Blood lead levels, clinico-pathological findings and erythrocyte metabolism in dogs from different habitats

Biological markers of lead exposure were measured in 20 dogs from five different habitats chosen on the basis of the degree of anthropogenic influence. None of the dogs had clinical signs of lead poisoning. Compared to controls, blood lead concentrations were significantly higher in dogs from industrial areas, confirming the role of lead emissions in environmental pollution and the possible role of dogs as biomonitors of lead exposure in these areas. Whole blood lead concentrations were similar in dogs living in urban and rural areas, probably due to "indirect" lead sources and due to decreased urban lead contamination. As in humans, individual variability was detected. No significant correlation between clinico-pathological changes (hematology, clinical chemistry, Delta-aminolevulinic acid dehydratase activity and other intra-erythrocytic metabolic parameters) and lead concentration were observed. Our findings suggest dogs can be useful as sentinels of environmental lead exposure.     

Effect of filgrastim on serum lactate dehydrogenase and alkaline phosphatase values in early breast cancer patients

To improve chemotherapy dose intensity and to optimize the use of granulocyte-colony stimulating factor, 506 patients with early breast cancer were randomly assigned to high dose epirubicin and cyclophospamide (EC) with or without prophylactic subcutaneously filgrastim, according to 5 different schedules: 480 µg or 300 µg daily or every other day, on day 8 through day 14, and 300 µg daily on days 8 and 12 of each chemotherapy course, Serum levels of lactate dehydrogenase (LDH) and alkaline phosphatase (AP) were significantly higher in patients given EC plus filgrastim than EC alone (P + 0.0001), the rate of G1-3 toxicity being 33.4% and 13.1% vs. 1.6% and 1%, respectively. No clinical evidence of filgrastim-related hepatic damage or significant difference in transaminase and γ-GT elevation was seen between the two groups. LDH and AP closely resembled peripheral blood leukocytes count and increased with increasing leucocytosis, throughout the 5 schedules. Although no patient continued treatment for filgrastim-related side effects, and LDH and AP rises resolved spontaneously within 3 weeks following the chemotherapy course, physicians should be aware of the transient and innocuous change in serum chemistry associated to leucocytosis, since it could be misinterpreted as expression of disease activity.     

Effect of homocysteinylation on human high-density lipoproteins: a correlation with paraoxonase activity

We investigated the effect of homocysteine (Hcy)-thiolactone on the activity of the enzyme paraoxonase (PON) associated with human high-density lipoprotein (HDL-PON). HDL were isolated from plasma of normolipidemic subjects. The increase in the levels of sulfhydryl groups (-SH) in HDL incubated with Hcy-thiolactone demonstrates that homocysteinylation of HDL occurs. The increase of -SH groups correlated with the basal values of HDL-PON activity (r = -0.73, P <.001, and r = -0.70, P <.002 using 10 micromol/L and 1 mmol/L Hcy-thiolactone, respectively) suggesting a relationship between the susceptibility of HDL to homocysteinylation and HDL-PON activity. A decrease in the activity of the enzyme HDL-PON was observed in homocysteinylated HDL (Hcy-HDL). The negative correlation established between the basal levels of HDL-PON activity and the percentage decrease of HDL-PON activity (r = -0.76, P <.001, and r = -0.86, P <.001 using 10 micromol/L or 1 mmol/L Hcy-thiolactone, respectively) suggests that subjects with higher HDL-PON activity have a lower decrease in PON activity with respect to subjects with lower HDL-PON activity. The positive correlation established between the percentage decrease of PON activity and the percentage increase of -SH groups in Hcy-HDL (r = 0.80, P <.001, and r = 0.76, P <.001 in HDL incubated in the presence of 10 micromol/L and 1 mmol/L Hcy-thiolactone, respectively) suggests that the modifications of HDL-PON activity are likely related to the compositional changes at the lipoprotein surface of Hcy-HDL. The enzyme PON contributes to the protective role of HDL against the oxidative damage and against toxicity exerted by Hcy involved in the development of atherosclerosis. Therefore the significant decrease of the enzyme activity in HDL incubated with Hcy-thiolactone suggests that homocysteinylation could render HDL less protective against oxidative damage and against toxicity of Hcy-thiolactone.     

Limiting factors to oxygen transport on Mount Everest 30 years after: a critique of Paolo Cerretelli’s contribution to the study of altitude physiology

In 1976, Paolo Cerretelli published an article entitled Limiting factors to oxygen transport on Mount Everest in the Journal of Applied Physiology . The paper demonstrated the role of cardiovascular oxygen transport in limiting maximal oxygen consumption (O_2max). In agreement with the predominant view of O_2max limitation at that time, however, its results were taken to mean that cardiovascular oxygen transport does not limit O_2max at altitude. So it was argued that the limiting factor could be in the periphery, and muscle blood flow was proposed as a possible candidate. Despite this suggestion, the conclusion generated a series of papers on muscle structural characteristics. These experiments demonstrated a loss of muscle oxidative capacity in chronic hypoxia, and thus provided an unambiguous refutation of the then widespread hypothesis that an increased muscle oxidative capacity is needed at altitude to compensate for the lack of oxygen. This analysis is followed by a short account of Cerretellis more recent work, with a special attention to the subject of the so-called lactate paradox.     

Impact of successful transsphenoidal surgery on cardiovascular risk factors in acromegaly

BACKGROUND: Cardiac abnormalities develop in patients with acromegaly as a consequence of effects of GH/IGF-I on the heart and related cardiovascular risk factors. OBJECTIVE: To evaluate the possible contribution of postoperative variations in blood pressure (BP), glucose tolerance and insulin sensitivity to the cardiac improvement reported in patients who have been cured of acromegaly. DESIGN: Thirty-one patients with acromegaly were studied before and 6 Months after successful transsphenoidal surgery, defined by normal age-related IGF-I concentrations and glucose-suppressed GH concentrations <1 microg/l. METHODS: Cardiovascular parameters were assessed by Doppler echocardiography and 24-h ambulatory blood pressure monitoring. Insulin sensitivity indexes were calculated on the basis of fasting and post-load glycaemia and insulinaemia and referred to as HOMA(ISI) and OGTT(ISI), respectively. RESULTS: Successful surgery was confirmed to improve left ventricular mass index (LVMI) and diastolic filling significantly. Mean 24-h systolic BP values decreased (P=0.009) and BP rhythm was restored in 12 of 15 patients with a blunted preoperative profile. Glucose tolerance normalized in patients with preoperative glucose intolerance (n=7) or diabetes mellitus (n=3). HOMA(ISI) and OGTT(ISI) increased (P=0.0001 for each parameter), indicating a marked improvement in insulin sensitivity. The postoperative reduction in LVMI correlated with increased insulin sensitivity (P<0.001 for both indexes), but not with other parameters. Improved diastolic filling correlated with the reduction in LVMI. CONCLUSIONS: Successful surgery in patients with acromegaly induces a significant improvement in haemodynamic and metabolic risk factors. This study suggests a direct link between insulin resistance and acromegalic cardiomyopathy.     

Operative treatment of chronic Achilles tendinopathy

Seventy-six patients with Achilles tendinopathies (n=86) operated between 1980 and 1995 were retrospectively evaluated at an average follow-up of 13 (5–21) years. Total or gross partial ruptures were excluded. Patients' average age at surgery was 38 (18–58) years. The majority of patients were active in competitive or recreational sports. Tendinopathies were classified in peritendinitis, tendinosis, insertional tendinopathies, and mixed forms. The surgical technique depended entirely on the pathology encountered. For 32 cases of peritendinitis, results were excellent in 26, good in four, and poor in two. For eight cases of tendinosis, results were excellent in four and good in four. For 34 cases of insertional tendinopathy, results were excellent in 22, good in four, fair in four, and poor in four. For 12 cases of mixed tendinopathies, results were excellent in ten and good in two. Forty-nine patients (52 cases) were able to return to sport at the desired level.

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Résumé Soixante-seize malades avec une tendinopathie d'Achille (n=86) ont été opérés entre 1980 et 1995 et évalués rétrospectivement à un délai moyen de 13 (5–21) années. Les ruptures totales ou partielles importantes ont été exclues. L'âge moyen des malades à la chirurgie était 38 (18–58) années. La majorité des malades était des sportifs soit de loisir soit de compétition. Les tendinopathies ont été classés en: péritendinites, tendinites, tendinopathies d'insertion de et formes mixtes. La technique chirurgicale dépendait de la pathologie. Sur 32 péritendinites, les résultats étaient excellents pour 26, bon pour quatre et mauvais pour deux . Sur huit tendinites, il y avait quatre excellents et 4 bons résultats. Sur 34 tendinopathies d'insertion, les résultats étaient excellents pour 22, bon pour quatre, juste pour quatre, et mauvais quatre. Sur 12 tendinopathies mixtes, les résultats étaient excellents pour dix et bon pour deux. Cinquante-deux malades étaient capables de revenir au sport au niveau désiré.

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Risk factors for poor renal prognosis in children with hemolytic uremic syndrome

Many factors have been proposed as predictors of poor renal prognosis in children with hemolytic uremic syndrome (HUS), but their role is still controversial. Our aim was to detect the most reliable early predictors of poor renal prognosis to promptly identify children at major risk of bad outcome who could eventually benefit from early specific treatments, such as plasmapheresis. Prognostic factors identifiable at onset of HUS were evaluated by survival analysis and a proportional hazard model. These included age at onset, prodromal diarrhea (D), leukocyte count, central nervous system (CNS) involvement, and evidence of Shiga toxin-producing Escherichia coli (STEC) infection. Three hundred and eighty-seven HUS cases were reported; 276 were investigated for STEC infection and 189 (68%) proved positive. Age at onset, leukocyte count, and CNS involvement were not associated with the time to recovery. Absence of prodromal D and lack of evidence of STEC infection were independently associated with a poor renal prognosis; only 34% of patients D^–STEC^– recovered normal renal function compared with 65%–76% of D⁺STEC⁺, D⁺STEC^– and D^–STEC⁺ patients. In conclusion, absence of both D and evidence of STEC infection are needed to identify patients with HUS and worst prognosis, while D^– but STEC⁺ patients have a significantly better prognosis.     

Quantitative determination of sufentanil in human plasma by liquid chromatography-tandem mass spectrometry

A sensitive and specific method for the quantification of sufentanil in human plasma by liquid chromatography coupled with tandem mass spectrometry has been developed. Fentanyl was used as the internal standard. Rapid sample preparation involved purification on a C(18) solid-phase extraction column. Chromatographic separation of the analytes was obtained using an RP-C(18) mu-HPLC column. LC-MS-MS detection was performed by atmospheric pressure ionisation (API) source equipped with an ionspray (IS) interface operating in the positive ion mode. For unambiguous substance confirmation, three analyte precursor-product ion combinations were monitored during multiple reaction monitoring (MRM) LC-MS-MS analysis. The method's performance characteristics were evaluated in blank and spiked control plasma samples. Overall accuracy (relative error, R.E., %), repeatability (relative standard deviations, R.S.D., %) and within-laboratory reproducibility (R.S.D., %) ranged from -9.28 to -2.71%, from 6.42 to 2.82% and from 13.52 to 6.06%, respectively, for sufentanil. The limit of quantification for sufentanil in human plasma samples was 0.3 ng ml(-1). Due to its high sensitivity and specificity, the method was successfully employed for sufentanil determination in maternal plasma samples collected immediately before epidural administration of a single sufentanil dose to women in labour, 20 min after drug administration, and at birth in arterial and venous umbilical cord plasma samples from the newborn babies. Research is in progress to adopt the method for performance of complete pharmacokinetic studies of sufentanil in human plasma.     

Interpretation of chest radiographs in the intensive care unit: a hard- versus soft-copy comparative study

PURPOSE: To compare the reliability of hard- versus soft-copy interpretation of intensive care unit chest radiographs, using a non-specialized standard resolution computer screen. MATERIALS AND METHODS: 104 chest radiographs were included in this study. Three physicians (one radiology resident, one intensive care unit resident and one experienced intensive care unit physician) gave their interpretations on computerized grids. Results were analyzed statistically using ROC curves and Kappa (kappa) index of concordance with experts. RESULTS: Results for reanimation equipment detection are almost independent from the modality (kappa(soft-copy)=0.891+/-0.037, kappa(hard-copy)=0.899+/-0.037). Regarding pathology detection, a global analysis only shows a difference at the limits of significance to the advantage of hard-copy films (kappa(soft)=0.514 +/-0.028, kappa(hard)=0.572+/-0.028). Overall results were significantly better for the radiologist compared to the intensive care unit physicians (kappa(radiologist)=0.751+/-0.048, kappa(intensive-care)=0.405+/-0.048). CONCLUSION: Concerning the task that is studied here, which requires only routine computer equipment, our results suggest that human factors can be more important than material factors.     

Breast cancer metastatic to the choroid in a male patient: case report

Choroidal metastases have been observed in about 8% of patients with metastatic breast cancer, even if their true incidence is likely to be higher, as they are not routinely investigated in the absence of symptoms. Radiotherapy is the treatment of choice for symptom palliation. The prognosis is traditionally poor, with a reported average survival of one year. Here we describe the third case reported in the literature of a metastatic tumor to the choroid from a male breast carcinoma.