Labile assembly of a tardigrade protein induces biostasis.

Tardigrades are microscopic animals that survive desiccation by inducing biostasis. To survive drying tardigrades rely on intrinsically disordered CAHS proteins, which also function to prevent perturbations induced by drying in vitro and in heterologous systems. CAHS proteins have been shown to form gels both in vitro and in vivo, which has been speculated to be linked to their protective capacity. However, the sequence features and mechanisms underlying gel formation and the necessity of gelation for protection have not been demonstrated. Here we report a mechanism of fibrillization and gelation for CAHS D similar to that of intermediate filament assembly. We show that in vitro, gelation restricts molecular motion, immobilizing and protecting labile material from the harmful effects of drying. In vivo, we observe that CAHS D forms fibrillar networks during osmotic stress. Fibrillar networking of CAHS D improves survival of osmotically shocked cells. We observe two emergent properties associated with fibrillization; (i) prevention of cell volume change and (ii) reduction of metabolic activity during osmotic shock. We find that there is no significant correlation between maintenance of cell volume and survival, while there is a significant correlation between reduced metabolism and survival. Importantly, CAHS D's fibrillar network formation is reversible and metabolic rates return to control levels after CAHS fibers are resolved. This work provides insights into how tardigrades induce reversible biostasis through the self-assembly of labile CAHS gels.

Vulvar invasive squamous cell carcinoma occurring in a young woman with systemic lupus erythematosus.

BACKGROUND: Although several studies have demonstrated a possible relationship between systemic lupus erythematosus (SLE) and non-Hodgkin's lymphoma, Hodgkin's lymphoma, leukemia and several solid tumors, it is still debatable whether SLE patients have an increased incidence of cancer overall. CASE: We describe a 25-year-old patient with SLE who developed invasive squamous cell carcinoma of the vulva. The patient underwent radical vulvectomy and bilateral groin sentinel lymph node dissection and until to date, one year after surgery, she is alive without evidence of recurrent disease. CONCLUSIONS: Only three cases of vaginal/vulvar cancer associated with SLE have previously been mentioned in the literature, but not described in detail. This is the first detailed case report in the literature of vulvar invasive squamous cell carcinoma occurring in a SLE patient. It can only be speculated that the SLE itself and/or the treatment with immunosuppressive drugs provoked malignant transformation and the development of vulvar squamous cell carcinoma in such a young patient.

A human monoclonal anti-DNA antibody derived from a patient with polymyositis having the common lupus 16/6 idiotype.

A human IgM monoclonal antibody (Pol-1, SA-1) was generated by the human hybridoma technique from the peripheral blood lymphocytes (PBL) of a patient with active polymyositis. The antibody was found to bind to ssDNA, dsDNA, poly(I) and poly(G) and to carry the common lupus anti-DNA antibody idiotype (16/6 Id). Another human IgM monoclonal antibody (Pol-2, SA-2) produced by similar methods from the PBL of the same patient while in remission lacked the ligand-binding capacities of Pol-1 SA-1 and did not have the 16/6 Id. Analyses of 19 sera samples from patients with polymyositis showed no antinuclear antibodies, excluding a 40% prevalence of the 16/6 Id. The serum of the patient whose lymphocytes were employed to generate the hybridoma was negative for anti-DNA activity as well as for the 16/6 Id. This study suggests that the hybridoma technique may enable expression of dormant idiotypic affinities which do not normally appear in sera.

Musculoskeletal manifestations of brucellosis: a study of 90 cases in Israel.

Rheumatological manifestations are frequently reported in patients with brucellosis. In a retrospective study of 90 patients diagnosed with brucellosis over a period of 18 years, 83 (92%) patients were Bedouins, 55 of whom (61%) reported ingestion of unpasteurized goat milk and goat milk products. The male/female ratio was 1:1, and the adult to child ratio was 3:2. The mean age of the patients was 25 years (range, 1-72 years). Rheumatological manifestations (myalgia, arthralgia, and arthritis) were reported in more than half of the patients. These manifestations started on days 3 and 4 of the disease and were mild to moderate in severity. Myalagia was evident in 49 (54%) patients and was more common in adults than in children (67% versus 37%; P < .01) and in men (67%) than in women (42%; P < .01). Arthralgia was the most common musculoskeletal manifestation, found in 55 (61%) patients, and occurred more often in children than in adults (74% versus 52%; P < .05). Arthritis was detected in 37 (41%) patients. The hip and knee joints were the most common sites of arthritis (31% each) followed by sacroiliac involvement (17%) and shoulder or spine involvement (5% each). Arthritis was also more common in children (63% versus 29%; P < .01). The prevalence of arthritis was similar in men and women. Cure was achieved in all patients after antibiotic therapy.

Bronchioloalveolar carcinoma and generalized amyloidosis complicating progressive systemic sclerosis.

We report a patient with progressive systemic sclerosis in whom an autopsy, performed 13 years after diagnosis, revealed the presence of bronchioloalveolar carcinoma and of generalized amyloidosis. Characterization of the amyloid fibril protein suggested an immunoglobulin light chain (AL) origin.

The role of spa therapy in various rheumatic diseases.

Spa therapy seems to have a role in the treatment of a broad range of joint diseases. It cannot substitute for conventional therapy but can complement it. The improvement reported in some of the studies is of short duration, lasting for months. It should be considered for patients suffering from various types of inflammatory arthritides or noninflammatory arthritides who are symptomatic, despite accepted medical therapy and conservative physiotherapy, if they can afford the expense. The patients should be told that the effectiveness and success of this therapy cannot be predicted in advance. Because we have no way to date, of curing most rheumatic diseases, clinical trials of alternative therapeutic methods are justified. These methods may alleviate patient suffering and are almost totally devoid of serious adverse effects. No studies have been reported that evaluate their cost-effectiveness.

Different modalities of spa therapy for skin diseases at the Dead Sea area.

BACKGROUND: Balneology and spa therapy, although not accepted as well-established treatment modalities in dermatology, are used throughout the world. The therapeutic properties for skin and rheumatic diseases of the Dead Sea area may be attributed to unique climatic characteristics and unique natural resources. The mechanisms by which a broad spectrum of diseases are alleviated by spa therapy may involve mechanical, thermal, and chemical effects. OBJECTIVE: To review and discuss various spa therapy modalities, used at the Dead Sea area for a wide spectrum of skin diseases. CONCLUSIONS: Existing evidence indicates the therapeutic potential of Dead Sea spa therapy modalities for psoriasis and psoriatic arthritis. A beneficial effect is hinted at for other skin diseases, but the absence of relevant methodological and clinical information precludes the drawing of any scientific conclusions. It is essential to establish therapeutic guidelines to determine the optimal treatment modality for each disease, and the optimal protocol of each treatment component, adjusted individually for each patient, with respect to remission and long-term adverse effects.

Blood pressure changes at the Dead Sea (a low altitude area).

The Dead Sea (barometric pressure: 800 mm Hg) is an important balneotherapeutic centre for chronic dermatologic and arthritic diseases. In the past, hypertensive patients have complained sporadically of weakness and dizziness during a stay in the Dead Sea. It was therefore recommended that hypertensives do not stay at these health centres. The aim of our study was to investigate the changes in blood pressure (BP) parameters of 72 hypertensive and normotensive osteoarthritic and rheumatoid arthritic elderly patients during a 2-week stay in the Dead Sea, and to further evaluate the effect of different balneotherapeutic means on these BP changes. Following a primary BP assessment at the out-patient clinic (Beer Sheva barometric pressure: 745 mm Hg), the patients were divided into four groups: (1)thermomineral pool; (2)Dead Sea water baths; (3) combination of the aforementioned treatments; and (4) controls (no balneotherapy). We demonstrated that the systolic BP (SBP) of hypertensives and normotensives decreased by an average of 17 mm Hg and that diastolic BP (DBP) decreased by an average of 8 mm Hg from their basic clinic-measured values. These favourable results were sustained during the first 10 days duration, and by the end of their stay they had diminished slightly. Thermomineral water had an additional lowering effect on the BP of the normotensives, but the SBP of hypertensives increased. Immediately following Dead Sea bath immersion, we noted a temporary increase of SBP in normotensives only. No patient, hypertensive or normotensive, complained of dizziness, malaise, or any other complaint. In our experience, patients feel well at low altitudes, and there is no justification in upholding hypertension as a contraindication to balneotherapy in the Dead Sea.

Dead Sea bath salts for the treatment of rheumatoid arthritis.

Thirty patients with classical or definite rheumatoid arthritis were randomly divided into two groups of fifteen patients each of similar age, sex, duration and severity of disease, and medical treatment. All patients were treated once a day with bath salts heated to 35 degrees C for twenty minutes. Group I received Dead Sea bath salts and Group II, the control group, received sodium chloride (NaCl). The study was double-blind and of two weeks' duration. All patients were evaluated by one rheumatologist both before treatment, and two weeks later at the end of the treatment period. Follow-up evaluations were made one and three months after conclusion of the treatments. The clinical parameters evaluated included duration of morning stiffness, fifteen meter walk time, hand-grip strength, activities of daily living, circumference of proximal interphalangeal joints, number of active joints, Ritchie index and the patient's own assessment of disease activity. The laboratory parameters evaluated included erythrocyte sedimentation rate and serum levels of amyloid A, rheumatoid factor, sodium, potassium, calcium and magnesium. A statistically significant improvement (p less than 0.01 or p less than 0.05) was observed in Group I only, in most of the clinical parameters assessed. Maximal therapeutic effect was obtained at the end of the treatment and lasted up to one month.

Polyarthritis associated with hydatid disease (echinococcosis) of the liver.

A 36-year-old male developed asymmetric polyarthritis during the course of hydatid disease of the liver. Excision of the hydatid cyst was accompanied by full remission of the arthritis without recurrence during the 7-year follow-up period. This sequence of clinical events suggests an eventual cause and effect relationship. A "reactive" immune mechanism, triggered by a parasite located at a distant site, appears to be responsible for this type of arthritis.

Systemic sclerosis: another rheumatic disease associated with hepatitis C virus infection.

The first case of a patient with chronic infection with hepatitis C virus who developed systemic sclerosis, manifested by severe Raynaud's phenomenon, progressive skin thickening, painful fingertip ulcers, dysphagia and Sjogren's syndrome, is described. The role of interferon therapy is discussed.

Mud pack therapy in rheumatoid arthritis.

Twenty-eight patients with classical or definite rheumatoid arthritis were randomly divided into two groups of fourteen patients each. All patients were treated once a day with mud packs derived from the Dead Sea heated to 40 degrees C and applied over the four extremities, neck and back for 20 minutes. Group 1 was treated with the true mud packs and Group 2 with washed out and less concentrated mud packs. The study was double blind and of two weeks duration. All patients were evaluated by one rheumatologist both before treatment and two weeks later at the end of the treatment period. Follow-up evaluations were made one and three months after conclusion of the treatment. The clinical indices evaluated included duration of morning stiffness, hand-grip strength, activities of daily living, patient's own assessment of disease activity, number of active joints and the Ritchie index. A statistically significant improvement (p less than 0.01 or p less than 0.05) was observed in Group 1 only in most of the clinical indices, lasting between 1 to 3 months.

Influenza virus vaccination of patients with SLE: effects on generation of autoantibodies.

The sera of 24 women with SLE who received influenza vaccine were tested by ELISA for anti-DNA, anticardiolipin, anti-Sm, anti-Sm/RNP, anti-Ro and anti-La. Blood samples were withdrawn at the time of vaccination and 6 and 12 weeks after vaccination. The mean age at enrolment into the study was 46.1 years. The mean disease duration was 9.1 years. SLEDAI scores were 6.6 at vaccination, 4.9 at 6 weeks and 5.1 at week 12. The vaccine was not associated with the generation of anti-DNA. At time of vaccination a single patient had anti-Sm, four patients had anti-Sm/RNP antibodies, none of the patients had anti-La antibody and six had anti-Ro antibodies. Six weeks after vaccination four, eight, nine and three patients had autoantibodies reacting with Sm, Sm/RNP, Ro and La, respectively. Twelve weeks after vaccination none of the patients had anti-Sm, three had anti-Sm/RNP, five had anti-Ro and two had anti-La antibodies. Following vaccination six and three patients developed IgG and IgM anticardiolipin antibodies, respectively. In summary, although the influenza virus vaccine is clinically safe for patients with SLE it may trigger the generation of autoantibodies. This effect is usually short term and has no clinical significance.

Palindromic rheumatism in Israel--a disease entity? A survey of 34 patients.

Over a period of 10 years 34 patients were diagnosed as suffering from palindromic rheumatism. Eighty-one percent of the patients were of North African origin. This is significantly higher (p = 0.01) than the age-adjusted origin of the general population in the region. Attacks were usually monoarthritic or oligoarthritic in nature. The joint most often involved was the knee. Prophylactic therapy with colchicine was ineffective. Gold salts brought about partial remission in three of six patients. Despite a relatively long average follow-up period of 9.3 years and the finding of a positive rheumatoid factor in 12% of the patients, not one of the patients developed rheumatoid arthritis. In 50% of the patients we detected an unexplained elevation in serum globulins and immunoglobulins. The possible association between this syndrome and Familial Mediterranean Fever is discussed.

Cardiovascular manifestations of ankylosing spondylitis.

In a retrospective study, 40 patients with ankylosing spondylitis were assessed for extraspinal manifestations. Cardiovascular complications were found in 17 patients (42.5%): 5 (12.5%) had aortic insufficiency, 3 (7.5%) had atrioventricular block and 5 (12.5%) had bundle branch block. Wolff-Parkinson-White syndrome was diagnosed in one case and short PR syndrome in another. Cardiovascular complications were more common in patients with longer disease duration. Ischemic heart disease was found in 17.5% of the cases and pulmonary fibrosis in 15%. Peripheral arthritis was found in 42.5% and its prevalence did not differ in patients with or without cardiac involvement.

The effect of balneotherapy at the Dead Sea on the quality of life of patients with fibromyalgia syndrome.

Fibromyalgia (FS) is an idiopathic chronic pain syndrome defined by widespread non-articular musculoskeletal pain and generalised tender points. As there is no effective treatment, patients with this condition have impaired quality of life (QoL). The aim of this study was to assess the possible effect of balneotherapy at the Dead Sea area on the QoL of patients with FS. Forty-eight subjects participated in the study; half of them received balneotherapy, and half did not. Their QoL (using SF-36), psychological well-being and FS-related symptoms were assessed prior to arrival at the spa hotel in the Dead Sea area, at the end of the 10-day stay, and 1 and 3 months later. A significant improvement was reported on most subscales of the SF-36 and on most symptoms. The improvement in physical aspects of QoL lasted usually 3 months, but on psychological measures the improvement was shorter. Subjects in the balneotherapy group reported higher and longer-lasting improvement than subjects in the control group. In conclusion, staying at the Dead Sea spa, in addition to balneotherapy, can transiently improve the QoL of patients with FS. Other studies with longer follow-up are needed to support our findings.

Nabumetone induces less gastrointestinal mucosal changes than diclofenac retard.

The aim of the study was to compare the efficacy and the effects on the mucosa of the gastrointestinal tract (GIT) of nabumetone and diclofenac retard in patients with osteoarthritis (OA). An open, multicentre, randomised, comparative, endoscopy-blind parallel group study included 201 patients with nabumetone and 193 patients with diclofenac retard suffering from moderate to severe OA of the knee or hip joint. Twelve clinical efficacy variables were assessed and a portion of the population underwent gastroduodenoscopy. All patients exhibited significant improvement in pain severity and pain relief (p < 0.001 and p < 0.0001, respectively) but there were no differences between the groups for all the efficacy variables. Eleven per cent of patients on nabumetone and 19% on diclofenac experienced GIT side-effects. Sixty-nine patients with nabumetone and 61 with diclofenac underwent gastroduodenoscopy. The differences in the mucosal grade for the oesophagus, stomach and duodenum at baseline were not significant. In the oesophagus there were significantly less changes after treatment with nabumetone (p = 0.007) than with diclofenac; there were similar findings in the stomach (p < 0.001) but the difference in the duodenum was not significant. This study indicates that nabumetone and diclofenac retard have similar efficacy in the treatment of OA, but nabumetone has significantly fewer GIT side-effects.

Successful control of pheochromocytoma in pregnancy. Case report.

A patient found to have a pheochromocytoma in the 16th wk of pregnancy was successfully managed by medical treatment with phenoxybenzamine hydrochloride and propranolol. In the 38th wk of pregnancy she was electively delivered by cesarean section, and the tumor was simultaneously removed.

Balneotherapy at the Dead Sea area for knee osteoarthritis.

BACKGROUND: Balneotherapy at the Dead Sea area has been applied in various inflammatory rheumatic diseases such as rheumatoid arthritis and psoriatic arthritis. The efficacy of balneotherapy at the Dead Sea area for the treatment of degenerative rheumatic diseases has not yet been formally evaluated. OBJECTIVE: To evaluate the efficacy of balneotherapy at the Dead Sea area in patients suffering from osteoarthritis of the knees. METHODS: Forty patients were randomly allocated into four groups of 10 patients. Group I was treated by bathing in a sulphur pool, group 2 by bathing in the Dead Sea, group 3 by a combination of sulphur pool and bathing in the Dead Sea, and group 4 served as the control group receiving no balneotherapy. The duration of balneotherapy was 2 weeks. RESULTS: Significant improvement as measured by the Lequesne index of severity of osteoarthritis was observed in all three treatment groups, but not in the control group. This improvement lasted up to 3 months of follow-up in patients in all three treatment groups. CONCLUSION: Balneotherapy at the Dead Sea area has a beneficial effect on patients with osteoarthritis of the knees, an effect that lastas at least 3 months.

Balneotherapy at the Dead Sea area for patients with psoriatic arthritis and concomitant fibromyalgia.

BACKGROUND: Balneotherapy has been successfully used to treat various rheumatic diseases, but has only recently been evaluated for the treatment of fibromyalgia. Since no effective treatment exists for this common rheumatic disease, complementary methods of treatment have been attempted. OBJECTIVES: To assess the effectiveness of balneotherapy at the Dead Sea area in the treatment of patients suffering from both fibromyalgia and psoriatic arthritis. METHODS: Twenty-eight patients with psoriatic arthritis and fibromyalgia were treated with various modalities of balneotherapy at the Dead Sea area. Clinical indices assessed were duration of morning stiffness, number of active joints, a point count of 18 fibrositic tender points, and determination of the threshold of tenderness in nine fibrositic and in four control points using a dolorimeter. RESULTS: The number of active joints was reduced from 18.4 +/- 10.9 to 9 +/- 8.2 (P < 0.001). The number of tender points was reduced from 12.6 +/- 2 to 7.1 +/- 5 in men (P < 0.003) and from 13.1 +/- 2 to 7.5 +/- 3.7 in women (P < 0.001). A significant improvement was found in dolorimetric threshold readings after the treatment period in women (P < 0.001). No correlation was observed between the reduction in the number of active joints and the reduction in the number of tender points in the same patients (r = 0.2). CONCLUSIONS: Balneotherapy at the Dead Sea area appears to produce a statistically significant substantial improvement in the number of active joints and tender points in both male and female patients with fibromyalgia and psoriatic arthritis. Further research is needed to elucidate the distinction between the benefits of staying at the Dead Sea area without balneotherapy and the effects of balneotherapy in the study population.