Phase-II trial with vindesine for regression induction in patients with leukemias and hematosarcomas

Summary Vindesine (VDS) has been submitted to a phase-II trial, the results of which were assessed in terms of regression induction. VDS was given weekly IV in doses of 2 mg/m² on two consecutive days to 59 patients, 55 of whom were evaluable. A high proportion of complete (36%) and over 50% partial regressions were obtained in acute lymphoid leukemias (ALL) (overall response 63%) whatever the perceptible phase, in blastic crisis of chronic myeloid leukemia (55%), and some responses were recorded in lymphosarcoma (40%). No effect has so far been seen in acute myeloid leukemia or in Hodgkin's disease. Malignant neoplasms of the immunoblastic type seem to be particularly sensitive to VDS. Continuous 48 h IV infusion can induce a remission where an IV push administration of the same dose has failed. One remarkable characteristic of VDS is the apparent absence of cross-resistance with VCR: in acute leukemic forms, 55% of patients who failed to obtain remission induction after three weekly injections of VCR (used in combination chemotherapy) achieved a complete or partial remission with VDS. The toxicity was mainly neurologic (paralytic ileus, constipation, paresthesias, loss of reflexes) and hematologic (leukopenia and thrombopenia), and was not more significant than with the other agents: four patients died of infection or hemorrhage.     

Cardiac echinococcosis: echocardiographic diagnosis with a fatal clinical outcome

Hydatid disease HD is an endemic disease found in various regions of the world. The organs mostly affected are the liver and lung. Cardiac involvement in HD is rare. The symptoms are mainly due to the mass effect of the calcific hydatid cyst obstructing the blood or the lymphatic vessels. Other manifestations are secondary infection or cyst rupture in the involved organ. Here, we report a middle aged female patient with no history of medical illness who presented to the emergency room with an unrecordable blood pressure. Echocardiogram showed multiple calcific cysts of echinococcosis granulosa in the left ventricle cavity. In the clinical setting, where there is detection of HD elsewhere in the body, an echocardiogram is mandatory as cardiac involvement is serious and may be fatal.     

Cutaneous vasculitis

Vasculitis is defined as inflammation of blood vessels and can affect multiple organs. Several classification systems exist to categorize vasculitis such as vessel size, presence of anti-neutrophil cytoplasmic antibody, pathogenesis of the inflammation, and type of inflammatory cell infiltrate. Cutaneous vasculitis occurs as a manifestation of many diseases including rheumatologic diseases, hypersensitivity syndromes, infections, and malignancies. The diagnosis of the cutaneous vasculitis and the underlying cause requires a complete history and physical exam and usually a biopsy or angiogram. The treatment depends on the etiology of the inflammation and includes immunosuppression, withdrawal of the offending agent, antibacterial/antiviral agents, and chemotherapies. A clear understanding and approach to this condition will improve the physician’s ability to provide optimal patient care.     

Fungus-infected fluid collections in thorax or abdomen: effectiveness of percutaneous catheter drainage

PURPOSE: To retrospectively evaluate the effectiveness of percutaneous catheter drainage in the treatment of fungus-infected fluid collections in the thorax or abdomen and to identify any factor that may be predictive of a poor clinical outcome. MATERIALS AND METHODS: Approval for this study was obtained from the hospital ethics subcommittee on human studies. Because the study was retrospective, patient informed consent was not required. This study was compliant with the Health Insurance Portability and Accountability Act. Retrospective analysis was performed of cases of fungus-infected fluid collections in the thorax or abdomen treated by using percutaneous catheter drainage in 60 patients (36 male and 24 female patients; mean age, 57 years; range, 2 months to 91 years) during 5 years. The patient medical records were reviewed to identify recognized factors for predisposition to fungal infection. The details of percutaneous catheter drainage and microbiologic findings were recorded. The technical success (ability of catheters placed to drain collections treated) and the clinical success (ability of patients to recover fully without surgery) of percutaneous catheter drainage were determined. A multifactor logistic regression analysis was performed to identify any clinical or microbiologic factor predictive of a poor clinical outcome. RESULTS: Seventy-three fungus-infected fluid collections were drained in 60 patients. The collections originated from the pleura (n = 6), mediastinum (n = 2), liver (n = 3), pancreas (n = 5), obstructed biliary or urinary tract (n = 9), gallbladder (n = 1), and abdominopelvic area (n = 47). The technical success rate for catheter drainage was 79% (41 of 52 patients); the clinical success rate, 57% (34 of 60 patients). Twenty (33%) patients died from all causes during hospital admission. Multifactor logistic regression analysis was used to identify predictors of a poor clinical outcome; complexity of collection, history of malignancy, and admission to intensive care unit were significant (P < .03) and independent predictors. CONCLUSION: Despite a moderately high technical success rate with percutaneous catheter drainage of fungus-infected fluid collections, clinical success rate was much lower. Both imaging appearance (complexity of collection) and clinical factors (history of malignancy, admission to intensive care unit) influenced prognosis.     

Thin basement membrane nephropathy

Thin basement membrane nephropathy. Thin basement membrane nephropathy (TBMN) is the most common cause of persistent glomerular bleeding in children and adults, and occurs in at least 1% of the population. Most affected individuals have, in addition to the hematuria, minimal proteinuria, normal renal function, a uniformly thinned glomerular basement membrane (GBM) and a family history of hematuria. Their clinical course is usually benign. However, some adults with TBMN have proteinuria >500 mg/day or renal impairment. This is more likely in hospital-based series of biopsied patients than in the uninvestigated, but affected, family members. The cause of renal impairment in TBMN is usually not known, but may be due to secondary focal segmental glomerulosclerosis (FSGS) or immunoglobulin A (IgA) glomerulonephritis, to misdiagnosed IgA disease or X-linked Alport syndrome, or because of coincidental disease. About 40% families with TBMN have hematuria that segregates with the COL4A3/COL4A4 locus, and many COL4A3 and COL4A4 mutations have now been described. These genes are also affected in autosomal-recessive Alport syndrome, and at least some cases of TBMN represent the carrier state for this condition. Families with TBMN in whom hematuria does not segregate with the COL4A3/COL4A4 locus can be explained by de novo mutations, incomplete penetrance of hematuria, coincidental hematuria in family members without COL4A3 or COL4A4 mutations, and by a novel gene locus for TBMN. A renal biopsy is warranted in TBMN only if there are atypical features, or if IgA disease or X-linked Alport syndrome cannot be excluded clinically. In IgA disease, there is usually no family history of hematuria. X-linked Alport syndrome is much less common than TBMN and can often be identified in family members by its typical clinical features (including retinopathy), a lamellated GBM without the collagen alpha3(IV), alpha4(IV), and alpha5(IV) chains, and by gene linkage studies or the demonstration of a COL4A5 mutation. Technical difficulties in the demonstration and interpretation of COL4A3 and COL4A4 mutations mean that mutation detection is not used routinely in the diagnosis of TBMN.     

Sterically Stabilized Phospholipid Mixed Micelles: In Vitro Evaluation as a Novel Carrier for Water-Insoluble Drugs

Purpose. Sterically stabilized phospholipid micelles (SSMs) composed of poly(ethylene glycol-2000)-grafted distearoyl phosphatidylethanolamine (PEG(2000)-DSPE) are new and promising lipid-based carriers for water-insoluble drugs. This study investigates and compares sterically stabilized mixed micelles (SSMM), composed of (PEG(2000)-DSPE) plus egg-phosphatidylcholine, with SSM as a novel delivery system for improved solubilization of water-insoluble drugs using paclitaxel as a model. Methods. Paclitaxel was solubilized in SSM (P-SSM) and SSMM (P-SSMM) by coprecipitation and rehydration with isotonic 0.01M HEPES buffer, pH 7.4. After separation of excess drug by centrifugation, mean particle size and morphology of particles in the supernatant were determined by quasi-elastic light scattering and transmission electron microscopy. The solubilization potentials of SSMM and SSM for paclitaxel were determined by reverse phase high pressure liquid chromatography (RP-HPLC). Cytotoxic activity of paclitaxel in SSMM, SSM, and dimethyl sulfoxide (10% DMSO) was determined against human breast cancer cells (MCF-7). Results. Mean hydrodynamic diameter of P-SSMM and P-SSM were 13.1 ± 1.1 nm and 15 ± 1 nm (n = 3), respectively. SSMM solubilized 1.5 times more paclitaxel than SSM for the same total lipid concentration. Solubilized paclitaxel amount increased linearly with an increase in lipid concentration. A therapeutically relevant lipid concentration (15 mM) of SSMM solubilized 1321 ± 48g/ml of paclitaxel. Paclitaxel in the absence of sufficient SSM aggregated to form lipid-coated crystals. P-SSMM, P-SSM, and paclitaxel in DMSO had comparable cytotoxic activities against MCF-7 cells. Conclusions. SSMM showed increased solubilization potential compared with SSM while retaining all of its own advantages. Therefore, it can be used as an improved lipid-based carrier for water-insoluble drugs.     

A Novel Formulation of VIP in Sterically Stabilized Micelles Amplifies Vasodilation In Vivo

Purpose. To determine whether human vasoactive intestinal peptide (VlP)-poly(ethylene glycol) (PEG)-grafted distearoyl-phosphatidyleth-anolamine (DSPE) micelles elicit potent and stable vasodilation in vivo. Methods. PEG-DSPE micelles were prepared by co-precipitation. VIP was loaded into micelles by incubation at room temperature. Vasoactivity of VIP in SSM was determined by monitoring changes in diameter of resistance arterioles in the in situ hamster cheek pouch using intravital microscopy. Results. VIP easily undergoes self-assembly into small PEG-DSPE micelles (mean [±SEM] size, 18 ± 1 nm) in a time-dependent fashion. This generates a potent vasoactive matrix at nanomole concentrations of VIP as manifested by ~3-fold potentiation and prolongation of vasodilation relative to that evoked by aqueous VIP alone (p < 0.05). This response is specific and mediated by the L-arginine/nitric oxide (NO) biosynthetic pathway. Micellar VIP dispersion remains vasoactive for at least 14 days after preparation and storage at 4°C. Conclusions. A novel, self-associated, small and stable PEG-DSPE micellar formulation of VIP amplifies vasodilation in the in situ peripheral microcirculation in a specific fashion by elaborating NO. An optimized formulation could be considered for certain cardiovascular disorders associated with L-arginine/NO biosynthetic pathway dysfunction.