Is there an association between level of adult blood pressure and nephron number or renal filtration surface area?

BACKGROUND: Reductions in renal filtration surface area (FSA) have been linked to development of hypertension. This study investigated whether there are direct relationships, in the adult rat, between levels of blood pressure and nephron number or total renal FSA. METHODS: F1 and F2 offspring were generated from a spontaneously hypertensive rat (SHR)/Wistar Kyoto (WKY) rat cross. Tail-cuff systolic blood pressure was measured twice weekly from 5 to 15 weeks of age and mean arterial blood pressure determined prior to sacrifice. At 15 weeks of age, the rats were perfusion-fixed and glomerular (and thereby nephron) number, glomerular size, total length, and surface area of glomerular capillaries and total renal FSA were determined using unbiased stereologic techniques. RESULTS: In F1 offspring, blood pressure levels were midway between the SHR and WKY rats. Nephron number was significantly higher in the WKY rats compared to the SHR and F1 offspring. However, there was no difference in nephron number between the F1 rats and SHR and no difference in renal FSA between the three groups. In the F2 generation, where there is random segregation of the SHR and WKY genes, there was no significant correlation between either nephron number and adult blood pressure (r2= 0.16, P= 0.11) or total renal FSA and adult blood pressure (r2= 0.02, P= 0.58). There was a significant inverse correlation between nephron number and glomerular size (r2= 0.49, P= 0.0043). CONCLUSION: There is not a direct corollary between nephron number or renal FSA and level of blood pressure in this rat model.     

The development of bone metastases as the first sign of metastatic spread in patients with primary solid tumours

The purpose of this retrospective study was to investigate the incidence of bone metastases as the first sign of metastatic spread in patients with primary solid malignant tumours. Between January 1987 and December 1998, we treated 867 patients suffering from primary solid malignant tumours. Their average age was 67 (range: 30–96) years and all were thoroughly investigated with a complete physical examination and laboratory tests as well as imaging studies and bone scans. No bone metastases were found at the time of the initial diagnosis, and the patients were then re-assessed every 6 months for the first 5 years and then once a year. We found that, regardless of treatment, bone metastases appeared in a certain number of patients and that after excluding patients with prostate cancer a bone metastasis was the first sign of recurrence in 1.3% of the patients with a known primary solid malignant tumour.

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Résumé Le but de cette é tude r é trospective é tait de rapporter la fr é quence des m é tastases osseuses comme premier signe m é tastatique, chez des patients ayant une tumeur solide primitive connue. De janvier 1987 à décembre 1998 nous avons traité 867 malades souffrant de tumeurs solides primitives. Leur âge moyen était de 67 (30–96) ans. Tous les malades ont eu un examen complet y compris les études dimagerie et la scintigraphie osseuse. Aucune métastase osseuse na été trouvé au diagnostic initial. Les malades ont été évalués tous les 6 mois pendant les 5 premières années et ensuite une fois par an. Sans tenir compte du traitement, nous avons constaté que les métastases osseuses apparaissaient chez un certain nombre de malades. En excluant les malades avec un cancer prostatique, les métastases osseuses étaient le premier signe de récidive chez 1,3% des malades avec une tumeur solide primitive connue.

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First presented at the SICOT Congress in San Diego, CA, USA, 2002.     

Non-union of femoral neck fractures with osteonecrosis of the femoral head: treatment with combined free vascularized fibular grafting and subtrochanteric valgus osteotomy

Femoral neck fractures, frequently complicated by non-union and femoral head osteonecrosis,present a difficult clinical situation, especially when young patients are concerned.Existing treatment options are valgus osteotomy to address the biomechanical factors or bone grafting to address the biologic factor. The authors describe the operative technique and results of combined subtrochanteric valgus osteotomy and free vascularized fibular grafting in management of five young patients with both non-union and avascular necrosis.     

Diagnosis and management of the osteonecrotic triad of the knee

Generalized osteonecrosis of the knee may include, in addition to osteonecrosis of the medial femoral condyle that occurs most frequently, osteonecrosis of the patella or the tibial plateau. Such involvement is known as the osteonecrotic triad of the knee. Although the clinical picture of idiopathic osteonecrosis of the medial femoral condyle seems similar to several other disorders, certain distinct features, including its typical location,clinical symptoms, and late onset of cartilaginous erosion, facilitate differential diagnosis.Despite the progress made in the diagnosis and treatment of idiopathic osteonecrosis of the medial femoral condyle, the prognosis remains severe. More than 80% of the patients deteriorate to the extent that surgical reconstruction is necessary, whereas only about 20%of the patients demonstrate spontaneous resolution or no additional deterioration of the osteonecrotic lesion.     

Effect of frequency boundary assignment on vowel recognition with the Nucleus 24 ACE speech coding strategy

Two speech processor programs (MAPs) differing only in electrode frequency boundary assignments were created for each of eight Nucleus 24 Cochlear Implant recipients. The default MAPs used typical frequency boundaries, and the experimental MAPs reassigned one additional electrode to vowel formant regions. Four objective speech tests and a questionnaire were used to evaluate speech recognition with the two MAPs. Results for the closed-set vowel test and the formant discrimination test showed small but significant improvement in scores with the experimental MAP. Differences for the Consonant-Vowel Nucleus-Consonant word test and closed-set consonant test were nonsignificant. Feature analysis revealed no significant differences in information transmission. Seven of the eight subjects preferred the experimental MAP, reporting louder, crisper, and clearer sound. The results suggest that Nucleus 24 recipients should be given an opportunity to compare a MAP that assigns more electrodes in vowel formant regions with the default MAP to determine which provides the most benefit in everyday life.     

Low molecular weight heparins: the optimal treatment for venous thromboembolism

Venous thromboembolism (VTE) is a common vascular complication that requires immediate as well as long-term treatment. Unfractionated heparin (UFH), followed by oral anticoagulants (OAs), is of proved efficacy in the treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE). However, low molecular weight heparins (LMWHs) have successfully replaced UFH both in the prevention and in the initial treatment of DVT and PE. Recent trials evaluated the efficacy and safety of LMWH therapy as an alternative to vitamin K antagonists in long-term VTE secondary prophylaxis for all patients and in specific subgroups. LMWHs differ considerably from each other. These agents were studied separately, administered according to various protocols, in various doses and for different duration of treatment. Results from prospective randomized trials, conducted during the last decade, indicate that LMWHs are at least as effective and yet safer than OAs in the long-term treatment of VTE. In this brief overview, we consider the potential advantages of treatment with LMWH in patients with VTE.     

Fractional allele loss is a valuable marker for human lung cancer detection in sputum

Using PCR-based microsatellite DNA analysis with 48 markers we examined sputum and bronchial washing for genetic alterations compared with lymphocyte extracted DNA from 124 lung cancer patients and 36 healthy donors as normal control. Microsatellite alterations (MA) in at least one locus were detected in all cancer patient-derived specimens but only in 22.2% of the healthy donors. Loss of heterozygosity (LOH) was detected in bronchial washings from 101 non-small cell lung cancer (NSCLC) predominantly on 17p13.1-p13.3 (69.7%), 9p13.3-p24.1 (63.3%), 1p34.2-p36.22 (48.5%), 13q12.1-q13.1 (47.7%) and 3p22.3-p23 (42.7%). In bronchial washings from 23 small cell lung cancer (SCLC) LOH was detected mostly on 3p22.3-p23 (88.6%), 17p13.1-p13.2 (82.3%), 5q32-q33.1 (66.6%), 13q12.2-q13.1 (65.6%) and 9q22.33-q31.3 (52.9%). The different LOH patterns indicate that different genetic background may be responsible for the different physiology of NSCLC and SCLC. The fractional allele loss (FAL) mean value of all cancer specimens was 0.243+/-0.021 compared with 0.007+/-0.008 of healthy donors with a confidence interval (CI) 99.5%. Only seven out of 124 lung cancer specimens (5.2%) exhibited FAL value less than 0.083, the highest was observed in the healthy donors group. FAL appears to be a likely indicator for lung cancer detection. Microsatellite instability (MIN) was detected in 8.7% of SCLC and 4.0% of NSCLC bronchial washings in at least three loci tested. LOH and MIN detection in sputum and bronchial washing from the same patient was 77.6%. Calculation of these indexes per marker exhibits significant variations that could be attributed to diffuse lung disorders or non-cancer specific genetic alterations.     

Neuroprotective,anti-apoptotic effects of apomorphine

There is increasing experimental and clinical evidence that oxidation plays a pivotal role in causing neurodegeneration in general and Parkinson's disease in particular. The protective role of antioxidants in such conditions has not been fully examined, but certain neuroprotective agents that have antioxidant action are now being credited with an ability to prevent oxidation-induced neuronal dysfunction. One such agent is the dopamine agonist apomorphine, which is already in clinical use, providing symptomatic relief in Parkinson's disease patients. Far from having simple antioxidants properties, apomorphine is described as a pluripotent agent that can also afford neuroprotection through mechanisms independent of its antioxidant actions. It can, for example, salvage dopaminergic receptors and terminals, upregulate expression of neurotrophic factors, limit the rate of neuronal loss by interfering with several steps of apoptotic cascades, reduce excitotoxicity by modulating nitric oxide metabolism, and reverse ubiquitine-proteasome dependent pathology. This paper reviews the wide range of apomorphine's neuroprotective benefits, suggesting that it is a promising agent with regards to its potential to prevent, reduce, and retard age-related neurodegeneration.     

Intravenous administration of vitamin B12 in the treatment of hyperhomocysteinemia associated with end-stage renal disease

BACKGROUND: High serum levels of total homocysteine (tHcy) are common in dialysis patients with end-stage renal disease (ESRD). We assumed that these patients may have decreased response to conventional folic acid (FOL) and vitamin B12 (B12) administered orally. This study aimed to evaluate the efficacy of an intravenous (i.v.) B12 regimen in ESRD patients and compare it with the conventional regimen. METHODS: We designed an open label, crossover, non-randomized study of 72 ESRD patients. Our patients were hemodialyzed in two hospitals (HOSP1 and HOSP2). In HOSP1, patients were on 1 mg of FOL and 600 micog of B12 orally for 3 months, and then switching to 1 mg of B12 i.v. for 3 additional months, while the FOL dosage was constant. In HOSP2, patients received the same treatment in reverse. RESULTS: Patients in HOSP1 (n = 37) after i.v. B12 treatment, had significantly lower tHcy (p < 0.001) and FOL (p < 0.05) serum levels, compared with those at the end of oral B12 treatment. On the contrary in HOSP2 patients, serum tHcy levels increased significantly (n = 35, p < 0.0001) when i.v. was switched to oral treatment. There was a significant inverse correlation between tHcy and B12 (p < 0.0001) at the end of the i.v. treatment period; while treatment there was no correlation between tHcy and FOL serum levels. At the end of the oral treatment period, there was no significant correlation between tHcy and B12 serum levels, while tHcy and FOL serum levels had a significant inverse correlation (p = 0.002). CONCLUSIONS: Our results suggest that ESRD patients on dialysis have 'B12 resistance', and that they should have, in addition to their FOL therapeutic regimen, i.v. B12 treatment to reduce their elevated tHcy levels.