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Biomedical subjects

J M Berthelot

Publications and source records attributed to J M Berthelot.

At least 19 recordsLinked to original sources
PubMed1996

Selection of T cells reactive against autologous B lymphoblastoid cells during chronic rheumatoid arthritis.

The repertoire and Ag specificity of T cells infiltrating inflamed joints from a chronic rheumatoid arthritis (RA) patient were studied in detail. Repertoire analysis demonstrated a reduced clonality of joint-infiltrating lymphocytes (JIL) as compared with patient's PBL, which was presumably due to an intra-articular expansion of T cell clones with recurrent TCR features. Strikingly, a large fraction of these JIL T cell clones, which were predominantly CD8+, proliferated in vitro when exposed to autologous B lymphoblastoid cells (BLC), unlike randomly chosen PBL clones derived from the same patient. This proliferative response was HLA-restricted, which confirmed a classical TCR-mediated recognition of BLC and was not observed against autologous PHA blasts, suggesting recognition of either EBV or B cell-specific Ags. Finally, a preliminary analysis of synovial lymphocytes derived from another chronic RA patient demonstrated a similar enrichment for T cells reactive against autologous BLC within JILs as compared with patient's PBLs. Taken together, these results, which suggest frequent expansions of autologous BLC-reactive T cells within inflamed joints of chronic RA patients, provide a basis for future studies evaluating the fine specificity and pathogenicity of these lymphocytes.

Adult↗
PubMed1996

T cell response to Epstein-Barr virus transactivators in chronic rheumatoid arthritis.

Rheumatoid arthritis is a multistep disorder associated with autoimmune features of yet unknown etiology. Implication of viruses such as Epstein-Barr virus (EBV) in rheumatoid arthritis pathogenesis has been suspected on the basis of several indirect observations, but thus far, a direct link between EBV and rheumatoid arthritis has not been provided. Here we show that a large fraction of T cells infiltrating affected joints from a patient with chronic rheumatoid arthritis recognizes two EBV transactivators (BZLF1 and BMLF1) in a major histocompatibility complex-restricted fashion. Responses to these EBV antigens by synovial lymphocytes from several other chronic rheumatoid arthritis patients were readily detectable. Thus these results suggest a direct contribution of EBV to chronic rheumatoid arthritis pathogenesis. They also demonstrate for the first time the occurrence of T cell responses against EBV transactivating factors, which might be central in the control of virus reactivation.

Animals↗
PubMed1996

The economics of lung cancer management in Canada.

Because lung cancer is a major health care problem in Canada, it is imperative to understand how resources are used to diagnose and treat this disease. This paper describes a method of modelling the direct patient care costs for lung cancer from the perspective of the government as payer in a universal health care system. Clinical algorithms were developed to describe the management of non-small cell (NSCLC) and small cell (SCLC) lung cancer. Patients were allocated to the treatment algorithms in the model based on a knowledge of their distribution by cell type and stage in Canadian cases. A microsimulation model developed by Statistics Canada was used to integrate the data on type of lung cancer, extent of disease, clinical management, survival and health care resource utilization. The direct care costs for diagnosis and treatment of NSCLC ranged from $Cdn 17 889 for the surgery/post-operative radiotherapy treatment of Stages I and II to $Cdn 6333 for supportive care for patients with Stage IV disease. The costs of determining relapse for NSCLC were estimated to be $Cdn 1528 and terminal care costs, made up largely of hospitalization charges and some palliative radiotherapy, were $Cdn 10 331. Direct care costs for the diagnosis and initial treatment of SCLC ranged from $Cdn 18 691 for management of limited stage disease to $Cdn 4739 for the supportive care of patients with extensive disease. The cost of determining relapse for SCLC was estimated to be $Cdn 1590 and terminal care costs averaged $Cdn 9966. For all 15 624 cases of lung cancer diagnosed in Canada in 1988, it was estimated that the total cost of providing treatment and follow-up, and managing relapse over 5 years was $Cdn 328 million. Despite the large total cost of lung cancer management, estimates of cost effectiveness of therapy showed that the cost per life year gained was approximately $Cdn 11 000 for NSCLC and $Cdn 19 560 for SCLC. These estimates of the direct health care costs assume that all patients have access to care, treatment is uncomplicated and practice is standard, and must be viewed as an idealized assessment of the cost of lung cancer management. The microsimulation model, however, does provide a useful framework for evaluating the costs of new diagnostic procedures, treatment strategies and new drugs.

Canada↗
PubMed1996

Rheumatoid arthritis as a bone marrow disorder.

Both the concept of rheumatoid arthritis (RA) as an autoimmune process restricted to joints and the major role of T cells in its pathogenesis have been challenged in the literature. Fibroblastlike and macrophagelike synoviocytes play an important role in RA pannus, and these cells originate in or have their counterpart in bone marrow (BM). Yet the B cell autoimmunity characteristic of RA occurs early, and synovial tissue, like BM, favors the B cell response. Because BM is abnormal in RA, and because germinal centers are unique to RA synovium, RA could be regarded as a disorder of the microenvironments able to sustain B cell response. In fact, RA could even begin in BM, with its onset facilitated by stem cell abnormalities. Moreover, most viruses suspected of playing a role in RA share a BM tropism. This may explain why RA frequently overlaps with other autoimmune disorders and benign lymphoproliferations, such as large granular T lymphocytosis. Because remissions from RA have been reported after BM transplantation, careful studies of the rheumatological outcome of RA patients undergoing such therapeutic procedures are needed. Although RA is a complex process, it can be considered initially as a stem cell disorder requiring treatment similar to that administered to transplant patients. Animal models have provided convincing evidence for these assumptions.

Animals↗
PubMed1996

Assessment of the efficacy of sacroiliac corticosteroid injections in spondylarthropathies: a double-blind study.

Despite previously carrying out a first open study of sacroiliac injection of long-acting corticosteroid, it was not possible to evaluate the role of a placebo effect. We therefore performed a double-blind study in 10 patients/13 articulations, suffering painful sacroiliitis. At 1 month, 5/6 sacroiliac joints injected with corticosteroid described a relief of > 70%, in comparison to 0/7 of the placebo group (P < 0.05). Dolometry showed a marked decrease in the corticosteroid group from (mean +/- S.E.M.) 6.8 +/- 0.6 to 1.3 +/- 0.3, and decreases were mild in the placebo group: 7.0 +/- 0.6 to 5.2 +/- 0.5 (P < 0.005). Six of the seven sacroiliac joints of the placebo group and two patients with failure and relapse of the corticosteroid group were reinjected with corticosteroid. At 1 month, 12/14 (85.7%) were assessed as having a good result. Results were still significant at 3 months (62%) and 6 months (58%). Tolerance was good or very good in 86% of the cases, and we did not report any notable complication. This technique is safe and very efficient, and it has to be considered more widely in patients with contraindications or complications with NSAID, or if the medical treatment is unable to control sufficiently the active sacroiliitis.

Adrenal Cortex Hormones↗
PubMed1996

Follow-up of bone mineral density in 27 cases of anorexia nervosa.

Cortical and trabecular bone loss can lead to osteoporosis in chronic forms of anorexia nervosa (AN). As there is some debate about the reversibility of this condition, we performed a longitudinal follow-up study of 27 cases in which clinical, biological, X-ray and lumbar and femoral neck dual photon absorptiometry examinations were conducted every 6 months for up to 30 months. Three groups were distinguished: G1, untreated amenorrheic AN (N = 14, total follow-up 126 months); G2, effectively treated AN (N = 11, total follow-up 192 months), with two subgroups: fluoride (N = 5) and estrogen (N = 6); and G3, remitting AN with normalization of the gonadic function (N = 2, total follow-up 36 months). Results were adjusted for each patient to a 6-month variation. Semestrial variations in lumbar bone mineral density (BMD) were -2.1 +/- 1.3%, +2.8 +/- 1.5%, and -0.3 +/- 1.3% (mean +/- SEM), respectively for G1, G2 and G3; those for femoral neck BMD semestrial variations were -5.9 +/- 2.1%, -3.8 +/- 1.2% and -1.0 +/- 0.6%. Femoral neck and lumbar BMD variations for G1 were mainly correlated positively with bone-forming markers (serum osteocalcin, alkaline phosphatase) and negatively with initial lumbar BMD. Estrogen alone increased lumbar BMD by +1.4 +/- 2.3% every 6 months but did not stabilize femoral neck BMD (-3.5 +/- 1.4%). Fluoride increased lumbar BMD by 4.8 +/- 1.8%. Both lumbar and femoral neck BMD were stabilized in the remission group (-0.3 +/- 1.3% and -1.0 +/- 0.6%), despite half of the follow-up time with amenorrhea. In conclusion, untreated AN is associated with a marked trabecular and cortical bone loss (4-10% per year), which can lead to osteoporotic fractures. In prevention of bone loss, the efficacy of estrogen is difficult to investigate in AN, even with a well-controlled trial. Our study could provide argument that, when the observance of this preventive treatment is assessed, lumbar BMD can be stabilized in chronic forms of AN.

Absorptiometry, Photon↗
PubMed1996

Osteoporotic fractures revealing anorexia nervosa in five females.

Anorexia nervosa affects 0.5% to 1% of female adolescents. The course is chronic in 50% of cases, causing substantial bone loss with osteoporotic fractures after a few years of amenorrhea. This is probably an underestimated problem. The diagnosis of anorexia nervosa is readily missed, as illustrated by five cases reported herein. The five patients were females aged 17 to 44 years who were only slightly underweight (mean weight, 43.6 kg; body mass index < 20 kg/m2). The first fracture occurred seven to 24 years after the onset of anorexia nervosa. Three patients had vertebral crush fractures, and two had peripheral insufficiency fractures. Bone mineral density measured by absorptiometry was very low (mean lumbar z-score, -3.7 SD). Three patients, who were all members of health care professions, knew that they had anorexia nervosa but failed to report this condition. In the other two patients, the amenorrhea had been mistakenly ascribed to other causes (Stein-Leventhal syndrome and psychogenic anovulation). None of the patients was receiving medical follow-up. Anorexia nervosa should be considered routinely in women who are slightly underweight. The patients often deny abnormal menstruation or eating behaviors. The diagnosis rests on determination of the body mass index, a thorough history emphasizing current and past gonadal dysfunction, and evaluation of the diagnostic criteria for anorexia nervosa. Osteoporosis is probably a common but underestimated complication of anorexia nervosa, particularly before the menopause. Enhanced awareness of this condition should allow earlier detection of a greater number of cases.

Absorptiometry, Photon↗
PubMed1996

Myositis ossificans circumscripta with spontaneous healing of a cortical cyst.

We report a case of myositis ossificans circumscripta with an initial periosteal reaction and subsequent development of a cyst in the underlying cortex. All the roentgenographic abnormalities resolved spontaneously and permanently. The unusual course may have been due to formation of a subperiosteal hematoma at the time of development of the soft tissue ossification.

Adult↗
PubMed1996

A potentially underrecognized and treatable cause of chronic back pain: entrapment neuropathy of the cluneal nerves.

We describe a case of longstanding low back pain related to entrapment neuropathy of the L1-L2 dorsal ramus over the iliac crest. As 3 local anesthetic pain blocks (at the trigger point, 7 cm left of the L5 spine process and just above the iliac crest) were successful for 3 weeks each, a surgical procedure was performed. This corrected patient stricture of a voluminous dorsal ramus within a rigid osteofibrous orifice between the upper rim of the iliac crest and the thoracolumbar fascia. Pain decreased dramatically the same day and disappeared completely within less than a week.

Back Pain↗
PubMed1995

[Magnetic resonance imaging for lumbar disk pathology. incidence of false negatives].

Magnetic resonance imaging (MRI) has had an impressive impact on evaluation of degenerative diseases of the spine. Nevertheless, false negatives can occur on images involving lumbar discs. Degenerative disc diseases documented on discrography and/or pathology examination of the discs can go unrecognized. Likewise sensitivity for the detection of protruding discal hernias is not totally satisfactory (20% false negatives). Finally, a magnetic resonance image visualizing displacement of the disc is not specific (10 to 15% false positives); images showing protrusion or hernia can be seen in 30% of asymptomatic patients. Although MRI gives slightly more information than other imaging techniques, false images do exist. Moreover, the usefulness of MRI to demonstrate disc disease in case of a negative CT-scan remains to be demonstrated.

Diagnostic Errors↗
PubMed1995

[Sports, bones and hormones. Multiple interactions].

Classically, sports activities are thought to have a beneficial effect on bone tissues. Actually, there are many interactions between sports activities and bone tissue and in certain cases complex hormone disorders may develop. Recent progress in the evaluation of bone structure (absorptiometry) and better understanding of the neuroendocrine functions have improved our knowledge of these interactions and helped provide answers as to the true effect of sports, and particular high-level training, on bone tissue. Mechanical stimulation of bone increases the level of both cortical and cancellous bone formation. The mechanical effect is localized in areas under particular constraint such as the lower limbs in runners and the upper predominant limb in tennis players. Inversely, hypoestrogenism, similar to anorexia nervosa, has been observed to be the cause of general bone loss and increased risk of osteoporosis in certain high level athletes. When these two opposing phenomena occur simultaneously, there is generally an overall loss of cancellous bone mass while bones submitted to major mechanical stress may be relatively protected. Amenorrhoea, particularly in long distance runners, generally occurs when training exceeds 30 km per week. Menarche may be delayed by 1 or 2 years when training begins early and dismenorrhoea is seen in 50% or more of the athletes. Amenorrhoea results from a central disorder due to insufficient pulsatile secretion of luteo-releasing hormone and subsequent hypogonadism. The role of beta-endorphins or catelestrogens on hypothalamic receptors has been suggested as the underlying mechanism. These different observations help provide answers to the different problems raised when providing counselling and care for high level athletes.

Amenorrhea↗
PubMed1995

Dorsal scalloping by calcified disc herniation.

SUMMARY OF BACKGROUND DATA: Disc herniation responsible for scalloping of vertebral body had been reported only at the lumbar level. RESULTS: The authors report on an unusual etiology of dorsal scalloping. A voluminous and calcified dorsal disc herniation was responsible for this, and within the center of the mass there was an unexpected hypersignal on nuclear magnetic resonance imaging. CONCLUSION: Scalloping does not preclude disc herniation, even at the dorsal level. Hyperintensity in T1-weighted images can reveal calcifications, as indicated in previous studies.

Calcinosis↗
PubMed1995

Diagnostic and therapeutic approaches to lung cancer in Canada and their costs.

Escalating health care costs have made it imperative to evaluate the resources required to diagnose and treat major illnesses in Canadians. For Canadian men, lung cancer is not only the most common malignancy, but also the major cancer killer. As of 1994, lung cancer is expected to overtake breast cancer as the leading cause of cancer deaths in women. This paper presents a detailed description of the methodology used to determine the direct health care costs associated with 'standard' diagnostic and therapeutic approaches for lung cancer in Canada in 1988. Clinical algorithms were developed for each stage of non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). The algorithms were designed to take the form of decision trees for each clinical stage of lung cancer. The proportion of patients assigned to each branch was based upon questionnaire responses obtained from thoracic surgeons and radiation oncologists when presented with clinical scenarios, and information from provincial cancer registries. Direct care costs were derived primarily from one provincial fee schedule (Ontario), and costing information obtained during the conduct of several Canadian clinical trials in lung cancer. Direct costs for diagnosis and initial treatment of NSCLC (excluding relapse and terminal care costs) ranged from $17,889 for the surgery/post-operative radiotherapy arm of stages I and II to $6,333 for the supportive care arm (stage IV). The cost of determining relapse for NSCLC was estimated to be $1,528, and terminal care costs, which included palliative radiotherapy and hospitalisation, were $10,331. Direct costs for diagnosis and initial treatment of SCLC ranged from $18,691 for limited stage disease to $4,739 for the supportive care arm of extensive disease. The cost of diagnosing relapse for SCLC was estimated to be $1,590, and terminal care costs averaged $9,966. This report provides an estimate of the Canadian costs of managing lung cancer by stage and treatment modality. Because the actual costs of all components of care are not available from any combination of sources, these cost estimates must be viewed as an idealised estimate of the cost of lung cancer management. However, we believe that the lung cancer costing model that we have developed provides a level of sophistication which gives a reasonable estimate of the cost per case of treating NSCLC and SCLC.

Algorithms↗
PubMed1995

Specificity of antiperinuclear factor for rheumatoid arthritis in rheumatoid factor-positive sera.

Although antiperinuclear factor (APF) has the same specificity for rheumatoid arthritis (RA) as rheumatoid factor (RF), there is no evidence that this specificity is maintained in patients with positive RF-agglutination tests. Thus, we evaluated the specificity and usefulness of APF for RA diagnosis, regardless of RF titre. APF was tested (1:100 threshold) on 214 sera sent for RF evaluation over a 9-month period. These sera were previously determined to have latex or Rose-Waaler (RW) titres > or = 12 or 4 IU, respectively, but not necessarily above the threshold values of 100 and 32 IU. The APF test was performed blindly, and physicians were not advised of the results. In the patient population (119 RA and 95 non-RA) APF still demonstrated good specificity (0.82) for RA. As expected, APF proved useful for RA diagnosis in 28/33 (85%) RA cases with an RF level below 1:100 for latex and 1:32 for RW, thus reducing the number of 'seronegative' RA from 33/119 to 5/119. However, it also improved the serological positive predictive value for RA, even in cases when RW results were > or = 32 IU. Indeed, the positive predictive value for RA when both tests were positive was 0.94 (68/72), whereas concordant results (either positive or negative) for both APF and RW tests allowed correct classification (RA or non-RA) in 94% of cases.

Antibodies, Antinuclear↗