Lipophilic antioxidants in patients with phenylketonuria

BACKGROUND: Low serum ubiquinone-10 concentrations have been described in phenylketonuric patients fed natural-protein-restricted diets. Such low concentrations may be related to increased free radical damage. OBJECTIVE: We evaluated the relation between low serum ubiquinone-10 concentrations and other lipophilic antioxidants (tocopherol and retinol), selenium, glutathione peroxidase activity, and malondialdehyde concentrations as a marker of lipid peroxidation. DESIGN: This was a cross-sectional study of 58 patients with phenylketonuria (aged 2-36 y; median: 13 y) under dietary treatment, 58 age-matched control subjects, and 30 children with moderate hyperphenylalaninemia fed unrestricted diets (aged 3-17 y; median: 7.5 y). Serum ubiquinone-10 concentrations were analyzed by HPLC with electrochemical detection. Serum retinol, serum tocopherol, and plasma malondialdehyde were analyzed by HPLC with ultraviolet detection. RESULTS: A significant positive correlation was observed between ubiquinone-10 and tocopherol (r = 0.510, P < 0.001) in the patients with phenylketonuria. After the patients were stratified into 2 groups according to ubiquinone-10 values, significantly lower concentrations of tocopherol were observed in group 1 (low ubiquinone values) than in group 2 (normal ubiquinone values), the hyperphenylalaninemic children, and the control group. Plasma malondialdehyde concentrations were significantly higher in group 1 than in the other groups. No significant differences between groups 1 and 2 were observed in daily intakes of selenium, ascorbate, tocopherol, or retinol. CONCLUSIONS: Plasma lipid peroxidation seems to be increased in phenylketonuria. Low concentrations of ubiquinone-10 could be associated with either excessive tocopherol consumption or high malondialdehyde concentrations in patients with phenylketonuria.     

Factors influencing the choice to use modern natural family planning

A discrepancy exists between the interest in modern methods of natural family planning (NFP) and their actual use in developed countries. To explore reasons for this discrepancy, we analyzed data from a questionnaire administered to postpartum women in Berlin (n = 223) and Cracow (n = 233). Knowledge of NFP, past use of NFP and expected effects of abstinence on the partnership were independently associated with interest in using NFP, but not the choice to do so among those interested. Desire for future pregnancies, importance of religious belief and location in Cracow were independently associated with the choice to use NFP among those interested. Perceived accuracy of observation to identify the fertile time and acceptance of own body were independently associated with both interest in and choice to use NFP. Frequency of intercourse had no effect on interest. These results suggest that increased access and cultural support would likely lead to a higher prevalence of NFP use in developed countries.     

Off-label and unlicensed use of antidotes in paediatric patients

OBJECTIVE: To determine the extent of unlicensed and off-label antidotes among medicines recommended by the International Programme on Chemical Safety (IPCS) for children. MATERIALS AND METHODS: We considered 77 antidotes from the "IPCS List of antidotes and other useful agents in the treatment of human poisoning" (1996 version). Primary reference sources used were the Physicians' Desk Reference (PDR) and package inserts. Antidotes were assessed for off-label (outside of the term of product license) and unlicensed use in children. RESULTS: Our data show that only 31 (40.3%) of 77 recommended antidotes correspond to the demands of licensing systems for use in children. The rest (46 or 59.7%) are either off-label (32 or 41.5%) or unlicensed (14 or 18.2%). Five antidotes are off-label for two reasons; thus the total number of off-label use (37) is greater than the number of such drugs (32). Inappropriate age is the main reason for use outside the stipulations of the product license (24 of 77 antidotes or 31.2%), whereas different indication and route occur in 11 (14.3%) and 2 (2.6%) antidotes, respectively. The 14 unlicensed antidotes have been used only in animal experiments or in a small number of patients in certain poison centres. CONCLUSIONS: Sixty percent of antidotes and other useful agents in the poison treatment of children do not correspond to the demands of licensing systems. Drugs used in the treatment of poisoned children, as well as adults, must be evaluated scientifically.     

Assessment of Equine Autoimmune Thrombocytopenia (EAT) by flow cytometry

Rationale  

Thrombocytopenia is a platelet associated process that occurs in human and animals as result of i) decreased production; ii) increased utilization; iii) increased destruction coupled to the presence of antibodies, within a process know as immune-mediated thrombocytopenia (IMT); or iv) platelet sequestration. Thus, the differentiation of the origin of IMT and the development of reliable diagnostic approaches and methodologies are important in the clarification of IMT pathogenesis. Therefore, there is a growing need in the field for easy to perform assays for assessing platelet morphological characteristics paired with detection of platelet-bound IgG.     

Facial paralysis associated with glomus jugulare tumors.

OBJECTIVE: To review the intraoperative findings and facial nerve management in nine patients who presented with facial paralysis associated with glomus jugulare tumors. STUDY DESIGN: A retrospective analysis of patient medical records. SETTING: Tertiary care academic medical center. PATIENTS: All patients who presented with facial paralysis and a glomus jugulare tumor who underwent surgical resection of their tumors at our institution. INTERVENTION: A postauricular infratemporal fossa approach for tumor removal and greater auricular interposition neural repair. MAIN OUTCOME MEASURE: Intraoperative facial nerve findings and long-term facial recovery. RESULTS: One hundred two patients underwent a postauricular infratemporal approach for resection of glomus jugulare tumor from July 1988 through July 2005. Nine of these patients presented with ipsilateral facial paralysis. The medial surface of the vertical segment was invaded by tumor in all nine cases. Facial recovery at 2 years was House-Brackmann Grade III in eight patients and Grade IV in one individual. Facial recovery did not significantly change after 2 years (mean follow-up of 7.4 years). DISCUSSION: Facial nerve invasion of the vertical segment occurred in 9 (9%) of 101 patients in our series. Facial nerve resection with interposition grafting resulted in House-Brackmann Grade III in eight (89%) of nine patients. Facial nerve dissection and preservation was not possible when preoperative facial paralysis was evident.     

Management of Tracheobronchial Amyloidosis With Therapeutic Bronchoscopic Techniques

Amyloidosis is a systemic disease caused by abnormal deposition of amyloid material that is detected with Congo red staining and is difficult to diagnose. Involvement of the tracheobronchial tree is rare and is a challenge for pulmonologists because of the wide differential diagnosis of this disease. We present two cases where tracheobronchial affectation has been observed: in one of them as a primary disease, and in another as secondary affectation. The use of bronchoscopic techniques is essential for the diagnosis of tracheobronchial involvement. In the absence of an effective drug therapy, local management of this disease with endoscopic techniques for bronchial repermeabilization is able to provide clinical improvement and expand the treatment options and prognosis in this disease.     

Chemical and functional changes of human insulin by in vitro incubation with blood from diabetic patients in oxidative stress

Oxidative stress damage to biomolecules has been implicated in several diseases including diabetes mellitus. In the present study, we investigated the effect of oxidative stress in whole blood (WB) from diabetic patients (n = 60) on recombinant human insulin. Insulin was incubated with WB obtained from diabetic patients (DP) who had hyperglycemia (>300 mg/dL) or from 41 healthy volunteers (HV). Whole blood of DP, unlike WB of HV, induced higher values of formazan (142%), dityrosines (279%), and carbonyls (58%) in the insulin residues. Interestingly, the insulin modified by WB of DP showed less hypoglycemic activity in rat (30%) in comparison with insulin incubated with WB of HV. The incubation of insulin in WB from DP induces chemical changes in insulin and a decrease in its biological activity, events that might be associated with the high levels of oxidative stress markers found in the plasma of these patients.     

Algorithms for enhancing public health utility of national causes-of-death data

Background  

Coverage and quality of cause-of-death (CoD) data varies across countries and time. Valid, reliable, and comparable assessments of trends in causes of death from even the best systems are limited by three problems: a) changes in the International Statistical Classification of Diseases and Related Health Problems (ICD) over time; b) the use of tabulation lists where substantial detail on causes of death is lost; and c) many deaths assigned to causes that cannot or should not be considered underlying causes of death, often called garbage codes (GCs). The Global Burden of Disease Study and the World Health Organization have developed various methods to enhance comparability of CoD data. In this study, we attempt to build on these approaches to enhance the utility of national cause-of-death data for public health analysis.