Expression of pigment epithelium-derived factor in experimental choroidal neovascularization

PURPOSE: To investigate the expression of pigment epithelium-derived factor (PEDF) in the rat laser-injury model of choroidal neovascularization (CNV). METHODS: Retinas were immunostained for PEDF at different times (1, 2, and 3 weeks) after laser injury. Levels of PEDF protein in the vitreous at 1, 3, 7, 14, and 28 days after laser injury were also assayed by Western blot. RESULTS: Protein levels of PEDF in the vitreous were increased during the first 7 days after CNV induction. Immunostaining for PEDF was observed throughout normal nonlasered control retinas, sham-lasered retinas, and areas remote to laser lesions, which were generally more intense in the outer nuclear layer (ONL) and less intense in the internal nuclear layer (INL). Decreased expression of PEDF was observed in flanking areas adjacent to the injury site and was confined mainly to the ONL. In the injury sites, immunostaining within the ONL was either absent or decreased for up to 3 weeks after laser injury (the duration of the study). Preadsorption of the anti-PEDF antibody with the immunizing peptide blocked specific labeling in the retina. CONCLUSIONS: These results demonstrate an inverse correlation of expression of PEDF and formation of CNV in the experimental model and suggest that decreased expression of PEDF plays a permissive role in the formation of CNV. PEDF analogues may be a reasonable treatment strategy for CNV.     

Pharmacokinetics of teicoplanin in patients undergoing chronic haemodialysis

In order to define a dose regimen of teicoplanin for patients undergoing chronic haemodialysis so that they achieved trough drug serum levels above 10 mg/l, two single doses of 5 and 10 mg/kg were administered intravenously in seven anuric patients immediately after the end of haemodialysis. Concentrations of teicoplanin were determined by a microbiological assay in samples collected from peripheral veins via the arterial and the venous lines of the fistulae and from the dialysate during haemodialysis. The administration of a 5 and 10 mg/kg dose gave mean C(max) of 62.80 and 122.43 mg/l, mean AUC of 526.43 and 1103.98 mg h/l, mean half life (t(1/2)) of 109.09 and 107.06 h, mean clearance rates of 12.85 and 12.44 ml/min, mean apparent volumes of distribution of 1.68 and 1.68 l/kg and mean volumes of distribution at steady state of 0.31 and 0.28 l/kg, respectively. Trough serum levels above 10 mg/l were found for 24 h after the administration of the 5 mg/kg dose and for 48 h after the administration of the 10 mg/kg dose. Teicoplanin was not detected in the dialysate. Its concentrations in both the arterial and the venous lines of the fistulae were similar. Based on the time period after the administration of teicoplanin where the desired trough serum levels were found and on the observed t(1/2), it is proposed that teicoplanin should be administered at a dose of 10 mg/kg at 48-72 h intervals, in patients undergoing chronic haemodialysis for the therapy of infections caused by Gram-positive cocci.     

Serum levels of macrophage inflammatory protein-1 alpha (MIP-1alpha) correlate with the extent of bone disease and survival in patients with multiple myeloma

The role of serum macrophage inflammatory protein-1 alpha (MIP-1alpha) in bone disease and survival was evaluated in 85 newly diagnosed multiple myeloma (MM) patients. MIP-1alpha was elevated in MM patients and correlated with the extent of bone disease, bone resorption markers and levels of soluble receptor activator of nuclear factor-kappaB (RANK) ligand. MIP-1alpha was also associated with survival; the 3-year probability of survival was 85% and 44% for MIP-1alpha levels below and above 48 pg/ml respectively (P = 0.021). This suggests that MIP-1alpha contributes to the pathogenesis of bone disease in MM and possibly in tumour growth, as reflected by its impact on survival.     

Soluble receptor activator of nuclear factor kappaB ligand-osteoprotegerin ratio predicts survival in multiple myeloma: proposal for a novel prognostic index

Interaction between receptor activator of nuclear factor kappaB ligand (RANKL) and RANK/osteoprotegerin (OPG) plays a dominant role in osteoclast activation and possibly in plasma cell survival in multiple myeloma (MM). We measured soluble RANKL (sRANKL), OPG, and bone remodeling markers in 121 patients with newly diagnosed MM to evaluate their role in bone disease and survival. Serum levels of sRANKL were elevated in patients with MM and correlated with bone disease. The sRANKL/OPG ratio was also increased and correlated with markers of bone resorption, osteolytic lesions, and markers of disease activity. The sRANKL/OPG ratio, C-reactive protein (CRP), and beta2-microglobulin were the only independent prognostic factors predicting survival in multivariate analysis. We generated a prognostic index based on these factors that divided our patients into 3 risk groups. The low-risk group had a 96% probability of survival at 5 years, whereas the intermediate-risk and the high-risk groups had probabilities of survival of 52% and 0%, respectively. Not only do these results confirm for the first time in humans the importance of sRANKL/OPG in the development of bone disease, they also highlight the role of this pathway in the biology of plasma cell growth as reflected by its influence on survival.     

Multiple metabolic abnormalities in a patient with the syndrome of inappropriate antidiuresis

The syndrome of inappropriate ADH secretion (SIADH) is a common cause of hyponatremia. However, other metabolic abnormalities have infrequently been described in patients with the syndrome of inappropriate antidiuresis. Here, we describe a female patient with hyponatremia due to SIADH who presented with a cluster of metabolic abnormalities and specifically hypouricemia associated with uricosuria, hypokalemia caused by renal potassium wasting, hypomagnesemia with inappropriate magnesiuria, hypophosphatemia with renal phosphate wasting and inappropriate calciuria. These abnormalities could be partly due to the extracellular volume expansion and were corrected with the water restriction-induced increase in serum sodium levels.     

Modified anatrophic nephrolithotomy for complete staghorn calculus disease -- does it still have a place?

OBJECTIVE: To report our experience with open surgery for the management of complete staghorn calculi using a modified anatrophic nephrolithotomy technique. MATERIAL AND METHODS: Between 1990 and 2001, 24 patients underwent anatrophic nephrolithotomy in our department. Bilateral complex stone disease was present in 9 patients, so that a total of 33 procedures were carried out. Preoperative evaluation included excretory urography (intravenous pyelography) and routine laboratory study in all patients and in 9 patients renal function was assessed using (99m)Tc dimercaptosuccinic acid renal scans before and 6 months after surgery. Postoperative follow-up consisted of kidney-ureter-bladder (KUB), ultrasound (U/S), urinalysis and urine culture. RESULTS: The mean operative time was 180 min, mean blood loss was 500 ml and renal ischemia time ranged between 10 and 35 min. Deep vein thrombosis occurred on the 5th postoperative day in an obese female patient. No other operative or postoperative complications were observed. Mean hospital stay was 8.2 days (range 7-12 days). The stone-free rate was 83.3%. Long-term follow up demonstrated stone fragments <4 mm in diameter in 4 patients (16.6%). Renal function remained unchanged or slightly improved in 15 patients; a slight worsening of renal function was noted in 9 patients (from an average of 39% before to 35% after the procedure). CONCLUSIONS: Anatrophic nephrolithotomy, although a major operative procedure, remains the most appropriate method for the one-stage management of a selected group of patients harboring large staghorn calculi with infundibular stenosis, and is associated with the highest stone-free rates.     

Thalidomide in the treatment of myelodysplastic syndrome with fibrosis

A 67-year-old woman was admitted for investigation of pancytopenia. Bone marrow biopsy was compatible with myelodysplastic syndrome (MDS) with fibrosis. For the next 20 months the patient received transfusions of packed red cells, while a 3-month-trial of erythropoetin was unsuccesful. She was then treated with thalidomide 400mg per day. During the next months, a gradual rise in Hb value was noticed and the patient eventually became transfusion independent. Repeat bone marrow biopsy revealed a significant decrease on the degree of fibrosis. Thalidomide has shown excellent results in the treatment of multiple myeloma probably due to its anti-angiogenic activity. It is possible that in our patient thalidomide acted as an anti-fibrotic agent. It will be very interesting to test this novel activity of thalidomide in a large number of patients.     

Hypomagnesemia and concurrent acid-base and electrolyte abnormalities in patients with congestive heart failure

BACKGROUND: Patients with severe decompensated congestive heart failure (CHF) commonly exhibit acid-base and electrolyte disturbances mainly due to the activation of several neurohumoral mechanisms as well as to drugs regularly used in this population. Magnesium deficit is not infrequently observed in CHF patients but its pathophysiology remains less well-studied as compared with other electrolyte alterations, such as hypokalemia. However, there is evidence that early detection and correction of magnesium abnormalities could obviate potentially deleterious arrhythmogenic effects. AIM: To assess the incidence of magnesium level disorders and analyze the underlying pathophysiological mechanisms in patients with CHF. METHODS: Eighty-six consecutive CHF patients (NYHA class III or IV) admitted to our hospital over a period of 5 years were studied. Patients with diabetes mellitus, liver or renal failure, and chronic obstructive lung disease were excluded. All patients received conventional treatment with digoxin, diuretic agents and an angiotensin converting enzyme inhibitor. On admission, blood and urine electrolytes and renal function parameters were determined. Arterial blood gases and serum anion gap determinations were also performed. RESULTS: Hypomagnesemia was found in 15 [n=15 (17.4%)] CHF patients. The majority of these patients also exhibited other electrolyte abnormalities, such as hypokalemia, hypocalcemia and hypophosphatemia. Inappropriate magnesiuria (fractional excretion of magnesium >4%) was evident in eight hypomagnesemic patients. A variety of associated conditions, including poor dietary intake, also favored magnesium depletion. CONCLUSION: Magnesium deficit is a common electrolyte disorder in CHF (NYHA class III/IV) patients and several interrelated mechanisms are implicated in its pathogenesis. Clinicians' awareness of the incidence of hypomagnesemia in this population as well as its related pathophysiology could be useful for the early detection and appropriate treatment to inhibit its arrhythmogenic potential.