PubMed HealthSearch

Biomedical subjects

P J Miller

Publications and source records attributed to P J Miller.

At least 19 recordsLinked to original sources

Randomized, double-blind trial of mazindol in Duchenne dystrophy.

There is evidence that growth hormone may be related to the progression of weakness in Duchenne dystrophy. We conducted a 12-month controlled trial of mazindol, a putative growth hormone secretion inhibitor, in 83 boys with Duchenne dystrophy. Muscle strength, contractures, functional ability and pulmonary function were tested at baseline, and 6 and 12 months after treatment with mazindol (3 mg/d) or placebo. The study was designed to have a power of greater than 0.90 to detect a slowing to 25% of the expected rate of progression of weakness at P less than 0.05. Mazindol did not benefit strength at any point in the study. Side effects attributable to mazindol included decreased appetite (36%), dry mouth (10%), behavioral change (22%), and gastrointestinal symptoms (18%); mazindol dosage was reduced in 43% of patients. The effect of mazindol on GH secretion was estimated indirectly by comparing the postabsorptive IGF-I levels obtained following 3, 6, 9, and 12 months in the mazindol treated to those in the placebo groups. Although mazindol-treated patients gained less weight and height than placebo-treated patients, no significant effect on IGF-I levels was observed. Mazindol doses not slow the progression of weakness in Duchenne dystrophy.

Behavior

Univariate and multivariate statistical analysis of high-grade gliomas: the relationship of radiation dose and other prognostic factors.

Univariate and multivariate statistical analyses were used to examine the relationships between duration of survival and multiple variables in the presentation and treatment of 82 patients with high-grade gliomas (16 grade 3, 66 grade 4). The median survival time of the eight patients who received less than or equal to 40 Gy to the tumor bed was 16 weeks and was 17 weeks for the three who received between 40 and 50 Gy. Patients who received 50-60 Gy had a median survival time of 62 weeks, compared to 54 weeks in patients who received 60-70 Gy. These differences in median survival time were statistically significant between the extremes (p = 0.0001), as well as between the 40-50 Gy group and the 50-60 Gy group (p = 0.02). However, no significant difference could be detected between the groups receiving 50-60 Gy versus 60-70 Gy. Univariate analysis also identified preoperative performance status, age, histologic grade, extent of surgery, and seizure history as prognostic factors. Cox multivariate analysis was performed to identify variables that were significant in independently predicting duration of survival. Although contemporary studies have shown many variables to be significant in predicting survival, our analysis found that many of them were not independent predictors. The variables which independently predicted improved duration of survival were greater total radiation dose to the tumor bed (p less than 0.0001), superior preoperative performance status (p = 0.003), and grade 3 versus grade 4 (p = 0.04). Younger age at diagnosis was marginally significant (p = 0.07). In the group of 60 patients receiving greater than 50 Gy, a discriminant analysis was also performed. The patients were divided into two groups based on apparent clusters of survival times: greater than or equal to 60 weeks versus less than 60 weeks. The only variable that was found to be predictive of membership in the cluster with longer survival was the presence of seizure activity (p = 0.02). Although univariate and multivariate analyses both showed an apparent statistically significant improvement in survival with increasing total radiation dose to the tumor bed, no additional benefit could be demonstrated for doses greater than 60 Gy.

Age Factors

Differential release of mediators from human basophils: differences in arachidonic acid metabolism following activation by unrelated stimuli.

We have examined the release of histamine and LTC4 from purified human basophils challenged with several different stimuli, both physiological and nonphysiological. Basophils (n = 16) challenged with 0.1 micrograms/ml anti-IgE released 38 +/- 4% of their available histamine and 39 +/- 12 ng LTC4/10(6) basophils within 15-30 min. F-Met peptide (n = 8) caused the release of 54 +/- 8% histamine and 42 +/- 25 ng LTC4/10(6) basophils within a period of 2-5 min. C5a caused the release of 22 +/- 3% histamine from selected donors but failed to initiate any LTC4 release unless combined with D2O or 5 mM extracellular calcium. The two nonphysiological stimuli A23187 and TPA caused extensive histamine release, 67 +/- 8 and 82 +/- 11%, respectively, and while A23187 initiated a large and rapid release of leukotriene, TPA failed to release any LTC4 even when combined with D2O or 2-5 mM extracellular calcium. Increased concentrations of extracellular calcium enhanced anti-IgE and f-Met peptide induced release of LTC4 but inhibited the A23187 induced release of leukotriene. A single peak of immunoreactive leukotriene C4 that comigrated with the authentic standard was identified using HPLC followed by radioimmunoassay. No LTD4 or LTE4 could be detected. Purified human basophils incubated with 0.2 microM [3H]AA incorporated 290 pmol/10(6) cells, or 32 +/- 5% of the available label within 60 min. The [3H]AA was taken principally into the phospholipids (73 +/- 5%), with 20 +/- 3% as neutral lipid, and only 5 +/- 2% remaining as the free acid. Three phospholipid subclasses, phosphatidylcholine, PC (24 +/- 2%), phosphatidylinositol, PI (22 +/- 1%), and phosphatidylethanolamine, PE (15 +/- 3%), accounted for the majority of the incorporated [3H]AA while the remainder of the phospholipids accounted for less than 5% of the total cpm. HPLC analysis of the lipid mediators released during stimulation with 0.1 micrograms/ml anti-IgE revealed [3H]LTC4 (2.4 +/- 1.0%), [3H]5HETE (1.0 +/- 0.1%), unmetabolized [3H]AA (91 +/- 2%), and an unidentified peak (3.4 +/- 1.4%). The unknown metabolite eluted with the prostaglandins, was inhibited by indomethacin, and appeared to have a relatively high specific activity. It may thus represent an artifact of the labeling procedure rather than a novel basophil-derived prostaglandin.

Arachidonic Acids

Implantable electrical left ventricular assist system: bridge to transplantation and the future.

An implantable left ventricular assist system (LVAS) utilizing an electromechanically driven dual pusher-plate blood pump has been employed in a multiinstitutional trial as a bridge to cardiac transplantation. Under development for permanent circulatory support in patients with end-stage heart disease, the LVAS, in this application, derives power and control from an external console via a percutaneous lead. The LVAS was implanted in 20 patients (16 men, 4 women) who were hemodynamically unstable or in refractory cardiogenic shock. The mean age was 44.9 years (range, 25 to 63 years). Preoperative diagnosis was evenly divided between end-stage ischemic disease, cardiomyopathy, and acute myocardial infarction. Implanted in the left upper quadrant within the anterior abdominal wall, the blood pump was connected between the left ventricular apex and ascending aorta. Total support of the systemic circulation and substantial left ventricular unloading were achieved with synchronous counterpulsation for periods up to 90 days (mean, 22.7 days). All patients were stabilized hemodynamically. The mean preoperative cardiac index of 1.5 L/min/m2 increased by a factor of 2. Pulmonary arterial pressures decreased substantially. Serious complications occurred in 16 patients, precluding cardiac transplantation in 10. Most complications (greater than 70%) were in patients who did not receive transplants; the most common complication was bleeding. Twelve of 13 patients with LVAS implants for more than seven days were mobilized, and 4 were fully ambulatory and completely rehabilitated. Orthotopic cardiac transplantation was performed in 10 patients after implants ranging from two to 90 days (mean, 30.3 days).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Self-efficacy in alcoholics: clinical validation of the Situational Confidence Questionnaire.

Recent theory and empirical data suggest that self efficacy plays an important role in resistance to relapse for substance abusers. This study investigated the validity of the Situational Confidence Questionnaire (SCQ), a new instrument designed to measure self-efficacy expectations in purported high-risk drinking situations. The SCQ was administered to 46 short-term sober (STS) and 25 long-term sober (LTS) alcoholics. STS subjects were newly admitted alcohol treatment patients and LTS subjects had been abstinent for at least one year. Results indicated significantly higher self efficacy for LTS subjects than for STS subjects on total score and on 7 of the 8 subscales (p less than .001). Stepwise discriminant analysis yielded a linear combination of three subscales to account for 49% of the total variance; 92% of the LTS and 65% of the STS subjects were correctly identified by the classification function. These results extended earlier work with the SCQ using newly sober subjects and, in addition, provide encouraging validity data for the SCQ.

Alcoholism

Survey of patients' knowledge of nosocomial infections.

A survey of discharged patients revealed that 62% of respondents were aware of the risk of nosocomial infection before they received the survey. Of the respondents 12.4% said they had suffered from a nosocomial infection; 70% were concerned about their risk of acquiring a nosocomial infection in the future; 83% believed nosocomial infections were preventable; 69% said the risk of acquiring a nosocomial infection was never explained to them during hospitalization; and 62% were dissatisfied with the information that hospitals and the medical community provided concerning the risk of nosocomial infections. Fifty-seven percent were willing to pay an extra $7.14 mean per diem charge to enhance the hospital's infection control program if this payment would lower their risk of infection. This survey suggests that the subset of responding patients want to know more about the risk of nosocomial infections, and they are willing to pay for more resources to be channeled into effective infection control programs.

Adult

Morbidity and mortality associated with multiple episodes of nosocomial bloodstream infection: a cohort study.

A retrospective cohort study of patients with multiple nosocomial bloodstream infections (BSIs) compared with patients suffering only one BSI was conducted to assess morbidity and mortality. Three hundred forty-one patients with BSIs were identified, including 33 with multiple BSIs (9.7%). No significant differences existed between patients experiencing one BSI compared to those experiencing multiple BSIs in age, sex, race, severity of underlying disease, hypothermia, hypoxemia, oliguria, metabolic acidosis, or hypotension. Sixteen of 33 (49%) with multiple BSIs died compared with 124 of 308 (40%) with only one BSI (P = 0.36), leading to a relative risk of 1.23 for death and an attributable mortality of 9% in those with multiple BSIs.

Cohort Studies

A study of the rate of postexposure human immunodeficiency virus testing in a hospital requiring written informed consent.

Multiple authorities have recommended that human immunodeficiency virus (HIV) testing should be performed only with consent of the patient. After institution of a policy requiring written consent for testing patients and employees after blood/body fluid exposures, we prospectively studied incidents in which employees were exposed to the blood or body secretions of patients to determine the rate at which HIV testing could be performed under these circumstances. Two hundred four employees suffered an exposure. In 184/204 (90%) of incidents, the index patient was known. HIV testing was performed for 125/184 patients (68%). Patient consent was refused in one case, but consent could not be obtained from an additional 58/184 (32%) patients because of various logistical reasons. We conclude that a policy requiring informed consent for HIV testing of a patient after exposure of an employee to blood or body fluids of the patient results in an unacceptably low rate of testing and that an alternative approach must be developed.

AIDS Serodiagnosis

Analogical reasoning abilities of recovering alcoholics.

This study investigated analogical reasoning abilities of alcoholics who had been abstinent from alcohol for at least 1 year. Their performance was compared to that of nonalcoholic controls matched as a group for education, age, and gender. Solution times and error rates were modeled using a regression model. Results showed a nonsignificant trend for alcoholics to be faster, but more error prone, than controls. The same componential model applied to both groups, and fit them equally well. Although differences have been found in analogical reasoning ability between controls and alcoholics immediately following detoxification, we find no evidence of differences after extended periods of sobriety.

Adult

Isolated left ventricular assist as bridge to cardiac transplantation.

The electrically driven Novacor implantable left ventricular assist device has been implanted in six patients (four men and two women) since Sept. 7, 1984. In four of the six patients (67%) the device was a successful bridge to cardiac transplantation. One patient died of multiple organ failure and Candida sepsis after 16 days of support with the device. One patient died in the operating room of uncontrollable hemorrhage and biventricular failure caused by severe cardiac rejection. Three patients are alive with cardiac transplants 38, 17, and 10 months after transplantation. One patient died after cardiac transplantation of presumed sepsis. The Novacor left ventricular assist device performed in all cases without mechanical or electrical failure. Excluding the intraoperative death, assist duration ranged from 2 to 16 days. The cardiac index (synonymous with device output) ranged from 2.4 to 3.4 L/min/m2. No embolic events (cerebrovascular or systemic) occurred during assistance with the device. Minimal red cell hemolysis was documented during the period of support. The Novacor left ventricular assist device is a safe and effective bridge to cardiac transplantation in patients with refractory cardiogenic shock.

Adult

Expression and secretion of type beta transforming growth factor by activated human macrophages.

Alveolar macrophages activated with concanavalin A and peripheral blood monocytes activated with lipopolysaccharide secrete type beta transforming growth factor (TGF-beta). There is minimal TGF-beta secretion in unactivated monocytes, even though TGF-beta mRNA is expressed in these cells at a level similar to that in activated, lipopolysaccharide-treated cultures. U937 lymphoma cells, which have monocytic characteristics, also express mRNA for TGF-beta. Freshly isolated monocytes, both control and lipopolysaccharide-treated, secrete an acid-labile binding protein that inhibits TGF-beta action. We conclude the following: (i) that expression of TGF-beta mRNA is unrelated to monocyte activation, (ii) that secretion of TGF-beta is induced by monocyte activation, and (iii) that cosecretion of TGF-beta and its monocyte/macrophage-derived binding protein may modulate growth factor action. In contrast, monocytic expression of other growth factor genes, such as the B chain of platelet-derived growth factor, is not constitutive and requires activation.

Cell Line

Etiologic organisms as independent predictors of death and morbidity associated with bloodstream infections.

We studied 385 episodes of nosocomial bloodstream infections occurring over 45 months to ascertain if the etiologic organisms were independent predictors of death and morbidity. Independent predictors of death included respiratory failure, oliguria, metabolic acidosis, hypotension, increased age, antibiotic therapy in cases where susceptibility data were unknown, and infection with Pseudomonas aeruginosa. If parameters associated with septic shock were excluded, increased age, severity of disease, and infection with Candida spp. or P. aeruginosa predicted death. Infection with P. aeruginosa, Enterococcus, and Klebsiella pneumoniae predicted hypotension; severity of disease, polymicrobial infection, and infection with Candida spp., Enterococcus, Enterobacter, or Serratia marcescens predicted oliguria; infection with Candida spp. or P. aeruginosa, increased age, severity of disease, and inability to meet hospital financial obligations without assistance predicted respiratory failure. Inability to meet hospital financial obligations without assistance and severity of disease predicted hypothermia; infection with Candida spp. or P. aeruginosa and sex (male) predicted metabolic acidosis.

Acidosis