What Can Be Expected of Balloon Aortic Valvuloplasty in Adults?

Introduced more than 15 years ago, balloon aortic valvuloplasty (BAV) has clearly delineated indications and limitations. Although, aortic valve replacement is undoubtedly the treatment of choice for healthy patients with aortic stenosis, BAV has been demonstrated as a valuable and safe palliative procedure for patients considered too risky or old for current day surgery. Between January 1991 and December 1999, 858 patients (mean age 76 ± 11 years, 479 [57%] women) underwent BAV at our center. Indications for BAV were contraindication to surgery in 16.2% of the patients, high risk in 40.4%, refusal of surgery in 10.7%, personal decision in 18.5%, and other in 14.2%. The mean gradient decreased from 65 ± 23 to 27 ± 12 mmHg and the valve area increased from 0.56 ± 0.19 cm² to 1.0 ± 0.38 cm². Eleven (1.1%) patients died during the procedure. The other severe complications were complete AV block in 18 (1.8%) patients, stroke in 8 (0.8%), tamponade in 6 (0.6%), and massive aortic insufficiency in 4 (0.4%). In conclusion, BAV does not replace valve replacement, even in the elderly. All those who can be operated on, should be. However, if surgical intervention is not considered reasonable, BAV offers good immediate results with an acceptable complication rate. Furthermore, previous published series have demonstrated that BAV is particularly indicated in specific subgroups, such as very old patients with high operative risk, end-stage heart failure, cardiogenic shock, or general anesthesia for noncardiac surgery.     

A retrospective study on chemical and radioactive synovectomy in severe haemophilia patients with recurrent haemarthrosis

Between 1970 and 1994, 116 chemical and 90 radioactive synovectomies were performed in 107 patients with severe haemophilia and two with type 3 von Willebrand's disease. The products used were osmic acid (OA) in 100 cases, 90-Yttrium in 35 cases, 186-Rhenium in 48, 169-Erbium in two, hexacetonide triamcinolone in 16 and radioactive gold in five cases. The use of radioactive colloids is not allowed in France in patients under 15 years of age. Twenty-nine patients had more than one synovectomy per joint. All patients were evaluated for 6 months post-synovectomy, using both a clinical and a radiological score. Six months after synovectomy, a good or excellent result was obtained for 81% of the joints treated with isotopes, compared with 44% of those treated with OA, P<0.001. This superiority of isotopes over osmic acid was still observed after 6 months for the 89 joints that were re-evaluated, with follow-up ranging from 1 to 9 years. It was possible to calculate a radiological score in 84 cases. With OA the best results were from the joints with the lowest scores pre-synovectomy (<7). No correlation could be established between the clinical and the radiological scores, due to the small size of the sample. In summary: (1) chemical and radioactive synovectomy are simple and safe procedures for haemophilic arthropathy, (2) in our series, after 6 months the efficacy of isotopic synovectomy was greater than that of chemical synovectomy, and this benefit seems to persist after 6 months, and up to 9 years in the group of patients with longer-term follow-up.     

Understanding differences in past year psychiatric disorders for Latinos living in the US

This study seeks to identify risk factors for psychiatric disorders that may explain differences in nativity effects among adult Latinos in the USA. We evaluate whether factors related to the processes of acculturation and enculturation, immigration factors, family stressors and supports, contextual factors, and social status in the US account for differences in 12-month prevalence of psychiatric disorders for eight subgroups of Latinos. We report results that differentiate Latino respondents by country of origin and age at immigration (whether they were US-born or arrived before age 6: In-US-as-Child [IUSC]; or whether they arrived after age 6: later-arrival immigrants [LAI]). After age and gender adjustments, LAI Mexicans and IUSC Cubans reported a significantly lower prevalence of depressive disorders than IUSC Mexicans. Once we adjust for differences in family stressors, contextual factors and social status factors, these differences are no longer significant. The risk for anxiety disorders appears no different for LAI compared to IUSC Latinos, after age and gender adjustments. For substance use disorders, family factors do not offset the elevated risk of early exposure to neighborhood disadvantage, but coming to the US after age 25 does offset it. Family conflict and burden were consistently related to the risk of mood disorders. Our findings suggest that successful adaptation into the US is a multidimensional process that includes maintenance of family harmony, integration in advantageous US neighborhoods, and positive perceptions of social standing. Our results uncover that nativity may be a less important independent risk factor for current psychiatric morbidity than originally thought.     

Detection and viability of tumor cells in peripheral blood stem cell collections from breast cancer patients using immunocytochemical and clonogenic assay techniques [see comments]

Although peripheral blood stem cell collections (PBSC) are thought to have less tumor involvement than bone marrow (BM), the incidence of circulating tumor cells in patients with breast cancer has not been widely investigated. We prospectively investigated the incidence and viability of tumor cell involvement in PBSC and BM collections from breast cancer patients undergoing high-dose chemotherapy/hematopoietic stem cell transplantation. Paired samples of PBSC and BM from 48 patients were analyzed using an immunocytochemical technique that detects one epithelial-derived tumor cell per 5 x 10(5) mononuclear cells. Immunostained tumor cells were detected in 9.8% (13/133) PBSC specimens from 9/48 (18.7%) patients and in 62.3% (38/61) BM specimens from 32/48 (66.7%) patients, a significantly higher rate than in PBSC (P < .005). The geometric mean concentration of tumor cells in contaminated PBSC specimens was 0.8/10(5) mononuclear cells (range 0.33 to 2.0/10(5)) compared with 22.9/10(5) mononuclear cells in BM (range 1 to 3,000/10(5), P < .0001). In culture experiments, clonogenic tumor colonies grew in 21/26 immunocytochemically positive specimens. No tumor colony growth was detected in 30/32 immunocytochemically negative specimens. Immunocytochemical detection of tumor involvement in BM and PBSC correlated significantly with in vitro clonogenic growth (P < .0001). We conclude that PBSC contain fewer tumor cells than paired BM specimens from patients with advanced breast cancer and that these tumor cells appear to be capable of clonogenic growth in vitro.     

In vivo biologic effects of PIXY321, a synthetic hybrid protein of recombinant human granulocyte-macrophage colony-stimulating factor and interleukin-3 in cancer patients with normal hematopoiesis: a phase I study

PIXY321 is a novel fusion protein of recombinant human granulocyte- macrophage colony-stimulating factor and interleukin-3 that exhibits biologic effects of both its parent cytokines in vitro and in preclinical studies. To evaluate the clinical safety and hematopoietic effects of this hybrid cytokine, PIXY321 was administered by subcutaneous injection twice daily at doses of 25 to 1,000 micrograms/m2/day over 14 days to 24 patients with sarcoma before chemotherapy as part of a phase I trial. The treatment was associated with significant increases in white blood cell, neutrophil, platelet, and reticulocyte counts (all P < .001). The increase in neutrophil count was dose-related and was seen during treatment with the cytokine, whereas the increase in platelet count was gradual and peaked after the cessation of the cytokine treatment and was not clearly dose related. PIXY321 treatment also increased bone marrow (BM) cellularity and the percentage of BM cells in S phase (P < .001). In addition, there was a significant increase in the number of CD34+ cells and committed and multipotential progenitors in the peripheral blood. The ex vivo expansion capacity of peripheral blood and BM progenitor cells was preserved after the in vivo treatment with PIXY321. The treatment was well tolerated, with the most common side-effect being injection site reactions. The results of this study show the biologic and clinical activity of a genetically engineered fusion molecule of two hematopoietic cytokines in humans with normal hematopoietic function.     

Human platelets exert cytotoxic effects on tumor cells

Monocytes are thought to play a role in host resistance to tumor cell growth in animals and humans. In addition, platelets are known to be involved in tumor metastases. To investigate the interaction of these two cell types and their effect on tumor cells, human monocytes and platelets were examined using an in vitro monocyte-tumor cell cytotoxicity assay. Monocytes alone resulted in 32% +/- 1.5 (mean +/- SEM) tumor cell kill. When platelets were added to monocytes in a 1:1 ratio, an increase in cytotoxicity to 61% +/- 3.2 was observed. The cytotoxicity noted when platelets were added to a fixed number of monocytes and tumor cells was dependent on the number of platelets added. A decrease in cytotoxicity from 32% +/- 1.5 to 12% +/- 2.3 was observed when contaminating platelets were removed from monocyte preparations. Platelets added to tumor cells in the absence of any monocytes were also toxic, resulting in a maximum kill of 95% at a 4:1 platelet/tumor cell ratio. Secreted products of freshly isolated platelets may be responsible for much of the observed cytotoxicity, since supernatants from the platelets were toxic for tumor cells. Platelets pretreated with a cyclooxygenase inhibitor (ASA) or a lipoxygenase inhibitor had decreased cytotoxicity compared with untreated platelets. Our results indicate that products of platelet arachidonate metabolism are toxic for tumor cell lines. They also suggest that the role of the platelet must be considered when studying monocyte-tumor cell cytotoxicity.     

Hairy cell leukemia and myelomatosis: chance association or clinical manifestations of the same B-cell disease spectrum

We describe three patients who had typical features of hairy cell leukemia (HCL) and multiple myeloma (MM) at the same time. In two, both diagnoses were made within a short period of time, and in the third, HCL had been present for 2 yr before the appearance of a paraprotein, bone lesions, and plasma-cell infiltrates established the diagnosis of MM. Although this association has not been previously reported, cases of HCL with osteolytic lesions or a paraprotein band have been described. The cases described may represent clinical manifestations of closely related disorders arising from divergent differentiation from a common B-cell precursor rather than a chance association.     

Salt-dependent conformational diversity of alternating poly (Glu-Leu)

Alternating poly(Glu-Leu) was synthesized by the condensation of the corresponding dipeptide p-nitrophenyl ester at high concentration. It exhibits a random coil structure in pure water at neutral pH. Addition of monovalent cations, such as NH⁺₄ to a final 0.1 M solution, induces a transition to a water soluble β-structure. The salt effect is quite selective since no transition was observed with Li⁺, Na⁺ or Cs⁺ ions. Addition of 0.5 equiv. of calcium, cobalt or manganese chlorides per glutamyl residue induces similar coil to β-sheet transitions. No polymer precipitation was observed at these very low salt concentrations. Addition of 0.5 equiv. of Cu²⁺ or 0.15 equiv. of Fe³⁺ induces a coil to α-helix transition. Molecular modeling has been used to understand tentatively the main factors controlling the different conformations observed with the various metal ions. © Munksgaard 1997.     

Gingival and mucosal reactions after intensive chlorhexidine gel treatment with or without oral hygiene measures

Abstract – The aim of this study was to elucidate whether soft tissue reactions during chlorhexidine (CHX) treatment might be associated with meticulous oral hygiene measures. A commercially available 1% chlorhexidine digluconate gel (Hibitane Dental Gel) was applied in a custom tray for the mandibular arch, 10 min daily, for 14 days. A split mouth approach was used to allow evaluation of the effect of oral hygiene measures with toothbrush, toothpaste, and dental floss on one side of the arch. During the treatment period, 8 out of 12 subjects developed gingival and/or mucosal reactions appearing as white patches or ulcerations. Both the gingival reactions on the buccal marginal gingiva and the mucosal reactions near the margin of the custom tray occurred only when the gel treatment was combined with meticulous oral hygiene measures. The white patches, which could easily be detached, leaving ulcerated areas, consisted entirely of stratified squamous epithelium. The findings suggest that intensive treatment with chlorhexidine gel, in individually fitted custom trays, combined with meticulous oral hygiene measures may induce toxic effects on the surface layers of the gingiva and mucosa.