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Biomedical subjects

R G Robinson

Publications and source records attributed to R G Robinson.

At least 19 recordsLinked to original sources
PubMed1995

Strontium 89 therapy for the palliation of pain due to osseous metastases.

OBJECTIVE: To present the current state of systemic radiopharmaceutical therapy for the palliation of pain in individuals with metastatic cancer and to evaluate the palliative effect and degree of hemotoxicity of strontium chloride 89 (89Sr) in patients with painful osteoblastic metastases primarily from prostate and breast cancer. DATA SOURCES AND STUDY SELECTION: A MEDLINE search through December 1994 was performed to identify English-language studies that met the following criteria. All eligible studies reported treatment of patients with painful osteoblastic bony metastases primarily from prostate or breast cancer treated with intravenous 89Sr. For study eligibility, evaluation of clinical response as assessed by the Karnofsky index, need for pain medication, or changes in mobility or sleep patterns was required. Hemotoxicity data were a requirement. A minimum of 10 prostate cancer cases was necessary for study inclusion. Only those studies assessing clinical response following one injection of 89Sr were included. Preliminary reports of cooperative studies were not included. Doses of 89Sr ranged from 0.6 MBq/kg (16 microCi/kg) to 400 MBq (10.8 mCi) per patient. Evaluation of patients for at least 3 months following 89Sr treatment was required. In addition, two studies examining issues of cost with regard to 89Sr treatment were identified. DATA EXTRACTION: Baseline pain assessment and periodic pain estimates as measured by the Karnofsky index, medication diaries, changes in mobility, sleep patterns, and/or ability to work were the basis for assessment of response. Baseline and periodic complete blood cell counts were the basis for hemotoxicity evaluation. DATA SYNTHESIS: Palliation and hemotoxicity data were analyzed separately for each study. Some improvement occurred in as many as approximately 80% of patients. Several studies demonstrated complete relief of pain in at least 10% of patients The nadir of platelet and white blood cell counts appears at approximately 4 to 8 weeks following injection, with a partial return to baseline by 12 weeks. As many as 10 injections spaced 3 months apart have been given to some patients with repeated palliative effect and without serious hemotoxicity. Reinjection may be limited by a platelet count below 60 x 10(9)/L, a white blood cell count below 2.4 x 10(9)/L, or the absence of osteoblastic skeletal metastasis as seen on bone scan. Studies examining treatment costs suggest that 89Sr may decrease costs associated with palliation of pain due to metastatic disease. CONCLUSIONS: As many as 80% of selected patients with painful osteoblastic bony metastases from prostate or breast cancer may experience some pain relief following 89Sr administration. In addition, as many as 10% or more may become pain free. Duration of clinical response may average 3 to 6 months in some cases. Hemotoxicity is mild. A decrease in treatment costs with administration of 89Sr to patients with painful osteoblastic bony metastases from prostate cancer may occur. These observations reflect the preliminary nature of knowledge in this field and point to the need for larger clinical trials of the use of 89Sr palliation.

Bone Neoplasms↗
PubMed1995

Mechanism of action and antitumor activity of (S)-10-(2,6-dimethyl-4-pyridinyl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7 H- pyridol[1,2,3-de]-[1,4]benzothiazine-6-carboxylic acid (WIN 58161).

(S)-10-(2,6-Dimethyl-4-pyridinyl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H - pyrido[1,2,3-de][1,4]benzothiazine-6-carboxylic acid (WIN 58161) is an enantiomerically pure quinolone with outstanding bacterial topoisomerase II (DNA gyrase, EC 5.99.1.3) inhibitory and antibacterial activity. Unlike most quinolones, WIN 58161 also exhibits significant inhibitory activity against mammalian topoisomerase II (EC 5.99.1.3). DNA gyrase and topoisomerase II inhibitory activities are enantioselective. Consequently, WIN 58161 and its enantiomer (WIN 58161-2) provide useful tools to probe the contribution of topoisomerase II inhibition to the mechanism of cytotoxicity of quinolones and the potential utility of quinolone-topoisomerase II inhibitors as antitumor agents. WIN 58161 inhibited both highly purified Escherichia coli DNA gyrase and HeLa cell topoisomerase II by the promotion of enzyme-DNA covalent complexes. WIN 58161 did not bind stably to DNA via intercalation and did not enhance the formation of topoisomerase I (EC 5.99.1.2)-DNA covalent complexes. At drug concentrations that are cytotoxic to P388 murine leukemia cells, WIN 58161 promoted intracellular DNA single-strand breaks (SSBs) that exhibited the hallmarks of being mediated by topoisomerase. DNA fragments were complexed with protein, and SSBs were readily resealed at 37 degrees following drug removal. WIN 58161-2 was neither cytotoxic nor did it promote intracellular SSBs in P388. These observations suggest that the mechanism of cytotoxicity of WIN 58161 is predominantly, if not exclusively, a result of topoisomerase II inhibition. When studied in tumor-bearing mice, WIN 58161 exhibited a significant antitumor effect against each of five tumors tested, whereas neither toxicity nor antitumor activity was observed with WIN 58161-2. We conclude from these studies that WIN 58161 represents the prototype of a novel chemical class of topoisomerase II inhibitor with potential clinical utility in treating cancer.

Animals↗
PubMed1995

Comparison between acute and delayed onset major depression after spinal cord injury.

Sixty patients with spinal cord injury were examined to assess major depression during the in-hospital period and at 3- and 6-month follow-up. Thirteen patients had depression during the initial in-hospital evaluation (acute onset depression) and eight had depression first diagnosed at either 3- or 6-month follow-up (delayed onset depression). Acute onset depression was related to the severity of impairment and premorbid history of psychiatric disorder, suggesting a psychological reaction to impairment or premorbid vulnerability as a possible mechanism for developing depression. Delayed onset depression was not related to severity of physical impairment but was associated with more rostral spinal injury, suggesting the possibility that neurophysiological response to injury more proximal to the brain may play a role in delayed onset depression. These data also suggest that the etiology and pathophysiology of these two types of depression may be different.

Adult↗
PubMed1995

The heterogeneity of temporal lobe epilepsy. Neurology, neuropsychology, and psychiatry.

The present paper introduces the reader to the behavioral variability of patients with temporal lobe epilepsy. The neurobiological variability is evidenced by reviewing neurological, neurophysiological, and neuropsychological investigations. The behavioral variability of persons affected by epilepsy with a temporal focus is proposed to be an expression of the neurobiological complexity of temporal lobe epilepsy. The aim of this paper is to encourage endeavors in behavioral taxonomy. Efforts to foster homogeneity through improved classification are considered fundamental in behavioral science and should be applied to epilepsy. The achievement of a behavioral taxonomy may help in both understanding the mechanism(s) of these behavioral disorders and targeting more specific treatments.

Brain↗
PubMed1995

Clinical correlates of early-onset and late-onset poststroke generalized anxiety.

OBJECTIVE: The authors' goal was to determine if generalized anxiety diagnosed while a patient was hospitalized for stroke (early onset) had the same clinical correlates as anxiety beginning 3 months or more after the stroke (late onset). METHOD: Patients with acute stroke (N = 142) were examined while they were in the hospital and 3, 6, 12, and 24 months later for the presence of anxiety symptoms. Patients underwent a structured psychiatric interview as well as assessment of cognitive, physical, and social function at each visit. Patients with early-onset and late-onset poststroke generalized anxiety were identified and compared to patients without poststroke generalized anxiety. RESULTS: The frequency of early-onset poststroke generalized anxiety was 27% and that of late-onset poststroke generalized anxiety was 23%. Three-quarters of the anxious patients had comorbid major or minor depression. Patients who developed early-onset or late-onset poststroke generalized anxiety were no more socially, cognitively, or physically impaired than patients who did not develop anxiety. Early-onset but not late-onset anxiety was associated with a previous history of psychiatric disorder. The median duration of late-onset anxiety was 3.0 months, and that of early-onset anxiety was 1.5 months. The presence of anxiety was significantly associated with depression; onset of depression and onset of anxiety occurred at approximately the same time. CONCLUSIONS: These findings suggest that although early-onset and late-onset poststroke generalized anxiety are phenomenologically similar, they may be the result of different pathophysiological mechanisms.

Anxiety Disorders↗
PubMed1995

Hereditary late-onset chorea without significant dementia: genetic evidence for substantial phenotypic variation in Huntington's disease.

We examined five individuals and obtained information concerning six other members from two unrelated families, nearly all of whom developed chorea after age 50 (one patient developed chorea at age 40). The severity of chorea progressed in all patients and became disabling in some individuals approximately 15 years after onset. Cognitive impairment was absent or minimal. All five examined patients were cognitively normal, even 10 to 30 years following the onset of chorea. Formal neuropsychometric testing demonstrated mild cognitive impairment in two individuals. Nevertheless, all patients were able to maintain employment or carry on with their usual household tasks until chorea was severe. One individual first became demented 30 years after the onset of chorea. Neuroimaging (with CT or MRI) in four patients failed to demonstrate significant caudate or putaminal atrophy 8 to 15 years following the onset of chorea. Three other family members (who were not available for examination) were said to have suffered chorea (without any mental decline) beginning after age 50, with subsequent survival of 20 years (in one) and 30 years (in two). Given this constellation of history and findings, three experienced neurologists and two medical geneticists concluded that these patients had a familial chorea syndrome distinct from Huntington's disease (HD). However, genetic analysis of the trinucleotide (CAG) repeat length associated with HD (in 4p16.3) determined repeat lengths of 44 and 46 in four patients tested (within the HD range). We conclude that these patients have HD and that such families represent further convincing examples of significant phenotypic variation for HD.

Age of Onset↗
PubMed1995

Personality neuroticism and depression after stroke.

AIM: The aim of this study was to determine whether personality neuroticism or extroversion traits are associated with post-stroke depression. METHOD: Ninety-four stroke inpatients undergoing rehabilitation were examined two months post-stroke for the presence and severity of depression and a retrospective assessment was made of life-time neuroticism and extroversion. RESULTS: Depressed patients (N = 35) had higher neuroticism scores than non-depressed patients. Neuroticism was correlated positively with depressive symptomatology. Extroversion was not associated with depression diagnosis or depressive symptomatology. CONCLUSION: We conclude that personality neuroticism may be a risk factor for depression following stroke.

Aged↗
PubMed1995

DNA sequence preferences at sites cleaved by human DNA topoisomerase II in response to novel quinolone derivatives.

We have examined the DNA cleavage site specificity of human type II DNA topoisomerase in the presence of each of five novel quinolone derivatives. Each quinolone derivative inhibited the human enzyme, inducing double-strand breaks with a four-base stagger. Break sites generated in response to each derivative had a predominance of C in the 3'-terminal position. Consensus sequences derived for cleavage sites induced by each derivative were strikingly similar, not only at the 3'-terminal position, but also at additional positions on either side of the broken phosphodiester bond. Analysis of these consensus sequences yielded information about possible interactions of specific substituents on the quinolone derivatives with DNA and/or topoisomerase. Comparison of the quinolone-based consensus sequences with those derived for cleavage sites generated by the human type II topoisomerase in the presence of either m-AMSA or VM-26, or in the absence of drug, provided compelling evidence that DNA cleavage sites include two domains: one which interacts with drug and a second, larger domain which interacts with topoisomerase.

Amsacrine↗
PubMed1994

Prospective longitudinal study of depression following spinal cord injury.

A group of 60 patients with spinal cord injury was examined to assess mood disorders during the rehabilitation hospital admission and 6 months of follow-up. During the initial evaluations, 13 patients (22%) had major depression and 5 patients (8%) had minor depression. The development of mood disorders during the hospital admission appeared to be related to heterogeneous etiological factors, including previous psychiatric history and severity of impairment in activities of daily living. During the first 3 months after SCI, about half of the depressions resolved. Nonrecovery from depression may be related to lack of adequate social support.

Adult↗
PubMed1994

Depression following myocardial infarction: a one year longitudinal study.

OBJECTIVE: The purpose of this study was to examine the course and clinical correlates of depression during the first year after myocardial infarction. METHOD: A group of seventy patients hospitalized for the treatment of myocardial infarction (MI) were assessed for the presence of mood disorders during their hospital admission and at three, six, nine, and twelve months follow-up. Patients were evaluated and diagnosed using the Present State Examination and DSM-III criteria. Impairment in activities of daily living was measured by the Johns Hopkins Functioning Inventory and impairment in social functioning was measured by the Social Functioning Examination. RESULTS: A total of twenty-four patients met DSM-III criteria for major depression at some time during the study (18 in the acute stage, 6 during follow-up). There were two patients with minor depression (dysthymia) at intake and six developed minor depression during the follow-up period. The median duration of major depression was 4.5 months. Patients with depression at intake had greater impairment in activities of daily living than non-depressed patients. Depressions lasting more than six months were more likely to be anxious depressions than those lasting less than six months. After the acute MI period, there was a consistent relationship between the existence of depression and impaired social functioning. CONCLUSIONS: This is a pilot study and needs further replication due to the low rate of follow-up participation. However, these data suggest that there may be two types of depression following MI: an acute depression associated with greater functional impairment, and a prolonged depression that may be associated with inadequate social support.

Acute Disease↗
PubMed1994

Influence of major depression on 1-year outcome in patients with traumatic brain injury.

The authors examine those factors that contributed to deterioration in social functioning, activities of daily living, or intellectual functioning during a 1-year period after traumatic brain injury (TBI). Fifty-two patients suffering an acute TBI were evaluated for existence and severity of mood disorders and impairment during their hospital stays and at 3-, 6-, and 12-month follow-up examinations. Patients whose scores on intellectual function, social function, or daily activities deteriorated during the 1-year period after trauma were considered to have a poor outcome. Eleven of 52 patients had a poor outcome in social function, which was associated with race, right-hemisphere lesions, intellectual impairment, and prolonged major depression. Seven of 52 patients had a poor outcome in daily activities, which was associated with a major depression of more than 6 months' duration and severity of Hamilton Depression Rating Scale scores. Eleven of these patients had a poor outcome in cognitive function, which was associated with cognitive impairment immediately after TBI. A major depression lasting more than 6 months was associated with deterioration of social functioning and activities of daily living during the 1-year period after TBI.

Activities of Daily Living↗
PubMed1992

Clinical depression is associated with impaired recovery from stroke.

OBJECTIVE: To examine the effect of clinical depression on recovery from stroke. METHOD: We examined a cohort of inpatients with stroke initially at two months after their stroke and again 14 months later. Patients were included if they: (i) provided informed consent; (ii) were able to understand the interview questions; and (iii) survived to follow-up without suffering another stroke or major medical illness. Of 61 consecutive patients, 49 met these criteria. Depression was diagnosed using a structured clinical interview. Three aspects of recovery were measured: (i) functional status; (ii) activities of daily living; and (iii) cognitive performance. RESULTS: Twenty (41%) of the 49 patients were depressed at initial assessment. There were no significant differences in demographic, clinical, stroke or lesion characteristics between the depressed and non-depressed patients. At follow-up, depressed patients improved less than non-depressed patients in functional status (mean change from baseline, 23% versus 48%) (P = 0.001) and cognitive performance (-1% versus 11%) (P = 0.096). Mean recovery in activities of daily living was not different between the two groups (33% versus 32%) but more of the depressed patients deteriorated over time (20% versus 0%) (P = 0.047). CONCLUSION: Clinical depression occurring soon after stroke is associated with impaired recovery when patients are assessed 14 months later. Depression has a negative effect on recovery in functional status and cognitive performance and may produce deterioration in physical capacity in a number of patients. Physicians would be well advised to be alert for depression and intervene early. Effective treatment of depression may enhance stroke rehabilitation.

Activities of Daily Living↗
PubMed1992

Estrogen and progesterone replacement therapy reduces glucocorticoid-induced bone loss.

This is a retrospective study of 15 postmenopausal or amenorrheic women aged 34-78 years who had taken prednisone for 6-108 months and were followed for 1 year while continuing to take doses of 5-15 mg/day. A total of 8 patients were treated with 0.6256 mg Premarin daily for 25 days and 5 mg/day of medroxyprogesterone on days 15-25 (ERT, group 2); 7 were followed without ERT (group 1). A group of 17 women, matched for age, were randomly selected from our computerized data base to serve as a control group (group 3), and 10 women of similar age who were taking ERT only (group 4) were selected to compare the response to ERT to that of group 2. Bone density (BD) was measured in the lumbar spine baseline and at 1 year using dual-photon or dual-energy x-ray absorptiometry. Spine density did not change significantly during the year of observation in group 1. Although BD decreased in 5 of 7 patients, the change was not significant (-0.034 +/- 0.018 g/cm2, p = 0.10). In group 2 BD increased significantly, with 7 of 8 patients showing an increase (0.037 +/- 0.011 g/cm2, p = 0.008). BD did not change significantly in the control group (0.013 +/- 0.008 g/cm2, p = 0.16). Loss of bone from the spine was significantly greater in group 1 than in controls (p = 0.02), but changes in group 2 were similar to those in the control group (p = 0.66).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1992

Reactogenicity and immunogenicity of a double-strength acellular pertussis vaccine.

The reactogenicity and immunogenicity of a double-strength acellular pertussis vaccine were evaluated after administration to 16 4-6-year-old children. The vaccine contained toxoided lymphocytosis-promoting factor (6.0 micrograms/dose), filamentous haemagglutinin (70 micrograms/dose), agglutinogens (1.4 micrograms/dose) and the 69 kDa protein (approximately 8.0 micrograms/dose). The vaccine was extremely well tolerated with few minor side effects following immunization. Significant increases in antibodies to all pertussis vaccine components were noted. In summary, this double-strength acellular pertussis vaccine, containing a very high dose of filamentous haemagglutinin, had minimal reactogenicity and was immunogenic. These findings, as well as other studies with this vaccine, indicate that filamentous haemagglutinin is not a major determinant of vaccine reactogenicity.

Antibodies, Bacterial↗