Survival of multiple myeloma patients who are potential candidates for early high-dose therapy intensification/ autotransplantation and who were conventionally treated

PURPOSE: To analyze the outcome of patients with multiple myeloma (MM) who were potential candidates for early high-dose therapy (HDT) intensification followed by autotransplantation from a series treated with conventional chemotherapy. PATIENTS AND METHODS: From January 1985 through December 1989, 487 patients with symptomatic MM were entered onto a randomized study to compare melphalan and prednisone (MP) versus vincristine, cyclophosphamide, melphalan, and prednisone (VCMP) /vincristine, carmustine (BCNU), doxorubicin, and prednisone (VBAP). The sub-group of 77 patients who could have been candidates for early intensification with HDT followed by stem-cell support (ie, < 65 years of age, stage II or III disease, performance status < 3, and objective or partial response to initial chemotherapy) are the subjects of this report. RESULTS: Seventy-seven of 487 patients could have been candidates for early intensification. The median age was 56 years (range, 27 to 64). At diagnosis, 12% had abnormal renal function, 16% hypercalcemia, and 42% serum beta 2-microglobulin level > or = 6 mg/L; 62% had stage III disease at diagnosis. Thirty-six patients were initially treated with MP and 41 with VCMP/VBAP. The median response duration to initial chemotherapy was 22 months, and the actuarial probability of being in continued first response at 5 years was 14%. After a median follow-up time of 58 months, 59 patients have died, one was lost to follow-up evaluation, and 17 are still alive 69 to 119 months after initial chemotherapy. The median survival time from initiation of treatment was 60 months and from the time when autotransplantation would be considered, 52 months. The only independent prognostic parameter for survival was renal function at diagnosis. CONCLUSION: The median survival time of patients with MM who are less than 65 years of age and who respond to initial chemotherapy is 5 years. This survival duration is similar to that reported in selected series of patients given early HDT and stresses the importance of ongoing randomized trials to determine the role of HDT in the treatment of younger myeloma patients.     

Role for macrophage inflammatory protein-2 in lipopolysaccharide-induced lung injury in rats

Macrophage inflammatory protein-2 (MIP-2) is a C-X-C chemokine that possesses chemotactic activity for neutrophils. Rat MIP-2 was cloned and expressed as a 7.9-kDa peptide that exhibited dose-dependent neutrophil chemotactic activity at concentrations from 10 to 250 nM. Rabbit polyclonal Ab to the 7.9-kDa peptide showed reactivity by western blot analysis and suppressed its in vitro chemotactic activity. Cross-desensitization chemotaxis experiments suggested that the chemotactic responses elicited by MIP-2 and the related chemokine, cytokine-induced neutrophil chemoattractant, may be mediated through a common receptor. Also, chemotactic responses to human GRO-alpha were blocked by exposure of human neutrophils to either GRO-alpha or rat MIP-2, suggesting conservation of this receptor-mediated response. After LPS instillation into rat lung, mRNA for MIP-2 was up-regulated in a time-dependent manner, peaking at 6 h. MIP-2 protein was detected in bronchoalveolar lavage fluids of these animals and a significant amount of chemotactic activity present in these fluids was attributed to MIP-2. On the basis of intrapulmonary instillation of Ab to MIP-2, neutrophil accumulation in lungs after airway instillation of LPS was found to be MIP-2-dependent. These data indicate that MIP-2 plays a significant role in LPS-induced inflammatory response in rat lungs and is required for the full recruitment of neutrophils.     

Repeated bile acid therapy for the long-term management of cholesterol gallstones

BACKGROUND/AIMS: Following non-surgical treatment, cholesterol gallstones recur in a high proportion of patients, and recurrence cannot be predicted nor effectively prevented. Our aim was to test prospectively the viability and the efficacy of repeated bile acid therapy, in which recurrent stones are diagnosed at an early stage by regular ultrasound monitoring and promptly retreated, as a strategy for the management of these patients in clinical practice. METHODS: One hundred and seventy-two consecutive patients were recruited upon achieving complete gallstone dissolution using non-surgical therapy (bile acids or lithotripsy plus bile acids), and followed up at 6-monthly intervals by ultrasound scan. Gallstone recurrence was promptly treated by a combination of ursodeoxycholic acid plus chenodeoxycholic acid (5 mg/kg per day each) for a period of 2 years, or less if complete redissolution was achieved. Median follow-up period was 34 months (range 6-70). RESULTS: Forty-five patients had gallstone recurrence; of these, 39 underwent one or more repeated courses of bile acid therapy (follow-up data available in 27). Gallstone recurrence rate was 15% at 1 year and 47% at 5 years. Average annual redissolution rate of recurrent gallstones (intention to treat) was 41%. The proportion of gallstone-free patients in the whole population was 88%, 84%, 77%, 78%, 75% at 1-5 years, respectively, and rose to > 90% at 3 years onwards in patients with single primary stones. CONCLUSIONS: We conclude that repeated bile acid therapy maintains the majority of patients gallstone free, and is therefore an effective long-term management strategy, especially in patients with primary single gallstones.     

Sire breed of calf influences peripartum endocrine profiles and postpartum anestrus in Brahman cows

The literature indicates that sire breed of calf influences beef calf performance. However, there is little information concerning sire breed of calf effects on reproduction in beef cows. In this experiment, Angus (A), Brahman (B), or Tuli (T) bulls were bred to 136 Brahman (B) cows to examine sire breed of calf influence on peripartum hormone profiles and the length of postpartum anestrus. Cows were bled from 7 d prepartum to 28 d postpartum to determine peripartum hormone concentrations. Cows carrying AB calves had greater (P < 0.05) prepartum estradiol-17 beta concentrations than did cows carrying BB and TB calves. Prepartum and postpartum progesterone concentrations did not differ between cows with AB, BB, and TB calves. Cows with TB calves had lower (P < 0.01) 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) concentrations than did cows with AB and BB calves during the early postpartum period. Adjusting for birth weight removed the sire breed of calf effect on postpartum PGFM concentrations, but not prepartum estradiol-17 beta. Postpartum anestrus was shorter (P < 0.05) for cows nursing BB calves (84 +/- 6 d) than for cows nursing AB (101 +/- 6 d) or TB calves (110 +/- 7 d). Adjustment for estradiol or PGFM concentrations did not reduce sire breed of calf effects on the length of postpartum anestrus. Further work is heeded to determine how calf genotype may modulate the postpartum reproductive function of the dam.     

Primary craniosynostosis: imaging features

In 1851, Virchow introduced the term craniosynostosis to describe a variety of abnormalities in calvarial growth. These skull deformities are usually apparent in infancy. When an abnormal calvarial configuration is detected, a radiologic evaluation is necessary to characterize the deformity and to guide the corrective surgical procedure. Affected children are believed to have an improved outcome when diagnosis and surgical intervention occur at an early age. CT with three-dimensional reconstruction optimally evaluates the presence and degree of sutural involvement and assesses associated facial and intracranial abnormalities. This pictorial essay illustrates the imaging findings, nomenclature, and associated abnormalities of the various types of primary craniosynostosis.     

Spinal epidural abscess: evaluation of factors influencing outcome

OBJECTIVE: The goal of this study was to critically evaluate the predictive efficacy of various clinical factors in spinal epidural abscess influencing outcome after surgical and/or medical treatment. METHODS: A retrospective analysis of 41 cases of spinal epidural abscess treated at Henry Ford Hospital between 1984 and 1992 was performed. RESULTS: Thirty patients underwent open surgery and received antibiotic therapy, and 11 patients received medical treatment alone. After a mean follow-up period of 20.9 months (range, 4-45 mo), 24 patients (58.5%) had no or minimal deficits, 9 patients (22%) had severe paresis or plegia and/or bowel/bladder dysfunction, and 8 patients (19.5%) died. Univariate analysis revealed patient age, degree of thecal sac compression, spinal location, surgical findings, and septic presentation to be significantly associated with outcome. In multiple logistic regression analysis, increasing age and degree of thecal sac compression were the only factors with significant independent association with poor outcome (P = 0.01 for both). A simple grading system (Grades 0-III) was developed, with patient age, degree of thecal sac compression, and duration of symptoms as the determining criteria. The incidence of poor outcome for patients with Grade 0 was 0%, compared to 85.7% for patients with Grade III. CONCLUSION: We conclude that long-term outcome after treatment of spinal epidural abscess can be predicted with the use of the proposed grading scheme. Surgical drainage plus parenterally administered antibiotics remains the recommended treatment, although medical treatment alone can also be used for certain patients.     

Left ventricular ejection fraction: comparison of results from planar and SPECT gated blood-pool studies

Global ejection fraction (EF) from planar gated blood-pool (GBP) imaging is a widely accepted measure of cardiac function. It has been suggested that planar GBP could be replaced by SPECT. In this article, we compare counts-based global EF measured from SPECT and planar images and investigate reasons for discrepancies between the two. METHODS: Twenty-three subjects were imaged with both planar and SPECT GBP. SPECT short-axis slices were projected to create reprojected images. Reprojected SPECT (rSPECT) images were created in both the true long-axis view and also in a view typical of planar studies (found to be 60 degrees from the true long-axis). Thus, angle of view effects on global EF could be investigated. In addition, we studied the effects of background and attenuation. RESULTS: Long-axis rSPECT EF correlated well with planar EF (r = 0.89) but EF values were significantly higher for rSPECT than for planar (slope = 1.4, intercept = -8 EF units; p < 0.001). We found that background correction may not be necessary with rSPECT, but neither background nor attenuation explained the observed discrepancy between rSPECT and planar EFs. This discrepancy was found to be caused by atrial overlap in the planar image and disappeared when the SPECT slices were reprojected at the same angle of view as the planar images. CONCLUSION: Global EF can be easily measured from rSPECT GBP images. Long-axis rSPECT EFs are, however, greater than planar EFs by a factor of 1.4 because atrial overlap causes a significant drop in planar EF in planar images. These results suggest that (long-axis) rSPECT EFs may be more accurate than planar EFs.     

Characterization of PepB, a group B streptococcal oligopeptidase

Group B streptococci were recently reported to possess a cell-associated collagenase. Although the enzyme hydrolyzed the synthetic collagen-like substrate N-(3-[2-furyl]acryloyl)-Leu-Gly-Pro-Ala, we found that neither the highly purified enzyme nor crude group B streptococcal cell lysate solubilized a film of reconstituted rat tail collagen, an activity regarded as obligatory for a true collagenase. We cloned and sequenced the gene for the enzyme (pepB). The deduced amino acid sequence showed 66.4% identity to the PepF oligopeptidase from Lactococcus lactis, a member of the M3 or thimet family of zinc metallopeptidases. The group B streptococcal enzyme also showed oligopeptidase activity and degraded a variety of small bioactive peptides, including bradykinin, neurotensin, and peptide fragments of substance P and adrenocorticotropin.