Dynamics of CD4 and CD8 T cell responses to cytomegalovirus in healthy human donors

To study the dynamics of cytomegalovirus (CMV) immunity in healthy immunocompetent hosts, interferon-gamma-producing CD4 and CD8 T cell responses in the presence or absence of CMV antigens were measured from 15 CMV-seropositive donors and 13 CMV-seronegative donors. Cytokine responses in the absence of antigen were significantly higher in CMV-seropositive donors. Also, a disproportionate number of CD69(+) cells isolated ex vivo from CMV-seropositive donors were specific for CMV, suggesting recent reactivation in vivo. To examine changes in cellular responses over time, 10 seropositive donors were tested over a 6-month period. About half of the donors showed significant variability over time, but staphylococcal enterotoxin B responses remained relatively constant. These findings suggest that CMV can present a considerable and recurrent burden to the human immune system. By understanding the normal dynamics of CMV responses over time, it may be possible to better identify aberrant responses to CMV in immunocompromised hosts.     

Ocular side-effects in breast cancer patients treated with tamoxifen and toremifene: a randomized follow-up study

PURPOSE: 3Tamoxifen and toremifene are non-steroidal anti-oestrogens widely used in the treatment of advanced breast cancer and as adjuvant therapy following surgery in early stage disease. Tamoxifene has also been approved for use in reducing the incidence of breast cancer amongst high risk women. However, certain well documented adverse effects, mainly involving the reproductive organs, have been reported amongst users of both drugs. The aim of this study was to monitor the ocular side-effects of both of these commonly used anti-oestrogens. METHODS: Sixty postmenopausal (age range 50-79 years) breast cancer patients were randomized into adjuvant tamoxifen or toremifene therapy groups for 3 years. Prior to commencement of medication, a thorough ocular examination was undertaken. The first follow-up visit took place after 6 months and the remaining three at 12-month intervals thereafter. RESULTS: Sixteen patients had cataract at the first visit (seven in the tamoxifen group and nine in the toremifene group). Ten patients developed cataract during the study period (five in each group), giving annual cataract rates of 6.8% and 6.2% in the tamoxifen and toremifene groups, respectively. Three patients had macular crystals at the first visit (one in the tamoxifen group and two in the toremifene group). The crystals remained stable throughout the follow-up. Macular drusen were diagnosed in five patients at the first ophthalmological check-up (two in the tamoxifen and three in the toremifene group). Two patients in the toremifene group developed drusen maculopathy during follow-up visits. Yellowish spots in the macular area were found in one tamoxifen-treated patient at the second visit. At the final visit after 3.5 years' follow-up the spots had disappeared. No abnormal corneal findings or keratopathy were documented during the follow-up. CONCLUSION: We observed no serious ocular side-effects among the 60 breast cancer patients treated with tamoxifen or toremifene over a 3.5-year period.     

Comparison of pharmacokinetics of clodronate after single and repeated doses.

OBJECTIVE: Pharmacokinetics of orally given clodronate disodium, a drug for the treatment of hypercalcemia and bone resorption, were studied after a single dose of 400, 800 and 1600 mg given randomly to 11 healthy volunteers in a crossover manner, in 7-14 hospitalized cancer patients given 400, 800 and 1600 mg twice daily, each dosage for one week, and during the customary therapy in 15 additional cancer patients treated in hospital with 400 mg thrice daily for > or = 2 weeks. METHODS: Clodronate concentrations in serum and urine were measured by capillary gaschromatography with mass-selective detection. Pharmacokinetic parameters were calculated with a three-compartmental model. RESULTS: After a single oral dose to healthy volunteers the absolute clodronate concentrations increased almost dose-dependently. The mean cumulative excretion in urine was 1.72-2.77% of the dose, an interindividual range being from 0.92% to 5.52%. With 800 and 1600 mg twice daily for one week to cancer patients the serum drug concentrations increased almost progressively with increasing the dose. In cancer patients serum drug concentrations were clearly higher and renal drug clearances (mean 25-62 ml/min) lower than in healthy volunteers (mean 123-149 ml/min). The mean urinary excretions were 2.24-3.14% of the dose and interindividual ranges from 0.18% to 19.0%. During the routine cancer therapy with 400 mg thrice daily, the clodronate excretions in urine on two successive days were on an average 3.26% (range 0.0-10.5%). CONCLUSIONS: Absolute concentrations in serum and excretions in urine of orally given clodronate increase dose-dependently, but during the maintenance therapy in hospitalized cancer patients the renal drug clearances seem to be lower than in healthy volunteers. This and the large interindividual variation in kinetics propose therapeutic monitoring of clodronate for optimizing the oral dose of the drug.     

Is the medical record an accurate reflection of patients' symptoms during acute myocardial infarction?

Documentation of symptoms in the medical record provides clinicians and researchers with valuable information about the patient's experience during acute myocardial infarction (AMI). To examine the consistency between the patient's reported symptoms and the medical record, 215 patients were interviewed and their medical records examined for information about their admission symptoms. Chest pain was the most frequently reported and recorded symptom, and there was good agreement between the patient's report and the medical record. Although fatigue was the second most frequently reported symptom by patients, it was rarely documented in the medical record. Time of symptom onset was identified by 87.9% of patients but only documented in 60.5% of medical records. Clinicians may be recording those symptoms that support the AMI diagnosis and not those perceived to be less relevant. Findings suggest that the medical record is an inaccurate and inadequate source of information about patients' actual experience of AMI symptoms.     

Mixed phenotype (T/B/myeloid) extramedullary blast crisis as an initial presentation of chronic myelogenous leukemia

Background

Chronic myelogenous leukemia (CML) is a myeloproliferative disorder characterized by the Philadelphia (Ph) chromosome generated by the reciprocal translocation t(9,22)(q34;q11). The natural progression of the disease follows a biphasic or triphasic course. Most cases of CML are diagnosed in the chronic phase. Extramedullary blast crisis rarely occurs during the course of CML, and is extremely rare as the initial presentation of CML.

Comorbidity of obesity and pain in a general population: results from the Southern Pain Prevalence Study.

This cross-sectional study examines the relation between obesity and self-reported pain (moderate or severe pain occurring at least monthly) in a general population sample of adults in the southeastern United States (N = 3637). Results of the study suggest that obese adults (body mass index [BMI] >30) are more likely to experience pain than their normal-weight and underweight counterparts. Respondents classified as class I obese (BMI of 30 to 34.9) were 1.762 times as likely as the underweight and normal weight participants to report severe pain. Class II obese respondents (BMI of 35 to 39.9) were 1.888 times as likely to experience severe pain. Those respondents categorized as class III obese were most likely to report severe pain--2.297 times as likely as the underweight and normal-weight respondents. Analyses demonstrated a similar trend for respondents reporting moderate to severe pain. Adults who are obese are also more likely to report experiencing pain in multiple locations. This study complements clinical research that links pain and obesity and extends it into a general population. Because this is a cross-sectional study, further research is needed to discern causal explanations for the relation between self-reported pain and obesity. PERSPECTIVE: This article provides a population-level depiction of the positive relation between obesity and self-reported pain, which complements clinical research on the topic. It may prompt future research to shape interventions and treatment for both pain and obesity.     

Stroke. Risks, recognition, and return to work.

1. The two major classifications of stroke are ischemic and hemorrhagic. Ischemic strokes account for 75% of all strokes and result from the complete occlusion of an artery. Hemorrhagic strokes, often caused by aneurysm or hypertension, are caused by the rupture of a cerebral blood vessel and bleeding into the surrounding tissue. 2. The signs and symptoms of stroke may include unilateral weakness or paralysis, a sagging of one side of the face, double or blurred vision, vertigo, numbness or tingling, and language disturbances. 3. Management of ischemic stroke may include thrombolytic agents (e.g., heparin, warfarin) if the individual is treated within 6 hours after the onset of symptoms. Diagnostic tests may include, computed tomography scan, transesophageal echocardiagraphy, Doppler ultrasonography, and electrocordiography. 4. Occupational health nurses can be actively involved in helping workers modify their risks for stroke, developing and implementing an action plan if an individual is experiencing a stroke, and facilitating the individual's reentry into the worksite after rehabilitation is completed.