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Biomedical subjects

J Harris

Publications and source records attributed to J Harris.

At least 163 records · Page 9Linked to original sources

Why and how to combine chemotherapy and radiation therapy in breast cancer patients.

The ideal sequencing of CT and radiation therapy in early-stage breast cancer treated with breast-conserving surgery and RT is not known. There is evidence that delaying CT might have an adverse impact on systemic control, while delaying RT might adversely affect local control. Concurrent CT and full-dose RT might minimize the above tradeoffs, but is associated with increased toxicity. Concurrent CT and reduced-dose RT is a novel approach to address these issues, but requires additional formal evaluation before clinical use. In the absence of definitive information, clinicians should balance each patient's risk for systemic recurrence and local-regional recurrence. For example, a patient with a large number of positive nodes but clearly negative margins would be an appropriate candidate for adjuvant therapy starting with CT and continuing with RT at the completion of CT. Alternatively, a patient with node-negative disease with close or focally positive margins might be an appropriate candidate for initiating RT sooner. Current treatment regimens which deliver CT in a "short" time period [i.e., Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide) delivered in four 3-week cycles] may represent a reasonable tradeoff with regard to promptly starting systemic therapy while initiating RT within 3 months of surgery. It is possible that optimizing the way RT and CT are combined is important in achieving the highest survival rate and in reducing long-term adverse effects. There is unfortunately very little solid information from randomized clinical trials addressing this question, and considerable controversy remains regarding the optimal approach to integrating these modalities. Additional randomized clinical trials addressing this important clinical question are needed.

Breast Neoplasms↗

Opioidergic modulation of spinal reflexes activated by mechanical stimulation of the heel in the decerebrated, spinalized rabbit.

The effects of opioid receptor blockade on reflex responses elicited in medial gastrocnemius and semitendinosus motor nerves by controlled mechanical stimulation of the skin over the heel have been investigated in decerebrated, spinalized rabbits. Pinch forces of 173 mN, 561 mN (light touch), 1642 mN (firm pinch) and 4632 mN (firm to painful) were used. In the control state, background activity was absent from gastrocnemius motoneurones and low in semitendinosus. Pinches of 561 mN and above evoked brisk reflexes in gastrocnemius motoneurones, whereas delayed responses (median latency 1 s) were elicited in semitendinosus by pinches of 1642 mN and 4632 mN. Intravenous administration of the non-selective opioid receptor antagonist (-)-quadazocine (1-781 microg kg(-1)) dose-dependently and stereospecifically increased background activity and enhanced reflex responses to all pinch strengths in both medial gastrocnemius and semitendinosus muscle nerves. Pinches of 173 mN became reflexogenic and higher intensity stimuli evoked significantly larger responses than in the control state. These findings show that tonic opioidergic inhibition in rabbit spinal cord is wide-spread and non-selective, having a powerful influence on transmission of signals to motoneurones from high- and low-threshold cutaneous afferents.

Animals↗

Advice-giving in community pharmacy: variations between pharmacies in different locations.

The advice and services provided by community pharmacies are viewed by policy makers as having an increasingly important contribution to make as a primary health care resource to local populations. However, little attention has been given to the variations which may exist between pharmacies operating in different localities. Findings from an ethnographic study of pharmacies illuminate differences in the nature and quality of advice and services provided by pharmacies operating in disparate localities. Analysis of qualitative data suggests that differences in the environment within which pharmacies are located and organised influence the type of service provided to local populations. The possibility of an inverse care law operating in relation to the nature of services in poor urban localities compared to those in rural areas is also discussed.

Adult↗

The development of general practice standards in Australia. Royal Australian College of General Practitioners.

The Royal Australian College of General Practitioners has spent 4 years developing a set of entry standards which define the minimum features of general practices expected for the mid-1990s. The project design followed a slow, iterative process, with several opportunities for wide consultation with professional, consumer and Government groups. The draft standards were piloted in 25 volunteer practices, modified and then field-tested in 200 randomly selected practices representing urban and rural practices. Results of this field testing showed that the standards had content validity and that reliable measures were possible using triangulation from several data sources. The current version of the standards has been distributed widely for voluntary application in Australian general practices from early 1997.

Australia↗

Induction chemotherapy of dibromodulcitol, Adriamycin, vincristine, tamoxifen, and Halotestin with methotrexate in metastatic breast cancer: an Eastern Cooperative Oncology Group Study (E1181).

Patients who have metastatic breast cancer are seldom curable. Chemotherapy given by conventional doses and schedules generally produces complete remissions in 10% to 20% of patients. This study sought to determine 1) whether a combination of dibromodulcitol, Adriamycin, vincristine, tamoxifen, Halotestin, and methotrexate with leucovorin rescue (DAVTHML) can produce a complete remission rate of 50%; and 2) the toxicity of this combination in patients with chemotherapy-naive metastatic breast cancer. Patients were treated with six 28-day cycles of DAVTHML induction chemotherapy consisting of dibromodulcitol, 135 mg/m2 perorally days 1 to 10; Adriamycin 45 mg/m2 intravenously day 1; vincristine, 2 mg intravenously day 1; tamoxifen and Halotestin, 20 mg perorally daily; methotrexate, 800 mg/m2 intravenously days 15 and 22; and leucovorin, 15 mg/m2 perorally every 6 hours for 9 doses, starting 4 hours after methotrexate. After induction, patients who had stable disease or a partial response were treated with a cyclophosphamide, methotrexate, and 5-fluorouracil-based regimen (CMF). Patients in complete remission were treated with three additional cycles of DAVTHML after achieving complete remission and then observed off therapy until relapse, when DAVTHML was to be given again. Fifty-eight patients were included in this study. During induction, 26% of eligible patients experienced a complete remission; overall response rate was 80%. The median time to treatment failure and the median survival time of eligible patients was 11.1 and 24.0 months, respectively. This did not change significantly when all the patients were included in the evaluation. The 3-year and 5-year survival rates were 37% and 11%, respectively. Ninety percent of the eligible patients experienced grade III or IV toxicity. They were leukopenia (75%), anemia (20%), thrombocytopenia (20%), and vomiting (17%). No lethal toxicity was documented during therapy; however, 1 patient later died of myelodysplastic syndrome induced by dibromodulcitol. The overall response and complete remission rates from our study were encouraging. The toxicity of DAVTHML was tolerable, with the exception of myelodysplastic syndrome from dibromodulcitol. The concept of using mid-cycle nonmyelosuppressant agents to increase complete remission rate is feasible.

Adult↗

Alteration in the recommended dosing schedule for risperidone.

OBJECTIVE: The authors' goal was to study the recommended dose schedule for risperidone. METHOD: They obtained computerized pharmacy data on 1,283 inpatients with the diagnoses of schizophrenia or schizoaffective disorder who were treated with risperidone. Continuance on risperidone was defined as remaining on the drug for 16 days or until discharge. RESULTS: The majority of the patients (84%) continued on resperidone. Use of the recommended dose schedule decreased greatly over time. Patients were more likely to continue on risperidone if they had a higher maximum dose (5.7 mg/day versus 4.7 mg/day), a longer number of days to maximum dose (5.7 days versus 3.9 days), and a maximum rise in dose of 0.5-2 mg/day. CONCLUSIONS: These findings suggest that the recommended dose schedule should be altered to one that recommends a less rapid titration (over 6 days to a week) and that the dose increments consist of 0.5-2 mg/day.

Adult↗

Advice provided in British community pharmacies: what people want and what they get.

OBJECTIVES: This study explored advice-giving behaviour in community pharmacies in order to understand the nature and process of pharmaceutical consultations and consumers' views of the advice-giving role. METHOD: An ethnographic research strategy was used, combining patient interviews with non-participant observation of interactions between consumers and pharmacy staff. One week was spent in each of 10 pharmacies. RESULTS: The study demonstrated that the advice given in a community pharmacy is almost wholly focused on product recommendation and use. Advice-giving varies according to whether consultations concern prescription or non-prescription medicines. When the latter are involved, advice-giving is mostly consumer-led. Consumers' major 'need' for pharmacy services appears to be for information about the effectiveness of products they buy, whilst pharmacists and pharmacy assistants concentrate on providing advice on the safety of medicines. CONCLUSION: The notion of pharmacists as general health advisors does not appear to be shared by the public and may be at odds with how the public view and use pharmacies. Protocols to guide staff may be improved by including the consumer perspective. Most consumers have previous experience of their ailments and use pharmacies as one of several resources available to them to treat their minor illness, having made their own diagnosis and assessment before entering the pharmacy. The scope for giving new advice is therefore limited. The broader role of community pharmacies merits further attention.

Counseling↗

Cardiac effects of adjuvant doxorubicin and radiation therapy in breast cancer patients.

PURPOSE: To assess the cardiac effects of two different cumulative doses of adjuvant doxorubicin and radiation therapy (RT) in breast cancer patients. PATIENTS AND METHODS: Two hundred ninety-nine breast cancer patients were prospectively randomized to receive either five cycles (CA5) or 10 cycles (CA10) of adjuvant treatment with cyclophosphamide (500 mg/ m2) and doxorubicin (45 mg/m2) administered by intravenous bolus every 21 days. One hundred twenty-two of these patients also received RT. Estimates of the cardiac RT dose-volume were retrospectively categorized as low, moderate, or high. The risk of major cardiac events (congestive heart failure, acute myocardial infarction) was assessable in 276 patients (92%), with a median follow-up time of 6.0 years (range, 0.5 to 19.4). RESULTS: The estimated risk (95% confidence interval) of cardiac events per 100 patient-years was significantly higher for CA10 than for CA5 [1.7 (1.0 to 2.8) v 0.5 (0.1 to 1.2); P=.02]. The risk of cardiac events in CA5 patients, irrespective of the cardiac RT dose-volume, did not differ significantly from rates of cardiac events predicted for the general female population by the Framingham Heart Study. In CA10 patients, the incidence of cardiac events was significantly increased (relative risk ratio, 3.6; P < .00003) compared with the Framingham population, particularly in groups that also received moderate and high dose-volume cardiac RT. CONCLUSION: Conventional-dose adjuvant doxorubicin as delivered in the CA5 regimen by itself, or in combination with locoregional RT, was not associated with a significant increase in the risk of cardiac events. Higher doses of adjuvant doxorubicin (CA10) were associated with a threefold to fourfold increased risk of cardiac events. This appears to be especially true in patients treated with higher dose-volumes of cardiac RT. Larger studies with longer follow-up periods are needed to confirm these results.

Adult↗

Family history and treatment outcome in young women after breast-conserving surgery and radiation therapy for early-stage breast cancer.

PURPOSE: To evaluate the safety and efficacy of breast-conserving therapy for young women with a family history (FH) suggestive of inherited breast cancer susceptibility. MATERIALS AND METHODS: A total of 201 patients aged 36 or younger at diagnosis treated with breast-conserving surgery and radiation therapy (> or = 60 Gy) for early-stage breast cancer were categorized by FH. FH was considered positive in 29 patients who, at the time of diagnosis, had a mother or sister previously diagnosed with breast cancer before age 50 or ovarian cancer at any age. Clinical, pathologic, and demographic variables; sites of first failure; disease-free survival; and overall survival (OS) were compared between FH-positive and -negative groups. Median follow-up time was 11 years. RESULTS: Patient and tumor features were similar between those with and without an FH. Regression analysis of sites of first failure at 5 years demonstrated a risk ratio (RR) of 5.7 for opposite breast cancer for FH-positive patients. Rates of local, regional, and distant failure and disease-free survival or OS did not differ between FH-positive and -negative patients. Age at diagnosis and Ashkenazi heritage were not significantly predictors of patterns of failure. CONCLUSION: Breast-conserving surgery combined with radiation therapy is not associated with a higher rate of local recurrence, distant failure, or second (non-breast) cancers in young women with an FH suggestive of inherited breast cancer susceptibility compared with young women without an FH. However, their increased risk of opposite breast cancer should be taken into account when considering breast conservation as a treatment option.

Adult↗

Myasthenic hand.

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Aged↗

A successful PPMC (physician practice management company) acquisition strategy: vision, focus and discipline.

Acquisitions have become increasingly necessary for managed care organizations to create product value and operating synergies. Physician practice management companies (PPMCs) that have successfully acquired and consolidated group practices and IPAs have a clear vision of their mission, focus on their target markets, and adhere to a disciplined methodology of financial evaluation, negotiation, and transition. Growing a PPMC entails risks, but expectations are for continued expansion of these organizations. The vision-focus-discipline method can help buyers adhere to a successful strategy during the acquisition process.

Economics, Medical↗

Potentiation and inhibition of nicotinic acetylcholine receptors by spermine in the TE671 human muscle cell line.

Nicotinic acetylcholine receptors (nAChR) of the TE671 cell line were investigated using whole-cell and membrane patch recording techniques. At negative holding potentials (VH), pulses of acetylcholine (ACh) elicited whole-cell inward currents that rapidly desensitized. The EC50 value for ACh at VH = -60 mV was 7.8 microM. The ACh-induced current reversed at approximately 0 mV. Desensitization of nAChR by ACh was biphasic and reversible within approximately 20 sec. Spermine (1-100 microM) potentiated responses to ACh (10 microM - 1 mM) by reducing the rate of onset of desensitization; potentiation was inhibited by arcaine (10-100 microM). Spermine (1 mM) noncompetitively antagonized the AChinduced current. Antagonism by 1 to 5 mM spermine was voltage-dependent, increasing with negative VH. In 100 microM arcaine, this antagonism was shown to contain a voltage-independent component. Spermine (10 mM) increased the EC50 values for ACh, suggesting that at this concentration the polyamine is also a competitive antagonist. Single channel openings elicited during application of ACh to outside-out patches had a conductance of 47 pS at VH = -60 mV. At 10 and 100 microM, spermine increased channel open probability (po), but at 1 mM spermine, po was not significantly different from controls. The single channel conductance for ACh was unaffected by 10 and 100 microM spermine, but was decreased by 1 mM spermine. Spermine promoted the occurrence of approximately 27 pS openings. It is proposed that spermine acts at an excitatory modulatory site similar to that present on N-methyl-D-aspartate receptors and at least three inhibitory sites on nAChR of TE671 cells.

Acetylcholine↗