, however, three episodes of severe epistaxis responded promptly to intravenous infusion of desmopressin. We conclude that desmopressin may be useful in the management of bleeding in patients with hereditary hemorrhagic telangiectasia with or without von Willebrand factor deficiency.

Adult↗

Antithrombin III levels in preeclampsia.

Antithrombin III (AT-III) activity was measured and compared in 29 patients with preeclampsia and 31 women with normal pregnancies. AT-III levels were 83 +/- 25% in preeclamptic patients with greater than 5 g/l proteinuria compared with 102 +/- 11% in the controls. Less severe proteinuria was not associated with decreased AT-III levels. Multivariate analysis revealed that the duration of pregnancy and the degree of proteinuria had an independent negative effect on AT-III levels. AT-III activity correlated poorly with platelet counts and blood pressure measurements. We conclude that urinary loss appears to be the major mechanisms of lower AT-III levels observed in our patients with preeclampsia.

Adult↗

Blood pressure response to exercise in normotensive and hypertensive young men.

We attempted to determine the optimal cut-off value of blood pressure defining a hypertensive response to exercise testing in 90 asymptomatic Israeli candidates for flight training with casual resting blood pressure of 140/90 mm Hg or more, and 72 age-matched normotensive controls tested in the Israel Air Force Aeromedical Center. Exercise testing (Bruce protocol) was performed using a calibrated Quinton Treadmill and a Hewlett Packard 151711-A three-channel ECG recording system. Recordings were made at 3-min intervals. At 3 min of exercise 12/87 (14%) of the hypertensive subjects had a SBP of greater than or equal to 210, compared to only 1/71 (1%) of the control group (relative risk 14). At 12 min of exercise 27/51 (53%) of the hypertensives and 9/55 (16%) of the controls had similar elevations of SBP (relative risk 3.3). At 6 min of exercise 11/87 (13%) of hypertensives had SBP greater than or equal to 220, whereas none of the normal controls had SBPs elevated to that degree. We concluded that an increase in SBP to 210 mm Hg or more after 3 min or to 220 mm Hg after 6 min of exercise testing by the Bruce protocol best separates the hypertensive group from the control group. This occurs at the expense of sensitivity. Only appropriate longitudinal studies can compare the degree to which various definitions of the hypertensive response to exercise will predict future hypertension.

Adolescent↗

Decreased natural killer (NK) activity in patients with myeloproliferative disorders.

Natural killer (NK) cell number and activity were measured in 26 patients with myeloproliferative disorders and the results were compared with 16 age-matched control patients. The percent of Leu-11b-positive cells was 11% +/- 3% in the patients, compared with 12% +/- 4% in the control patients. Ten of 26 patients, however, had NK activity lower than all of the control values at three different effector to target cell ratios (E:T) (P less than 0.005). The values of those patients with low unstimulated NK activity remained low despite stimulation with interleukin-2 (IL-2) or alpha-interferon (alpha-IFN), whereas the values of those patients with normal unstimulated activity responded to IL-2 and alpha-IFN like the control patients. Three of the ten patients with low NK activity had a history of malignant neoplasms. None of the 16 patients with normal NK activity had a history of malignant neoplasms (P less than 0.05). We conclude that patients with myeloproliferative disorders frequently have low endogenous NK cell activity in vitro. The dysfunction of the NK system appears to be intrinsic because the relative number of NK cells was similar to control values and the response to stimulation with IL-2 and alpha-IFN was suboptimal. There may be a relationship between low NK activity and the development of malignant disease in such patients.

Bloodletting↗

Mitral leaflet motion: age and implications for the diagnosis of mitral valve prolapse.

The extent of posterior mitral leaflet motion (PMLM) during systole in relation to age was studied in 300 asymptomatic men aged 18-42 years. PMLM of 4 mm or more on two-dimensional directed M-mode echocardiography was found in 8% (16/200) of subjects under age 35 years, but in only 2% (2/100) of those aged 35 years or more (p less than 0.05). On two-dimensional echocardiography, 16% (31/200) of men under 35 years old had PMLM greater than or equal to 0.40 mm2 compared with 1% (1/100) of those 35 years or more (p less than 0.001). The findings were not related to differences in left ventricular cavity dimensions or in the extent of systolic ventricular contraction. Body mass index (BMI) increased with age, but there was a significant and independent negative correlation of age with PMLM after controlling for BMI. The data are compatible with the hypothesis that the aging process is associated with decreased mobility of the mitral valve or annulus with lesser degrees of backward bowing or billowing of the leaflets during systole. Age should be taken into account in determining "normal" values for mitral leaflet motion.

Adolescent↗

Systolic tricuspid leaflet prolapse in asymptomatic young men.

The degree of systolic movement of the tricuspid valve (TV) leaflets was measured in 100 consecutive apparently healthy men 18-20 years old at the time of maximum posterosuperior motion toward or into the right atrium. Backward bowing of greater than 0.20 mm2 of the anterior leaflet, and greater than 0.15 mm2 of either the posterior or septal leaflets beyond the plane of the tricuspid annulus was found in 5% or less of the cohort irrespective of the echocardiographic view in which it was recorded. The upper 5% of these young men had greater than 0.80 mm2 of backward bowing when the leaflet motion was summed from all three views. The anterior leaflet demonstrated more bowing than either the septal or posterior leaflets. The systolic TV prolapse area correlated highly with the degree of mitral leaflet prolapse (r = 0.654, p less than 0.001). We conclude that there is a wide continuous spectrum of tricuspid valve leaflet prolapse area in healthy young men. This quantitative approach may help standardize the echocardiographic evaluation of tricuspid leaflet motion.

Adolescent↗

The mean leukocyte myeloperoxidase index in hematological patients.

A Technicon H-1 hematologic analyzer was used to measure the mean leukocyte myeloperoxidase (MPX) in 160 patients seen in a hematology clinic. The normal range was -15 to +10, which included 95% of 300 consecutive hospitalized patients. No abnormalities in the MPX were found in 35 patients with beta-thalassemia minor, 8 with iron deficiency, 14 with myeloproliferative disorders, 17 with autoimmune disorders, and 37 patients with lymphoma in complete remission. On the other hand 36% (10/28) of lymphoma patients with active disease either at diagnosis or relapse had a MPX of greater than 10 compared to only 2.3% (7/300) in hospitalized patients (P less than 0.001). Increased levels of MPX were found primarily in patients with non-Hodgkin's lymphoma (NHL) of intermediate or high grades, or Hodgkin's disease [56% (9/16) compared to only 8.3% (1/12) in those with low grade NHLs, P less than 0.05]. The MPX levels returned to normal after successful treatment. Of the various chemotherapeutic agents used, only hydroxyurea led to a consistent elevation of the MPX. The authors conclude that MPX is commonly increased in patients with lymphoma and in those receiving hydroxyurea. Further studies are required to determine if the MPX is a sensitive test for relapse in patients with lymphomas who had an elevated pretreatment value.

Hematologic Diseases↗

Retirement of fighter pilots with incidentally detected illnesses: a decision analytic model.

Decisions regarding professional fitness after an incidental detection of a clinical disorder are often problematic. The added risk of an occupational error related to the detected disorder may be smaller than the risk of an error due to lack of experience if a veteran is replaced by a novice. In this paper, we examine the choice between grounding or granting a waiver to an experienced fighter pilot with an incidental finding of premature ventricular contractions. The decision considers the probability of sudden incapacitation during flight and of pilot error-related air accidents in novices and veterans. Although deliberately biased in favor of grounding the veteran, the analysis indicates that the risk of sudden death or incapacitation in an experienced fighter pilot with an incidentally detected illness should be increased ten-fold to 46-fold to justify his or her replacement by a novice. In the specific case considered, the analysis suggests that the risk of an air accident due to sudden death or incapacitation of a veteran with incidentally detected premature ventricular contractions is similar to the estimated added risk of an error-related air accident if she or he is grounded and replaced by a novice. When reliable data on the frequency of human error by age and experience become available, the proposed model may be applied to other situations in which trained professionals develop a potentially disabling disease.

Accidents, Aviation↗

Increase in the suppressor-inducer T cell subset in multiple myeloma and monoclonal gammopathy of undetermined significance.

The expression of CD4 (helper-inducer), CD8 (suppressor-cytotoxic) and CD4 subpopulations (2H4 and 4B4) were studied in patients with multiple myeloma, monoclonal gammopathy of undetermined significance (MGUS) and in healthy controls. The percentages of CD4+ cells and CD8+ cells among total T cells were not different between the three groups studied. However the percentage of CD4+ cells of the suppressor-inducer type (CD4 + 2H4 +) was 53 +/- 9% in patients with MGUS, and 51 +/- 9% in those with MM, compared to 46 +/- 5 in the controls (P = 0.033 and P = 0.07 respectively). A significant negative correlation between serum polyclonal IgM and the percentage of CD4 + 2H4 + cells was found in patients with MM but not in those with MGUS. No difference was found in the percentage of CD4 + 4B4 + (helper CD4+ cells) between the various groups. These findings suggest that the elevation of the suppressor-inducer subset occurs prior to clinical manifestations of MM, perhaps as an immune response to the malignant clone. The existence of elevated proportions of CD4 suppressor-inducer cells was associated with the hypogammaglobulinaemia observed in patients with MM. Since no hypogammaglobulinaemia was present in those with MGUS, additional factors are needed to explain the influence of the CD4 + 2H4 + cells on the production of immunoglobulins.

Aged↗

Immature cells identified by the H-1 hematology analyzer predicts thymidine incorporation after mitogenic stimulation.

The incorporation of thymidine by lymphocytes stimulated by phytohemagglutinin (PHA) was correlated with the number of immature cells identified by the Technicon H-1 as blasts. The number of blasts and thymidine incorporation plateaued on day 3. At that time, a high linear correlation between the two variables was found (r = 0.949, p less than 0.01). The H-1 evaluated the samples in 60 seconds as compared to 3 hours of processing required to calculate thymidine incorporation. We conclude that the number of immature cells identified by the Technicon H-1 can predict the degree of thymidine incorporation after stimulation of peripheral blood cells with PHA. The H-1 may replace the more time consuming and dangerous use of radioactive thymidine incorporation in evaluating patients' functional immunologic status.

Blood Cell Count↗

Von Willebrand factor and mitral valve prolapse.

The levels of von Willebrand factor (vWF:Ag) were measured in 27 patients with mitral valve prolapse (MVP) and compared to 27 age matched controls. Decreased levels of vWF:Ag (less than 80%) were found in 59% (16/27) of those with MVP compared to only 7% (2/27) of the controls (p less than 0.001). Mean vWF: Ag levels were also significantly lower in those with MVP (68 +/- 30% versus 100 +/- 23%, p less than 0.001). In those with MVP and congestive heart failure secondary to rupture chordae tendineae, however, the mean level of vWF: Ag was not significantly different from control values (95 +/- 32). There was an increased incidence of recurrent nose bleeds in those with MVP and low levels of vWF:Ag. We conclude that there is a relationship between MVP and low levels of vWF:Ag which may explain the increased incidence of epistaxis in such patients. Increased release of vWF:Ag in those with MVP and concomitant congestive heart failure may account for the normal levels found in this subgroup.

Antigens↗