Therapeutic strategies using c-erbB-2 promoter-controlled drug activation.
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Breast Neoplasms↗
Biomedical subjects
J Harris
Publications and source records attributed to J Harris.
NHS and the law. Buyers' market.
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Consultants↗
NHS and the law. The price of failure.
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Costs and Cost Analysis↗
Chromosomal assignment of the human SA gene to 16p13.11 and demonstration of its expression in the kidney.
The SA gene is a novel gene of yet unknown function recently implicated in blood pressure regulation in rodent models of genetic hypertension. In this study we have located the human homologue of the SA gene to chromosome 16p13.11, by a combination of fluorescence in-situ hybridization and analysis of somatic cell hybrids carrying different segments of chromosome 16. This should facilitate investigation of its role in the genetic tendency to hypertension in humans. Increased expression of the gene in the kidney may be the mechanism through which some allelic variants of the gene raise blood pressure in rodent models. In this study we also demonstrate that the SA gene is expressed in human kidneys.
Animals↗
Environmental issues. The long arm of the law.
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Environmental Pollution↗
Neuropsychological deficits in schizophrenics. Relationship to age, chronicity, and dementia.
BACKGROUND: We sought to determine whether neuropsychological impairment in schizophrenia is related to current age, age at onset, or duration of illness, and whether the pattern of such impairment can be distinguished from that caused by progressive dementias of Alzheimer's type. We administered a comprehensive neuropsychological test battery to a normal control group (n = 38), a group of ambulatory patients with Alzheimer's disease (n = 42), and three ambulatory schizophrenic groups: early onset-young (n = 85), early onset-old (n = 35), and late onset (n = 22). Tests were grouped and analyzed according to eight major ability areas, and published procedures were used to remove the expected effects of normal aging. RESULTS: The three schizophrenic groups were found to be neuropsychologically similar to one another and different from normal controls and patients with Alzheimer's disease. There were no significant differences among the schizophrenic groups in level or pattern of neuropsychological functioning. Patients with Alzheimer's disease demonstrated less efficient learning and particularly more rapid forgetting than did the other groups. CONCLUSIONS: These findings suggest that neuropsychological impairment in schizophrenia is unrelated to current age, age at onset, or duration of illness. The study further suggests that the encephalopathy associated with schizophrenia is essentially nonprogressive and produces a pattern of deficits that is different from that seen in progressive cortical dementias.
Adult↗
Skeletal unloading induces resistance to insulin-like growth factor I.
In previous studies with a hindlimb elevation model, we demonstrated that skeletal unloading transiently inhibits bone formation. This effect is limited to the unloaded bones (the normally loaded humerus does not cease growing), suggesting that local factors are of prime importance. IGF-I is one such factor; it is produced in bone and stimulates bone formation. To determine the impact of skeletal unloading on IGF-I production and function, we assessed the mRNA levels of IGF-I and its receptor (IGF-IR) in the proximal tibia and distal femur of growing rats during 2 weeks of hindlimb elevation. The mRNA levels for IGF-I and IGF-IR rose during hindlimb elevation, returning toward control values during recovery. This was accompanied by a 77% increase in IGF-I levels in the bone, peaking at day 10 of unloading. Changes in IGF binding protein levels were not observed. Infusion of IGF-I (200 micrograms/day) during 1 week of hindlimb elevation doubled the increase in bone mass of the control animals but failed to reverse the cessation of bone growth in the hindlimb-elevated animals. We conclude that skeletal unloading induces resistance to IGF-I, which may result secondarily in increased local production of IGF-I.
Aging↗
Therapy of disseminated malignant melanoma with recombinant alpha 2b-interferon and piroxicam: clinical results with a report of an unusual response-associated feature (vitiligo) and unusual toxicity (diffuse pulmonary interstitial fibrosis).
Fifteen patients with disseminated malignant melanoma were treated with recombinant alpha 2b-interferon (20 mU/m2 intravenously 5 days per week for 4 weeks and then 10 mU/m2 subcutaneously tiw) and piroxicam (10 mg a day orally for 10 days prior to beginning interferon and daily thereafter). Two complete responses of soft tissue disease and stabilization of disease in two other patients were obtained. One complete response was associated with the development of vitiligo. One patient who had entered complete remission was removed from the study because of diffuse pulmonary interstitial fibrosis, believed due to therapy. The combination of alpha 2b-interferon and piroxicam offers no clinical advantage over the use of alpha 2b-interferon alone.
Adult↗
Brain lesions, central masking, and dichotic speech perception.
A dichotic CV syllables task and an auditory central masking task were administered to 10 right hemisphere stroke, 10 left hemisphere stroke, and 10 age-matched controls. When data for all subjects were considered within and across groups, it was found that lateralized performance measures for dichotic listening and central masking were highly correlated (r = .647, p < .05 for controls; r = .810, p < .005 for R-CVA; r = .648, p < .05 for L-CVA; r = .833, p < .0001 for all subjects). The data suggest that some aspects of dichotic performance that have been previously attributed to changes in verbal processing are more adequately explained as being the result of a general binaural asymmetry of auditory perception.
Acoustic Stimulation↗
Treatment of complex abdominal aortic aneurysms by a combination of endoluminal and extraluminal aortofemoral grafts.
PURPOSE: The purpose of this study was to test the hypothesis that abdominal aortic aneurysms (AAA) whose morphology makes them unsuited for repair with an endoluminal tube graft can be treated by a combination of a transluminally placed aortofemoral graft and a femorofemoral crossover graft. In addition the technique involves either ligation or balloon occlusion of the contralateral common iliac and internal iliac arteries in such a manner that excludes the AAA from the circulation. METHODS: We report the use of this technique in three male patients with 6.4 to 7.0 cm diameter AAA. Two had renal impairment and cardiac function too poor to permit open repair, and the third had an unfavorable abdomen caused by previous surgery and the presence of a permanent colostomy. Each patient had an individually tailored Dacron tube graft constructed on the basis of preoperative arteriograms and computed tomography scans. The grafts were delivered transluminally into the aorta through a sheath in the iliac arteries and anchored proximally with a stainless steel stent under radiographic control. The grafts were then anastomosed distally to the femoral artery. RESULTS: Recovery was complicated by a midgraft stenosis corrected by percutaneous balloon dilation in one patient, an episode of pulmonary edema in the second and an unexplained pyrexia in the third. Follow-up with duplex scanning confirmed normal flow through the grafts and the presence of thrombus between the prosthetic graft and the aneurysmal sac. CONCLUSIONS: We conclude that transluminal placement of an aortofemoral graft combined with a femorofemoral crossover graft is feasible in patients who are unsuited to repair with an endoluminal tube graft. The outcome with this technique is not known and requires further careful evaluation.
Aged↗
The duration of the movement aftereffect as an index of psychiatric illness.
The duration of the movement aftereffect (MAE) has sometimes been used to make inferences about the subject's state (for example, their level of arousal). Some studies are reviewed in which visual aftereffects (including the MAE) were measured in schizophrenia, with inconsistent results. Some relevant psychopharmacological and neurological evidence is considered. It is concluded that: (i) Differences in the clinical status of the schizophrenic subjects and whether they were receiving medication, but not the method used to measure aftereffects, may underlie the interstudy disagreements. (ii) The effect of schizophrenia is to increase MAE duration, and this is not due to some peripheral artefact. (iii) Longer MAEs in the illness could result from enhanced neurally signalled contrast and/or from the increased adaptability of cortical neurons.
Adult↗
An Eastern Cooperative Oncology Group phase II study of single agent DHAD, VP-16, aclacinomycin, or spirogermanium in metastatic pancreatic cancer.
There were 80 patients with measurable metastatic or unresectable pancreatic cancer randomly assigned to treatment with either DHAD, VP-16, aclacinomycin, or spirogermanium. There were no complete or partial responses. Two deaths from leukopenia occurred in patients treated with DHAD. One patient receiving spirogermanium experienced a seizure. No other life-threatening toxicities occurred. Maximal toxicities were not significantly more frequent with any treatment group. Median survival was 10 weeks, and median time to progression was only 6 weeks, with no difference among these four therapies.
Aclarubicin↗
Measurement of airborne rat urinary allergen in an epidemiological study.
The suitability of radioallergosorbent test (RAST) inhibition to quantify occupational exposure to rat urinary aeroallergen (RUA) has been assessed. When using a constant pool of rat allergic sera, the reproducibility of the assay over 1 year was comparable to that reported for other immunoassays; at 50% RAST inhibition the inter-assay coefficient of variation (CV) was 7.0% and the intra-assay CV was 3.0%. The assay was highly specific for rat urine; mouse urine was 1100-fold less potent at inhibiting the rat urine RAST system. Significant inter-assay variation in the 'high' control was not due to batch variation and was relatively small when compared with the variation in RUA concentrations in the occupational environment. Measurement of workplace RUA exposure demonstrated that those directly involved in the care of rats experienced the highest RUA exposure of the nine occupational groups studied (animal technicians GM = 23.10 micrograms/m3), dead animals (e.g. post mortem GM = 1.60 micrograms/m3, scientists GM = 0.67 microgram/m3) and rat tissue (e.g. slide production GM = 0.04 microgram/m3). In view of the complexity of rat allergens, RAST inhibition is an appropriate method for the quantification of occupational exposure to rats.
Air Pollution, Indoor↗
Oral LY217896 for prevention of experimental influenza A virus infection and illness in humans.
The efficacy and safety of oral LY217896 for prevention of experimental influenza A/Kawasaki/86 (H1N1) virus infection were assessed in susceptible males randomly assigned to receive LY217896 (75 mg) or placebo once daily for 7 days beginning 24 h prior to viral challenge. The rates of virus shedding (100% in both groups), days of viral shedding (3.1 +/- 1.3 for the LY217896 group; 2.8 +/- 1.3 for the placebo group), and titers of virus in nasal washings did not differ between the groups. Mild upper respiratory tract illness (72% in the LY217896 group; 69% in the placebo group) developed in similar proportions of each group. LY217896 was associated with asymptomatic rises in serum uric acid levels and was ineffective in modifying the virologic or clinical course of experimental influenza A (H1N1) virus infection.
Adolescent↗
Definition of thresholds for stereoscopic depth.
In the laboratory, thresholds for stereoscopic depth perception are usually determined by asking observers to discriminate between a stimulus with a given depth offset and its mirror image. Threshold is most often defined as the disparity difference that yields 75% or 83% correct responses. Disparities used for clinical tests of stereopsis are much higher. Here it is argued that, among other factors, this is because of the fact that clinical tests usually require the detection of a depth difference (offset versus no offset), rather than the discrimination between two directions of depth difference (in front versus behind). From a formal comparison of the two tasks, the data show that discrimination, or classification is easier by at least a factor of 2 than detection. The contribution of variations of the threshold criterion and learning to the differences between stereoacuity as measured in laboratory and clinic is also discussed. These differences are relevant to the design of tests for clinical use.
Adolescent↗
Expression of the genes for insulin-like growth factors and their receptors in bone during skeletal growth.
Insulin-like growth factors (IGF) are important regulators of skeletal growth. To determine whether the capacity to produce and respond to these growth factors changes during skeletal development, we measured the protein and mRNA levels for IGF-I, IGF-II, and their receptors (IGF-IR and IGF-IIR, respectively) in the tibia and femur of rats before and up to 28 mo after birth. The mRNA levels remained high during fetal development but fell after birth, reaching a nadir by 3-6 wk. This fall was most pronounced for IGF-II and IGF-IIR mRNA and least pronounced for IGF-I mRNA. However, after 6 wk, both IGF-I and IGF-IR mRNA levels recovered toward the levels observed at birth. In the prenatal bones, the signals for the mRNAs of IGF-II and IGF-IIR were stronger than the signals for the mRNAs of IGF-I and IGF-IR, although the content of IGF-I was three- to fivefold greater than that of IGF-II. IGF-II levels fell postnatally, whereas the IGF-I content rose after birth such that the ratio IGF-I/IGF-II continued to increase with age. We conclude that, during development, rat bone changes its capacity to produce and respond to IGFs with a progressive trend toward the dominance of IGF-I.
Aging↗
Altered skeletal pattern of gene expression in response to spaceflight and hindlimb elevation.
Spaceflight leads to osteopenia, in part by inhibiting bone formation. Using an animal model (hindlimb elevation) that simulates the weightlessness of spaceflight, we and others showed a reversible inhibition of bone formation and bone mineralization. In this study, we have measured the mRNA levels of insulin-like growth factor I (IGF-I), IGF-I receptor (IGF-IR), alkaline phosphatase, and osteocalcin in the tibiae of rats flown aboard National Aeronautics and Space Administration Shuttle Flight STS-54 and compared the results with those obtained from their ground-based controls and from the bones of hindlimb-elevated animals. Spaceflight and hindlimb elevation transiently increase the mRNA levels for IGF-I, IGF-IR, and alkaline phosphatase but decrease the mRNA levels for osteocalcin. The changes in osteocalcin and alkaline phosphatase mRNA levels are consistent with a shift toward decreased maturation, whereas the rise in IGF-I and IGF-IR mRNA levels may indicate a compensatory response to the fall in bone formation. We conclude that skeletal unloading during spaceflight or hindlimb elevation resets the pattern of gene expression in the osteoblast, giving it a less mature profile.
Alkaline Phosphatase↗
Reinduction with the same cytostatic treatment in patients with metastatic breast cancer: an Eastern Cooperative Oncology Group study.
PURPOSE: To investigate the therapeutic value of reinduction with the same cytostatic treatment that had been used in induction treatment for women with metastatic breast cancer. MATERIALS AND METHODS: One hundred six women with metastatic breast cancer were given dibromodulcitol (mitolactol), doxorubicin, vincristine, tamoxifen, and fluoxymesterone (DAVTH) for 6 months of induction treatment, then randomized to receive one of two chemotherapy regimens if they had obtained an induction partial response (PR) or no change (NC), or to receive observation versus chemotherapy if they had obtained an induction complete response (CR). Patients were then retreated with DAVTH reinduction after relapse. RESULTS: Seventy-four patients were eligible or had minor reasons for ineligibility. Severe or life-threatening toxicity was documented in 46%, and lethal toxicity in 4%. Eighteen percent had a response on reinduction (zero of 16 induction nonresponders, 15% induction PR, 44% induction CR). The median time to treatment failure (TTF) from reinduction was 3 months, and the median survival duration from reinduction was 14 months. In a logistic model, factors associated with more reinduction responses were observation after induction CR (P = .002) and age greater than 55 years (P = .04). Time since induction was not significant. CONCLUSION: Reinduction of response after treatment failure remains a therapeutic problem. The need for better salvage treatment underlines the importance of developing new regimens.
Antineoplastic Combined Chemotherapy Protocols↗