[Imaging of malignant bone tumors: impact of new imaging techniques on treatment methods].
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Biomedical subjects
Publications and source records attributed to M Forest.
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A parosteal osteosarcoma of the right radius has developed in a patient treated for a long time by etretinate (total dose: 73 g). If brachial ossifications have been reported to etretinate in 2 cases, they were benign tumours; so coincidence is possible in our case. Nevertheless, a relation between the tumour and the treatment cannot be excluded and justify the report of this observation.
Enzyme-inducing drugs such as phenobarbital (PB) increase serum concentrations of an acute-phase protein, alpha 1-acid glycoprotein (AGP), in man, dogs, and rats via an unknown mechanism. We studied the effects of PB on components of an acute inflammatory reaction in rats in order to determine if PB acts only on this biological marker of inflammation or is capable of altering the clinical course of inflammatory processes. Local carrageenan injection induces a similar time-dependent plantar edema and increases serum AGP levels in Sprague-Dawley (SD) and Dark Agouti (DA) rats. Pretreatment with PB for seven days modified neither parameter in SD rats while plantar edema was aggravated and serum AGP levels were increased in DA rats. The sedative-hypnotic properties of PB were not involved, since a single administration of this drug had no action in DA rats. On the other hand, chronic PB administration reduced the severity of an autoimmune disease, type II collagen-induced arthritis, in DA rats. These data indicate that PB, a potent inducer a cytochrome P-450-dependent enzymes, modifies the course of the inflammatory process. Preliminary results with macrophage transfer experiments suggest that this response to PB could be mediated by stimulated macrophages.
Bone infarction of the distal femur is reported in two patients with osteosarcoma of the leg (1 tibia, 1 fibula) treated by preoperative chemotherapy including intraarterial chemotherapy (IAC) by Cis-platinum. Both patients were examined by magnetic resonance imaging before chemotherapy and again prior to limb salvage surgery. The location of these lesions in the distal femur must suggest bone infarction especially if the tumor has decreased in size under treatment.
Revision surgery after failures of joint replacements leads to histological studies on joint and bone tissues close to the implanted material. Aspectic loosening is the main complication. The surgical pathologist has to identify wear debris (metal, polyethylene, polymethylmethacrylate, chiefly) which promotes a histiocytic granuloma. Some surgical procedures such as cup or resurfacing arthroplasties create a new articular surface and a bone remodeling or necrosis. Cemented joint prostheses show various membrane structures between bone and the cement mantle while there is an association of bone resorption and formation. Non-cemented, porous-coated joint prostheses induce little bone ingrowth, even in satisfactory clinical results. Mechanical factors are predominant in massive limb prostheses. For silicone elastomer implants or artificial ligaments, wear of material promotes many tissular reactions. Often used bone grafts show little creeping substitution process in case of homografts, even well-incorporated on X-rays. More retrieval specimen studies are necessary to delineate precise topographical histological lesions, including non-loosened joint implants.
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One hundred and seventy-eight patients suffering from 180 chondrosarcomas have been treated by the orthopaedic department of Cochin Hospital. Actuarial survival in these patients was 67 per cent after five years, 62 per cent after 10 years and 59 per cent after 15 years. The two main bases for survival prognosis were: --the histoprognostic grade in O'Neal and Ackerman's classification (survival after 5 years: 83 per cent for grade 1, 75 per cent for grade 2, and 15 per cent for grade 3); --the quality of the surgical resection (survival after 5 years: 78 per cent in cases of carcinological resection, and 52 per cent in cases of incorrect resection). Keeping the limb did not reduce the chances of a cure. Patients treated recently have a better prognosis than those treated before 1970: this improvement was mostly because carcinological treatment was used more often. The same prognostic factors govern local recurrences.
A series of analogues of neuropeptide tyrosine (NPY) was synthesized by solid-phase peptide synthesis using BOP as a coupling reagent for the complete synthesis. A structure-activity study of the N-terminal portion of the molecule was performed with the analogues obtained by the successive replacement of the first 10 amino acids by the residue L-alanine. NPY and its analogues [Ala1-10]hNPY were tested for their potency on rat vas deferens and for their affinity to central nervous system receptors on a rat brain membrane preparation. The results suggest that the hypothetical polyproline type II helix structure of the N-terminal segment is involved in both potency and affinity. Indeed, the substitution by L-Ala of proline residues in position 2, 5, or 8 showed important losses of activity and affinity. The more important losses were observed with the replacement of Pro-5 or Pro-8. A critical loss of potency of hNPY was also observed after the substitution of the Tyr-1 residue by L-Ala, thus confirming the important role played by this residue for the full expression of the biological activity of NPY.
The model peptide TRH was successfully synthesized using benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP reagent). The coupling reactions were carried out in N,N-dimethylformamide or N-methylpyrrolidone. These solvents allowed the incorporation of the N-terminal pyroglutamic acid residue into the peptide chain, without using the derivative bearing the N-benzyloxycarbonyl group, which acts as a solubility promoter. A comparative racemization study showed that Boc-His(Tos) can be coupled by means of BOP reagent with less racemization than with DCC when the amount of diisopropylethylamine (DIEA) is kept minimal (same ratio of equivalents as for Boc-His(Tos), i.e. 3 equiv.). However, with the use of a larger amount of DIEA in the coupling mixture (9 equiv.), approximately 3% of epimer was found in the crude product. Our study showed that even under low DIEA conditions, the rate of coupling of the residues with BOP remained comparable to that observed with DCC.
A series of fragments and analogues of neuropeptide Y (NPY), both human (hNPY) and porcine (pNPY), were synthesized and tested for their affinities at brain NPY receptor binding sites and their potencies in inhibiting the electrically stimulated twitch response of rat vas deferens. Results with N- and C-terminal fragments suggest that amino acid residues in the N-terminal portion of the molecule are mostly important for recognition of brain and vas deferens NPY receptors, in addition to being relevant for the maintenance of adequate receptor affinity. On the other hand, C-terminal amino acid residues appear to be responsible for triggering receptor activation in the rat vas deferens preparation, because full intrinsic activity is maintained with fragments up to NPY18-36. C-terminal fragment NPY25-36 and N-terminal fragment NPY1-15 were devoid of affinity for [3H]NPY brain receptor sites and showed no activity in the rat vas deferens preparation. Similarly, N-terminal fragment hNPY1-24CONH2 showed no affinity toward [3H]NPY brain receptor sites and no inhibition of the twitch response in the rat vas deferens preparation at concentrations up to 1.0 microM. On the contrary, this fragment appears to selectively increase the amplitude of the twitch response to electrical stimulation at low micromolar concentrations, an effect opposite to that of NPY and all other NPY fragments and analogues studied here. The exact mechanism mediating this contractile action of hNPY1-24CONH2 remains to be established. Modifications of the tyrosine residue in position 20 led to the development of two analogues, [D-Tyr20]hNPY and [D-Trp20]hNPY, which show an apparent preference for the vas deferens NPY receptor. On the other hand, substitutions of the tyrosine residue in position 21 by a phenylalanine ([Phe21]hNPY) or a methylated tyrosine residue ([Tyr-O-Me21]hNPY) produced analogues demonstrating an apparent preference for the brain receptor site. This suggests that modifications of tyrosine residues at positions 20 and/or 21 may eventually lead to the development of NPY analogues distinguishing between the most abundant class of sites present in the brain and vas deferens, respectively.
Massive bone allografts from cadavers have been sterilised by gamma-radiation from radioactive cobalt at a dose of 25,000 gray (Gy). The biological effects of radiation are discussed. Human cortical bone showed an acceptable 20% decrease in strength on bending tests after 27,000 Gy irradiation, but higher doses are more damaging and should be avoided. The procurement protocol used at the Cochin Hospital is described, and the importance of dosimetry and record-keeping emphasised. The clinical results of 150 massive bone allografts are reported. The infection rate was low. The evolution of the graft in each type of reconstruction is analysed and appears to be comparable to nonirradiated allografts. Very few complications occurred after composite reconstructions in the lower limb. Pelvic reconstructions had the highest complication rate, but most were not related to the use of the allograft.
The reported case is characterized by the original tumor site as well as by the recurrence site; by the slowly evolutive nature of the lesion over nine years from the time of surgical tumor excision to relapse; and by histological variations raising a nosological problem. Our clinical, anatomopathological and therapeutical observations are based on the characteristics of the case as well as published data. We only traced 5 cases in the literature of spermatic cord tumors with retroperitoneal localization. The progressive histologic polymorphism of these tumors compels us to raise the question of the very nature of this neoplasm: liposarcoma or malignant mesenchymoma. The potential clinical and histologic outcome of mesenchymal tumors of the spermatic cord cause us to propose direct orchidectomy and surveillance of the retroperitoneal space throughout the evolution of the process, even far off into the future.
Thirty cases of chondroblastoma treated (between 1950 and 1986) at the Cochin-St-Vincent de Paul group of hospitals in Paris were reviewed. The most frequent sites (63 per cent) were the proximal epiphyses of the femur, humerus and tibia. The male predominance is clear (63 per cent) and the lesion was generally discovered in the second decade of life (66 per cent). Three cases of intra-articular invasion were noted, of which one involved a meniscus. The treatment was surgical in every case (two cases had adjuvant radiotherapy besides, because of an initial erroneous diagnosis of malignancy). Five recurrences were noted, of which only one involved the soft tissues. Curettage with bone grafting has to be preferred to simple biopsy curettage which leads to 33 per cent of recurrences as against 6 per cent. Histological association with areas of aneurysmal cysts is not a factor predisposing to recurrence. No progression to malignancy was noted. Apart from infection following a joint replacement, no other complications, resulting from surgical treatment were noted.
According to the 2-cell theory, ovarian steroidogenesis requires the coordinate action of both FSH and LH. To evaluate the relative importance of these hormones in follicular maturation, a randomized cross-over study was performed in 10 women with complete gonadotropin deficiency (absence of pulsatile LH secretion and no LH response to LHRH). Five women were treated with highly purified FSH (LH bioactivity, 0.09%) and 3 months later with human menopausal gonadotropin (hMG; LH bioactivity, 65%), each given for 10 days at a daily dose of 225 IU FSH, im. The sequence was reversed in the other 5 women. hCG (5000 IU) was administered im 24 h after the last injection of FSH or hMG. Plasma estradiol (E2), estrone (E1), androstenedione (A), testosterone, LH, and FSH concentrations and urinary LH and FSH were measured daily by RIA. Ultrasonography was performed during each treatment and 2 days after each hCG injection. After FSH treatment, mean plasma and urinary FSH levels increased, mean plasma LH did not change, and urinary LH increased slightly but not significantly from 91 +/- 32 (SE) to 164 +/- 55 mIU/24 h (10(-3) IU/24 h). After hMG treatment, mean plasma and urinary LH and FSH levels increased accordingly. The mean basal plasma E2 [11 +/- 1 pg/mL (40 +/- 4 pmol/L)] and E1 [14 +/- 4 pg/mL (52 +/- 15 pmol/L)] levels increased after FSH treatment to 207 +/- 69 pg/mL (760 +/- 253 pmol/L) and 82 +/- 21 pg/mL (303 +/- 78 pmol/L), respectively (P less than 0.01), but plasma A did not change. In response to hMG, the mean plasma E2, E1, A, and testosterone levels increased more than during FSH treatment. Ultrasonography revealed multiple preovulatory follicles (greater than or equal to 16 mm) in 2 women after hMG and 1 woman after FSH treatment; therefore, hCG was not administered. In 3 women given FSH, hCG did not induce ovulation. hCG induced ovulation in 8 women given hMG and in 6 women given FSH, based on ultrasonography and plasma progesterone levels. Thus, in the presence of profound gonadotropin deficiency pharmacological doses of FSH, with minute LH contamination, are capable of stimulating ovarian follicular maturation, underlining the key role of FSH in folliculogenesis.
A series of 14 cases of circumscribed nontraumatic myositis ossificans is presented. It is important to recognize the clinical and radiographic findings of this benign entity whose appearance, especially early on, simulates a neoplasm. The natural history and therapeutic indications are also described.
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