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Biomedical subjects

R Jacobson

Publications and source records attributed to R Jacobson.

At least 19 recordsLinked to original sources

Evaluation of the accuracy of a pharmacokinetically-based patient-controlled analgesia system.

Bone marrow transplant patients having severe, prolonged oral mucositis pain (expected to last for one to three weeks) used a computer-controlled infusion system to self-administer morphine for pain control. Individual patient pharmacokinetic information, derived from a pretreatment bolus morphine dose, was used in a new bolus-elimination transfer algorithm to produce rapid adjustments of steady plasma morphine concentrations when the patient requested more or less drug. We evaluated the performance characteristics (bias and precision) of this pharmacokinetically based patient-controlled analgesic infusion system (PKPCA) in a group of 15 cancer patients over six to 14 days. Although we found a three- to fivefold pharmacokinetic variability in the tailoring morphine dose data, the PKPCA system was free of systematic bias (insignificant overall prediction error) during the patient-controlled infusions in this study population. The absolute prediction error was 19.9% for the group on the first study day and 25.6% over the entire study period (aggregate results; 6-14 days of continuous use). Two-thirds of the patients exhibited no bias throughout the study period, and individual bias in the others was symmetrically distributed (three patients with underpredictions and two overpredicted). Magnitude of prediction error during the patient-controlled morphine infusions was not related to the magnitude of pharmacokinetic deviation of individual subjects from group parameters. Our results indicate that this PKPCA system provides accurate control of plasma morphine concentration when used by patients to self-administer opioid for prolonged pain relief continuously over 1 to 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia, Patient-Controlled

Antibacterial properties of investigational, new, and commonly used antibiotics against isolates of Pseudomonas cepacia in Michigan.

Microdilution antimicrobial susceptibility testing was performed with 73 isolates of Pseudomonas cepacia collected from the sputum of patients throughout Michigan with cystic fibrosis. Susceptibility testing was done using new and investigational antibiotics (loracarbef, cefixime, cefpirome, desacetyl-cefotaxime, cefpodoxime, cefmetazole, cefepime, cefprozil, and fleroxacin) and commonly used antibiotics (ceftazidime, mezlocillin, piperacillin, ciprofloxacin, tobramycin, and amikacin). Ceftazidime was the most active antibiotic, and 91.8% of isolates were susceptible to it with MIC50 and MIC90 values of < or = 4 and 16 micrograms/ml, respectively. For mezlocillin, piperacillin, and ciprofloxacin 84.9, 89 and 39.7% of the isolates, respectively, were mostly moderately susceptible. Loracarbef, cefixime, cefprozil, cefmetazole, cefepime, fleroxacin, cefpodoxime, tobramycin, and amikacin did not show activity against P. cepacia. For cefpirome and desacetylcefotaxime 24.7 and 60.3% of the isolates, respectively, were moderately susceptible. Both MIC50 and MIC90 were > 32 micrograms/ml for cefpirome and 32 and > 64 micrograms/ml for desacetylcefotaxime.

Anti-Bacterial Agents

Steady-state infusions of opioids in human volunteers. I. Pharmacokinetic tailoring.

We report a method for controlling and adjusting plasma opioid concentration to preselected target values in individual human subjects in order to study analgesic and other effects of opioids at steady state. The method employs a computer-controlled infusion pump and an algorithm that utilizes individual subject pharmacokinetic parameters predetermined with tailoring bolus opioid doses. We used this approach to produce 3-step increases in plasma concentrations of alfentanil, fentanyl and morphine in each of 15 subjects. We maintained each plasma concentration plateau for 70 min, measured plasma opioid concentrations achieved during the infusions and analyzed the results for bias and precision of the individually tailored infusions. Our results show that pharmacokinetically tailored opioid infusions produce stable plasma opioid concentrations within 10 min for alfentanil and morphine; with each drug overall prediction error was 20% or less. Fentanyl was somewhat more difficult to control by this method than were the other 2 opioids. We conclude that individual tailoring of opioid infusions minimizes the impact of individual pharmacokinetic differences on achieving preselected plasma opioid concentrations and provides an accurate means of controlling steady-state drug concentrations for studies of concentration-effect relationships and comparisons of side-effect intensities produced by equianalgesic plasma opioid concentrations.

Adult

Capgras' syndrome with organic disorders.

Capgras' syndrome, one form of the delusional misidentification syndromes, is described. Three patients with the syndrome are reported. The first had a right cerebral infarction, the second had nephrotic syndrome secondary to severe pre-eclampsia in the puerperium, and the third had uncontrolled diabetes mellitus with dementia. Evidence is reviewed regarding an organic aetiology for Capgras' syndrome. We conclude that, when the syndrome is present, a thorough search for organic disorder should be made.

Adult

Clonazepam treatment of tardive dyskinesia: a practical GABAmimetic strategy.

Because of the efficacy of specific gamma-aminobutyric acid (GABA) agonists in tardive dyskinesia, the authors tested the benzodiazepine clonazepam in a 12-week, double-blind, placebo-controlled, randomized crossover trial in 19 chronically ill patients with tardive dyskinesia who were being treated with neuroleptics. They found a 35% decrease in dyskinesia ratings with clonazepam treatment. The six patients with predominantly dystonic symptoms showed greater benefit than the 13 patients with predominantly choreoathetoid dyskinesias. Tolerance developed to the antidyskinetic effect of clonazepam in the five patients whose long-term use of the drug was followed, but a 2-week clonazepam-free period recaptured its antidyskinetic effect.

Adult

Selective subcortical abnormalities in autism.

Nine physically healthy, adult autistic men, with normal or near normal intelligence, and 13 healthy male controls were examined in a CT brain scan study. CT scans were analysed with a fully automated computer-assisted program, and regional brain radiodensities were measured with careful attention to artefacts. Autistic patients revealed significantly larger third, but not lateral, ventricular size and significantly lower mean caudate, but equivalent mean frontal and thalamic, radiodensities compared to controls. The sizes of the Sylvian fissures and interhemispheric fissure were equivalent between groups. The findings are consistent with selective subcortical abnormalities in autism.

Adult

Morphology of the fibrinogen exudate during evolution of a mycobacterial-induced murine eye granuloma.

The intent of this study was to visualize changes in the density and location of fibrinogen-related antigen (FRA) depositions within the murine vitreous space during the formation of a chronic mycobacterial-induced uveitis (CMIU) granuloma. Concurrent changes in cellular morphology of the granuloma were also examined. Fibrinogen derivatives within the exudates of granulomatous cell-mediated inflammations may induce physical induration and numerous other phlogistic effects. However, technical limitations of conventional FRA staining methods have tended to underestimate the extent of their presence within this category of inflammatory lesions. Conventional H and E sections of the CMIU granuloma confirmed the classic progression-early PMN influx, monocyte maturation and final macrophage and epithelioid cell dominance-described for such lesions. Avidin-biotin-complex staining utilizing a polyclonal mouse antifibrinogen then revealed a progressive increase in amorphous extracellular fibrinogen-FRA-positive staining material as the granuloma evolved. Thus, on day one the PMN influx showed no evidence of fibrinogen-FRA staining; at one week heavy staining was evident in the anterior chamber and in consolidated (i.e. macrophage) regions of the granuloma; at one month a heavy uniform staining appeared throughout the indurated granuloma where macrophages and epithelioid cells predominated. Patterns of heavy deposition on macrophage surfaces were suggested. The likelihood that bulky accumulations of FRA in mature granulomas are not solely fibrin, and may account for granulomatous induration and persistence, is discussed.

Animals

Comparison of short-latency trigeminal evoked potentials elicited by painful dental and gingival stimulation.

Painful stimulation of tooth pulp and of the maxillary gingiva was undertaken in 16 volunteers. Short-latency evoked potentials (15-50 msec) were recorded over 800 trials in each case at F3-P3 of F4-P4, and the resultant averaged wave forms were compared. The gingival wave was distinct in all subjects and could be averaged across subjects while the dental waves were either noise or very inconsistent over subjects. Averaging of the dental wave forms across subjects yielded an uninterpretable result. It was clear that dental evoked potentials could not be recorded at the sites. These findings could be explained by either or both of two hypotheses: dental afferents are predominantly small fiber, nociceptive end organs that conduct more slowly than soft tissue afferents whereas gingival stimulation activates both large and small fiber populations; and dental representation in somatosensory cortex is different and phylogenetically more primitive than that of neighboring soft tissue. Therefore, the location of the generator sites in cortex and the orientation of the dipole may be different for dental than for gingival wave forms.

Adult

Disorders of facial recognition, social behaviour and affect after combined bilateral amygdalotomy and subcaudate tractotomy--a clinical and experimental study.

A case of a 37-year-old patient, 10 years after bilateral amygdalotomy and subcaudate tractotomy for chronic self-mutilation, is described. The clinical picture revealed a complex mental state, including disorders of facial recognition, social behaviour, affect and elements of the Kluver-Bucy syndrome. Mild selective deficits were demonstrated psychometrically in the recognition of familiar and unfamiliar faces. Certain features have been described in rhesus monkeys, but have not previously been reported in humans. Primate studies are discussed, with particular reference to the role of the amygdala in facial recognition.

Adult

The contributions of sex and drinking history to the CT brain scan changes in alcoholics.

Consecutive series of male and female alcoholics, Alcoholic Anonymous (AA) members and controls were examined by interview and with a CT brain scan. Male controls were shown to have larger CT brain parameters than healthy females of the same age. Female alcoholics revealed equivalent CT scan abnormalities, apart from less sulcal widening, after a markedly shorter drinking history and at a lower estimated peak alcohol consumption than male alcoholics. The CT scan findings persisted after accounting for body weight and after matching for age and length of drinking history. The CT scan parameters of female AA members approached control values more completely and after briefer abstinence than did those of male AA members. Methodological problems and sex differences in selection and other processes are discussed. The findings are consistent with sex differences in the vulnerability of the brain to alcohol toxicity, and in its recovery with abstinence.

Adult

Self-incineration: a controlled comparison of in-patient suicide attempts. Clinical features and history of self-harm.

A systematic survey of in-patient accidents and injuries in an inner London hospital over 9 years established that, after incisions and overdoses, self-incineration was one of the commoner methods of violent self-harm. A case-controlled study of in-patient suicide attempts compared a series of 12 self-incinerators with 12 patients using other methods. Irrespective of method, the suicide attempt was predominantly a psychotic act of young single people with chronic, severe disorders and considerable past parasuicide, in a setting of escalating self-harm. Younger age, greater psychiatric morbidity, absence of alcoholism, a history of childhood arson, past and current self-burning were the features specific to self-incineration, which had a 25% mortality rate.

Adjustment Disorders

Evidence for the involvement of B lymphoid cells in polycythemia vera and essential thrombocythemia.

Previous studies with the X-chromosome-linked glucose-6-phosphate dehydrogenase (G6PD) as a marker of cellular mosaicism demonstrated that polycythemia vera (PV) and essential thrombocythemia (ET) are clonal disorders of hematopoietic stem cells that can differentiate to erythrocytes, granulocytes, and platelets. To determine if the involved stem cells could also differentiate along the B-lymphoid pathway, we studied one woman with PV and one woman with ET. Of 117 Epstein-Barr virus-transformed B-lymphoblastoid lines expressing a single G6PD derived from the patient with PV, 108 expressed G6PD type A, the type characteristic of the abnormal clone. The ratio of 108:9 was significantly different from the one to one ratio predicted for this patient, which suggested that at least some circulating progenitors for B-lymphoid cell lines differentiate from the stem cell involved by the disease. Results obtained from the patient with ET were similar--104 of the 109 lymphoblastoid lines monotypic for G6PD expression displayed the enzyme type found in the abnormal clone of marrow cells. Therefore, in these patients, PV and ET, like chronic myelogenous leukemia, involve a stem cell pluripotent for the lymphoid as well as the myeloid series.

Adult

A study of the relationship between family interaction and individual symptomology over time.

The study was designed to answer two questions: (a) Can a relationship over time between family interaction and individual symptomatology be demonstrated? (B) Can it be shown that changes in interaction have more influence on changes in the symptom than vice versa. Five interaction dimensions were taped in weekly, three-quarter hour sessions over 20 weeks in five families, each consisting of a mother-father-child triad who met certain criteria and had an encopretic child. The interaction dimension scores were abstracted weekly from these sessions by content analyses relying on various scales. The derived ratio scores were then related to the number of days the child soiled himself in the week preceding and following the interaction measurement. The relationship was assessed by Pearson correlation coefficients and step-wise multiple regression analyses adjusted to account for the possible inflationary effects of taking measures from the same subjects more than once. The results of the analyses answered both questions posed by the study in the affirmative, thus supporting the rationale underlying family therapy.

Family