The anti-inflammatory target A(3) adenosine receptor is over-expressed in rheumatoid arthritis, psoriasis and Crohn's disease.

The Gi protein associated A(3) adenosine receptor (A(3)AR) was recently defined as a novel anti-inflammatory target. The aim of this study was to look at A(3)AR expression levels in peripheral blood mononuclear cells (PBMCs) of patients with autoimmune inflammatory diseases and to explore transcription factors involved receptor expression. Over-expression of A(3)AR was found in PBMCs derived from patients with rheumatoid arthritis (RA), psoriasis and Crohn's disease compared with PBMCs from healthy subjects. Bioinformatics analysis demonstrated the presence of DNA binding sites for nuclear factor-kappaB (NF-kappaB) and cyclic AMP-responsive element binding protein (CREB) in the A(3)AR gene promoter. Up-regulation of NF-kappaB and CREB was found in the PBMCs from patients with RA, psoriasis and Crohn's disease. The PI3K-PKB/Akt signaling pathway, known to regulate both the NF-kappaB and CREB, was also up-regulated in the patients' PBMCs. Taken together, NF-kappaB and CREB are involved with the over-expression of A(3)AR in patients with autoimmune inflammatory diseases. The receptor may be considered as a specific target to combat inflammation.

Arterial compliance: is it reduced in antiphospholipid syndrome?

To assess vascular compliance in patients with antiphospholipid syndrome (APS), or antiphospholipid antibodies (aPLs) positivity in comparison to healthy people and diabetes mellitus patients. Twenty-five patients with APS or aPLs, 33 healthy people (HP), 28 patients with diabetes mellitus (DM) underwent pulse wave analysis. Data calculated included the small artery elasticity (SAE), large artery elasticity (LAE) and systemic vascular resistance (SVR). Statistical analysis was performed as appropriate. The patient group was divided into two subgroups: APS-1 with warfarin treatment, and APS-2 without warfarin treatment. All patients and healthy subjects were matched by gender, body mass index and lipid profiles. Patients in APS-1 group were significantly younger in comparison to three other groups. After the adjustment for age, we found that SAE in APS-1 group did not differ from SAE in the HP group (6.4+/-1.8 ml/mmHg x 100 and 5.54+/-3.4 ml/mmHg x 100, respectively, P>0.05). In contrast, SAE in the group APS-2 was significantly lower (3.41+/-1.2 ml/mmHg x 100) than in the APS-1 and was almost equal to SAE in the DM group (4.2+/-2.37 ml/mmHg x 100). The SAE in the APS-2, DM and HP groups was inversely correlated with age, whereas in the APS-1 group we did not find such correlation. This pilot study showed abnormal small vascular elasticity in the patients with positive aPL, relative to the healthy subjects. The APS patients, treated with warfarin had the normal vascular function. This data support the hypothesis that APS may be associated with diffuse changes in the arterial wall, and may be a risk factor for atherosclerotic disease.

Increased 67gallium uptake among polymyalgia rheumatica patients. Is it additional evidence of its vasculitic nature?

Giant cell arteritis/temporal arteritis (GCA/TA) and polymyalgia rheumatica (PMR) are closely related conditions that affect middle age and older patients and frequently occur together. Many authorities consider them to be different phases of the same disease. A study was undertaken of the possible contribution of gallium-67 ((67)Ga) single photon emission tomography (SPECT) scintigraphy to the diagnosis of GCA/TA and PMR, and to support the possible hypothesis of vasculitic nature of PMR. Nine consecutive patients with PMR, and nine consecutive patients with GCA/TA were included in the study. All patients fulfilled the American College of Rheumatology criteria for GCA/TA and Healey's criteria for PMR. The control patients group consisted of those who underwent (67)Ga scintigraphy for febrile illness. All patients and controls underwent (67)Ga SPECT scan of the skull on a dual-head Helix gamma camera 2 days after I.V. injection of 8-10 mCi of (67)Ga citrate. (67)Ga uptake ratio of temporal bone region to bone out of temporal area (TR/Bone) was estimated on transaxial and coronary slices after SPECT scan reconstruction. For each patient and control the calculations of both temporal areas were done. All GCA/TA and PMR patients showed increased uptake in both temporal areas of the skull, while (67)Ga uptake among GCA/TA was the highest, 1.31+/-0.14 in tranaxial view and 1.47+/-0.16 in coronary view. (67)Ga uptake among PMR patients was lower, 1.19+/-0.11 and 1.28+/-0.13, respectively. In comparison, the control patients showed the lowest (67)Ga uptake, 1.04+/-0.09 in transaxial view and 1.11+/-0.06 in coronary view. The results differ significantly between the three groups. It seems that (67)Ga SPECT scan may become a useful tool in the investigation of patients with suspicion of GCA/TA and PMR. Our findings of the increased (67)Ga uptake in the temporal areas among PMR patients add new arguments for vasculitic nature of this disorder.

Gallium-67 SPECT scintigraphy may be useful in diagnosis of temporal arteritis.

BACKGROUND: Temporal arteritis (TA) is a common syndrome in the elderly, consisting of persistent pain in the temporal area of the skull, jaw claudication, sudden visual loss, high erythrocyte sedimentation rate, and tenderness on palpation in the temporal area. The diagnosis of this condition is relatively straightforward when the typical symptoms and a positive temporal artery biopsy are present. However, only half of the patients have a positive temporal artery biopsy. Other diagnostic procedures, such as colour Doppler sonography or superficial carotid artery angiography which have been proved to be useful for the diagnosis of TA, do not discriminate between inflammatory and non-inflammatory temporal artery disease and may be helpful only in experienced hands. Gallium-67 ((67)Ga) planar scan was reported to be useful in the diagnosis of the disease. Quantitative (67)Ga single photon emission computed tomography (SPECT) may raise the accuracy of the diagnosis. OBJECTIVE: To investigate the effectiveness and usefulness of (67)Ga SPECT scintigraphy in the diagnosis of TA. METHODS: Nine patients (five male, four female) and six controls were included in the study. All of them received 8-10 mCi (67)Ga intravenously 48 hours before the scan.(67)Ga uptake ratios were calculated on transaxial and coronal slices. RESULTS: All patients showed increased uptake in the temporal area of the skull compared with controls. CONCLUSION: The data suggest that (67)Ga skull SPECT may be useful in the diagnosis of TA, especially if the uptake ratio in the area of interest is calculated. Further studies are needed to confirm these data.

Primary antiphospholipid antibody syndrome masquerading as progressive supranuclear palsy.

We report a case of a patient with clinical features of progressive supranuclear palsy and raised titres of anticardiolipin antibodies in blood, thrombocytopenia and livedo reticularis on skin. Magnetic resonance imaging of brain and isotope scan of brain were distinctive of vascular disorder.

Fever of unknown origin in Israel.

INTRODUCTION: Fever of unknown origin (FUO) is still a diagnostic challenge for the family physician and the internist. In the last decades a few reports have emphasized a changing pattern in the prevalence of the 3 main categories of FUO: infections, malignancies and collagen diseases. AIMS: a. to find out if the changing pattern among the main diagnoses in patients with FUO is comparable to previous reports. MATERIAL AND METHODS: Medical files of patients that were admitted in two 450 beds rural Israeli hospitals were checked by two physicians. All files of patients with either the diagnosis of FUO, or files of patients with fever that were hospitalized for a week or longer in internal medicine departments were reviewed. RESULTS: 101 files of patients fulfilling the criteria of FUO were found. Surprisingly 54.5% of them had infectious diseases, 7.9% had malignant disease and only 2% had collagen disease. CONCLUSIONS: a. Infectious diseases are still the leading cause of FUO among Israeli patients. b. The prevalence of infectious and malignant diseases is comparable to other studies, however the low rate of connective tissue diseases in our study is unusual. c. The rate of undiagnosed FUO was remarkably high (32.7%), although all these patients recovered during hospitalization and probably had self limited infectious (viral) disease.

[An unusual coincidence of thrombotic thrombocytopenic purpura and pernicious anemia].

A 52 year old man was admitted for hospitalization due to dizziness and weakness that appeared in the previous 2 weeks. Anemia and thrombocytopenia, as well as elevated levels of lactic dehydrogenase, reticulocytosis and schistocytes on blood smear, all suggested thrombotic thrombocytopenic purpura. However, B12 deficiency was also diagnosed. The diagnosis of pernicious anemia was reassured by both fundic biopsy and the existence of antiparietal cells antibodies and anti-intrinsic cells antibodies. A few courses of plasmapheresis along with parenteral B12 stabilized his physical condition and he was released with no need for further treatment, and only required ambulatory follow-up.

The different patterns of blood pressure elevation by rofecoxib and nabumetone.

Hypertension and knee osteoarthritis (OA) are frequent comorbidities. Nonsteroidal anti-inflammatory drugs (NSAIDs) are often used to relieve pain in such patients. In the last decade selective NSAIDs are used more commonly since they lead to less gastrointestinal complications. As has been shown, the treatment with NSAIDs may cause a mild rise of arterial blood pressure (BP). The influence of selective NSAIDs on BP, particularly in hypertensive patients has still to be investigated. The aim of this study was to determine arterial BP changes in patients suffering from stable arterial hypertension and knee OA and treated with rofecoxib or nabumetone. Two groups of patients with knee OA and stable arterial hypertension received either 25 mg rofecoxib once daily or namebutone 2000 mg once daily during the first week of treatment and 1000 mg for the following 3 weeks. Twenty-four hour arterial BP monitoring was performed prior to initiation of treatment and at the end of a 4-week period. The results were that no changes were found in the mean systolic and diastolic characteristics of BP in the rofecoxib treatment group during day time (delta systolic BP -0.4 mm Hg and delta diastolic BP -0.4 mm Hg), while nocturnal BP increased significantly: delta systolic BP +15.7 mm Hg and delta diastolic BP +8.5 mm Hg. The mean systolic arterial pressure in the nabumeton group raised delta systolic BP 2.9 mm Hg in the daytime and 5 mm Hg during the night-time after the treatment. The mean diastolic arterial pressure also rose delta diastolic 3.2 mm Hg and 4.9 mm Hg at day and night hours respectively. In conclusion rofecoxib treatment did not change arterial BP during day time hours, however, there was a distinct increase in night-time systolic and diastolic BP leading to a disappearance of the physiological diurnal variation. Nabumetone caused a moderate increase of day and night BP, without changes in biological diurnal variation.

[Myocardial infarction due to cocaine].

Cocaine is a common drug. Myocardial infarcts and brain infarcts related to the use of cocaine were previously reported in the medical literature. We report a 34 year old patient admitted for severe chest pain, a few minutes after cocaine use. He was found to have an acute myocardial infarction with significant left ventricle dysfunction. Coronarography conducted a few days later was found to be normal. Cocaine use may cause acute myocardial infarction in young and healthy people with no other risk factors.