Valgus intertrochanteric osteotomy for neglected femoral neck fractures in young adults

Twenty cases of neglected (more than 1 month old) displaced femoral neck fractures in young adults were treated with a valgus intertrochanteric osteotomy. A fracture union rate of 85% (17 cases) was achieved. Two of the healed cases developed avascular necrosis. After 30 months 15 patients (75%) had achieved good to excellent results. We believe that intertrochanteric osteotomy provides good alternative management for neglected femoral neck fractures.     

Clinical utility of monitoring tacrolimus blood concentrations in liver transplant patients

The relationship between the dose of tacrolimus, trough tacrolimus blood concentration, and selected clinical endpoints (acute rejection, nephrotoxicity, and other toxicities) were examined in a prospective, multicenter clinical trial to validate the use of an enzyme-linked immunosorbent assay (ELISA) for monitoring whole-blood concentrations of tacrolimus in liver transplant patients. A total of 111 subjects from six transplant centers were evaluated over 12 weeks posttransplantation. In addition to trough tacrolimus blood concentrations, hematocrit, ALT, AST, GGTP, alkaline phosphatase, total bilirubin, serum creatinine, BUN, serum potassium, serum magnesium, blood glucose, and serum albumin were also measured. The relationship between trough tacrolimus blood concentrations and clinical endpoints was analyzed using both a logistic regression model and a Cox proportional hazard model. By logistic regression analysis, a statistically significant (p = 0.0465) relationship between increasing trough tacrolimus blood concentrations and decreasing risk of acute rejection was demonstrated over a 7-day time window. Nephrotoxicity and other toxicities also demonstrated statistically significant relationships with trough tacrolimus blood concentrations. The results of the Cox analysis were consistent with the logistic regression analysis. Using receiver operator characteristic curves, trough tacrolimus concentrations as measured by the ELISA method were able to differentiate the occurrence of nephrotoxicity and toxicity from nonevents. To minimize nephrotoxicity of tacrolimus, it is necessary to maintain trough blood concentrations below 15 ng/ml. This study demonstrates that the ELISA method used to measure tacrolimus blood concentrations in this study provides information of predictive value for managing the risk of nephrotoxicity, other toxicity, and rejection in liver transplant patients.     

Hygroscopicity, phase solubility and dissolution of various substituted sulfobutylether beta-cyclodextrins (SBE) and danazol-SBE inclusion complexes

The aim of the present work was to characterize hygroscopicity, phase solubility and dissolution properties for various substituted sulfobutylether beta-cyclodextrins (SBEs) and danazol-SBE inclusion complexes. Moisture sorption was measured using a symmetric gravimetric analyzer. The complexes were characterized by powder X-ray diffraction (XRD) and differential scanning calorimetry (DSC). Moisture sorption isotherms for the SBEs and the complexes showed low moisture sorption at RH <60%. The moisture absorption desorption isotherms for the various SBEs showed very little hysteresis, indicating almost complete desorption. Moisture adsorbed by the various SBE was in the order SBE 7>SBE 4>SBE 5 at 95% RH. Powder XRD data for complexes showed the disappearance of characteristic crystalline peaks for danazol or the formation of amorphous entities and DSC showed the disappearance of the peak of fusion of danazol indicating complex formation. Phase solubility of danazol with various substituted SBEs indicated 1:1 stoichiometry of complexes. The apparent stability constant, as determined by the method of Higuchi and Connors, increased as the degree of substitution of SBEs increased and decreased as the temperature increased. The dissolution of the complexes was significantly greater than that of the corresponding physical mixtures indicating that the formation of amorphous complex increased the solubility of poorly soluble danazol. More than 85% of danazol was released in <10 min, compared to 15% danazol release from the physical mixtures.     

Formulation and process optimization to eliminate picking from market image tablets

A tablet formulation when compressed using market image tooling may cause picking of powder. A D-optimal statistical experiment was designed to optimize the direct compression formulation and the process to alleviate picking of powder. The effects of levels of magnesium stearate, colloidal silicon dioxide (CSD), and lubrication time on picking were investigated using original compression tooling. These optimization results provided a small robust manufacturing region, hence a change in the cut angles of embossed letters and numbers from 70 degrees to 90 degrees in the modified compression tooling was evaluated. A statistical analysis of the data identified a robust manufacturing region that included formulations containing magnesium stearate 1-1.25% w/w, CSD 0.1-0.3% w/w, with a lubrication time of 5-10 min when compressed using modified compression tooling. The results indicate a significant reduction in picking by increasing the cut angles of embossed letters and numbers in the modified compression tooling. By evaluating interactions between various variables, we demonstrate a concentration dependent effect of CSD on the lubrication efficiency of magnesium stearate and compactability of microcrystalline cellulose containing formulation. In addition, the lubrication efficiency of magnesium stearate is maintained by blending CSD with powder blend prior to lubrication with magnesium stearate.     

Solubilization of NSC-639829

Solubilization using pH combined with cosolvents, surfactants, and complexants are investigated for NSC-639829, an investigational anti-tumor agent. The intrinsic solubility of the drug is approximately 30 ng/ml and it has an ionizable dimethyl aniline group with an approximate base pK(a) of 5. Samples buffered at pH 1.0, 2.0, and 7.0 with various concentrations of the solubilizing agents were used to study the solubilization of NSC-629829 when present as charged and uncharged species. The solubilization of NSC-639829 was found to be much more effective when the drug was present primarily in ionized form. At pH values 1.0 and 2.0 where the surfactant (SLS) and complexant (SBEbetaCD) carried a negative charge enhanced solubilities of more than a million-fold were observed for the drug.     

Antibacterial activity of Ailanthus excelsa (Roxb)

The antibacterial activity of different fractions of a methanol extract obtained from the dried stem bark of Ailanthus excelsa (Roxb) was studied using different bacterial strains. The ethyl acetate fraction inhibited the growth of all test bacteria. The MIC of the EA fraction was found to be 6 mg/disc. Copyright -Copyright 2001 John Wiley & Sons, Ltd.     

Non-invasive intravascular monitoring in the pediatric hemodialysis population

Assessment of dry weight in pediatric hemodialysis (HD) patients is difficult, since small fluid shifts may result in dialysis-associated morbidity (DAM) and children may not verbalize complaints. Achieving dry weight is critical since chronic fluid overload can result in hypertension and left ventricular hypertrophy. To determine if non-invasive monitoring of hematocrit (NIVM) is useful in preventing DAM in pediatric HD patients, we reviewed 200 HD treatments performed with or without NIVM (no NIVM). DAM was defined as an ”event” (e.g., hypotension, headache, cramping) that required nursing intervention. Patient age, weight, and gender were similar in both groups. Desired ultrafiltration was obtained in both groups. The event rate was lower in NIVM than no NIVM for all treatments (0.22 vs. 0.3, P=0.07) and significantly lower in patients <35 kg (0.25 vs. 0.47, P=0.01). The second event rate (fraction of treatments with one event that had a subsequent event occurring at least 15 min later) was lower with NIVM (P<0.01). For the NIVM group, events in the first 90 min occurred when blood volume changed >8% per hour; 71% of events (43/60) at 90–240 min occurred when blood volume changed >4% per hour. NIVM decreases DAM in pediatric HD patients, especially those <35 kg. Ultrafiltration with blood volume change <8% per hour is safe in the 1st h and <4% after 1 h reduces DAM in children. Received: 5 June 2000 / Revised: 29 August 2000 / Accepted: 6 September 2000     

Allograft liver biopsy in patients with Epstein-Barr virus-associated posttransplant lymphoproliferative disease

Allograft liver biopsy specimens (n = 24) obtained in the clinical setting of primarily extrahepatic posttransplant lymphoproliferative disease (PTLD) were studied for histopathology, lymphocyte subsets, and Epstein-Barr virus (EBV)-encoded EBER RNA. Acute rejection was found in 20 (83.3%) of 24 biopsy specimens and graded as indeterminate in 7 (35%) of 20 (35%), mild in 3 (15%) of 20, and moderate in 10 (50%) of 20 cases. EBV hepatitis was the primary diagnosis in two biopsy specimens and a secondary finding in six others. Four biopsy specimens showed nonspecific reactive hepatitis, and five showed recurrence of primary liver disease. Immunoperoxidase staining showed primarily T cells. EBER RNA was detected in 14 (58.3%) of 24 biopsy specimens: 12 (60%) of 20 with and 2 (50%) of 4 without acute rejection. Antirejection therapy resulted in complete or partial response in 4 (36.3%) of 11 and 7 (63.7%) of 11 treated cases, respectively, despite the presence of EBV-infected cells in some tissues. Subsequent follow-up showed early or late chronic rejection in 6 (25%) of 24 patients. Gamma glutamyl transferase, a marker for early or late chronic rejection, was greater than five times the upper limit of normal in 9 (37.5%) of 24 patients. In conclusion, liver biopsy specimens in patients with PTLD show a spectrum of pathologic changes. Rejection may be treated even if EBV is concurrently present. Long-term graft is suboptimal, because low immunosuppression results in a tendency to develop chronic rejection.     

Occult nonhematopoietic malignancies present at autopsy in solid organ transplant patients who died within 100 days

BACKGROUND: Patients are at an increased risk for developing malignancies after transplantation. Lymphomas, skin malignancies, Kaposi's sarcomas, and cervical/vulvar neoplasms are the most common, but visceral malignancies are also well documented, with a reported frequency ranging from 1% to 6%. These visceral tumors represent a mix of neoplasms that were clinically occult at the time of transplantation and those that arise de novo after transplantation. Little information, however, is available on the frequency of clinically occult malignancies at the time of transplantation and their contribution to the number of posttransplant malignancies. METHODS: A retrospective study was performed of all patients who received an organ transplant from January 1981 to June 1997 and died within 100 days, a time interval in which epithelial malignancies found at autopsy were presumed to have been present, but clinically occult, at the time of transplantation. RESULTS: A total of 375 patients were studied who received the following organ transplants: 231 liver, 52 heart, 26 heart and lung, 32 lung, and 34 kidney. Eleven malignancies were identified for an overall frequency of 2.9% and included three thyroid carcinomas, three carcinoids of the small bowel, two lung carcinomas, one laryngeal carcinoma, one renal cell carcinoma, and one seminoma. CONCLUSION: The 2.9% frequency of malignancies seen in this study suggests that a small, but significant, number of patients have occult malignancies at the time of transplantation and that these occult tumors contribute substantially to the number of malignancies that present clinically after transplantation.