Evaluation of drugs for elimination of leukemic cells from the bone marrow of patients with acute leukemia

Relatively nonmyelotoxic drugs and drug combinations were investigated for their ability to eliminate malignant cells from human bone marrow. In vitro 90% inhibitory concentration (IC90) doses were established on granulocyte macrophage colony-forming units (GM-CFU) in culture of bone marrow by using the GM-CFU assay for the following drugs: 4- hydroperoxycyclophosphamide (4-HC), Adriamycin, L-asparaginase, bleomycin, hydrocortisone, VP-16, spirogermanium, Taxol, and vincristine. The leukemic cell kill efficiency of these drugs at IC90 doses was compared with that of 4-HC on acute lymphoid leukemia (ALL) cell lines by using the limiting-dilution assay. Under these conditions, no single drug was superior to 4-HC. To increase the in vitro effect in leukemic cell kill, combinations of vincristine with hydrocortisone, Adriamycin, VP-16, and 4-HC were investigated. Vincristine at 1 to 5 micrograms/mL increased the marrow cytotoxicity of hydrocortisone, Adriamycin, and VP-16, but it was protective (subadditive) with 4-HC. Vincristine and 4-HC in combination was additive to supraadditive on ALL cell lines, increased the leukemic cell kill by one to two logs above 4-HC alone at IC90 doses (P less than .05), and was not affected by the addition of excess marrow cells. The recommended doses for chemopurging in clinical studies are vincristine, 1 to 5 micrograms/mL, plus 4-HC, 5 micrograms/mL.     

Analytical and clinical evaluation of DiaSorin Liaison® Calprotectin fecal assay adapted for serum samples

BackgroundCalprotectin is a calcium‐binding protein that can be measured in serum, plasma, and feces. Increased serum and plasma calprotectin concentrations have been found in chronic inflammatory rheumatic disorders. An analytical and clinical evaluation of the DiaSorin Liaison® fecal Calprotectin assay using LIAISON® XL was performed.MethodsThe protocol included an analytical and clinical evaluation in which imprecision, the linearity of dilution, differences between serum and plasma samples and method comparison with CalproLab™ ELISA kit were assessed. Serum calprotectin concentrations in active (n = 26) and remission (n = 23) rheumatoid arthritis (RA) patients were compared.ResultsThe intra‐day and inter‐day analytical imprecision CVs ranged from 2.9% to 4.0% and 2.7% to 10.4%, respectively. Correlation between measured and expected values was high (R > 0.99), indicating good linearity. The Wilcoxon signed‐rank test showed that serum and plasma matched samples presented statistically significant differences (p < 0.001) being the highest concentrations of calprotectin observed in serum samples. Deming regression equation was as follows: Diasorin calprotectin (μg/ml) = −0.32 (95% CI: −0.65 ‐ −0.05) +1.58 (95% CI: 1.42–1.79).* Calprolab calprotectin (μg/ml). Significantly higher serum calprotectin levels were found in RA patients with active disease when compared to patients with low disease activity or in clinical remission (mean ± SD) [(3.35 μg/ml ± 1.55) vs. (1.63 μg/ml ± 0.52), p < 0.001] and these levels correlated well with all disease activity indices.ConclusionsThe DiaSorin Liaison® fecal Calprotectin assay adapted for serum samples showed adequate technical performances and the clinical performances were similar to other assays.     

Therapy of patients with human T-cell lymphotrophic virus I-induced adult T-cell leukemia with anti-Tac, a monoclonal antibody to the receptor for interleukin-2

Human T-cell lymphotropic virus I (HTLV-I)-induced adult T-cell leukemia (ATL) cells constitutively express interleukin-2 (IL-2) receptors identified by the anti-Tac monoclonal antibody (MoAb), whereas normal resting cells do not. This observation provided the scientific basis for a trial of intravenous anti-Tac in the treatment of nine patients with ATL. The patients did not suffer untoward reactions and did not have a reduction in the normal formed elements of the blood, and only one of the nine produced antibodies to the anti-Tac MoAb. Three patients had transient mixed, partial, or complete remissions lasting from 1 to more than 8 months after anti-Tac therapy, as assessed by routine hematologic tests, immunofluorescence analysis of circulating cells, and molecular genetic analysis of HTLV-I provirus integration and of the T-cell receptor gene rearrangement. The precise mechanism of the antitumor effects is unclear; however, the use of a MoAb that prevents the interaction of IL-2 with its receptor on ATL cells provides a rational approach for the treatment of this malignancy.     

Migraine and the hypothalamus

Migraine is a complex brain disorder where several neuronal pathways and neurotransmitters are involved in the pathophysiology. To search for a specific anatomical or physiological defect in migraine may be futile, but the hypothalamus, with its widespread connections with other parts of the central nervous system and its paramount control of the hypophysis and the autonomic nervous system, is a suspected locus in quo. Several lines of evidence support involvement of this small brain structure in migraine. However, whether it plays a major or minor role is unclear. The most convincing support for a pivotal role so far is the activation of the hypothalamus shown by positron emission tomography (PET) scanning during spontaneous migraine attacks. A well-known theory is that the joint effect of several triggers may cause temporary hypothalamic dysfunction, resulting in a migraine attack. If PET scanning had consistently confirmed hypothalamic activation prior to migraine headache, this hypothesis would have been supported. However, such evidence has not been provided, and the role of the hypothalamus in migraine remains puzzling. This review summarizes and discusses some of the clues.     

von Willebrand factor-collagen binding activity is increased in newborns and infants

ABSTRACT. von Willebrand factor (vWF) antigen (vWF:Ag) and vWF-collagen binding activity (vWF:CBA) were measured in plasma by parallel quantitative ELISAs in normal newborns and infants ( n =71). The medians for vWF:Ag (IUjml) and vWF:CBA (Ujml), respectively, were 1.46 and 1.91 for 2-7 day-old (n = 43), 1.22 and 1.40 for 2-4 week-old (n = 14), 1.22 and 1.15 for 2-6-month-old (n = 14) infants and 0.98 and 1.08 (n = 36) in normal adults. Elevated levels of vWF:Ag, but particularly vWF:CBA were seen for up to 4 weeks of life reaching adult levels between 2 and 6 months of life. The elevated levels of the vWF parameters indicate that caution should be exercised when interpreting laboratory data and diagnosing von Willebrand disease in newborns and young infants and warrant the use of age-specific reference ranges. The efficient haemostasis observed during early neonatal life may in part be due to the increased ability of vWF to interact with collagen.     

Selenium status of New Zealand infants fed either a selenium supplemented or a standard formula

Objective: New Zealand soils are deficient in the essential micronutrient, selenium. New Zealand infants have low selenium levels at birth and experience a further decline if fed cows milk based formula. This study examined the selenium status of infants fed with a new commercially available selenium supplemented formula.
Methodology Forty-four newborn infants, whose mothers wished to formula feed, were randomized in an open controlled trial to be fed a commercially available selenium supplemented cows milk formula (containing 17 μg Se/L) or an unsupplemented formula (containing 4.6 μg Se/L). Cord, 1 and 3 month blood samples were obtained for selenium status (plasma and red cell selenium and glutathione peroxidase) and thyroid function.
Results Mean plasma selenium and glutathione peroxidase values were significantly higher in supplemented than unsupplemented infants at 1 month (unpaired t -tests; P <0.0001 and P = 0.001 respectively) and 3 months ( P <0.0001 and P = 0.0005). Analysis within treatment groups between time points (paired t -tests) showed that selenium supplementation prevented the fall in plasma selenium from birth to 1 month seen in unsupplemented infants and was associated with a rise in levels between 1 and 3 months ( P = 0.002).
Conclusions Supplementing cows milk formula with selenium to replicate the levels found in breast milk is nutritionally sound. Feeding from a few days of age with a formula containing 17 μg Se/L in infants with low selenium status at birth is sufficient to cause a rise to 80% of adult levels at 3 months of age.     

Ureteral stents and their use in endourology

Ureteral stents have assisted urologists in the performance of surgery of the urinary tract for many years. They can have both diagnostic and therapeutic value, but are used most frequently as adjuncts to endoscopic or minimally invasive procedures. This review provides an update of the current uses for ureteral stents, technology of biomaterials, complications associated with indwelling ureteral stents and the future of stents in urology.     

Neoinfundibulotomy for the management of symptomatic caliceal diverticula

PURPOSE: Direct percutaneous access provides effective treatment for complex caliceal diverticula. Yet, access into the diverticulum alone is usually tenuous and passage of a guide wire across a stenotic infundibulum is often impossible. An alternative technique is described which creates a "neoinfundibulum" to assist in the management of symptomatic caliceal diverticula. MATERIALS AND METHODS: During a 6-year period 22 patients with symptomatic caliceal diverticula were treated via a percutaneous approach, of whom 21 had calculi within the diverticula. After accessing the diverticulum directly, it was impossible to pass a guide wire through the stenotic infundibulum in 18 (82%) patients, prompting advancement of the access needle through the diverticular wall into the renal pelvis. Once secure access was established, balloon dilation was performed to 30Fr to create the "neoinfundibulum." Percutaneous ultrasonic lithotripsy was performed in the usual fashion. A 22Fr Councill catheter was placed to keep the infundibular tract open for 5 to 7 days to allow complete epithelialization and drainage. Stone-free, symptom-free and complication rates were assessed. RESULTS: Pain, recurrent urinary tract infections and hematuria were the presenting complaints in the subgroup of patients undergoing "neoinfundibulotomy." Average stone burden was 11.7 x 12 mm. and average hospital stay was 2.8 days. Of the patients 94% were symptom-free at 6-week followup, and 80% were stone-free on followup excretory urography. The remaining patients had residual stone fragments less than 3 mm. in diameter. Complications related to access were identified in 2 patients who sustained a pneumothorax after a supra-11th rib access, which was successfully managed with tube thoracostomy. CONCLUSIONS: Percutaneous management of complex caliceal diverticula provides a safe and effective option for symptomatic patients. When the stenotic infundibulum cannot be traversed with a guide wire, creation of a new infundibulum offers a secure alternative for accessing the collecting system, while providing equally effective results.     

Routine postoperative imaging is important after ureteroscopic stone manipulation

PURPOSE: Improved fiber optics and advanced intracorporeal lithotripsy devices have significantly decreased the incidence of complications during ureteroscopic procedures. Despite recent reports suggesting that radiographic imaging may not be necessary in all individuals after routine ureteroscopy silent obstruction may develop in some, ultimately resulting in renal damage. We determined the incidence of postoperative silent obstruction at our institution and assessed the need for routine functional radiographic studies after ureteroscopy. MATERIALS AND METHODS: We retrospectively reviewed the charts of 320 patients who underwent a total of 459 ureteroscopic procedures for renal or ureteral calculi in a 3-year period. Complete followup with imaging was available for 241 patients (75%). Average patient age was 47.2 years. The variables of interest reviewed included preoperative pain, preoperative obstruction, targeted calculous site, stone-free rate, postoperative pain and postoperative obstruction. Mean followup was 5.4 months (range 2 to 43). RESULTS: A total of 241 patients with complete followup were identified in this analysis. Preoperative pain was present in 202 patients (84%) and 168 (70%) had preoperative obstruction. Overall targeted calculous clearance was successful in 73% of the patients and an additional 15.8% had residual fragments less than 4 mm. The renal, proximal or mid and distal ureteral stone-free rate was 32.1%, 81.9% and 90.5%, while in an additional 46.4%, 6.3% and 6.7% of cases, respectively, residual fragments were less than 4 mm. Of the 241 patients 30 (12.3%) had obstruction postoperatively due to residual stone in 25 (83.3%), stricture in 3 (10%), edema of the ureteral orifice in 1 (3.3%) and a retained encrusted stent in 1 (3.3%). Postoperatively obstruction correlated with postoperative pain in 23 of the 30 patients (76.7%). Pain was present postoperatively in 30 of the 211 patients (14%) without evidence of ureteral obstruction postoperatively. However, silent obstruction developed in 7 patients (23.3%) or 2.9% of the total cohort. All 7 patients underwent secondary ureteroscopy to alleviate obstruction. A single patient ultimately received chronic hemodialysis for renal failure, 1 was lost to followup and in 5 there was documented successful resolution of the cause of obstruction. CONCLUSIONS: Our analysis suggests that silent obstruction remains a potentially significant complication after stone management. Relying on postoperative pain to determine the necessity of postoperative imaging places patients at risk for progressive renal failure due to unrecognized obstruction. Therefore, we recommend that imaging of the collecting system should be performed by excretory urography, spiral computerized tomography or ultrasound within 3 months after routine ureteroscopic stone treatment to avoid the potential complications of unrecognized ureteral obstruction.     

Dysgerminoma of the ovary: A retrospective study

A retrospective analysis of 22 patients with ovarian dysgerminoma who were treated between 1980 and 1987 was carried out. The median age at presentation was 24.5 years. A total of 15 patients were in stage I, one patient was in stage II and six patients were in stage III. Bilateral ovarian involvement was present in four patients. Conservative surgery was carried out in nine patients and 11 patients underwent radical surgery. Two patients had biopsy only. Fourteen patients received adjuvant radiotherapy and three patients received salvage radiation for recurrent disease. The 10-year actuarial survival rate was 81.8%. All 15 patients in stage I were alive and disease-free at a median follow-up of 125 months. Four patients (one in stage II and three in stage III) died of progressive or recurrent abdominopelvic disease. Pelvic recurrence occurred after conservative surgery in two patients in stage IA who had a tumour size greater than 10 cm, but they were salvaged with radical surgery, chemotherapy and radiotherapy. There were seven patients aged 20 years or less. All were alive and disease-free at a median follow-up of 127 months.