The relevance of therapeutic drug monitoring in plasma and erythrocytes in anti-cancer drug treatment.

Therapeutic drug monitoring generally focuses on the plasma compartment only. Differentiation between the total plasma concentration and the free fraction (plasma water) has been described for a number of limited drugs. Besides the plasma compartment, blood has also a cellular fraction which has by far the largest theoretical surface and volume for drug transport. It is with anti-cancer drugs that major progress has been made in the study of partition between the largest cellular blood compartment, i.e., erythrocytes, and the plasma compartment. The aim of the present review is to detail the progress made in predicting what a drug does in the body, i.e., pharmacodynamics including toxicity and plasma and/or red blood cell concentration monitoring. Furthermore, techniques generally used in anti-cancer drug monitoring are highlighted. Data for complex Bayesian statistical approaches and population kinetics studies are beyond the scope of this review, since this is generally limited to the plasma compartment only.     

Improved Performance of Hip DXA Using a Novel Region of Interest in the Upper Part of the Femoral Neck: In Vitro Study Using Bone Strength as a Standard of Reference

We tested the hypothesis that bone mineral density (BMD) and bone mineral content (BMC) in proximal human femur specimens in the upper neck region of interest (ROI) and femoral neck axis length (FNAL) provide a significantly better prediction of femoral bone strength than standard ROIs in vitro. BMD and BMC were measured in 110 proximal femur specimens using a standard dual-energy X-ray absorptiometry (DXA) scanner. The analysis included a new ROI in the upper neck as well as the standard ROIs. FNAL was obtained from the scan images. The specimens' failure-load was measured in a mechanical loading device, simulating a fall on the greater trochanter. For the standard ROIs, correlations between failure-load and BMD ranged from R2 = 0.64 (shaft ROI) to R2 = 0.70, p < 0.001 (femoral neck). Prediction of strength by BMD did not significantly differ from those of BMC (R2 ranging from 0.65 to 0.75, p < 0.001). In the upper neck ROI, for both BMD and BMC correlations with failure-load were higher (R2 = 0.76 and 0.81, respectively; p < 0.001). A lower, yet still significant, correlation was found between FNAL and bone strength (R2 = 0.23, p < 0.001). Normalization of failure-load with respect to FNAL did not significantly increase the correlations with densitometric measures. This study provides in vitro evidence indicating that among the ROIs of the proximal femur the newly defined upper neck ROI provides the best prediction of bone strength. Only a weak association was observed between failure load and FNAL.     

Clinical symptoms and signs in sore throat patients with large colony variant β-haemolytic streptococci groups C or G versus group A

BACKGROUND: The role of large colony streptococci groups C or G as pathogen agents in sore throat has been questioned. AIM: To analyse clinical features of patients with large colony streptococci groups C or G compared with patients with group A streptococci (GAS) and with negative cultures. DESIGN OF STUDY: Prospective study of patients with sore throat. SETTING: Two Norwegian general practices in Stokke and Kongsberg communities with 6500 patients.METHOD: Frequency of clinical features in the three patient categories including the four Centor criteria (fever, anterior cervical lymphadenopathy, tonsillar exudates, and lack of cough), degree of pain on swallowing, pharyngeal rubor, C-reactive protein (CRP) values, patient age between 3 and 14 years, and duration of symptoms before seeing the doctor. A logistic regression analysis to find independent predictors was performed. RESULTS: Out of 306 patients with a sore throat, 244 were adults and 62 were children under 10 years old; 40% were men. One hundred and twenty-seven had GAS, 33 had streptococci groups C or G, and 146 had negative throat cultures. Forty-eight per cent of the GAS patients and 45% of the C or G patients met three or four of the Centor criteria. The logistic regression revealed that in patients with GAS considerable pain on swallowing, an age of 3-14 years and a duration of symptoms of < or =3 days or less were significantly associated with GAS infection in addition to the Centor criteria. The same results were found when all streptococci were analysed together, in addition elevated CRP was significant. In patients with streptococci group C or G an elevated CRP-value was significantly associated. CONCLUSION: Patients with tonsillitis caused by streptococcus groups C or G have, to a large extent, the same clinical picture as patients with GAS. Large colony streptococci groups C and G should be considered as throat pathogens in line with GAS.     

Obstructive and restrictive ventilatory impairment in polyvinylchloride fabrication workers

Responses to a standardized respiratory symptom questionnaire, spirometry, and cross-shift decreases in lung function between 70 current employees of a polyvinylchloride (PVC) fabrication plant and a control group consisting of 48 men employed in a vegetable packing plant were compared. FEV1/FVC was significantly lower in the PVC workers. Cross-shift drops in Vmax75 of 15% or more were also more prevalent in the exposed group (p = .01). When examining the association between months of work within the exposed workforce and spirometric indices of airway obstruction, no relationship could be demonstrated. However, an inverse dose-response relationship was seen between level of FVC and duration of employment, suggesting a restrictive impairment. While the specific exposures have not been identified, it appears that employment in PVC fabrication may be associated with both obstructive and restrictive ventilatory effects.     

Urinary oxalate and glycolate excretion in healthy infants and children

The molar ratios of oxalate and glycolate over creatinine were determined in single urine samples of 26 infants and 27 children aged 1–5 years. In 135 children aged 5–16 years, two urine specimens were collected, one before breakfast and one at noon. Oxalate was determined by oxalate oxidase, and glycolate was measured by a colorimetric method (improved chromatotropic acid-sulphuric acid assay after prior purification by cation and anion exchanger). Both ratios (expressed in mmol/mol creatinine and analysed on a log-normal basis) were highest in infants 0–6 months old [mean oxalate 147 (95% confidence interval: 60–360), mean glycolate 175 (72–425)]. The mean oxalate ratio was 72 mmol/mol (29–174) at the age of 7–24 months, 44 (19–101) at the age of 2–5 years and 22 (12–40) in adolescents aged 16 years. Molar glycolate ratios were higher, but disclosed the same pattern. Oxalate and glycolate ratios in fasting urines did not differ significantly from those in noon samples (except glycolate in the oldest age group). Oxalate ratios correlated well with glycolate ratios in children up to 5 years of age only. Random urine samples are thus suitable for screening. However, interpretation of data requires use of age-specific reference values that are based on comparable methods.