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Biomedical subjects

A Kahan

Publications and source records attributed to A Kahan.

At least 37 records · Page 2Linked to original sources
PubMed2004

Increased prevalence of ocular glaucomatous abnormalities in systemic sclerosis.

BACKGROUND: Cardiovascular diseases, vasospasm, and dysimmunity have been implicated in normal tension glaucoma (NTG). OBJECTIVE: To investigate the prevalence of ocular abnormalities suggestive of glaucoma damage in systemic sclerosis (SSc). METHODS: 61 patients with SSc (mean (SD) age 56.2 (12) years, mean (SD) disease duration 9.9 (9) years; 41 with limited cutaneous disease) and 37 control subjects with osteoarthritis (mean (SD) age 55.9 (12) years) were studied. They were systematically referred to an ophthalmologist. The evaluation was based on aplanation tonometry, ophthalmoscopy with retinal photography (evaluation of cup/disc ratio (c/d)), and automated static perimetry (determination of mean defects (MD)). Statistical analyses were performed with the chi(2), Mann-Whitney, and Spearman tests. RESULTS: The mean visual acuity and intraocular pressure were similar in both groups. An excavation with a c/d >0.3 was found in 27 eyes from patients with SSc and 5 eyes from controls (p = 0.009); a c/d >0.7 was found in 4 eyes from patients with SSc and none in the controls (NS). Visual field defects (MD <-2 dB) were found in 55 eyes from patients with SSc and in 18 eyes from controls (p<0.0001). A concomitant c/d >0.3 and MD <-2 dB was found in 21 eyes from 12 patients with SSc but in none of the control eyes (p<0.0001). CONCLUSION: Ocular abnormalities suggesting glaucomatous neuropathy without ocular hypertension were dramatically more prevalent in patients with SSc. These abnormalities seem to be mild but justify long term follow up. They are consistent with the vascular pathogenic hypothesis for NTG.

Adult↗
PubMed2003

Sacral inflammatory pseudotumor revealed by paraneoplastic syndrome.

There is still debate on whether inflammatory pseudotumor should be considered benign or malignant. This lesion has only been reported twice in bone, apart from cases complicating foreign body reaction to joint replacement arthroplasty. We report here a third case, localized at the sacrum. A 31-year-old man had inflammatory dorsalgia and polyarthralgia without synovitis but with fever, asthenia, and erythema nodosa. Biological tests and X-rays were not informative, but technetium scintigraphy revealed a high level of left sacroiliac tracer binding. Several nonsteroidal anti-inflammatory drugs and sulfasalazine treatment were given over 3 months but ineffective. Pelvic magnetic resonance imaging showed an osteolytic tumor of the sacrum. Biopsy suggested a malignant fibrosarcoma, but complete evaluation after surgical resection demonstrated an inflammatory pseudotumor. All clinical symptoms disappeared within a few days after surgery, which is suggestive of a paraneoplastic syndrome. No relapse has occurred after 4 years.

Adult↗
PubMed2003

N-terminal pro-brain natriuretic peptide as a diagnostic marker of early pulmonary artery hypertension in patients with systemic sclerosis and effects of calcium-channel blockers.

OBJECTIVE: To evaluate N-terminal pro-brain natriuretic peptide (NT-proBNP) as a marker of early pulmonary artery hypertension (PAH) and to study changes in the levels of this marker following treatment with dihydropyridine-type calcium-channel blocker (DTCCB) in patients with systemic sclerosis (SSc). METHODS: We evaluated 40 consecutive SSc patients who had been hospitalized for followup care (mean +/- SD age 56 +/- 11 years and mean +/- SD duration of cutaneous disease 9 +/- 9 years; 27 with limited cutaneous and 13 with diffuse cutaneous disease) but who had no clinical symptoms of heart failure and had a normal left ventricular ejection fraction. At baseline, 10 patients had PAH, defined as a systolic pulmonary artery pressure (sPAP) >40 mm Hg, as measured by echocardiography. Levels of NT-proBNP were determined at baseline (after discontinuation of DTCCB treatment for 72 hours), after taking 3 doses of DTCCB following treatment reinitiation (assessment 1), and after 6-9 months of continuous DTCCB treatment (assessment 2) in the 20 patients who attended regular appointments (including the 10 patients with PAH at baseline). RESULTS: At baseline, 13 patients had high NT-proBNP values for their ages. High NT-proBNP levels identified patients with PAH with a sensitivity of 90%, a specificity of 90.3%, a positive predictive value of 69.2%, and a negative predictive value of 96%. The NT-proBNP level correlated with the sPAP (r = 0.44; P = 0.006). By assessment 1, the number of patients with PAH and high levels of NT-proBNP had decreased from 9 of 10 to 2 of 10 (P = 0.02). This decrease was partially sustained at assessment 2 (4 of 10 patients; P = 0.06). CONCLUSION: NT-proBNP is a useful biologic marker that can be used to diagnose early PAH in SSc patients without clinical heart failure. Measurement of NT-proBNP may be valuable for the evaluation of treatment with DTCCB and vasodilators in patients with PAH.

Aged↗
PubMed2002

Brachial plexopathy associated with systemic sclerosis.

Neurological involvement is uncommon in systemic sclerosis. Most of the reported cases concern trigeminal neuropathy or peripheral nerve entrapment. We report a third case of brachial plexopathy, presumably related to vasculitis, in a patient with systemic sclerosis, which improved after cyclophosphamide therapy.

Brachial Plexus Neuropathies↗
PubMed2002

The use of placebo-controlled and non-inferiority trials for the evaluation of new drugs in the treatment of postmenopausal osteoporosis.

Registration of new agents for the treatment of postmenopausal osteoporosis has been based over the past few years on placebo-controlled phase III trials with the incidence of patients with new vertebral/nonvertebral fractures as the most usual primary endpoint. The use of a placebo in diseases where an active treatment is available has been a matter of debate following the update of the Declaration of Helsinki by the World Medical Association which questioned this trial design. Current regulatory recommendations within the European Union suggest that placebo-controlled trials are still the best option when assessing the efficacy and safety of new drugs intended for the treatment of postmenopausal osteoporosis. This suggestion seems to be in apparent contradiction with the current content of the Declaration of Helsinki. This paper addresses the ethics and feasibility of placebo-controlled trials in the treatment of postmenopausal osteoporosis, in the light of available therapeutic options, and discusses possible alternative approaches in those patients where placebo treatment could be deemed to be unethical. It is concluded that placebo-controlled trials remain the most efficient design to establish the efficacy and safety of a new agent for the treatment of postmenopausal osteoporosis. Such trials are feasible and ethically acceptable in patients with osteoporosis but without prevalent vertebral fractures. Conversely, in patients with prevalent vertebral fractures, placebo-controlled trials are ethically questionable and non-inferiority trials are more appropriate. A relative margin of non-inferiority of 20-30% is suggested, to be discussed on a case by case basis.

Aged↗
PubMed2002

Quantitative assessment of joint space width with an electronic caliper.

UNLABELLED: The progression of joint space narrowing (JSN) is considered to be the best available marker of osteoarthritis (OA) progression. Several techniques have been proposed for the measurement of joint space at its narrowest point in OA of the hips and knees. OBJECTIVE: To evaluate the properties of the technique using an electronic caliper for the measurement of JSN in OA patients. DESIGN: We used an electronic caliper to measure joint space width (JSW) for hips on 100 plain radiographs. JSW was measured in the vertical position at the center of the femoral head. Femoral head diameter was also determined to correct for variations due to differences in magnification of digitized X-rays. All films were read twice by each of two rheumatologists (one junior, one senior) and two radiologists (one junior, one senior). Intraclass correlation coefficients and their 95% confidence intervals were calculated. RESULTS: Detailed results are given for right hips (38 with OA, 18 inflammatory, 44 normal); very similar results were obtained for left hips. For JSW, the intraclass correlation coefficient was between 0.96 and 0.99 for intraobserver reliability. The level of reliability was similar for analysis of the diameter of the femoral head (R:0.84 to 0.98) and for the ratio of these two measurements (0.96 to 0.99). The most reliable measurements were those made by the senior radiologist, followed by those made by the two rheumatologists. In assessments of interobserver reliability for the measurement of JSW, R varied from 0.91 to 0.96 for the first reading and from 0.88 to 0.96 for the second reading. For the measurement of femoral head diameter, R varied from 0.86 to 0.96 for the first reading and from 0.74 to 0.96 for the second reading. CONCLUSION: The electronic caliper technique is an accurate method for measuring JSW in the hip. This technique seems to be reproducible, is simple, and could be used for routine evaluation. Further validation is required, with the measurement of serial X-rays from the same patients.

Electronics, Medical↗
PubMed2001

Tetracyclines inhibit nitrosothiol production by cytokine-stimulated osteoarthritic synovial cells.

OBJECTIVE AND DESIGN: To evaluate the capacity of doxycycline and minocycline to inhibit NO production and N-nitrosation reactions in vitro. METHODS: Synovial cells obtained from 6 patients with osteoarthritic joint disease were incubated for 24 hours with (i) or without (ii) IL-1beta (1 ng/ml), TNF-alpha (500 pg/ml), IFN-gamma (10(4) U/ml) plus minocycline or doxycycline (10(-4) to 10(-6) M), diclofenac (10(-5) M), or cortisol (10(-5) M). Nitrosothiols were determined by fluorimetry, nitrite by the Griess reaction, nitrate by a spectrophotometric assay using oxidation by nitrate reductase and iNOS by immunoblotting. RESULTS: After 24 hours of stimulation, the level of NO production was much higher than that in untreated cells: about 5.5 times higher for nitrosothiols, 5.2 times higher for nitrate and about 3.5 times higher for nitrite. Doxycycline and minocycline induced a dose-dependent decrease in the production of nitrosothiols, nitrate and nitrite, and inhibited the synthesis of the iNOS protein. Doxycycline and minocycline inhibited the N-nitrosation reaction of DAN effectively, with IC50 values close to 100 microM. Diclofenac and cortisol had no effect. CONCLUSION: This study provides new information on the mechanism by which tetracyclines exert anti-inflammatory effects, via inhibiting nitrosothiols.

Anti-Bacterial Agents↗
PubMed2001

Management of a patient with sarcoid calcaneitis and dactylitis.

Dactylitis and calcaneitis developed in a patient with untreated sarcoidosis of the skin and lungs. Radiographs showed a defect in the second phalanx of the left middle finger. Radiographs of the feet were normal, but magnetic resonance imaging demonstrated a defect in the left calcaneus. Methylprednisolone therapy (1 g per day for 3 consecutive days) induced a dramatic improvement within 48 hours. Low-dose oral glucocorticoid therapy was given subsequently. One year later, a recurrent episode of dactylitis responded promptly to the same regimen. Maintenance therapy was given, and no further recurrences were noted during the four-year follow-up. Sarcoid bone lesions are uncommon and arise selectively in the small bones of the hands and feet. Involvement of the calcaneus is exceedingly rare, and its treatment is not standardized. In our patient, glucocorticoid therapy combined with methotrexate and hydroxychloroquine were effective in controlling the disease.

Adult↗
PubMed2001

Postpartal sacral fracture without osteoporosis.

Stress fractures of the sacrum during pregnancy or the postpartum seem uncommon. We report a new case of nontrauma-related postpartal sacral fracture. Only four similar cases have been reported to date. The patient was 36 years of age and her fracture was diagnosed four weeks after her first delivery. Vitamin D levels were low, but there was no osteomalacia. Other standard laboratory tests were normal, as were absorptiometry measurements at the lumbar spine and femur. Rheumatologists should consider sacral fracture in pregnant or nursing patients with buttock pain. Magnetic resonance imaging is the diagnostic investigation of choice.

Absorptiometry, Photon↗
PubMed2001

Chronic recurrent multifocal osteomyelitis: five-year outcomes in 14 pediatric cases.

OBJECTIVE: To determine the clinical presentation and outcomes of chronic recurrent multifocal osteomyelitis (CRMO) in pediatric patients. PATIENTS AND METHODS: Ten girls and four boys were followed up between 1993 and 1999 for CRMO diagnosed on the basis of radiographic bone lesions with, at the same sites, increased radionuclide uptake, negative microbiological specimens, and histological evidence of nonspecific osteomyelitis. RESULTS: Mean age at CRMO was 9.6+/-3.4 years, mean disease duration was 5.3+/-2.5 years, and mean number of flares per patient was 5.9+/-3.7. Thirty-four percent of lesions were in the metaphyses of the lower limb bones, 14% in the pelvis, and 13% in the chest wall (with clavicular lesions in four patients). Three patients had skin lesions (psoriasis in two and palmoplantar pustulosis in one). Eight patients received antibiotic therapy, for 2 months at the most, to no advantage in the short term. Nonsteroidal anti-inflammatory drugs were used in all 14 patients and glucocorticoid therapy in four. Sulfasalazine was used in five patients, to good effect in four. Mean follow-up was 5.3+/-2.5 years. At last follow-up, eight patients had active disease, including one with synovitis and one with Takayashu's disease. CONCLUSION: As compared to SAPHO syndrome, skin lesions and chest wall involvement are less common in CRMO. The long-term prognosis is guarded: in our study only six of 14 patients were in remission at last follow-up.

Acquired Hyperostosis Syndrome↗
PubMed2001

DHEA in bone and joint diseases.

Serum concentrations of dehydroepiandrosterone (DHEA) and its sulfate ester (sDHEA) decrease dramatically with age in parallel with the appearance of age-related health problems, leading to the suggestion that DHEA replacement therapy may be beneficial in older patients. Daily oral doses that restore sDHEA levels to the values seen in young adults are well tolerated in the short-term (6 months to 1 year) and seem to have a positive although modest beneficial effect on bone in elderly women, particularly those with low pretreatment sDHEA levels. This effect seems ascribable to both decreased bone resorption and increased bone formation, which are probably related mainly to conversion of DHEA into active sex steroids, i.e., estradiol and testosterone; this explains why there is no effect on bone in men, whose testes continue to produce testosterone throughout life. Other mechanisms of action, including an increase in insulin growth factor-1, may be operative also. DHEA cannot be recommended as a treatment for osteoporosis at present given the absence of studies evaluating possible efficacy in reducing the fracture rate and possible long-term side effects.

Administration, Oral↗
PubMed2001

Low levels of nitric oxide (NO) in systemic sclerosis: inducible NO synthase production is decreased in cultured peripheral blood monocyte/macrophage cells.

OBJECTIVE: To investigate nitric oxide (NO) production and inducible NO synthase expression by cultured peripheral blood mononuclear cells (PBMC) in patients with systemic sclerosis (SSc). METHODS: Eighteen patients with SSc were compared with two control groups: 16 patients with rheumatoid arthritis (RA) and 23 patients with mechanical sciatica. Nitrate was determined by fluorimetry in plasma and by spectrophotometry in supernatants. Inducible NO synthase (iNOS) was detected in cultured PBMC by immunofluorescence, immunoblotting and flow cytometry with or without treatment of the cells with interleukin (IL) 1beta+ tumour necrosis factor alpha (TNF-alpha), IL-4 or interferon gamma (IFN-gamma) from day 1 to day 5. RESULTS: NO metabolite concentrations were lower in SSc patients (mean+/-s.e.m. 34.3+/-2.63 micromol/l) than in RA (48.3+/-2.82 micromol/l; P<0.02) and sciatica (43.3+/-5.24 micromol/l; P<0.03) patients. iNOS was detected in cultured monocytes in all three groups but induction occurred on day 1 in RA, day 2 in sciatica and only on day 3 in SSc, whatever the stimulus. CONCLUSIONS: The concentrations of NO metabolites are decreased in SSc patients and the metabolism of these compounds in PBMC is altered. Low levels of NO, a vasodilator, may be involved in vasospasm, which is critical in SSc. This may have therapeutic implications.

Adult↗
PubMed2001

Physical and biological dosimetry in patients undergoing radiosynoviorthesis with erbium-169 and rhenium-186.

Physical and biological dosimetry were investigated in 45 rheumatoid arthritis patients treated by radiosynoviorthesis (RSO) with 186Re-sulphide (medium-sized joints) and 169Er-citrate (digital joints). Biological dosimetry involved scoring dicentrics in lymphocytes, cultured from blood samples withdrawn just before and 6 h, 24 h and 7 days after treatment. Physical methods included repeated blood sample counts and scintigraphy data. For erbium-169 (pure beta emitter), only bremsstrahlung could be measured and solely in the injection area. For rhenium-186 (both beta and gamma emitter), whole body scans and static images of joints and locoregional lymph nodes were performed. Dosimetry calculations were in accordance with the MIRDOSE 3 software and tables. For erbium-169 (21 patients), either metacarpophalangeal (30 MBq) or proximal interphalangeal (20 MBq) joints of the hands were treated (one joint per patient); 18 patients (out of 21) were interpretable for biological dosimetry, 10 (out of 11) for physical dosimetry and six (out of 10) for both. For rhenium-186, 23 wrists, nine elbows, three shoulders and two ankles were injected in 24 patients, with a maximum of three joints per patient (70 MBq per joint); 20 patients (out of 24) and 10 (out of 10) were interpretable for biological and physical dosimetry, respectively, and eight (out of 10) for both methods. Erbium-169 biological dosimetry was negative in all interpretable patients, and physical dosimetry gave a blood dose of 15 +/- 29 microGy and an effective dose lower than 1 mSv/30 MBq. For rhenium-186, biological results were negative in 16 patients (out of 20), but showed a blood irradiation around 200 mGy in the last four. A significant cumulative increase of dicentrics 7 days after injection (16/10,000 instead of 5/10,000 prior to treatment; p < 0.04) was also noted. Gamma counts gave a blood dose of 23.9 +/- 19.8 mGy/70 MBq and the effective dose was found to be 26.7 +/- 5.1 mGy/70 MBq, i.e. about 380 microGy.MBq-1. Erbium-169 RSO is very safe from both physical and biological dosimetry standpoints. Rhenium-186 leak is greater, as demonstrated by the higher blood activity and the measurable, although limited, dicentrics induction in blood lymphocytes. However, the effective dose remains moderate, i.e. 30 times lower than in 131I therapy in benign thyroid diseases.

Adult↗
PubMed2001

[Inducible nitric oxide synthase expression and nitric oxide production by monocytes in systemic sclerosis].

We investigated nitric oxide (NO) production and inducible NO synthase (iNOS) expression by cultured peripheral blood mononuclear cells (PBMC) in systemic sclerosis (SSc). Eighteen patients with SSc were compared to two control groups: 16 rheumatoid arthritis patients (RA) and 23 mechanical sciatica patients. The sum of nitrites and nitrates was determined by fluorimetry in sera and spectrophotometry in supernatants. Inducible iNOS was detected in cultured PBMC by immunofluorescence, immunoblot and flow cytometry with or without IL-1 beta + TNF alpha, IL-4 or IFN gamma from day 1 to day 5. NO metabolite concentrations in the plasma were lower in SSc (34.3 mumol/l +/- 2.63 SEM) than in RA (48.3 mumol/l +/- 2.2; p < 0.02) and sciatica (43.3 mumol/l +/- 5.24; p < 0.03) patients. iNOS was detected in cultured monocytes in the 3 groups but induction occurred on day 1 in RA, day 2 in sciatica and only on day 3 in SSc, whatever the stimulus. The concentrations of NO metabolites are decreased in SSc patients and the induction of iNOS in PBMC is delayed. Low levels of NO, a vasodilator, may be involved in vasospasm, which is critical in SSc. This may suggest therapeutic implications.

Arthritis, Rheumatoid↗
PubMed2000

Reduced incidence and prevalence of atopy in rheumatoid arthritis. Results of a case-control study.

OBJECTIVE: To determine the cumulative incidence and the point prevalence of atopy in patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: A standardized questionnaire was sent to 300 RA patients. Questions concerned previous or present characteristics of atopy (hay fever, asthma and constitutive eczema) and RA. RA patients were matched with genetically unrelated controls (sister- or brother-in-law, neighbour or friend). The same questionnaire (except for questions about RA) was sent to the control subjects. In cases of atopy, patients, controls and the treating physicians were contacted by a physician to check the validity of the responses. RESULTS: Paired responses were obtained in 173 cases. Information about atopy was obtained for 69 other RA patients. The characteristics of RA were similar for patients who responded and those who did not respond. The frequency of atopy was significantly lower in RA patients than in controls, both for cumulative incidence (RA 7.5%, controls 18.8%; P: < 0.01) and point prevalence (RA 3.5%, controls 16.2%; P: < 0.0001). The clinical manifestations of atopy stopped before the onset of RA in eight of the 17 RA patients with an allergic condition, and there was no subsequent relapse. No effect of RA treatment could account for the remission of atopy. CONCLUSION: These data support the concept that atopy protects against the future development of RA and that the two diseases could counterbalance one another.

Arthritis, Rheumatoid↗
PubMed2000

[Nonsteroidal anti-inflammatory agents in the management of rheumatic disorders].

Nonsteroidal anti-inflammatory drugs (NSAIDs) have become one of the most commonly used drug classes. However, the gastrointestinal adverse effects, including ulcers, perforation and bleeding, constitute a major problem, although the risk of their occurrence appears to vary according to the different classical NSAIDs used. These drugs inhibit the key enzyme in prostaglandin biosynthesis, cyclo-oxygenase or COX. COX exists in 2 isomeric forms, COX-1 and COX-2, which are inhibited to different extents by the classical NSAIDs. COX-1 leads, for example, to the production of prostaglandins that are cytoprotective for the gastric mucosa. COX-2 is inducible in a number of cells by pro-inflammatory stimuli. The selective COX concept predicts that inhibition of COX-1 may result in gastrointestinal adverse effects, whereas inhibition of COX-2 may underlie the anti-inflammatory actions of NSAIDs. These observations have led to the development of new drugs with high inhibitory potency for COX-2 and low potency for COX-1. These selective COX-2 inhibitors appear to be promising in animal models and endoscopic studies in humans. If large clinical and epidemiological studies confirm that (i) selective COX-2 inhibitors are as effective as classical NSAIDs, (ii) the frequency of severe gastrointestinal complications is considerably reduced with these new drugs, and (iii) no unexpected complications of selective COX-2 inhibition are detected, then selective COX-2 inhibitors will prove to be a significant advance in the treatment of patients with rheumatic diseases.

Animals↗
PubMed2000

Upper cervical spine surgery in rheumatoid arthritis: retrospective study of 30 patients followed for two years or more after Cotrel-Dubousset instrumentation.

PURPOSE: To evaluate the efficacy of upper cervical spine surgery in symptomatic atlantoaxial instability due to rheumatoid arthritis (RA). MATERIAL AND METHODS: Thirty RA patients (29 women and one man) with a mean age of 56 years were studied retrospectively. Symptomatic forward slippage of the atlas on the axis with a synovial pannus surrounding the odontoid and magnetic resonance imaging evidence of spinal cord compression was present in all 30 patients; 18 patients had vertical translocation of the odontoid and 14 had basilar invagination. Surgery, performed between 1991 and 1997, consisted of occipitocervical fusion in 18 patients and atlantoaxial fusion in 12. Cotrel-Dubousset instrumentation was performed in all 30 patients. RESULTS: Mean follow-up was four and a half years. All patients were satisfied with the procedure and exhibited marked functional gains and objective neurological improvement (by one class in the Ranawat scheme). Stable fusion was documented in all 30 patients. CONCLUSION: Cervical instrumentation and bone grafting seems to provide functional and neurological gains in carefully selected RA patients with atlantoaxial instability and spinal cord compression. Long term follow-up suggests that the benefits are sustained and that morbidity is low.

Adult↗