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Biomedical subjects

D W Alling

Publications and source records attributed to D W Alling.

At least 19 recordsLinked to original sources
PubMed1992

A controlled trial of naloxone infusions for the pruritus of chronic cholestasis.

To test the hypothesis that opioid agonist activity contributes to the pruritus of cholestasis, a placebo-controlled single-blinded trial of naloxone, an opioid antagonist, was conducted in eight patients with primary biliary cirrhosis. After discontinuation of all conventional antipruritic medications, one or two continuous (24-hour) IV infusions of naloxone (0.2 micrograms.kg-1.min-1) and placebo solution were administered consecutively in an order that was not predetermined. Pruritus was assessed subjectively by means of four hourly recordings of a visual analogue score. In addition, objective measurements of scratching activity that were independent of gross body movements were continuously recorded using an apparatus specifically designed to measure the frequencies associated with this activity. No side effects associated with naloxone infusions were observed. Only scratching activity data obtained for the same periods of day and night during both naloxone and placebo infusions were compared. Naloxone infusions were consistently associated with a decrease in values of the scratching activity index. In addition, in 50% of the patients the infusions were associated with a decrease in visual analogue score. The mean decrease in scratching activity ranged from 29% to 96% (mean, 50%; P less than 0.001). These findings imply that increased opioid agonist activity contributes to scratching activity in cholestatic patients.

Adult↗
PubMed1992

Binding of tricyclic antidepressant drugs to trophozoites of Giardia lamblia.

1. Parameters affecting the binding of the tricyclic drugs imipramine and 3-chloroimipramine to Giardia lamblia trophozoites were studied. 2. Two to three times more chlorimipramine than imipramine was bound, consistent with a similar difference in suppressing parasite growth (Weinbach et al., 1985). 3. Kinetic analysis and the ease with which bound drugs can be washed out of the parasites indicate that noncovalent forces are involved in the drug-parasite interaction. 4. Evidence is presented that such drugs probably bind to parasite protein at common binding sites. 5. The data relate to our earlier observation that chlorimipramine is about ten times more effective than metronidazole (Crouch et al., 1986) in suppressing G. lamblia growth in vitro. Tricyclic drugs, therefore, merit serious consideration as novel therapeutic agents against giardiasis.

Animals↗
PubMed1992

Immunologic tolerance in lymphatic filariasis. Diminished parasite-specific T and B lymphocyte precursor frequency in the microfilaremic state.

To explore the mechanisms of antigen-specific immune unresponsiveness seen in microfilaremic patients with bancroftian filariasis, T and B cell precursor frequency analysis was performed using PBMC from individuals with either asymptomatic microfilaremia (MF, n = 7) or chronic lymphatic obstruction (CP, n = 20). Highly purified CD3+ cells were partially reconstituted with adherent cells and their proliferative response to parasite antigens determined in cultures of T cells by limiting dilution analysis. A filter immunoplaque assay also assessed the frequency of both total and parasite-specific Ig-producing B cells. While the lymphocyte proliferation to mitogens and to a nonparasite antigen (Streptolysin-O, [SLO]) were similar in all groups of patients, the frequency of parasite-specific CD3+ T cells was significantly lower (geometric mean [GM], 1/3,757) in MF patients when compared to that in CP patients (GM 1/1,513; P less than 0.001). Similarly, the proportion of lymphocytes producing parasite-specific IgE or IgG was significantly lower in MF patients (IgE mean, 0.2%; IgG mean, 0.33%) compared with CP patients (IgE mean, 3.2%; IgG mean, 1.76%; P less than 0.05 for both comparisons). These observations imply that low numbers of parasite-specific T and B lymphocytes may be partially responsible for the severely diminished capacity of lymphocytes from patients with MF to produce parasite-specific antibody and to proliferate to parasite antigen in vitro. Such differences in parasite-specific lymphocyte responses suggest that tolerance by clonal anergy may be a critical mechanism for maintaining the microfilaremic state.

Animals↗
PubMed1991

Daily meatal care for prevention of catheter-associated bacteriuria: results using frequent applications of polyantibiotic cream.

OBJECTIVE: To determine the efficacy of meatal treatment with a polyantibiotic cream in the prevention of bacteriuria during transurethral bladder catheterization. DESIGN: Randomized controlled trial. SETTING: Community teaching hospital. PATIENTS: Adult patients who underwent closed urinary catheter drainage for short and intermediate durations (two to 30 days). INTERVENTION: Polyantibiotic cream containing polymyxin B sulfate, neomycin sulfate, and gramicidin was applied to the urethral meatus-catheter interface three times daily from the first day of catheterization until bacteriuria was found. The onset of bacteriuria was defined as the day the colonizing species first achieved a colony count of greater than or equal to 1000 colonies/ml. Patients randomized to the control group received routine meatal care with cleansing of the meatal surface during daily bathing. RESULTS: Among 2,923 patients who were randomly allocated to receive either the protocol meatal care or routine care, the evaluable study population consisted of 747 patients who were nonbacteriuric and who remained catheterized for more than two days. Overall, 26 (6.8%) of 383 patients given the polyantibiotic treatment acquired bacteriuria, as compared to 37 (10.1%) of 364 patients not given this treatment (p = .167). A Cox proportional hazards regression analysis showed that, among putative risk factors including lack of meatal care, only female gender, a meatal swab culture yielding gram-negative rods or enterococci, and lack of antibiotic use during catheterization were independently associated with the development of bacteriuria. CONCLUSIONS: The adverse effect of meatal care noted in earlier studies of a disinfectant ointment applied twice daily was not found in this study of an antimicrobial preparation in a cream vehicle applied three times daily. However, the results do not support meatal care as an efficacious method to prevent catheter-associated bacteriuria in all patients.

Aged↗
PubMed1991

Factors that determine the hemodynamic response to inhalation anesthetics.

The hemodynamic response to inhalation anesthesia is influenced by three factors: 1) the specific drug, 2) the dose, and 3) individual characteristics of the subject. To investigate the importance of these factors on the cardiovascular response, we administered five doses [0, 0.5, 1.0, 1.5, and 2.0 minimum alveolar concentration (MAC)] of enflurane, halothane, and isoflurane to each of six dogs. Twelve hemodynamic variables were measured. For all variables, a change in the dose of each drug produced a consistent effect in each dog. Increases in dose resulted in significant decreases in seven variables [left ventricular ejection fraction, cardiac index (CI), stroke volume index (SVI), mean arterial pressure (MAP), mean pulmonary arterial pressure (MPAP), left ventricular stroke work index (LVSWI), and heart rate (HR)] and a significant increase in one variable [central venous pressure (CVP)]. In contrast, the response of individual dogs to different drugs was not consistent. For seven variables [MAP, MPAP, LVSWI, CVP, pulmonary capillary wedge pressure (PCWP), end-diastolic volume index (EDVI), and end-systolic volume index (ESVI)], a significant difference in the responses of a dog to two drugs was greater than zero, whereas a significant difference in the response of at least one other dog to the same two drugs was less than zero (discordant dog-drug interactions). Thus, in contrast to the consistency of the cardiovascular response to changes in dose, the hemodynamic response to different drugs was inconsistent among dogs. We also studied the effect of fluid challenge on hemodynamic response at 1.5 or 2.0 MAC of the three drugs given to each dog.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1990

Frequency of variant antigens in Giardia lamblia.

Giardia lamblia undergoes antigenic variation. The rate of antigenic variation and the size of the variant antigen repertoire were estimated in clones of Giardia lamblia which reexpresses surface variant antigens that are characteristics of its parent. Calculations were based on determinations of the number of trophozoites expressing defined or nondefined epitopes as well as the total number of trophozoites in newly established clones. The rate of appearance of variant antigens containing defined epitopes was expressed as the number of generations until the first trophozoite expressing a defined epitope appeared. In clones of isolate WB, tested because their major surface variant antigens were largely nondefined, variants expressing epitopes recognized by Mabs 6E7 or 3F6 appeared after approximately 12 generations. Variants expressing epitopes recognized by Mab 5C1 appeared at about 13 generations, significantly greater than for the other epitopes. The rate of antigenic variation was studied in another isolate, GS/M, whose surface epitope repertoire differs from that of isolate WB. A single epitope recognized by Mab G10/4 was tested. Trophozoites reexpressing this epitope first appeared after about 6.5 generations, significantly less than in WB. Therefore, the single epitope studied in isolate GS/M is reexpressed much more frequently than those of WB. In isolate WB, the epitopes recognized by Mab 6E7 and 3F6 tended to appear at the same time. The median number of variant antigens in WB was estimated to lie between 20.5 and 184.

Analysis of Variance↗
PubMed1990

Trimethoprim-sulfamethoxazole prophylaxis in the management of chronic granulomatous disease.

Long-term oral antimicrobial prophylaxis is accepted practice in the management of patients with chronic granulomatous disease (CGD). Reports of adverse outcome with trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis in other patient groups, and the recent occurrence of several severe fungal infections in patients followed at the National Institutes of Health (NIH), prompted a review of the NIH experience to examine the incidence of nonfungal and fungal infections in CGD patients with and without TMP-SMX prophylaxis. Prophylaxis decreased the incidence of nonfungal infections from 7.1 to 2.4 per 100 patient-months in patients with autosomal CGD (P less than .01) and from 15.8 to 6.9 infections per 100 patient-months (P = .06) in X-linked CGD patients. There was no significant change in the incidence of fungal infection in CGD patients on TMP-SMX (1.5-0.3 fungal infections/100 patient-months in autosomal CGD and 1.7-0.2 fungal infections/100 patient-months in X-linked CGD patients). TMP-SMX prophylaxis is indicated for the management of patients with CGD and decreases the incidence of non-fungal infections without increasing the incidence of fungal infections.

Genetic Linkage↗
PubMed1989

Cardiac morphologic and functional changes induced by epirubicin chemotherapy.

Cardiac toxicity was evaluated in 24 patients who received epirubicin as a single chemotherapeutic agent, in doses of either 30 mg/m2 every week (11 patients) or 90 mg/m2 every 3 weeks (13 patients). The total doses of epirubicin ranged from 180 mg/m2 to 918 mg/m2 (mean, 491 +/- 187). No patient had prior heart disease, hypertension, mediastinal irradiation, or chemotherapy with other anthracycline agents. None of the patients developed overt heart failure, significant arrhythmias, ECG alterations, or roentgenographic changes in heart size. There was no significant change in the mean value of echocardiographic percent fractional shortening before and after epirubicin therapy. Patients receiving epirubicin doses less than 450 mg/m2 had minimal hemodynamic disturbances; however, no cut-off point separating two significantly different subpopulations could be demonstrated. Endomyocardial biopsy was performed on all patients; 20 biopsies were evaluable. Histologic and ultrastructural changes were similar to those caused by other anthracycline agents. A strong correlation was demonstrated between total dose of epirubicin and pathologic change as quantified using the Billingham scale (r = .7, P = .0006). A cut-off point beyond which there was a probability of increased pathologic damage was statistically defined at 450 mg/m2 of epirubicin. Severe pathologic alterations and moderate hemodynamic changes were observed in only one patient, who received 918 mg/m2 of epirubicin. Patients who are expected to receive epirubicin in excess of 450 mg/m2 should be monitored for cardiac toxicity, and continuation of epirubicin therapy beyond 900 mg/m2 should be based on the results of monitoring.

Adult↗
PubMed1988

Human T-cell recognition of the circumsporozoite protein of Plasmodium falciparum: immunodominant T-cell domains map to the polymorphic regions of the molecule.

The definition of human T-cell antigenic sites is important for subunit vaccine development of a peptide immunogen if the goal is to allow antibody boosting during infection or to stimulate antibody-independent T-cell immunity. To identify such sites on the circumsporozoite (CS) protein of Plasmodium falciparum, 29 overlapping synthetic peptides spanning the entire CS protein were made and tested for their ability to stimulate peripheral blood lymphocytes from 35 adults living in a P. falciparum malaria-endemic region of West Africa. Three immunodominant domains were located outside the repetitive region. These domains, however, occurred in the polymorphic regions of the molecule, suggesting that parasite mutation and selection has occurred in response to immune pressure from T cells. Such polymorphism may impose an obstacle for vaccine development.

Adult↗
PubMed1987

Serial cardiovascular variables in survivors and nonsurvivors of human septic shock: heart rate as an early predictor of prognosis.

Forty-eight septic shock patients with positive blood cultures had conventional serial hemodynamic evaluations until recovery or death to identify early cardiovascular variables that predicted outcome. There were 19 (40%) survivors and 29 nonsurvivors. At the initial evaluation, both survivors and nonsurvivors demonstrated an elevated cardiac index (CI), low systemic vascular resistance index (SVRI), and normal stroke volume index. However, only an initial heart rate (HR) less than 106 beat/min significantly predicted survival. Twenty-four hours after the onset of shock, both an HR less than 95 beat/min and an SVRI greater than 1529 dyne.sec/cm5.m2 predicted survival. Comparing the hemodynamic profiles from the initial to the 24 h time point, a decrease in HR greater than 18 beat/min or a decrease in CI greater than 0.5 L/min.m2 predicted survival. Twenty-two deaths occurred in the first week of study, of which 18 (82%) were due primarily to low SVRI and four (18%) to low CI. Seven deaths occurred after 1 wk, all of which were due to multiple organ failure.

Adolescent↗
PubMed1987

Antigenic relatedness between glycoproteins of human respiratory syncytial virus subgroups A and B: evaluation of the contributions of F and G glycoproteins to immunity.

The degree of antigenic relatedness between human respiratory syncytial virus (RSV) subgroups A and B was estimated from antibody responses induced in cotton rats by respiratory tract infection with RSV. Glycoprotein-specific enzyme-linked immunosorbent assays of antibody responses induced by RSV infection demonstrated that the F glycoproteins of subgroups A and B were antigenically closely related (relatedness, R approximately 50%), whereas the G glycoproteins were only distantly related (R approximately 5%). Intermediate levels of antigenic relatedness (R approximately 25%) were seen in neutralizing antibodies from cotton rats infected with RSV of the two subgroups. Immunity against the F glycoprotein of subgroup A, induced by vaccinia-A2-F, conferred a high level of protection which was of comparable magnitude against challenge by RSV of either subgroup. In comparison, immunity against the G glycoprotein of subgroup A, induced by vaccinia-A2-G, conferred less complete, but significant, protection. Importantly, in vaccinia-A2-G-immunized animals, suppression of homologous challenge virus replication was significantly greater (13-fold) than that observed for the heterologous virus.

Animals↗
PubMed1986

A prospective trial of colchicine for primary biliary cirrhosis.

We entered 60 patients with primary biliary cirrhosis in a double-blind randomized controlled trial to determine whether colchicine is therapeutically effective. Thirty patients had early disease (Stages 1 and 2), and 30 had advanced disease (Stages 3 and 4). Fifteen patients with early disease and 15 with advanced disease received colchicine (0.6 mg twice daily), and the remainder received placebo. Patients were studied about every two months; those remaining in the blind phase at two years underwent repeat liver biopsy and were then placed on open-label colchicine (0.6 mg twice daily). With a few exceptions, the results in patients with early disease were similar to those in patients with advanced disease; hence, data on patients in all stages were combined in the main analysis. During the two-year study period the colchicine-treated patients, as compared with the placebo-treated patients, had improvement in levels of serum albumin, serum bilirubin, alkaline phosphatase, cholesterol, and aminotransferases. However, there was no such improvement in the severity of symptoms or physical findings; moreover, there was no significant difference in the histologic changes noted at liver biopsy in the two treatment groups. At four years after entry, the cumulative mortality from liver disease was 21 percent in patients given colchicine and 47 percent in those given placebo (P = 0.05). The only side effect of colchicine was diarrhea, noted in three patients. The consistent and significant improvement in a number of markers of liver disease and the apparent decreased mortality from liver disease suggest that colchicine may provide some long-term clinical benefit in patients with primary biliary cirrhosis. However, the failure of colchicine to reduce hepatic inflammation and fibrosis leaves uncertain the effect of the drug on the longterm outcome of this disease.

Alkaline Phosphatase↗
PubMed1986

Interleukin 2 receptor expression in unstimulated murine splenic T cells. Localization to L3T4+ cells and regulation by non-H-2-linked genes.

The present study reports the surprising observation that IL-2-R+ cells can be detected in fresh, unstimulated, murine spleen T cells from unimmunized mice by flow cytometry using the monoclonal anti-receptor antibody 7D4. Also, unexpectedly, these cells were found exclusively in the L3T4+Lyt-2- population by two-color fluorescence, in contrast to receptor+ cells after stimulation, in which both L3T4+Lyt-2- and Lyt-2+L3T4- cells were found. The fraction of splenic T cells bearing IL-2-R reproducibly varies twofold under non-H-2-linked genetic control, with high expression in DBA/2 and BALB/c (approximately 6-7%) and low expression in B10.D2 and C57BL/6 (3%). This correlates quantitatively with a greater responsiveness of the DBA/2 and BALB/c splenic T cells to high doses of IL-2, compared with B10.D2 T cells; twice as many B10.D2 T cells as DBA/2 T cells were required to get the same response. Studies with 23 B X D RI strains revealed that the level of IL-2-R+ cells in unstimulated spleen cells was regulated by multiple genes, very likely including at least one gene on chromosome 7, near the HBB locus. The mapping makes novel use of nonparametric (Smirnov) statistics, which we suggest may be of general usefulness in similar analyses of RI strains.

Animals↗
PubMed1986

Effect of age and preexisting antibody on serum antibody response of infants and children to the F and G glycoproteins during respiratory syncytial virus infection.

The serum antibody response of 50 infants and children infected with respiratory syncytial virus (RSV) was determined by a glycoprotein-specific enzyme-linked immunosorbent assay, and the effects of age and preexisting antibody titer at the time of RSV infection on response to the G and F glycoproteins of RSV were examined. The immune response to the G and F glycoproteins was assessed with anti-human immunoglobulin A to permit measurement of the response of young infants in the presence of maternally derived immunoglobulin G. The findings suggested that age primarily affects the response to the F glycoprotein and that preexisting antibody titer affects the response to the G glycoprotein.

Aging↗
PubMed1986

Norepinephrine and thyroid-stimulating hormone induce inositol phosphate accumulation in FRTL-5 cells.

3H-Labeled inositol phosphate accumulation is observed when prelabeled FRTL-5 cells (a rat thyroid cell line) are exposed to norepinephrine (NE) or TSH. The presence of inositol trisphosphate among the products implicates a phosphodiesterase-catalyzed hydrolysis of phosphatidylinositol 4,5-bisphosphate. The response to NE is much greater than that to TSH. This may be explained by the ability of cAMP to inhibit inositol phosphate accumulation in these cells. The stimulation by NE is inhibited by alpha 1-adrenergic receptor antagonists and is markedly potentiated in medium of reduced Ca2+ concentration. After chronic withdrawal of TSH from the growth medium, the magnitude of the response to NE is considerably reduced; however, there is no substantial shift in the dose-response curve. This reflects the dependency of alpha 1-adrenergic receptor expression on TSH in the FRTL-5 cell. In contrast, the characteristics of inositol phosphate accumulation induced by acute treatment with TSH are similar in cells maintained in the presence or absence of a low concentration of this hormone, and correlate well with the iodide efflux and iodination of thyroglobulin observed in response to TSH. These results support the hypothesis that TSH may mediate certain of its physiological effects through cAMP-independent mechanisms, such as phospholipid/Ca2+ and C-kinase pathways.

Animals↗
PubMed1986

Transmission of Giardia lamblia from a day care center to the community.

An outbreak of giardiasis was investigated in one urban day care center; another day care center was selected as a control. In the study day care center, 35 per cent of the children were infected. Infection was spread to at least one household contact of 47 per cent of the infected children. The data suggest person-to-person transmission of giardiasis and the need for measures to prevent its dissemination. Early recognition and treatment of Giardia lamblia infections in children may be indicated.

Adult↗
PubMed1986

Antibody to hepatitis B core antigen as a paradoxical marker for non-A, non-B hepatitis agents in donated blood.

The relationship between the presence of antibody to hepatitis B core antigen (anti-HBc) in donor blood and the development of hepatitis in recipients of that blood was studied in 6293 blood donors and 481 recipients who were followed for 6 to 9 months after transfusion. Of 193 recipients of at least 1 unit of blood positive for anti-HBc, 23 (11.9%) developed non-A, non-B hepatitis compared with 12 (4.2%) of 288 recipients of only anti-HBc-negative blood (p less than 0.001). Donor anti-HBc status was not significantly associated with the development of hepatitis B in the recipient and was negatively associated with the development of cytomegalovirus hepatitis. The relationship of donor anti-HBc status and the development of non-A, non-B hepatitis in the recipient was independent of transfusion volume and elevated donor transaminase level. Although 88% of anti-HBc-positive blood units were not associated with recipient non-A, non-B hepatitis, calculation of maximal corrected efficacy predicted that exclusion of anti-HBc-positive donors might have prevented 43% of the cases of non-A, non-B hepatitis with a donor loss of 4%. Because of the serious chronic consequences of non-A, non-B hepatitis, surrogate tests for non-A, non-B virus carriers must be seriously considered.

Alanine Transaminase↗
PubMed1985

Comparison of the therapeutic efficacy of cromolyn sodium with that of combined chlorpheniramine and cimetidine in systemic mastocytosis. Results of a double-blind clinical trial.

Both antihistamines and cromolyn sodium have been suggested for the treatment of systemic mastocytosis. To determine if one drug regimen was superior to the other, eight patients with systemic mastocytosis were admitted to a double-blind, double-crossover study in which the therapeutic efficacy of cromolyn sodium was compared with that of a combination of chlorpheniramine and cimetidine. Response to therapy was assessed by the patients using symptom scores and by the attending physicians during clinic examinations in addition to sequential plasma and urinary histamine determinations. In the six patients who completed the trial, the patient symptom scores and the physician evaluations indicated that there was no advantage of one drug regimen over the other. Plasma and urinary histamine levels, markedly elevated in most of the patients, were not consistently altered by administration of either cromolyn sodium or the combined antihistamines. Thus, cromolyn sodium and the combined antihistamines were indistinguishable when used for the symptomatic treatment of systemic mastocytosis, and neither regimen altered systemic histamine levels.

Adult↗