Prognostic significance of B-lineage leukemic cell growth in SCID mice: a Children's Cancer Group Study

Primary leukemic cells isolated from children (N = 681 ) with newly diagnosed B-lineage ALL enrolled on risk-adjusted treatment protocols of the Children's Cancer Group (CCG) were injected via the tail vein into 7-10 week old SCID mice. Leukemic cells from 104 of 681 patients (15.3%) were able to engraft and proliferate in one or more SCID mouse organs. These SCID+ patients were somewhat more likely than SCID patients to be older than 10 years of age (p = 0.03) and have WBC counts >20,000/microL (p = 0.04), but the groups were similar with respect to all other presenting features. Event-free survival (EFS) outcome at 3 years of follow-up was similar for SCID+ patients compared with SCID- patients (79.2%, SD = 5. 1% vs. 84.8%, SD = 2.8%; p = 0.20). Overall survival also was similar between the two groups (p = 0.93). This result was maintained within the subgroups of lower risk (N = 448) and higher risk (N = 233) patients. However, there were trends for poorer outcome among patients whose cells caused overt leukemia in SCID mice and infiltrated either 6 or more organs (p = 0.03), skeletal muscle (p = 0.0003), kidney (p = 0.05), or spleen (p = 0.06). Thus, engraftment of primary leukemic cells in SCID mice was not a significant predictor of outcome for the aggregate population of B-lineage ALL patients, the majority of whom were low risk, treated according to contemporary intensive chemotherapy programs of the CCG. However, development of disseminated overt leukemia and infiltration of SCID mouse skeletal muscle by primary leukemic cells from adjacent bone marrow may reflect a biologically more aggressive disease and identify patients at higher risk for treatment failure.     

Effects of airway obstruction on transmural pulmonary artery pressure in exercising horses

OBJECTIVE: To determine whether laryngeal hemiplegia would increase transmural pulmonary artery pressure (TPAP). ANIMALS: 6 horses. DESIGN: Horses were studied under 5 conditions: control conditions, after induction of left laryngeal hemiplegia, during obstruction of the left nostril, after placement of an instrumented tracheostomy, and after placement of an open tracheostomy. Horses were evaluated after being given saline solution and after being given furosemide. PROCEDURES: Horses were exercised on a high speed treadmill, using a maximum speed of 13 m/s. During each exercise, airway pressures, airflow, esophageal and pulmonary artery pressures, and blood gas partial pressures were measured. RESULTS: When adjusted for horse, speed, and obstruction condition, mean TPAP (pulmonary artery pressure-esophageal pressure) and minimum TPAP were significantly lower after administration of furosemide than after administration of saline solution. In horses given saline solution, respiratory obstruction that increased intrapleural pressure significantly increased mean TPAP, and respiratory obstruction that decreased intrapleural pressure significantly decreased minimum TPAP. CONCLUSIONS: Changes in intrapleural pressure appear to play an important role in pulmonary artery pressure and TPAP. CLINICAL RELEVANCE: Because induction of laryngeal hemiplegia did not increase TPAP, laryngeal hemiplegia is unlikely to contribute to development of exercise-induced pulmonary hemorrhage.     

Haloperidol and reduced haloperidol plasma concentrations after a loading dose regimen with haloperidol decanoate

1. Haloperidol and reduced haloperidol plasma levels were measured in schizophrenic patients who received both oral (10 mg, N=16 and 20 mg, N=4) and depot haloperidol treatment 2. Patients were of Asian ethnicity and were safely and effectively converted from oral to depot therapy using a loading dose regimen using a 100 mg weekly injection interval for 4 weeks, biweekly for one month and then monthly. 3. Significant correlations were found for plasma haloperidol and reduced haloperidol levels and reduced haloperidol/haloperidol ratios between oral and depot therapy in these non-smoking patients. 4. A loading dose regimen is needed due to the long elimination half-life of decanoate of 26 days otherwise steady-state condition will not occur until 34 months of therapy. 5. Patients were maintained on monthly depot treatment for 40 weeks after the loading dose regimen and only one patient relapsed during treatment despite dosage increases. 6. The formation of reduced haloperidol remained consistent for oral and depot haloperidol treatment.     

1997 Volvo Award winner in clinical studies. Degenerative lumbar spondylolisthesis with spinal stenosis: a prospective, randomized study comparing decompressive laminectomy and arthrodesis with and without spinal instrumentation

STUDY DESIGN: This prospective study analyzed the influence of transpedicular instrumented on the operative treatment of patients with degenerative spondylolisthesis and spinal stenosis. OBJECTIVES: To determine whether the addition of transpedicular instrumented improves the clinical outcome and fusion rate of patients undergoing posterolateral fusion after decompression for spinal stenosis with concomitant degenerative spondylolisthesis. SUMMARY OF BACKGROUND DATA: Decompression is often necessary in the treatment of symptomatic patients who have degenerative spondylolisthesis and spinal stenosis. Results of recent studies demonstrated that outcomes are significantly improved if posterolateral arthrodesis is performed at the listhesed level. A meta-analysis of the literature concluded that adjunctive spinal instrumentation for this procedure can enhance the fusion rate, although the effect on clinical outcome remains uncertain. METHODS: Seventy-six patients who had symptomatic spinal stenosis associated with degenerative lumbar spondylolisthesis were prospectively studied. All patients underwent posterior decompression with concomitant posterolateral intertransverse process arthrodesis. The patients were randomized to a segmental transpedicular instrumented or noninstrumented group. RESULTS: Sixty-seven patients were available for a 2-year follow-up. Clinical outcome was excellent or good in 76% of the patients in whom instrumentation was placed and in 85% of those in whom no instrumentation was placed (P = 0.45). Successful arthrodesis occurred in 82% of the instrumented cases versus 45% of the noninstrumented cases (P = 0.0015). Overall, successful fusion did not influence patient outcome (P = 0.435). CONCLUSIONS: In patients undergoing single-level posterolateral fusion for degenerative spondylolisthesis with spinal stenosis, the use of pedicle screws may lead to a higher fusion rate, but clinical outcome shows no improvement in pain in the back and lower limbs.     

Isolation and characterisation of nocardia from clinical specimens

Sixteen isolations of nocardia of which 12 were from pulmonary infections, one from wound infection, one from mycetoma and 2 from eye infections were studied from June, 1989 to May, 1990. The importance of Gram's stain findings of primary smear is being highlighted. The nocardia species were identified utilising the morphological characters including acid fastness and cultural and biochemical characters. Notable among the isolates were Nocardia brasiliensis, one each from mycetoma and pulmonary infection, which are rare in South India and Nocardia asteroides from a case of endophthalmitis probably of endogenous origin.     

Glucose dynamics during continuous hemodiafiltration and total parenteral nutrition

OBJECTIVE: To determine glucose balance during dextrose-free continuous hemodiafiltration with or without dextrose-containing ultrafiltrate replacement fluid and full nutritional support. DESIGN: Prospective, nonrandomized, observational study. SETTING: A 24-bed multiple trauma critical care unit in a level-I trauma center. PATIENTS: Seventeen multiple trauma patients with multiple organ dysfunction syndrome requiring hemodialysis for acute renal failure. INTERVENTIONS: Continuous hemodiafiltration effluent volume and glucose concentration were measured. Study days were classified according to whether dextrose was used in the ultrafiltrate replacement therapy. Use of dextrose in replacement therapy was determined clinically. Parenteral nutrition was not altered for potential glucose absorption from continuous hemodiafiltration. Ultrafiltrate replacement consisted of 5% dextrose in saline on 21 study days (D5YES) and dextrose-free solutions on 54 study days (D5NO). RESULTS: The D5YES group received 316 +/- 145 g glucose/day from the ultrafiltrate replacement fluid, in addition to glucose in total parenteral nutrition (total glucose intake = 942 +/- 229 g/day in D5YES, 682 +/- 154 g/day in D5NO) (p < 0.05). Glucose loss in continuous hemodiafiltration effluent was 82 +/- 61 g/day in D5YES and 57 +/- 22 g/day in D5NO (P < 0.05), for a net glucose uptake of 8.1 +/- 2.1 mg/kg per min in D5YES and 5.4 +/- 1.5 mg/kg per min in D5NO (p < 0.05). Glucose loss was predictable when dialysate and ultrafiltrate replacement fluids were dextrose-free (R2 = 0.77), but less so when dextrose was used as ultrafiltrate replacement (R2 = 0.47). CONCLUSION: Dextrose-free dialysate promotes glucose loss during continuous hemodiafiltration, but the loss is small and predictable. Use of a dextrose-containing ultrafiltrate replacement fluid results in a significant increase in glucose intake without a commensurate increase in glucose loss, and makes glucose loss in effluent less predictable.     

Effects of three prepubertal body growth rates on performance of Holstein heifers during first lactation

beta1A integrin subunits with point mutations of the cytoplasmic domain were expressed in fibroblasts derived from beta1-null stem cells. beta1A in which one or both of the tyrosines of the two NPXY motifs (Y783, Y795) were changed to phenylalanines formed active alpha5 beta1 and alpha6 beta1 integrins that mediated cell adhesion and supported assembly of fibronectin. Mutation of the proline in either motif (P781, P793) to an alanine or of a threonine in the inter-motif sequence (T788) to a proline resulted in poorly expressed, inactive beta1A. Y783,795F cells developed numerous fine focal contacts and exhibited motility on a surface. When compared with cells expressing wild-type beta1A or beta1A with the D759A activating mutation of a conserved membrane-proximal aspartate, Y783, 795F cells had impaired ability to transverse filters in chemotaxis assays. Analysis of cells expressing beta1A with single Tyr to Phe substitutions indicated that both Y783 and Y795 are important for directed migration. Actin-containing microfilaments of Y783,795F cells were shorter and more peripheral than microfilaments of cells expressing wild-type beta1A. These results indicate that change of the phenol side chains in the NPXY motifs to phenyl groups (which cannot be phosphorylated) has major effects on the organization of focal contacts and cytoskeleton and on directed cell motility.     

Hormonal studies and Doppler flow imaging of ovarian lipoid cell tumors: report of two cases

Ovarian lipoid cell tumors are very rare. We report two cases with abnormal menstruation, hirsutism, clitoromegaly and marked elevations of serum testosterone. Sonography revealed unilateral adnexal solid tumors. Flow velocity wave form study showed apparent flow within the tumor with the resistance index ranging from 0.42 to 0.49 in both cases. Unilateral oophorectomy and contralateral ovarian biopsy were performed. Frozen sections showed lipoid cell tumors without malignant change. During surgery, direct ovarian venipuncture showed a discrepancy in testosterone level in the bilateral ovaries of both patients and large ovarian-peripheral venous gradients in case 2. The testosterone concentration returned to normal postoperatively in both cases. Flow velocity wave form study and direct ovarian venipuncture are useful tools for evaluation of androgen-secreting tumors preoperatively and intraoperatively.