Cerebral angiitis caused by periarteritis nodosa

INTRODUCTION: We report a case of periarteritis nodosa revealed by a cerebral angiitis which recovered under treatment. OBSERVATION: A 52-year-old patient suddenly presented with a left sensory syndrome and a fluctuating aphasia due to ischemia involving both parietal lobes. The diagnosis of periarteritis nodosa was based on the following criteria: severe loss of weight, renal insufficiency, hypertension, angiography suggesting an arteritis. Instead of an ileo-cecal perforation, the patient recovered under corticosteroid and immunosuppressive therapy. CONCLUSIONS: Stroke in periarteritis nodosa may occur early be and associated with a good outcome.     

Factors affecting pharmacokinetic variability of oral topotecan: a population analysis

The aim of this study was to characterise the pharmacokinetics of the anticancer agent topotecan, and explore the influence of patient covariates and interoccasion variability on drug disposition. Data were obtained from 190 patients who received the drug as a 30-min infusion (N=72) or orally (N=118). The population model was built with the use of NONMEM to identify candidate covariates, and obtain models for clearance (CL) and volume of distribution. The final models were based on first-order absorption with lag-time (oral data), and a two-compartment model with linear elimination from the central compartment. The Cockcroft-Gault creatinine clearance (CrCl) and WHO performance status (PS) were the only significant covariates: CL=(12.8+2.1 x CrCl) x (1-0.12 x PS). For the volume of distribution, a correlation was found between body weight and the central volume (V1)=0.58 x body weight. Based on the structural models, a limited-sampling strategy was developed with minor bias and good precision that can be applied a posteriori using timed samples obtained at 1.5, and 6 h after the administration of topotecan. In conclusion, a population pharmacokinetic model for topotecan has been developed that incorporates measures of renal function and PS to predict CL. In combination with drug monitoring, the limited sampling strategy allows individualised treatment for patients receiving oral topotecan.     

Association between blood pressure level and the follow up of the guidelines concerning the use of self blood pressure measurement

OBJECTIVES: To evaluate the characteristics of hypertensive subjects who practise self measurement of blood pressure (SMBP) and their conditions of use, and to identify the properties of subjects using SMBP according the usual guidelines. METHODS: In 531 consecutive hypertensive subjects, referred to hypertension specialists, possessing a SMBP a questionnaire evaluating the condition of use of SMBP was given. Subjects following the guidelines about the use of SMBP have been compared to those using SMBP without specific design of supervision. RESULTS: In this population, aged 62 +/- 14 years, with 57% of men and a mean blood pressure of 147 +/- 23/82 +/- 12 mmHg, the SMBP devices have been bought without medical advice in 50% of cases (265/531). In 45% of cases (239/531), SMBP were made at the wrist. SMBP device was used every days in 26% of cases, every weeks in 27% of cases, every month or more in 22% of cases and only in case of uneasiness in 25% of cases. Blood pressure was measured only in the morning in 25% of cases, in the morning and evening in 31%, only the evening in 8% and at any time of the day in 36% of cases. More frequently 2 BP measurements were realized (47%) and in 19% of cases 3 measurements have been performed. In 15% of cases, the measurements were performed on 3 or 4 days consecutively, more frequently (85%) the measurements were realized without specific design ("once in awhile"). The data of SMBP were noted and showed to the doctor in 34% of cases. Only 12% (64/531) of subjects followed the usual guidelines concerning the use of SMBP (2 or 3 measurements, in the morning and the evening, during 3 or 4 consecutive days). Subjects following the guidelines for SMBP use have a higher SBP at the office than those using SMBP without specific design of supervision (155 +/- 25 mmHg vs 146 +/- 22 mmHg; p<0.01). CONCLUSION: Among hypertensives referred to hypertension specialists most of subjects use SMBP device without a specific design of supervision. Subjects with the most severe hypertension are those who have the best formation for SMBP.     

Evaluation of drug therapy knowledge in liver transplant patients after pharmacy counseling

The analysis of the literature demonstrated that pharmacy counselling influenced patient outcome after transplantation. This was the reason we established pharmacy consultation in 1999. The aim of this study was to determine patient knowledge before and after pharmacy counselling. Twenty-nine patients were questioned about the identification, role and dosage of prescribed drugs. The mean duration of pharmacy counselling was 54 minutes. Before pharmacy consultation, the knowledge score was 53.7%. Afterwards, the mean score value reached 75% and seven patients had a score of 100%. The anti-rejection therapy was understood by 93% of patients. However, the associated drugs were poorly known: less than 15% of patients initially knew about the purpose of the antimicrobial agent, compared with 50-60% after counselling. During counselling, two women were identified as regularly using St John's Wort and were informed that this herbal medicine can endanger the success of organ transplantation. Five patients or family members called the pharmacist to obtain additional information. Among these, two medication errors, both with corticosteroid drugs, were reported by family members of patients of foreign origin who had difficulty in understanding and speaking French. Pharmacy counselling improved patient knowledge about therapy after transplantation.     

The relationship between lower urinary tract symptoms and health status: the UREPIK study

OBJECTIVES: To assess the hypothesis that as lower urinary tract symptoms (LUTS) increase in severity, the impact as measured by the BPH impact index (BII) would also increase. SUBJECTS AND METHODS: The UREPIK survey collected information on this relationship from men and their partners in the Netherlands, Korea, France and the UK. Culturally and linguistically validated versions of three standard questionnaires, the SF-12, the BII and the International Prostate Symptom Score (IPSS) were used to assess the distribution of symptoms and the impact on health status. Stratified random samples of men aged 40-79 years in each community were recruited. Response rates were 72% in Boxmeer, 28% in Auxerre, 60% in Birmingham and 68% in Seoul. Regression analyses were undertaken on total SF-12, BII and IPSS. RESULTS: In all, 4800 index men and 3674 women responded; the BII increased with increasing IPSS. The correlation coefficients were; Boxmeer 0.69, Auxerre 0.56, Birmingham 0.60 and Seoul 0.68. For women, the correlations were slightly lower except in Birmingham, at 0.65 (Boxmeer), 0.44 (Auxerre), 0.71 (Birmingham), 0.57 (Korea). BII scores were higher in women than in men with the same level of IPSS. Adjusting for IPSS there was no association between age and BII. There was an association between IPSS quality-of-life (QoL) score and BII; for men the correlation was 0.62 and for women 0.60. Men and women with the same score on the IPSS QoL reported the same bother. Among those with an IPSS of 20-35 women expressed significantly more bother (P < 0.001). The SF-12 scores decreased as the IPSS and the BII increased in both men and women. Furthermore, the SF-12 mental score decreased with increasing symptoms in the partner. CONCLUSIONS: The relationship between the severity of LUTS and BII was similar in all centres. There is a clear association between the BII and the IPSS QoL question in men and women. The BII discriminates between people who are unhappy about their urinary condition compared with those who are pleased. Although designed for use in men with benign prostatic hyperplasia, the index also appears to be a useful among women. The severity of symptoms of LUTS has an adverse effect on the health status of the individual and his/her partner.     

Relationships between catecholamine or 3-methoxy 4-hydroxy phenylglycol changes and the mental performance under submaximal exercise in man

Eleven young students were tested to determine the relationship between the improvement of mental performances observed under prolonged submaximal work and central or peripheral catecholamine changes. The subjects pedaled a bicycle ergometer for 1 h at a work load individually calculated to approximate 75% of maximal oxygen uptake. The mental test, consisting of 1-h sessions of time-limited word tests and arithmetical calculations, required a high degree of concentration (vigilance and short-term memory). Catecholamines [epinephrine (E), norepinephrine (NE), dopamine (DA)], metanephrine (MN), normetanephrine (NMN) and the glucuronide conjugate of 3-methoxy 4-hydroxyphenylglycol (MHPG) were assayed in urine to assess peripheral activity: E and MN as indexes of adrenomedullary secretion, NE, NMN and MHPG glucuronide as markers of NE metabolism in sympathetic nerves. Urinary MHPG sulfate was determined as a possible marker of central noradrenergic metabolism. When compared to the effect of single tests, the combination of prolonged submaximal work and mental task induced significant increases in MHPG sulfate and E+MN excretions. Both these increases were correlated each to one another and also correlated to the number of discriminated words. Altogether, the present data show that prolonged submaximal work under mental load activates catecholamine systems and suggest that a relationship exists between adrenomedullary activation and the improvement of mental performance. Based on literature data, the possible modulatory role of peripheral E on mental processes and central noradrenergic activity is discussed.     

Chromosomal changes associated with resistance to doxorubicin: correlation with tumorigenicity

Chromosome analysis was performed on Friend leukemia cells sensitive and resistant to doxorubicin. With increasing levels of resistance, increased numbers, of metacentric chromosomes and several chromosomal markers were observed. When sensitive cells were exposed to a toxic dose of doxorubicin, multiple chromosomal breaks were observed in 62% of cells. In contrast, when doxorubicin resistant cells were exposed to cytotoxic concentrations, the pulverization phenomenon was not observed. This striking difference suggests a different mechanism for cytotoxicity in sensitive and resistant cells. Moreover, when logarithmically growing cells were grafted subcutaneously in DBA2 mice, the tumorigenic property was related to the level of doxorubicin resistance.     

Oxidative stress and mitochondrial dynamics malfunction are linked in Pelizaeus‐Merzbacher disease

Pelizaeus‐Merzbacher disease (PMD) is a fatal hypomyelinating disorder characterized by early impairment of motor development, nystagmus, choreoathetotic movements, ataxia and progressive spasticity. PMD is caused by variations in the proteolipid protein gene PLP1, which encodes the two major myelin proteins of the central nervous system, PLP and its spliced isoform DM20, in oligodendrocytes. Large duplications including the entire PLP1 gene are the most frequent causative mutation leading to the classical form of PMD. The Plp1 overexpressing mouse model (PLP‐tg^66/66) develops a phenotype very similar to human PMD, with early and severe motor dysfunction and a dramatic decrease in lifespan. The sequence of cellular events that cause neurodegeneration and ultimately death is poorly understood. In this work, we analyzed patient‐derived fibroblasts and spinal cords of the PLP‐tg^66/66 mouse model, and identified redox imbalance, with altered antioxidant defense and oxidative damage to several enzymes involved in ATP production, such as glycolytic enzymes, creatine kinase and mitochondrial proteins from the Krebs cycle and oxidative phosphorylation. We also evidenced malfunction of the mitochondria compartment with increased ROS production and depolarization in PMD patient''s fibroblasts, which was prevented by the antioxidant N‐acetyl‐cysteine. Finally, we uncovered an impairment of mitochondrial dynamics in patient''s fibroblasts which may help explain the ultrastructural abnormalities of mitochondria morphology detected in spinal cords from PLP‐tg^66/66 mice. Altogether, these results underscore the link between redox and metabolic homeostasis in myelin diseases, provide insight into the pathophysiology of PMD, and may bear implications for tailored pharmacological intervention.     

MR imaging, proton MR spectroscopy, ultrasonographic, histologic findings in patients with chronic lymphedema

Lymphedema is a progressive disease with multiple alterations occurring in the dermis. We undertook this study using high-frequency ultrasonography (US), magnetic resonance imaging, proton MR spectroscopy and histology to examine structural changes occurring in the subcutaneous tissue and precisely describe the nature of intralobular changes in chronic lymphedema. Four cutaneous and subcutaneous tissue biopsies from patients with chronic lymphedema during lymphonodal transplantation were studied. We performed US with a 13.5 MHz transducer, TSE T1 and TSE T2 magnetic resonance images with and without fat-suppression, MR Chemical Shift Imaging Spectroscopy and histological evaluation on these biopsies. We found that normal subcutaneous septa are seen as hyperechogenic lines in US and hyposignal lines in MRI and that hyperechogenic subcutis in US can be due to interlobular and intralobular water accumulation and/or to interlobular and intralobular fibrosis. Our study also confirms the usefulness of MR spectroscopy to assess water or fat content of soft tissue. Thus, multiple imaging modalities may be necessary to precisely delineate the nature of tissue alterations in chronic lymphedema.