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Biomedical subjects

K Harris

Publications and source records attributed to K Harris.

At least 109 records · Page 6Linked to original sources
PubMed1986

Metabolic response of skeletal muscle to ischemia.

To evaluate the temporal relationship and potential correlation between intramuscular phosphagen levels, lipid oxidation, and extent of muscle injury, a canine gracilis muscle model was used to study the consequences of a global ischemic episode for up to 7 h duration with reperfusion for 4 h. In this model the contralateral gracilis muscle was prepared identically to the test side but was not subjected to ischemia and thus served as a control. Blood flow, oxygen consumption, and lactate and glycerol release were measured before and after 2- and 7-h ischemic stress periods. The intramuscular metabolites, glycogen, lactate, phosphocreatine, and ATP, as well as free fatty acid conjugated dienes, were measured before, during, and after the ischemic insult. A 2-h ischemic insult resulted in minimal ultrastructural damage and complete regeneration of intramuscular phosphagens and glycogen on reperfusion with complete normalization of lipid oxidation products. In contrast, a 7-h ischemic insult resulted in profound injury at the ultrastructural level with an inability to restore intramuscular phosphagens and glycogen on reperfusion. This severe muscle injury correlated with a 2.5-fold increase in lipid oxidation products (free fatty acid conjugated dienes) and a decline in ATP levels below 5 mumol/g dry wt on reperfusion. Our results emphasize the prolonged glycolytic activity of skeletal muscle during global ischemia and document the increased production of oxygen free radical-mediated lipid oxidation products in irreversibly injured muscle.

Adenosine Triphosphate↗
PubMed1985

The effect of renal function on enalapril kinetics.

Enalapril maleate (MK-421), a nonmercapto-containing angiotensin converting enzyme (ACE) inhibitor, is converted in vivo to enalaprilat (MK-422), the active diacid. We evaluated serum profiles and urinary excretion of oral enalapril maleate in patients with renal disease (group I, creatinine clearance less than 3 ml/min, patients undergoing dialysis, n = 10; group II, creatinine clearance 10 to 79 ml/min, n = 9) compared with healthy subjects (group III, creatinine clearance greater than 80 ml/min, n = 10). Group I received a 10 mg dose during a day while not receiving dialysis and a 10 mg dose 1 hour before dialysis 2 weeks later. Groups II and III received a single 10 mg dose. Blood samples and urine were collected for 48 hours. Impaired renal function resulted in elevated serum and plasma concentrations of enalapril maleate and decreased excretion rates and urinary recovery of enalapril maleate and enalaprilat. The data suggest an apparent increase in the extent of metabolism of enalapril maleate to enalaprilat or an increase in nonrenal elimination of unchanged enalapril maleate in renal disease compared with normal health. Enalaprilat was dialyzable.

Administration, Oral↗
PubMed1984

Influence of food on the bioavailability of enalapril.

In a randomized, two-period crossover study in 12 normal volunteers, serum and urine concentrations of the angiotensin-converting enzyme inhibitor enalapril and its active metabolite enalaprilat were determined following administration of a single 40-mg tablet of enalapril maleate administered both in the fasting state and with a standard breakfast. A 7-d interval separated the two treatment periods. Area under the serum concentration-time curves for enalaprilat and urinary recoveries for enalaprilat and total drug did not differ significantly between the fed and fasted conditions. The mean observed maximum serum concentration of enalaprilat was slightly higher for the fasting treatment, but the time to peak concentration was almost identical for the two treatments. Enalapril maleate is unlike the prototype angiotensin-converting enzyme inhibitor captopril in that a standard meal does not appear to influence absorption of this new drug.

Adult↗
PubMed1984

Clinical experience with continuous monitoring of mixed venous oxygen saturation in respiratory failure.

The amount of oxygen in mixed venous blood (SvO2) is a reliable indicator of the status of oxygenation of tissue in most clinical settings. Monitoring levels of SvO2 might, therefore, aid in managing critically ill patients. A recently developed adult pulmonary arterial catheter provides continuous measurement of SvO2 via fiberoptic bundles incorporated into the catheter, in addition to measuring hemodynamic pressures and cardiac output by thermodilution. We evaluated 100 consecutive fiberoptic catheters for accuracy and reliability of the system in 86 critically ill adult patients and determined the clinical usefulness that knowledge of SvO2 provided. Over a range of hemoglobin saturations from 24 to 85 percent, the correlation coefficient between in vivo SvO2 vs photometrically measured samples for 199 paired measurements was 0.95. Mean duration of usage for 33 catheters in the medical intensive care unit was 6.1 days; all catheters functioned normally until clinical conditions permitted removal. Continuous measurements of SvO2 detected unsuspected increases in tissue oxygen consumption during coughing spasms and positioning of the patient. In nine of 13 patients with hypoxemic respiratory failure requiring positive end-expiratory pressure (PEEP), we found a strong correlation (r = 0.88) between oxygen delivery and SvO2. Of the four patients not showing correlation, two had sepsis, and two had nearly normal values of SvO2 and oxygen delivery at all levels of PEEP studied. Continuous measurement of SvO2 improves monitoring of patients, facilitates titration of respiratory therapies, detects abrupt changes in tissue oxygen consumption, and identifies levels of PEEP associated with greatest oxygen delivery.

Adult↗
PubMed1983

Electrophysiological studies in Tourette's syndrome.

The value of standard electrophysiological studies using electroencephalography and evoked responses was evaluated in patients with Tourette's syndrome. Sixteen-channel electroencephalograms were obtained in 40 patients (36 males, 4 females) awake and asleep, and evoked responses were obtained in a subgroup of 17 patients. Evoked response variables evaluated included latencies and amplitudes of visual evoked responses, brainstem auditory evoked responses, and somatosensory evoked responses to median and peroneal nerve stimulation. Only 5 of the 40 patients (12.5%) demonstrated electroencephalographic abnormalities, which included central spikes, generalized and paroxysmal slow activity, and slowing of the normal basic frequency. Evoked response studies demonstrated no consistent differences between the patients with Tourette's syndrome and age- and sex-matched controls. The data demonstrate no notable diagnostic or therapeutic value for routine electroencephalographic or evoked response studies in Tourette's syndrome.

Adolescent↗
PubMed1983

Plasma exchange in acute renal allograft rejection. A controlled trial.

A controlled trial was carried out to assess the value of intensive plasma exchange in 27 renal transplant recipients with clinical and histological evidence of acute vascular rejection. In addition to standard immunosuppression, 13 patients received plasma exchange on six consecutive days at a mean exchange volume of 40.6 ml/kg of body weight each day using an intermittent cell separator. A further 14 patients received standard immunosuppression only. In addition, 10 patients exchanged prior to the controlled trial have been studied. Analysis of short-term benefit, as evidenced by a reduction in serum creatinine, and by subsequent graft survival revealed no significant difference in these parameters between the two groups in the controlled trial. This regimen of plasma exchange has not, therefore, been shown to modify acute renal allograft rejection.

Creatinine↗
PubMed1981

Chronic pruritic dermatitis in asthmatic monkeys: a subhuman primate analogue of atopic dermatitis?

In a group of adult normal rhesus monkeys and monkeys with IgE-mediated asthma observed over a period of 15 years, 2 of the latter group were found to have chronic, generalized pruritus and dermatitis. The skin lesions were recurrent and located on the flexural surfaces of the forearms leading to the thickened, scaling, lichenified dermatitis in that area in the skin of 1 monkey. The pruritus and skin lesions subsided following therapy with depot methylprednisolone but recurred after this therapy was discontinued. Both animals had recurrent severe cutaneous infections in excoriated lesions following scratching without infections in other organs. The cutaneous infections responded to penicillin therapy but recurred with scratching. No deficiencies in immunoglobulin levels, or lymphocyte responses to phytohemagglutinin were found in these 2 monkeys. The 2 animals differed from normal animals by their high titers of immediate skin reactivity to ascaris antigen, persistent and severe asthmatic responses to ascaris antigen, high IgG antibody levels to ascaris antigen but all of the latter findings were also present in asthmatic monkeys without dermatitis. Cutaneous biopsies of lesions were nonspecific but provided no evidence for other explanations for the dermatitis which appears to be an analogue of human atopic dermatitis.

Adrenal Cortex Hormones↗
PubMed1980

Long-term corticosteroid effect on lymphocyte and polymorphonuclear cell function in asthmatics.

The effect of long-term alternate-day steroid administration on lymphocyte and polymorphonuclear cell (PMN) functions was studied in 10 steroid-dependent adult asthmatic patients. The duration of alternate-day prednisone usage ranged from 3 to 12 yr with an average of 6.7 +/- 3.6 yr. Maintenance steroid dosage at the time of study ranged from 20 to 50 mg on alternate days, averaging 31 +/- 8 mg. Prednisone caused marked lymphopenia, suppression of phytohemagglutin (PHA) lymphocyte transformation and PMN adherence 4 hr after ingestion. By 24 hr these measurements returned to normal or higher. These effects appeared at all doses between 20 and 50 mg of prednisone. In contrast, there was no statistically significant suppression of the total leukocyte count, total and active erythrocyte (E) rosette-forming lymphocytes, serum immunoglobulin concentrations, polymorphonuclear cell (PMN) phagocytosis, or delayed skin reactivity. We conclude that the acute effects of prednisone on lymphocyte and PMN function are transient and return to normal levels by 24 hr. The continued administration of beclomethasone dipropionate by inhalation did not interfere with the recovery of the transient leukocyte abnormalities induced by oral prednisone.

Asthma↗
PubMed1979

The effect of histamine-1 and histamine-2 antagonists on airway responses to histamine in the rhesus monkey.

This study used rhesus monkeys with consistent respiratory responses to aerosolized histamine. Two systems of histamine challenge were evolved to study the effects of histamine antagonists on the histamine-induced respiratory response. One system consisted of administering increasing subreactive concentrations of histamine until an airway response (H) occurred. This threshold histamine dose was repeated (H'). The pulmonary function changes occurring with the H' challenge were less intense than those with H. M, a histamine-2 receptor antagonist, when given before the H' dose was associated with a potentiated H' response compared with the threshold H response. This provides evidence for histamine-2 receptor sites in rhesus monkey airways. A second system used duplicate histamine challenges with a known reactive dose of histamine. In this system, the pulmonary function changes occurring with the repeated challenge (H') were greater than with the first reactive challenge dose (H). This H' response was inhibited partially with diphenhydramine, a histamine-1 receptor antagonist. These two systems of histamine challenge provide an experimental model for evaluating pharmacologic alteration of histamine-induced respiratory responses. There is evidence for the existence of histamine-1 and histamine-2 receptor sites in the airways of the rhesus monkey.

Animals↗
PubMed1979

The evaluation of selected parameters of immune function in asthmatics after long-term corticosteroid therapy.

The availability of inhaled beclomethasone diproprionate permitted the discontinuation of continuous, long-term systemic corticosteroid therapy (SCT) in a group of asthmatics who had previously required SCT to control their asthma. Twelve patients had been on SCT for a period of 2-22 years with an average duration of 7 years. To determine whether this previous long-term SCT and the current use of inhaled beclomethasone diproprionate had an effect on leucocyte functions, a variety of studies reflecting T lymphocyte, B lymphocyte and granulocyte function was done. The results were compared with those of twelve asthmatic patients of similar age ranges who had never received steroids. Results showed that the two patient populations could not be differentiated on the basis of phytohaemagglutinin stimulation of lymphocytes, sheep erythrocyte rosette formation, IgG, IgA, IgM and IgE concentrations or granulocyte bactericidal activity. Delayed skin reactivity was present in both groups, with more positive reactions in the non-SCT group. Polymorphonuclear adherence values were slightly lower in the SCT female population using beclomethasone diproprionate. The latter two minor differences may be due to the previous SCT, the use of beclomethasone diproprionate or the limited population of patients studied. We conclude from these studies that the long-term use of SCT at the low doses required for control of asthma resulted in little permanent effect on the variety of lymphocyte and granulocyte functions tested.

Adrenal Cortex Hormones↗
PubMed1979

In vitro activities of some synthetic substance P analogs.

Substance P (SP) and several analogs and fragments have been synthesized and evaluated on non-stimulated and stimulated guinea-pig ileum. In the former test system the potency order was as follows: SP(4--11) greater than SP = [Tyr7]-SP = [Eth11]-SP = [Nle11]-SP greater than [Dala9]-SP greater than SP(7--1) = [Tyr7]-SP(7--11) greater than [Eth11]-SP(7--11) greater than [DAla9]-SP(7--11) greater than [Nle11]-SP(7--11) greater than SP(1--7). The spasmogenic activity of SP and analogs was preserved in the same potency order on stimulated guinea-pig ileum; none of these modifications resulted in an analog with narcotic-like activity. These data are discussed in terms of a hypothetical SP receptor in extravascular smooth muscle.

Animals↗
PubMed1978

Characterization of a unique cell line (LAZ 221) from human acute lymphocytic ("null" cell) leukemia.

A unique human cell line designated LAZ 221 has been established from the peripheral blood of a patient with acute lymphocytic leukemia of the "null" cell type. The cell line does not possess the Epstein-Barr virus nuclear antigen and has a karyotype of 45,XX,-9,-12,+(9q12q). Both the established cell line and the patient's uncultured blast cells share the same phenotypic markers. They both lack T-cell markers. They fail to form sheep erythrocyte rosettes and do not react with T-cell-specific antisera (TH1-, HTL-), nor do they possess B-cell markers. They do not form rosettes with erythrocytes sensitized with complement, and they are surface immunoglobulin negative. However, they do possess an HLA-D-related glycoprotein complex of 23,000 to 30,000 daltons, an la-like antigen. Thus, LAZ 221 shares the phenotype of the patient's uncultured blasts and is a cell line representative of about 75% of all human acute lymphocytic leukemias. In this respect it differs from previously described human hematopoietic cell lines.

Adult↗
PubMed1978

Dynamic parameters of membrane lipids in normal and leukemic human lymphocytes isolated from peripheral blood and bone marrow.

The degree of microviscosity (eta), and lipid fluidity (LFU) of cellular membranes of normal and leukemic lymphocytes obtained from peripheral blood and bone marrow of normal donors and acute lymphatic leukemic (ALL) patients was quantitatively monitored by fluorescence polarization analysis with the aid of the fluorescent lipophilic probe 1,6-diphenyl-1,3,5-hexatriene when embedded in cellular membranes of intact cells. The results have shown a marked decrease in eta and a significant increase in LFU in lymphocytes obtained from both peripheral blood and bone marrow of ALL patients at admission when compared to both T- and B-lymphocytes obtained from peripheral blood of normal donors. Moreover, both dynamic parameters, eta and LFU, show normal characteristic values in lymphocytes obtained from bone marrow of ALL patients in complete hematological remission. Since in few cases a decrease in eta and an increase in LFU were observed in bone marrow lymphocytes isolated from ALL patients in remission, the possibility that these dynamic parameters may serve as a diagnostic tool for an early detection of a new relapse is discussed.

B-Lymphocytes↗
PubMed1976

Pigeon breeders disease. III. A study of a family exposed to doves.

A family of five individuals exposed to doves in their home were studied to evaluate possible factors leading to sympotmatic hypersensitivity pneumonitis documented in one member of the family, while the other exposed members remained asymptomatic. Antbodies against pigeon serum were domenstrated by radioimmunoassay in all subjects, and significant lymphocyte reactivity against pigeon antigens was demonstrable in three of the five members. The presence of serum antibody activity or lymphocyte reactivity against avian antigens or both did not differentiate the sick from the well family subjects. However, the possibility that increased exposure to antigen may correlate with higher degrees of antibody and lymphocyte reactivity as well as clinical disease is suggested from observation made in this family. No correlation was found between HL-A type and either symptomatic disease or immunological reactivity in these subjects.

Adolescent↗