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Biomedical subjects

K Daly

Publications and source records attributed to K Daly.

At least 73 records · Page 4Linked to original sources
PubMed1988

Determining risk for chronic otitis media with effusion.

Chronic otitis media with effusion (OME) has been observed in 10 to 20% of children following acute, symptomatic otitis media. To determine factors that place children at increased risk of chronic OME, we conducted a 6-week prospective study of 386 children who had 3 or more recent episodes of otitis media and who had middle ear effusion present for at least 2 weeks. Of these children 23% developed chronic OME (i.e. effusion lasting 8 continuous weeks or more), and 26% developed chronic OME complicated by acute, symptomatic otitis media. Predictors for chronic OME were (1) bilateral OME, (2) duration of effusion for greater than 2 weeks at enrollment and (3) day care attendance. Children with these 3 factors had twice the risk of developing chronic OME as children lacking all 3 factors. These risk factors can be used to target children for early, aggressive OME therapy.

Child↗
PubMed1988

Relapse after interferon alfa-2b therapy for hairy-cell leukemia: analysis of prognostic variables.

Sixty-nine patients with hairy-cell leukemia (HCL) were treated with interferon alfa-2b (IFN) in a single-institution study. The dose used was 2 x 10(6) U/m2 self-administered subcutaneously three times weekly, for a planned treatment duration of 12 to 18 months. Of the 68 evaluable patients, the major response rate was 75%, with 13% complete responses (CRs) and 62% partial responses (PRs). An additional eleven patients (16%) had minor responses (MRs). Duration of response was denoted as failure-free survival (FFS), defined as the time from the end of IFN therapy to a need for further antileukemic therapy. Of the 60 responding patients followed after discontinuation of IFN, 27 have relapsed, requiring further therapy. The median actuarial FFS for these 60 patients is 25.4 months. All but five patients are alive, and the actuarial overall survival for the 69 patients is 91% +/- 4% at 4 years from the start of IFN. The best indicators of relapse were the neutrophil alkaline phosphatase (NAP) score and degree of residual bone marrow hairy cells (%HCL) at the completion of therapy. Patients with NAP less than 30 (n = 21) had the best prognosis (median FFS, 30.4 months), while those with NAP greater than or equal to 30 and %HCL less than or equal to 30 (n = 21) or %HCL greater than 30 (n = 16) had intermediate and poor prognoses, respectively (median FFS, 23.5 and 12.4 months) (P = .0005). Fourteen of the relapsing patients are evaluable for response to a second course of IFN, with seven PRs and four MRs. Stratified randomized trials are indicated to determine the role of maintenance therapy for responding patients.

Adult↗
PubMed1987

Flow cytometry in hairy cell leukemia before and during interferon alfa-2b therapy.

Mononuclear cells from 15 patients with hairy cell leukemia were studied before and during therapy with interferon alfa-2b (IFN) by regular peripheral blood differential counts and flow cytometry, using a panel of monoclonal antibodies (Moab). Seven leukemic phase patients (Group 1) had a mean leukocyte count of 48,870/microliter at entry with a mean absolute hairy cell (HC) count of 40,100/microliter. After 3 months on IFN, both parameters decreased significantly (WBC 3,500/microliter; HC count 130/microliter). In eight patients with a cytopenic form of the disease (Group 2) the mean leukocyte count rose from 2950/microliter to 3890/microliter while the mean absolute HC count decreased from 300/microliter to 120/microliter. The morphologic shifts correlated well with changes in the Moab reaction pattern. In Group 1 the activity of all Moab decreased significantly. In Group 2, only cells expressing Leu 3a and Leu 11a (a marker of natural killer cells) showed a significant shift, the latter increasing from 170/microliter to 360/microliter. This increase in natural killer cell antigen expression was not obvious based on routine morphologic observations alone. We show that flow cytometry may be a useful adjunct in monitoring the response of HCL to therapy. Changes in populations of cells that may be difficult to discriminate on morphologic grounds alone may be observed.

Antibodies, Monoclonal↗
PubMed1987

Molecular characterization of Mycoplasma genitalium species-specific and cross-reactive determinants: identification of an immunodominant protein of M. genitalium.

Species-specific proteins of Mycoplasma genitalium as well as proteins cross-reactive with M. pneumoniae have been identified using monoclonal antibodies generated against these mycoplasmas in enzyme-linked immunosorbent assays (ELISA) and Western blot analyses. Specificity of the antibodies was examined using M. hominis, M. orale M. salivarium and Acholeplasma laidlawii. A 140-kDa (kilodalton) protein of M. genitalium that appeared to be immunodominant in mice was also shown by radioimmunoprecipitation to be immunodominant in experimentally infected chimpanzees.

Animals↗
PubMed1987

Durability of responses to interferon alfa-2b in advanced hairy cell leukemia.

Previous studies have demonstrated that significant hematologic improvement occurs in the majority of patients with hairy cell leukemia (HCL) treated with partially purified or recombinant interferon (IFN). Fifty-three patients received IFN alfa-2b for at least 3 months in a dose of 2 X 10(6) U/m2 subcutaneously thrice weekly. Of the 49 patients evaluable for response (at least 6 months of IFN therapy), there were ten complete responses and 29 partial responses for a total response rate of 80%. The peripheral blood counts and bone marrow continued to improve over the course of a full year of therapy. IFN was well tolerated, with no patients discontinuing therapy because of toxicity. Transient myelosuppression occurred in most patients during the first 1 to 2 months of therapy, occasionally precipitating a transfusion requirement. After IFN treatment was discontinued, there was a marked decrease in normal marrow elements and a relative increase in marrow hairy cells. This was associated with a transient increase in normal elements in the peripheral blood. Only one of 24 patients followed after receiving IFN for a median of 8.5 months (range, 3 to 16 months) has required further therapy. We conclude that low-dose IFN alfa-2b is highly effective in advanced HCL; responding patients should be treated for at least 1 year. The decision to initiate a second course of IFN therapy should be based primarily on peripheral blood counts and the clinical status of the patient rather than on the bone marrow.

Adult↗
PubMed1985

Electrophysiologic, hemodynamic and metabolic effects of intravenous bepridil hydrochloride.

Bepridil, a fast and slow channel blocking drug, was administered intravenously over 5 minutes in a dose of 3 mg/kg body weight to 19 patients. Ten patients received intravenous bepridil during electrophysiologic study, performed for the investigation of known or suspected cardiac arrhythmias. Sinus cycle length increase from 764 +/- 56 to 886 +/- 62 ms (p less than 0.002). AH interval increased from 101 +/- 6.9 to 137 +/- 11.9 ms (p less than 0.01). HV and QRS durations were not significantly affected. QTc interval increased from 395 +/- 13 to 423 +/- 13 ms (p less than 0.001). Atrial effective refractory period increased from 211 +/- 8 to 242 +/- 8.7 ms (p less than 0.005), and atrioventricular nodal effective refractory period increased from 299 +/- 26 to 366 +/- 30 ms (p less than 0.02). Right ventricular effective refractory period increased from 233 +/- 9.3 to 259 +/- 8.1 ms (p less than 0.001). In an additional 9 patients with coronary artery disease, a hemodynamic and metabolic study was performed. A transient mean decrease dP/dt max from 1,646 +/- 164 to 1,506 +/- 238 mm Hg/s (p less than 0.05) and a mean increase of 2.6 mm Hg (p less than 0.05) in left ventricular end-diastolic pressure were observed. Both values had returned to control levels 15 minutes after drug infusion. Blood pressure, cardiac output, coronary sinus blood flow and myocardial lactate extraction ratio did not change significantly. This profile of powerful electrophysiologic and minor hemodynamic changes indicates a potentially useful role for bepridil in the acute management of supraventricular arrhythmias and, possibly, ventricular arrhythmias.

Adolescent↗
PubMed1985

Effects of methylene blue on electrical behavior of myenteric neurons.

Intracellular recording methods were used to investigate the action of methylene blue on electrical behavior of myenteric neurons in guinea pig small intestine. The neurophysiological studies were done in parallel with studies on contractile activity of the intestinal musculature. Methylene blue depolarized the membranes, increased the input resistance, augmented excitability and reduced postspike hyperpolarizing potentials in AH/Type 2 myenteric neurons. These effects, with the exception of suppression of postspike hyperpolarization, were reversed by exposure to elevated calcium. The mechanism of action of methylene blue appeared to be suppression of calcium-dependent potassium conductance in the neuronal membranes. The neuronal action of methylene blue was manifest as a release of excitatory neurontransmitter substances which evoked contraction of the small intestinal longitudinal muscle.

Acetylcholine↗
PubMed1985

Beneficial effects of diltiazem combined with beta blockade in angina pectoris.

The effects of combining diltiazem, a calcium channel blocking agent, with beta adrenergic blockade were evaluated in 11 patients with obstructive coronary artery disease. All patients had stable angina pectoris and were receiving oral beta blocking therapy. Symptomatic, metabolic, coronary and systemic haemodynamic responses were monitored at rest and during atrial pacing. Following the administration of diltiazem, resting arterial blood pressure, systemic vascular resistance and heart rate fell significantly with no adverse effects on left ventricular function. During pacing diltiazem produced significant decreases in rate-pressure product and myocardial oxygen consumption. As a consequence there was a significant increase in mean pacing time to angina from 151 +/- 42 to 406 +/- 72 s (P less than 0.001). Concomitantly, myocardial lactate extraction was improved significantly from mean lactate production of -2 +/- 12% to mean lactate extraction of 12 +/- 7% (P less than 0.05). This study indicates that intravenous diltiazem can be administered to patients receiving chronic oral beta blockade without adverse haemodynamic effects and that combination therapy has significant beneficial effects in coronary artery disease.

Adrenergic beta-Antagonists↗
PubMed1985

Right atrial embolus. Echocardiographic features.

Although the value of echocardiography in detecting left heart thrombus is well recognised, right atrial thromboembolism has rarely been identified in life. In two patients with pulmonary embolism of varying severity cross sectional echocardiography identified a thrombus moving freely within the right atrium and clearly showed its string-like or even tubular structure. An embolectomy, based on the echocardiographic diagnosis, was undertaken successfully in one patient. The value of routine echocardiography in patients with suspected pulmonary embolism is yet to be confirmed.

Aged↗
PubMed1985

Milrinone in heart failure. Acute effects on left ventricular systolic function and myocardial metabolism.

Milrinone, a new bipyridine compound related to amrinone, is a potent non-adrenergic inotrope in experimental preparations and also shows vasodilator activity. In the present study the haemodynamic and metabolic effects of milrinone were evaluated in 12 patients with congestive heart failure. Milrinone 5 mg given orally produced a sharp reduction in left ventricular end diastolic pressure without significantly affecting stroke volume. The improvement in left ventricular function was due to a combination of vasodilation and positive inotropism. Thus small reductions in blood pressure and systemic vascular resistance were associated with increments in the isovolumic indices of left ventricular function. The relation between left ventricular end systolic pressure and dimension was displaced leftwards and downwards. Only reductions in left ventricular cavity dimension were statistically significant, however. Though myocardial oxygen consumption did not change significantly, it tended to increase whereas lactate consumption tended to decrease. This trend towards oxygen imbalance suggests the need for caution in the use of milrinone in patients with severe coronary artery disease.

Adult↗
PubMed1985

Treatment of hairy cell leukemia with recombinant alpha 2 interferon.

Nine patients with progressive hairy cell leukemia were treated with subcutaneous injections of recombinant alpha 2 interferon (2 to 10 X 10(6) U/m2) three times weekly. Eight patients completed at least eight weeks of treatment and were evaluable; one patient with refractory thrombocytopenia died of an intracerebral hemorrhage after two doses of interferon. Seven of eight patients responded, with responses occurring as early as two weeks. Four patients also had resolution of their monocytopenia. No complete responses were seen with up to 30 weeks of treatment. Bone marrow biopsies demonstrated improvement in all eight patients. No unforeseen toxicity occurred, but most patients had transient myelosuppression during the first few weeks of treatment. Recombinant alpha 2 interferon is effective in the treatment of hairy cell leukemia, with acceptable toxicity.

Adult↗
PubMed1984

Acetaldehyde utilization and toxicity in Drosophila adults lacking alcohol dehydrogenase or aldehyde oxidase.

Metabolic utilization and toxicity of acetaldehyde were studied in flies lacking alcohol dehydrogenase (ADH), aldehyde oxidase (AO), or both functions. Prior to the experiments, mutant alleles Adhn4 and mal were transferred to the same genetic background by 10 successive backcrosses. By comparison with wild-type flies, various deleterious, pleiotropic effects could be attributed to the mal allele but not to Adhn4. Of the four genotypes studied (mal, Adhn4, mal Adhn4, and wild), all were able to use acetaldehyde as a resource in a similar way. In spite of its high toxicity, acetaldehyde appeared a better resource than ethanol. Flies treated with intermediate acetaldehyde concentrations (around 0.5%) exhibited a very high interindividual heterogeneity which could reflect a physiological adaptation occurring as a consequence of the aldehyde treatment. Toxicity tests showed that ADH-negative flies were more sensitive to acetaldehyde than wild type, but this is most likely explained by the transformation of the aldehyde into alcohol. Our results show that the aldehyde metabolizing enzyme (AME) system in Drosophila is neither ADH nor AO. The existence of an aldehyde dehydrogenase is plausible.

Acetaldehyde↗
PubMed1984

Acute myocarditis. Role of histological and virological examination in the diagnosis and assessment of immunosuppressive treatment.

Twelve patients, who presented with congestive cardiac failure after a recent influenza like illness, had a clinical diagnosis of acute myocarditis confirmed histologically after endomyocardial biopsy. Eight were under 30 years of age. Serological testing suggested a viral aetiology in six patients. Nine patients were treated with immunosuppressive drugs (prednisolone and azathioprine in seven, prednisolone alone in two). At two months, seven patients showed clinical and haemodynamic improvement (ejection fraction rose from 26.8 to 49% and left ventricular end diastolic pressure fell from 26.4 to 16.2 mm Hg) with biopsy evidence of healed myocarditis. In two, activity persisted. At six months' follow up only four of these patients had maintained their improvement. One patient relapsed after stopping treatment, subsequently improving on its reinstatement. Two patients developed severe interstitial myocardial fibrosis with gradual deterioration. Virology and myocardial histology were complementary in the diagnosis of acute myocarditis in these young patients, whose response to immunosuppressive treatment was variable. An apparent early response could not be clearly separated from variables in the natural history of the condition. Serial endomyocardial biopsies showed a progression to congestive cardiomyopathy in two patients. Multicentre controlled trials will be necessary to assess fully the role of immunosuppressive treatment in this condition.

Acute Disease↗
PubMed1984

Beneficial effects of diltiazem in coronary artery disease.

The effects of the new calcium channel blocking agent diltiazem were evaluated in 11 patients with stable angina pectoris and confirmed obstructive coronary artery disease at rest and during rapid atrial pacing. Symptomatic, metabolic, coronary, and systemic haemodynamic indices were monitored at rest and during pacing induced ischaemia. At rest, after the administration of intravenous diltiazem, potent vasodilator effects were observed with a significant fall in mean blood pressure and an increase in cardiac index. Importantly, however, the systemic vasodilator effect of diltiazem was associated with no significant increase in heart rate. During pacing there was similar decrease in mean blood pressure after diltiazem, and mean pacing time to angina increased significantly. Three patients did not develop angina on repeat pacing. Coupled with an improved pacing time to angina there was a significant improvement in myocardial lactate extraction during pacing, changing from lactate production to lactate extraction after diltiazem. This study confirms the antianginal effects of diltiazem and suggests that this agent may have advantages in the management of angina pectoris. The results suggest that diltiazem may exert its beneficial effect not only by reducing afterload reduction but also by a direct metabolic effect on the myocardium.

Angina Pectoris↗
PubMed1984

Effect of timolol maleate on pacing induced myocardial ischaemia.

The effects of timolol maleate administered intravenously on coronary and systemic haemodynamics, myocardial metabolism, and plasma catecholamine concentrations were assessed in 10 patients with confirmed coronary artery disease. Rapid atrial pacing to the onset of angina was performed in all patients. Timolol reduced cardiac output at rest and during pacing and reduced resting heart rate but did not affect arterial blood pressure. Left ventricular stroke work index fell during pacing. Coronary sinus blood flow was unchanged, but pulmonary artery diastolic pressure rose after timolol. The drug produced clinical improvement in nine of the 10 patients with prolongation of the mean pacing time to angina. There was evidence of improved myocardial metabolism with a change from production to extraction of lactate: Arterial noradrenaline concentrations at rest rose after timolol. In these patients with coronary artery disease timolol produced an increased tolerance to atrial pacing stress, which appears to be due to a combination of effects including reduced myocardial contractility and decreased lipolysis.

Angina Pectoris↗
PubMed1983

Prognostic implications of karyotype and morphology in patients with non-Hodgkin's lymphoma.

Clonal chromosome abnormalities were observed in 30 patients with non-Hodgkin's lymphoma; the type of lymphoma was characterized on the basis of the International Working Formulation. The 30 patients were classified into five groups according to the chromosome abnormality. There were 8 patients with t(14;18), 3 with t(8;14), 7 with a translocation to the long arm of chromosome 3 (a 3q+ chromosome), 5 with near-tetraploidy, and 7 with other abnormalities. Among the 8 patients with t(14;18), 5 had follicular small cleaved-cell lymphoma (FSC), I had follicular mixed cell lymphoma (FM), and 2 had diffuse large-cell lymphoma (DL); the diagnosis in these 2 patients was based on extranodal tissue. All 3 patients with t(8;14) had DL and B-cell markers. Except for 1 patient, all those with a 3q+ chromosome had DL; 4 of those who were tested had B-cell or pre-B-cell markers. Four of the 5 patients with near-tetraploidy had follicular mixed-cell lymphoma, and 2 of the 7 patients with other abnormalities had T-cell lymphoma. Thus, patients with a t(8;14), a 14q+ chromosome, or a 3q+ chromosome all tend to have diffuse large-cell lymphoma, usually of the non-cleaved type. On the other hand, our data suggest that patients with FSC generally have a t(14;18) whereas those with follicular and diffuse mixed small cleaved cells and large noncleaved cells have a different pattern with modal chromosome numbers in the tetraploid range. We added 17 previously reported patients to the 30 presented here and correlated the karyotype with survival. The 6 patients with near-tetraploidy had the longest median survival, 69 months, the 15 patients with t(14;18) had the next longest, 48 months. The 4 patients with t(8;14) had the shortest survival, 12 months, and the 9 with other abnormalities had the next shortest, 17 months. Intermediate survivals of 27 and 30 months were observed in patients with a 14q+ or a 3q+ chromosome, respectively. The median survival of these various categories differs and our data, thus, indicate that the karyotypic pattern of the malignant cell may be a significant independent prognostic feature influencing the survival of patients with non-Hodgkin's lymphoma.

Adult↗