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Biomedical subjects

N R Anderson

Publications and source records attributed to N R Anderson.

At least 19 recordsLinked to original sources

Plasma nitrotyrosine in reversible myocardial ischaemia.

BACKGROUND: Nitric oxide (NO) plays a vital role in vascular homeostasis and in the pathophysiology of coronary heart disease. Its metabolites, nitrite and nitrate, have vasculoprotective properties, whereas peroxynitrite, an oxidant metabolite of NO, is cytotoxic and can aggravate myocardial damage during ischaemic reperfusion injury. Peroxynitrite nitrates free and protein bound tyrosine residues to produce nitrotyrosine. The measurement of nitrotyrosine provides an indirect estimation of plasma peroxynitrite concentrations. AIMS: To measure plasma nitrotyrosine concentrations to see whether peroxynitrite could contribute to myocardial dysfunction during myocardial ischaemia induced by an exercise tolerance test (ETT). MATERIALS/METHODS: Plasma free nitrotyrosine concentrations were compared before and after exercise in 29 subjects with a positive ETT and 34 subjects with a negative ETT. RESULTS: Plasma nitrotyrosine concentrations were similar in patients with exercise induced myocardial ischaemia and controls. CONCLUSION: Peroxynitrite does not contribute to the myocardial dysfunction in reversible myocardial ischaemia.

Adult↗

Raised serum prolactin in rheumatoid arthritis: genuine or laboratory artefact?

OBJECTIVES: Serum prolactin concentrations have been reported as higher, similar or lower in patients with rheumatoid arthritis (RA) compared with control subjects. We investigated whether low biological activity macroprolactin (a prolactin antibody complex), which is detected variably in different prolactin immunoassays, could account for the discrepant total prolactin results reported in RA. METHODS: We compared serum total prolactin and free prolactin in 60 women with RA and 31 female controls. RESULTS: No subject had hyperprolactinaemia or macroprolactinaemia. Serum concentrations of total and free (monomeric) prolactin were higher (P<0.05) in women with RA [mean (s.d.), 225.6 (104.6) and 201.6 (95.4) mU/l respectively] compared with controls [175.0 (68.5) and 154.0 (60.9) mU/l respectively]. CONCLUSIONS: We report higher serum free prolactin concentrations in women with RA compared with control subjects. This result indicates that the higher serum total prolactin levels in patients with RA are the consequence of increased free prolactin concentrations and are not due to macroprolactin.

Arthritis, Rheumatoid↗

Serum prolactin in human immunodeficiency virus infection.

Patients infected with human immunodeficiency virus (HIV) have higher serum prolactin compared to healthy controls but this is controversial. As part of a laboratory audit investigating the interference of macroprolactin in our prolactin assay, we investigated whether low biological activity macroprolactin could account for the increased serum prolactin concentrations observed in HIV infection. We, therefore, compared serum total prolactin and free prolactin in 32 subjects infected with HIV (HIV+ve) with 52 subjects not infected with HIV (HIV-ve). Serum total prolactin concentrations were similar in HIV+ve and HIV-ve patients [median (95% confidence limits); 167.0 (122.4 - 313.8) vs 206.5 (187.8 - 248.4) mU/L respectively]. Serum free prolactin concentrations were lower (p <0.005) in HIV+ve subjects than in HIV-ve subjects [112.0 (91.1-141.8) vs 171.0 (154.5 - 200.9) mU/L respectively; p<0.0005]. These results are consistent with the notion that low biological activity macroprolactin contributes to circulating prolactin concentrations in HIV+ve subjects.

Adult↗

Lipaemia: an overrated interference?

Reagent method sheets for analysis of common serum analytes often highlight the possibility of interference from lipaemia but the information given is often brief and may not be instrument-specific. Thus study assesses the degree of interference from lipaemia in a range of common serum analytes on the Bayer Opera (with a serum blank) using a commercial polymer, LipoClear, as a lipid-clearing agent. Serum samples (mean serum triglyceride 6.89 [range 0.58-28.4] mmol/L) are analysed for 14 common chemistry analytes and the results compared before and after treatment with LipoClear. Results showed no significant critical differences in analyte values before and after treatment, except for an expected fall in total protein, phosphate, cholesterol and triglyceride concentrations. Most of the common analytes in use on the Bayer Opera are not subject to interference from lipaemia; however, we recommend that where method sheets indicate interference from lipaemia then this should be quantified for the analyte in question.

Artifacts↗

Effect of a protease inhibitor on in vitro stability of intact parathyroid hormone.

BACKGROUND: We investigated whether increased protease activity explains the increased in vitro degradation of intact parathyroid hormone (iPTH) observed in serum when compared to EDTA plasma. METHODS: Pre-dialysis blood samples for iPTH were taken from 11 patients with chronic renal failure and collected into plain glass tubes, tubes containing 200 KIU/mL aprotinin (a protease inhibitor) and EDTA tubes. All sample aliquots were separated at 20 min, 1 h, 2 h, 4 h, 8 h and 24 h post collection. RESULTS: Over 24 h, iPTH concentrations remained unchanged in EDTA tubes. iPTH concentrations were significantly lower in both plain tubes (P < 0.01) and aprotinin tubes (P < 0.001) at 24 h when compared to the baseline sample (20 min). At 24 h, iPTH concentrations in EDTA tubes were higher than in plain tubes (P < 0.001) and aprotinin tubes (P < 0.01). The addition of aprotinin to plain tubes significantly reduced the degradation of iPTH (P < 0.05) at 24 h. CONCLUSION: Aprotinin significantly reduces the in vitro degradation of iPTH in plain tubes at 24 h from 24.7% to 9.6%. We suggest that increased protease activity contributes to the decline in serum iPTH over time. As this is observed in serum and not plasma it suggests that the increased protease activity may be due to the clotting process.

Aprotinin↗

Comparative evaluation of the new Sheffield table and the modified joint British societies coronary risk prediction chart against a laboratory based risk score calculation.

BACKGROUND: Management of borderline hypertension and hypercholesterolaemia is based on an individual's coronary heart disease (CHD) risk rather than arbitrary values for blood pressure or serum cholesterol. Prediction of CHD risk involves using tables, charts, or computer programs based on the Framingham equations. The new Sheffield table and modified joint British societies coronary risk prediction (JBS) chart are widely used. The JBS chart approximates age and systolic blood pressure, and the new Sheffield table dichotomises blood pressure, and these simplifications may lead to diagnostic inaccuracy. METHODS: The diagnostic performance of the charts against an individualised laboratory based CHD risk calculation in 1102 subjects in primary care were evaluated and compared. RESULTS: The new Sheffield table and modified JBS chart performed equally well with a respective diagnostic sensitivity and specificity of 91.6% (95% confidence interval 86.7% to 95.1%) and 93.8% (91.1% to 97.9%), and 93.6% (90.4% to 96.0%) and 94.7% (92.6% to 96.1%) at 10 year CHD risk of 15%; and of 95.2% (82.8% to 99.4%) and 97.9% (96.8% to 98.7%), and 90.5% (75.6% to 97.4%) and 100% (99.7% to 100%) at 10 year CHD risk of 30%. The modified JBS chart graphic display provides graded risk, which may be an advantage over the new Sheffield table, which identifies thresholds of risk. The new Sheffield table, unlike any other method, can be used as screening tool for cholesterol measurement. CONCLUSIONS: The new Sheffield table and modified JBS chart are valid for use in primary care since their diagnostic accuracy is unaffected by approximations in age and blood pressure. It is suggested that practitioners should choose whichever risk assessment tool they are comfortable with and use it.

Adult↗

Ethnic differences in total and HDL cholesterol concentrations: Caucasians compared with predominantly Punjabi Sikh Indo-Asians.

BACKGROUND: In comparison with Caucasians, Indo-Asians resident in the UK have similar total cholesterol but lower HDL cholesterol (HDLC) concentrations. It is however possible that cardiovascular risk factors may vary between culturally different Indo-Asians. METHODS: We present data on 223 Indo-Asians (129 men, 94 women) and 787 Caucasians (421 men, 366 women) in whom a laboratory-based coronary heart disease (CHD) risk score calculation had been requested. RESULTS: Total cholesterol concentrations were similar in Indo-Asians and Caucasians. HDLC concentrations were higher (P < 0.001) in Caucasians [1.4 (1.3-1.4) mmol/L; median (95% confidence intervals)] than in Indo-Asians [1.2 (1.2-1.3) mmol/L]. Indo-Asian women [1.2 (1.2-1.3) mmol/L], Indo-Asian men [1.2 (1.2-1.3) mmol/L] and Caucasian men [1.2 (1.2-1.3) mmol/L] had similar HDLC concentrations but these were all lower (P < 0.001) than those in Caucasian women [1.4 (1.3-1.4) mmol/L]. CONCLUSION: We confirm low HDLC concentrations in Indo-Asians, but propose that this is solely due to low HDLC concentrations in Indo-Asian women. Since Indo-Asians in Wolverhampton are predominantly Punjabi Sikhs, we suggest that the difference between this study and previous reports may be due to heterogeneity of CHD risk factors within culturally diverse Indo-Asians.

Adult↗

Ethnic variation in C-reactive protein: UK resident Indo-Asians compared with Caucasians.

BACKGROUND: The increased prevalence of coronary heart disease (CHD) in UK resident Indo-Asians is unexplained by the traditional cardiovascular risk factors of dyslipidaemia, hypertension, smoking and diabetes mellitus. C-reactive protein (CRP) has been implicated in the pathogenesis of CHD but the data on ethnic variation in CRP is conflicting. We therefore investigated whether CRP could help explain the increased prevalence of CHD in Indo-Asians. DESIGN AND METHODS: We measured CRP, using a highly sensitive assay, in 102 men (63 Caucasians and 39 Indo-Asians) and 89 women (58 Caucasians and 31 Indo-Asians). All subjects, aged between 40 and 70 years, were nondiabetic and nonsmokers. RESULTS: Serum CRP correlated (P < 0.05) positively with coronary risk. Serum HDL cholesterol concentrations were lower (P<0.05) in Indo-Asian women when compared with Caucasian women, but otherwise the ethnic groups were matched for calculated coronary risk and cardiovascular risk factors. Serum CRP concentrations were similar in Indo-Asians (women 2.29 (1.52) mg/l [mean (SD)]; men 1.77 (1.46) mg/l) and Caucasians (women 2.23 (1.54) mg/l; men 1.94 (1.45) mg/l). CONCLUSIONS: Altered CRP concentrations does not appear to be implicated in the increased prevalence of CHD in UK resident Indo-Asians.

Asia↗

Herbal remedy poisoning presenting with acute abdomen and raised urine porphyrins.

We describe a case of lead poisoning due to herbal remedies, presenting with an acute abdomen, raised porphyrins and increased liver enzyme activities. We suggest that lead poisoning should be considered in the differential diagnosis of the 'acute abdomen', and that the presence of liver dysfunction points to the possibility of Asian herbal remedies as the source of the lead poisoning.

Abdomen, Acute↗

Combined paclitaxel, cisplatin, and etoposide for patients with previously untreated esophageal and gastroesophageal carcinomas.

BACKGROUND: Paclitaxel (T), etoposide (E), and cisplatin (P) are each active in gastric carcinoma, either as single agents or as part of a multidrug regimen. To the authors' knowledge, the combination of these three agents in the treatment of patients with esophageal or gastroesophageal carcinoma has not been previously studied. METHODS: Previously untreated patients with locally advanced carcinoma of the stomach, esophagus, or gastroesophageal (GE) junction received at least 2 cycles of TPE administered twice weekly for 3 weeks, with the cycle repeated every 28 days. Drug doses, administered over 3 hours on either Monday and Thursday or Tuesday and Friday, consisted of T 50 mg/m2/dose, P 15 mg/m2/dose, and E 40 mg/m2/dose. For patients with local disease only, subsequent therapy consisted of radiation with or without surgical resection. RESULTS: Twenty-five patients with gastric (10) or gastroesophageal or GE junction (15) carcinoma were treated. Eighteen had locally advanced disease and 7 had liver metastases at presentation. Hematologic toxicity, namely, Grade 3 anemia and neutropenia, was experienced by all patients. The median number of treatment cycles was 4 (range, 2-6). Three patients were not evaluable for response. All 22 evaluable patients responded; 3 were complete responders and 19 were partial responders. Eleven patients received radiation therapy with (6) or without (5) concomitant 5-fluorouracil, and 8 patients subsequently underwent surgical resection. Three of 8 patients had no tumor at surgery, 4 had minimal microscopic tumor at the primary site, and 3 had microscopic lymph node involvement. Twenty-three patients are alive, of whom 14 are without evidence of disease. Two patients with metastatic disease at presentation died at 9 and 29 months, respectively. The median survival was 12.5 months (range, 6 to 30+ months). CONCLUSIONS: Multifractionated TPE chemotherapy is a highly active regimen in gastric and gastroesophageal carcinoma. It could be evaluated in Phase III trials against other active regimens for the treatment of patients with this disease. The introduction of 5-fluorouracil could also be an interesting direction to explore because of its primary role in the treatment of patients with gastric and esophageal carcinoma.

Adult↗

Comparison of costs for infusion versus bolus chemotherapy administration: analysis of five standard chemotherapy regimens in three common tumors--Part one. Model projections for cost based on charges.

BACKGROUND: The cost of infusional administration of cancer chemotherapy has been assumed to be more expensive than the traditional bolus schedule related to the use of durable medical equipment and other components of the delivery system. The objective was to develop a model of projected charges as a basis for the cost estimate for selected common chemotherapy regimens comparing the cost based on charges for bolus and infusional chemotherapy schedules. METHODS: Chemotherapy programs using either bolus or infusional delivery were selected representing standard or commonplace regimens for the treatment of patients with breast cancer (cyclophosphamide, methotrexate, fluorouracil [CMF] or CA); colon cancer (5-fluorouracil[5-FU] infusion vs. 5-FU bolus + leucovorin [LCVI] or lymphoma (cyclophosphamide, hydroxydaunomycin, Oncovin (vincristine), prednisone [CHOP] or CDE [cyclophosphamide, doxorubicin, etoposide]). Cost projections were estimated based on charges and were calculated in a model system using six charge (cost) centers including medical doctor [MD] and/or clinic visit; laboratory; drug cost based on average wholesale price (AWP); cost of disposables; and pump rental fee. Standard dosages were applied for each regimen using total mg/M2 for a 1.5 M2 person. RESULTS: Projected charges or chemotherapy for colon cancer (5-FU infusion vs. 5-FU + LCV) are variable depending on the LCV dose and the infusion duration. The longer infusion duration or higher doses of LCV result in a 40 to 50% increment in monthly charges excluding cost related to toxicity. For breast cancer, the charges for bolus or infusion administration CMF are similar, but for CA bolus charges are higher than infusion charges related to higher drug doses. For lymphoma, CHOP chemotherapy dosage costs are approximately half of those for CDE infusion related to the specific drug regimen and drug dosage used. CONCLUSIONS: The perception that infusional delivery of chemotherapeutic agents adds to the cost of cancer care is appropriate for some regimens but the absolute amount of cost increment is generally modest. The principle cost differences between bolus and infusional schedules relate to drug dosage and the toxicity profile. Generally, but not consistently, infusional schedules use lesser doses and are associated with lesser toxicity. Although the benefit of infusional delivery of chemotherapy in terms of response rates and survival are comparable to bolus schedules for 5-FU infusion and 5-FU + LCV in colon cancer, this has not been established for the regimens analyzed for breast cancer (CMF, CA) or lymphoma (CDE, CHOP). The misperception of cost advantages for bolus delivery should not preclude comparative trials of bolus versus infusional chemotherapy schedules and cost should be studied prospectively in clinical trials comparing different schedules of administration in addition to studies of quality of life and toxicity.

Antibiotics, Antineoplastic↗

Comparison of costs for infusion versus bolus chemotherapy administration--Part two. Use of charges versus reimbursement for cost basis.

BACKGROUND: The costs of infusion versus bolus administration of chemotherapy has been a point of controversy as has been the method of quantitating the cost. The present study analyzes the reimbursement for chemotherapy administration by infusion compared with bolus delivery based on reimbursement and relates this to cost based on projected charges and actual charges in a private practice setting. METHODS: Actual reimbursement records were retrieved for selected patients receiving infusion or bolus administration of specific chemotherapy regimens for three tumors: colon carcinoma, breast carcinoma, and lymphoma. All services were included except for radiology and hospitalization. Medicare reimbursement represented 90% of the treatment cycles analyzed. RESULTS: Actual reimbursement per month for each infusion regimen was as follows: colon carcinoma, $528 (5-fluorouracil [5-FU]); breast carcinoma, $621 (doxorubicin and cyclophosphamide [AC]) and $685 (cyclophosphamide, methotrexate, and fluorouracil [CMF]); and lymphoma, $603 (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP]). Actual reimbursement per month for a bolus regimen was colon carcinoma, $393 (5-FU + leucovorin); breast carcinoma, $991 (AC) or $453 (CMF); and lymphoma, $749 (CHOP). Actual reimbursement represents 21-36% of actual charges. Projected charges based on the model system are generally less than the actual charges. CONCLUSIONS: The cost of chemotherapy as defined by reimbursement are substantially less than actual charges and are also less than projected costs based on charges. Data comparing bolus versus infusion reimbursement costs for colon carcinoma, breast carcinoma, and lymphoma indicate that differences between reimbursement for bolus and infusion administration are not substantial.

Antibiotics, Antineoplastic↗