A new histologic approach to the differentiation of enchondroma and chondrosarcoma of the bones. A clinicopathologic analysis of 51 cases

Fifty-one cases of central, hyalin cartilage tumors of the long and flat bones were analyzed. Although Grade 2 and 3 chondrosarcomas could be diagnosed on the basis of cytologic features alone, low-grade chondrosarcoma could not be adequately differentiated from pure, benign enchondroma(s) by cytology alone. The tumors can be distinguished by a new histologic approach based on tissue patterns. The crucial enchondroma patterns consist of multiple nodules of hyalin cartilage separated by normal marrow in conjunction with partial to complete encompassing plates of lamellar bone that conform to the irregular shapes of the cartilage nodules. The chondrosarcomatous patterns consist of a single confluent mass of cartilage, which commonly permeates the marrow, "trapping" host lamellar bone on all sides, and which forms bands of fibrosis between the confluent peripheral cartilage lobules. Other less common patterns included cartilagenous infiltration of the Haversian systems or marrow fat and/or the development of a soft tissue mass. A central secondary chondrosarcoma is defined as one that shows the combination of both the enchondromatous and chondrosarcomatous patterns. All 18 of the pure enchondromas diagnosed by the methods proposed in this article behaved with strict benignity (i.e., without evidence of recurrence or metastasis with an average follow-up period of 7.2 years). The 33 primary and secondary chondrosarcomas diagnosed using the described patterns behaved with the predicted frequency of recurrence, metastasis, and patient demise.     

Number of cortisol time-points and dexamethasone suppression test sensitivity for major depression

Failure to suppress cortisol secretion after administration of dexamethasone has been reported to be a diagnostic marker for major depression and to have prognostic implications when repeated after antidepressant treatment. The pulsatile pattern of cortisol secretion suggested to us that increasing the number of post-dexamethasone cortisol determinations might significantly increase the sensitivity of the dexamethasone suppression test (DST) for major depression. With a conventional two-point DST (1600 h and midnight), 5% of 20 normal volunteers, 8% of 13 inpatients with non-major depressions, and 31% of 65 inpatients with primary major depression failed to suppress. With six post-dexamethasone points (0800 h, 1200 h, 1600 h, 2000 h, 2200 h, midnight), the respective percentages were 10, 15 and 44%. The additional points increased the sensitivity from 31 to 44%, mostly by identifying more major depressives with a "late escape" pattern. If a clinician is using the DST to establish a marker for major depression that can be repeated to monitor response to treatment and the likelihood of relapse, then perhaps the increased sensitivity of the six-point DST would be helpful, despite a modest decrease in specificity from 94 to 88%.     

"High-dose" calcitriol for control of renal osteodystrophy in children on CAPD

High doses of calcitriol were used prospectively for 11 to 29 months to raise serum calcium levels in an effort to control renal osteodystrophy in 16 children undergoing CAPD. Serum Ca, P, iPTH and alkaline phosphatase were measured monthly; hand radiographs were obtained every six months, and a semiquantitative score of bone abnormalities was evaluated by two independent observers. During the study, serum Ca increased from 9.9 +/- 0.9 to 11.0 +/- 0.6 mg/dl (P less than 0.001); serum iPTH decreased by 113 +/- 131 microliter Eq/ml (P less than 0.005); serum P was unchanged; and serum alkaline phosphatase fell by 33 +/- 46% (P less than 0.02), 530 +/- 397 to 204 +/- 551 IU/liter. The radiographic score fell from 4.8 +/- 4.6 to 0.9 +/- 1.2 (P less than 0.005). The average and maximal doses of calcitriol were 0.61 +/- 0.37 and 0.95 +/- 0.56 microgram/day or 28 +/- 18 and 46 +/- 28 ng/kg body wt/day, respectively. Transient and asymptomatic hypercalcemia occurred in nine patients and two patients had reversible conjunctivitis in association with the hypercalcemia. Thus, "high dose" calcitriol prevented or controlled progression of hyperparathyroid bone disease in most pediatric CAPD patients. The failure to suppress PTH or reverse secondary hyperparathyroidism until the serum Ca rose to 10.5 to 11.0 mg/dl could reflect an increase in the "set point" for PTH suppression by serum calcium in many uremic children.     

The effect of subchronic feeding of 1,1-dichloro-2,2-bis(4'-chlorophenyl)ethene (DDE) on its metabolism in mice

1,1-Dichloro-2, 2-bis(4’-chlorophenyl)ethene (DDE), amajor lipophilic metabolite of 1,1,1-trichloro-2, 2-bis(4'-chloro-phenyDethane(DDT), is a hepatic carcinogen in both the mouse and hamsterupon chronic exposure. DDT is tumori-genic only in the formerspecies. The metabolism in the mouse of [¹⁴C-UL-phenyl]DDE withand without 5-month DDE pretreatment, is reported. The urine,feces and liver were analyzed and in all cases most of the radioactivityobserved was identified as unchanged DDE. The only metaboliteidentified was the phenolic derivative l, l-dichloro-2-(4’-chloro-phenyl)-2-(3"-hydroxy-4"-chlorophenyI)ethene,which was found in significant amounts only in the feces. Noother potential metabolites derived from the oxidation of DDEwere observed. The effect that pretreatment with DDE had onits own metabolism was to decrease the urinary excretion ofDDE and to increase the hepatic levels. It appears from theseresults that any oxidative metabolism of DDE constitutes a veryinsignificant pathway in the mouse. It is also concluded thatthere is no significant change in the metabolism of DDE afterprolonged exposure to the pesticide, and there is no indicationfor the metabolism of DDE to a reactive electrophilic species.     

Sizes, laminar and topographic origins of cortical projections to the major divisions of the red nucleus in the monkey

The retrograde transport of horseradish peroxidase was used to study the topographic and laminar origins of the cortical projections to the parvocellular and the magnocellular divisions of the red nucleus in Macaca mulatta and Macaca fascicularis. Approximately 90% of the corticorubral projection is directed to the parvocellular division of the nucleus. Corticoparvocellular (CRp) neurons are pyramidally shaped, are smaller in size than corticospinal neurons, and are more numerous. They are found principally in sublamina Va of cytoarchitectonic areas 4 and 6, and in moderate quantities in sublamina Vb of posterior area 8 and area 5. In areas 4 and 6, the cells are grouped in clusters of three to 15 neurons each and are arranged in cellular bands of varying rostrocaudal thickness which course mediolaterally. With respect to functionally defined zones, CRp neurons are found throughout the supplementary motor area and the precentral motor cortex. In addition, they are found in parts of areas 5, 6, and 24 that project to these cortical motor areas, and that are thought to have "premotor" or movement-programming functions. The corticomagnocellular (CRm) projection arises principally from cells in sublamina Vb of the precentral arm and leg areas (area 4), and from adjacent parts of posterior area 6, CRm cells are pyramidally shaped, and their size distribution is bimodal, with peaks that correspond, respectively, to the modal diameters of CRp and of corticospinal neurons. These results and those of previous studies suggest that CRm neurons are involved principally in the control of hand and foot movements, with little effect on more proximal musculature. The massive CRp projection, however, is clearly part of a large cerebrocerebellar communication system, with motor and/or movement programming functions that have yet to be clearly defined.     

Primary repair with semitendinosus tendon augmentation of acute anterior cruciate ligament injuries

A retrospective review of 72 acute ACL injuries in 70 athletically active patients (50 recreational and 20 competitive athletes) treated with primary repair and semitendinosus tendon augmentation was conducted (mean follow-up time, 38.5 months). All patients had open primary multiple loop depth-varying suture repair and semitendinosus tendon augmentation at a mean injury to surgery interval of 9.1 days. Fifty-one cases (70.8%) were supplemented with an extraarticular procedure consisting in all cases of an iliotibial band lateral sling reinforcement. All patients underwent 6 weeks of postoperative immobilization followed by a graduated rehabilitation regimen lasting a mean 7.2 months. In 22 of the ACL tears, no other associated injury could be defined at arthrotomy, while in 27, significant medial collateral ligament injuries were noted. Lateral meniscal injuries (24) were more commonly noted than medial meniscal injuries (19). Good to excellent subjective results were reported in 82%, while 77.1% returned to preinjury sport level and participation without limitation. One patient developed "giving way" symptoms and overall, only four patients did not return to sports participation. Objective examination revealed 93.1% to have a 1+ or less Lachman test and 86.1% to have a negative pivot shift. Of 60 knees tested, 93.3% had KT-1000 side-to-side difference values (measured at 25 degrees +/- 5 degrees of flexion with an 89 N load) of less than or equal to 3 mm of anterior displacement. A 100 point Hospital for Special Surgery ligament rating score was used with 25 points assigned to subjective, 45 points to objective, and 30 points to functional assessment. The mean score at followup was 93.1. Analysis of results in patients with or without an extraarticular reinforcement revealed no difference in objective outcome. The incidence of patellofemoral pain was 27.8%. Thirty knees had some degree of loss of range of motion. Loss of terminal flexion was noted in 29, while 5 had loss of terminal extension. No correlation could be found between patellofemoral pain and diminished range of motion. Generalized ligamentous laxity was found in 37.1% of the patients; this was not associated with a poor result. This study suggests that primary repair with semitendinosus tendon augmentation of acute ACL injuries with a graduated rehabilitation regimen provides good subjective, and excellent functional and objective, results in active patients that were followed for more than 3 years.     

Domains of initiator tRNA and initiation codon crucial for initiator tRNA selection by Escherichia coli IF3.

Initiation factors are used by Escherichia coli to select the initiator tRNA over elongator tRNAs during translation initiation. IF3 appears to "inspect" the anticodon end of the tRNA, probably along with the initiation codon. The anticodon stem and loop of the initiator tRNA, together with part of the initiation codon of the mRNA, can be thought of as a unit. Changes made in the anticodon stem, the anticodon loop, or the anticodon of an initiator tRNA fragment result in a loss of selection by IF3 in an in vitro assay for translation initiation. IF3 allows the selection of an initiator tRNA anticodon stem and loop fragment on GUG and UUG codons but does not select that tRNA fragment in response to AUU.