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Clinical analysis of 570 cases with juvenile rheumatoid arthritis: results of a nationwide retrospective survey in Japan.

The purpose of the present study was to investigate the incidence of juvenile rheumatoid arthritis (JRA) among Japanese children and to evaluate the clinical features of this disease. A questionnaire was sent to the department of pediatrics of 1290 hospitals in Japan, in 1994, asking for the number of rheumatic patients during the past 10 years. Subsequently, a second questionnaire was sent asking for the type of onset, clinical features, treatment, and other details. The results of 570 cases were obtained. Of these, 310 cases (54%) were the systemic onset type, 140 cases were the polyarticular onset type (25%), and 120 cases (21%) were the pauciarticular onset type. Hence, in the present series of children, the proportion of the pauciarticular type was less than the other two types of JRA. In the laboratory findings of the systemic onset type, hyperferritinemia and thrombocytosis were noted, in addition to leukocytosis, positive C- reactive protein (CRP) and accentuated erythrocyte sedimentation rate (ESR). The rheumatoid factor was positive in 50% of patients with the polyarticular onset type. Chronic uveitis was recognized in 13 cases (10.8%) of the pauciarticular onset type. In four girls, uveitis started before the onset of arthritis. Non-steroidal anti-inflammatory drugs were used in almost one-third of cases, and methotrexate (MTX) was used in 12.8% of cases. The quality of life of children with JRA was disturbed in almost 20% of cases. Therefore, for the early and definitive diagnosis of the systemic type of JRA, diagnostic procedures including thrombocyte counts and serum ferritin level, should be performed. In order to obtain good results and to avoid side effects, a protocol for the use of disease modifying anti-rheumatic drugs and immunosuppressants, especially for the use of MTX, must be established.

Anti-Inflammatory Agents, Non-Steroidal↗

Relationship of serum interleukin-7 concentration and the coagulation state in children with nephrotic syndrome.

BACKGROUND: Enhanced platelet reactivity may play a significant role in the hypercoagulable state of nephrotic syndrome (NS). Thrombocytosis with platelet aggregation cause the release of some cytokines, among them interleukin-7 (IL-7). The aim of the study was to evaluate serum IL-7 levels in children with the symptoms of NS and to determine a correlation between its concentration and platelet count, other hemostatic factors, and NS intensity. METHODS: The study was performed in two groups. I--the examined group of 26 children with NS (12 boys, 14 girls) aged 6.8 +/- 2.1 years, subjected to two examinations: A--before treatment, B--during treatment with prednisone (60 mg/kg 24 h after albuminuria regression); and II--the control group (C) of 20 healthy children. Serum IL-7 level was assayed by enzyme-linked immunosorbent assay method using a R & D Quantikine set. RESULTS: In group I, IL-7 level in examination A (33.33 +/- 33.24 pg/mL) was higher than in the control subjects (P < 0.01). In examination B, IL-7 concentration was reduced to the level of 10.86 +/- 5.22 pg/mL and did not differ from the controls (P > 0.05). A positive correlation was observed between IL-7 and platelet count and serum fibrinogen level. A negative correlation was noted with antithrombin III concentration. No correlation was found with serum levels of albumin and cholesterol or urine protein. CONCLUSION: In children with NS, serum IL-7 level increases proportionally to the elevated platelet count and other hemostatic components, but shows no correlation with serum albumin or urine protein.

Child↗

Myeloproliferative and lymphoproliferative disorders in the same patient.

A 67-year-old man developed a Philadelphia-negative myeloproliferative disorder which initially manifested as marked thrombocytosis, followed two years later by marked leucocytosis. He subsequently developed an IgG lambda plasma cell dyscrasia together with a monoclonal proliferation of circulating lymphocytes with IgM kappa surface immunoglobulin. The lymphoid neoplasm was associated with a rapidly progressive and fatal course.

Aged↗

Venous thrombosis in haemoglobin H disease after splenectomy.

While venous thrombosis and pulmonary embolism are rare among the Chinese, two of nine patients with haemoglobin H disease developed these complications after splenectomy. The clinical data of the two patients were reported and the relevant literature reviewed. It was concluded that the persistent thrombocytosis and an intravascular haemolysis, particularly prominent in this form of thalassaemia, are contributory to the hypercoagulable state.

Adult↗

Oral isotretinoin and haemophilia A.

The effects of oral isotretinoin on the coagulation system are still not well known: some case reports describe thrombocytopenia or thrombocytosis, others present different effects on fibrinolysis. We report a case of severe acne treated with oral isotretinoin in a patient affected with haemophilia A. In this case, which differs from the only other case reported in the literature, oral isotretinoin did not appear to influence the haemophilic patient's need of factor VIII.

Acne Vulgaris↗

Stauffer's syndrome variant with cholestatic jaundice: a case report.

Cholestasis is a common feature of several malignant diseases, including pancreatic, hepatic, gallbladder, and ampullary carcinomas. It is usually secondary to main bile duct obstruction or widespread hepatic metastasis, but it can also be a paraneoplastic syndrome of other underlying malignancies. Stauffer's syndrome is a rare paraneoplastic manifestation of renal cell carcinoma (RCC) that is characterized by elevated alkaline phosphatase, erythrocyte sedimentation rate, alpha-2-globulin, and gamma-glutamyl transferase, thrombocytosis, prolongation of prothrombin time, and hepatosplenomegaly, in the absence of hepatic metastasis and jaundice. A rare variant of this syndrome with jaundice has recently been described in 3 cases in the literature. We report a patient who presented with abdominal pain and cholestatic jaundice in whom RCC was incidentally found during initial workup. Jaundice and liver dysfunction resolved completely after surgical resection of the tumor. This case illustrates the protean manifestations of RCC, and the importance of considering Stauffer's syndrome and its variant in the differential diagnosis of anicteric and icteric cholestasis, which may allow early recognition and treatment of an underlying malignancy.

Adult↗

Rapid succession of peripheral blood progenitor cell mobilization cycles in patients with chronic heart failure: effects on the hematopoietic system.

BACKGROUND: Circulating hematopoietic peripheral blood progenitor cells (PBPCs) may contribute to the regeneration of nonhematopoietic organs. An increase in circulating PBPC numbers may enhance this process. Therefore, an exploratory trial of repeated PBPC mobilization in patients with chronic heart failure was conducted. The safety and cardiovascular efficacy data have been described elsewhere. In the hematopoietic system, the trial offered an opportunity to study several new aspects of granulocyte-colony-stimulating factor (G-CSF) action. STUDY DESIGN AND METHODS: Fourteen male patients with chronic heart failure were treated successively with G-CSF (four 10-day treatment periods interrupted by treatment-free intervals of equal length; daily dose adjustment to maintain a white blood cell [WBC] count of 45 x 10(9)-50 x 10(9)/L). RESULTS: G-CSF induced a rapid increase in cells of all WBC lineages with return to levels equal to (neutrophilic, eosinophilic, and basophilic granulocytes) or lower than those before treatment (monocytes, lymphocytes) during the treatment-free intervals. Red cell counts remained unchanged, but platelet counts decreased followed by rebound thrombocytosis. The extent of CD34+ cell mobilization was highly variable. For each patient, the changes induced were identical through all cycles, but the G-CSF dose required in the first cycle was significantly higher than in subsequent cycles. In the cohort of patients, an inverse correlation was observed between the WBC level reached and the dose of G-CSF administered. CONCLUSIONS: Rapid alternation between PBPC mobilization and recovery periods is feasible, with identical alterations in all treatment cycles. G-CSF responsiveness varies among patients and is increased by pretreatment with G-CSF.

Aged↗

Platelet aggregation and thromboxane B2 formation after ethanol abuse: is there a relationship to stroke?

Formation of thromboxane B2 (TXB2), a metabolite of the potent platelet-aggregating and vasoconstrictor agent thromboxane A2 (TXA2), during ADP-induced platelet aggregation was studied in 10 healthy men and in 10 male alcoholics during the 2-week period of detoxification. None of the alcoholics had anemia or thrombo-embolic disease. The platelets of the alcoholics were more sensitive for ADP and synthesized as much as triple the amount of TXB2 compared to those of the nonalcoholic donors. The effect was most striking during the rebound thrombocytosis and suggests that it could possible contribute to the increased incidence of various thrombotic diseases in the alcoholic.

Adult↗

Occurrence of oral sebaceous glands in 43,654 industrial workers of Gujarat, India.

In 10 cancer patients platelet concentration, platelet consumption, platelet half-life time and plasma concentration of platelet factor 4 were determined. A high frequency of thrombocytosis and increased platelet consumption were observed, and the plasma concentration of platelet factor 4 was increased. However, no significant correlation was found between platelet consumption and the result of a single determination of platelet factor 4 concentrations in plasma.

Adult↗

Platelet production in hypoxic and RBC-transfused mice.

Platelet production rates were studied in hypoxic, red blood cell (RBC) transfused, and normal mice. In addition, platelet depletion was induced in some of the mice by injection of rabbit anti-mouse platelet serum (RAMPS) to stimulate platelet production. Hypoxia alone caused an increase in haematocrit and platelet count at 1-3 d, followed by a decrease in platelet counts to below normal values at 6-7 d. On the otherhand, RBC transfusion caused increase haematocrit and decreased platelet count of mice at 1-4 d, with a return of platelet counts to normal by 5-6 d. Normal mice and mice transfused with RBC responded to platelet depletion with rebound-thrombocytosis with maximum platelet production 3-5 d later and elevated platelet counts on days 5-6. However, platelet production in platelet-depleted mice exposed to hypoxia was less marked, and platelet counts did not reach normal levels. The data are consistent with the hypothesis that hypoxia causes thrombocytopenia by stem cell competition between erythroid and megakaryocytic cell lines and/or inhibition of thrombopoietin production.

Animals↗

Platelet function in preleukaemia.

Platelet function was studied in 17 patients with preleukaemia and the results were compared with those of 28 patients with other chronic myeloproliferative disorders. The test pattern included bleeding time (Ivy), platelet retention (Hellem II), PF-3 activity and availability after exposure to ADP and kaolin, and ADP-, epinephrine-, collagen- and ristocetin-induced aggregations. Platelet function was frequently impaired in patients with preleukemia. The defects were similar to those found in other myeloproliferative disorders. The most consistent finding was defective aggregation. Patients with thrombocytosis and/or with increased amounts of megakaryocytes in the bone marrow had fewer defects in platelet function. Retention defect was more common in patients with hypolobulated megakaryocytes, especially in those having a specific marker, the 5q- chromosome, in their bone marrow cells.

Adult↗

Exercise-induced changes in the in vivo distribution of 111In-labelled platelets.

In order to throw some light on the mechanisms underlying exercise-induced thrombocytosis, we investigated 15 healthy persons subjected to short-term vigorous pedalling on a bicycle ergometer 1 d after injection of autologous 111In-labelled platelets. Scintigraphic studies during the post-exercise period showed the spleen to be the major platelet-releasing organ. There was, however, a considerable interindividual variability manifested as signs of a contributing platelet release from the lungs in some cases and of deposition of a surplus of released platelets in the liver of others. Our results also seem to be compatible with the existence of an intravascular marginal platelet pool.

Adolescent↗

Management of polycythaemia vera, essential thrombocythaemia and myelofibrosis with hydroxyurea.

A total of 59 symptomatic patients with myeloproliferative disorders (polycythaemia vera 24 pats., essential thrombocythaemia 25 pats., myelofibrosis 10 pats.) and elevated platelet counts were studied during 1653 months of continuous treatment with hydroxyurea. Reduction of the platelet level to less than 500 x 10(9)/l was achieved within 8 weeks in 86% of polycythaemia pats., 80% of thrombocythaemia pats., 60% of myelofibrosis pats. Control of disease-related symptoms was achieved within 1 year in 78% of the patients. There was no instance of severe bone marrow toxicity. Side-effects of hydroxyurea were modest. Survival was excellent, with 86% probability of survival after 5 yr of therapy. We consider hydroxyurea a first-choice alternative in the treatment of patients with polycythaemia vera, essential thrombocythaemia and mylofibrosis with thrombocytosis.

Drug Evaluation↗

Effectiveness of partial splenic embolization as treatment for hypersplenism in thalassaemia major: a 7-year follow up.

Partial splenic embolization is an alternative procedure to total splenectomy in patients with hypersplenism, and was performed in 10 patients with beta-thalassaemia major who were then followed for 5 to 7 years. The results were compared with those of a 7-yr follow-up of 6 splenectomized thalassaemics. The blood consumption decreased and the leucocyte counts increased in both groups of patients. However, after partial splenic embolization, severe thrombocytosis--which is typical of splenectomized patients--did not develop and there were no severe complications from the operation, such as infections or reappearance of hypersplenism. In addition, the minor surgical injury and avoidance of abdominal scars were further advantages of partial splenic embolization over total splenectomy.

Adolescent↗

Automated measurement of reticulated platelets in estimating thrombopoiesis.

We described a fully automated measurement of reticulated platelets using a fluorescent dye, auramine O, and a reticulocyte counter, the R-3000, equipped with special software. Reproducibility and linearity were shown to be good. In the normal subjects studied (n = 60), the mean value for reticulated platelets was 0.98% +/- 0.41% and the mean absolute count was 2.12 +/- 0.69 x 10(9)/l. The absolute count for reticulated platelets was significantly lower (p < 0.05) in patients with reduced thrombopoiesis as seen in acute myeloblastic leukemia, aplastic anemia or chemotherapy-induced thrombocytopenia and it was elevated (p < 0.05) in essential thrombocythemia and in chronic myelocytic leukemia with thrombocytosis. All 20 patients with chronic idiopathic thrombocytopenic purpura had a high percentage of reticulated platelets. The percentage of reticulated platelets was significantly increased (p < 0.05) in patients with impaired thrombopoiesis despite the reduction in the absolute count. In 2 leukemic patients, an apparent rise was noticed in the percentage of reticulated platelets which preceded by several days a progressive increase in the platelet count at the recovery phase of thrombocytopenia. The results suggest that an automated measurement of reticulated platelets can be applied to routine laboratories for clinical use.

Adolescent↗

Serum thrombopoietin and interleukin 6 concentrations in tumour patients and response to chemotherapy-induced thrombocytopenia.

The relation between the number of platelets in blood and the concentrations of immunoreactive thrombopoietin (TPO), interleukin 6 and interleukin 11 (IL-6, IL-11) was studied in the sera of 32 normal subjects, of 29 untreated tumour patients and of 6 tumour patients following chemotherapy with ifosfamide, carboplatin and etoposide (ICE). Platelet counts, TPO and IL-6 concentrations were higher than normal in blood of tumour patients before chemotherapy. However, no statistical relation existed between these variables. Following chemotherapy, the number of circulating platelets decreased reaching a nadir at d 10-13, while the serum concentration of TPO increased concomitantly. Circulating IL-6 did not increase during chemotherapy-induced thrombocytopenia. IL-11 was not detectable in any serum. Thus, the reactive thrombocytosis in tumour patients could be related to elevated TPO and IL-6 levels. In contrast to circulating TPO, however, neither serum IL-6 nor IL-11 levels increase significantly in thrombocytopenia following myelosuppressive. chemotherapy.

Adult↗

Periodontal therapy: a novel non-drug-induced experimental model to study human inflammation.

BACKGROUND: Chronic periodontitis causes a low-grade systemic inflammatory response; its standard treatment, however, induces an acute inflammatory response. The aim of this study was to describe the systemic inflammatory reactions to an intensive periodontal treatment regimen. METHODS: Fourteen otherwise healthy subjects suffering from severe chronic periodontitis were enrolled in a 1 month pilot single-blind trial. Intensive periodontal treatment, consisting of full-mouth subgingival root debridement delivered within a 6-h period, was performed. Periodontal parameters were recorded before and 1 month after completion of treatment. Blood samples were taken at baseline and 1, 3, 5, 7 and 30 days after treatment. Interleukin-1 receptor antagonist (IL-1Ra), Interleukin-6 (IL-6) and C-reactive protein (CRP) serum concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Complete blood counts were also performed. RESULTS: One day after treatment, mild neutrophilia and monocytosis (p < 0.05) and lymphopenia (p < 0.01) were accompanied by a sharp increase in inflammatory markers (IL-1Ra, IL-6, p < 0.01). A 10-fold increase in CRP (p < 0.001) was detected on day 1 and its kinetics followed a pattern of a classical acute phase response (significantly raised concentrations up to 1 week, p < 0.01). At 3-7 days after treatment, subjects presented also with a mild tendency towards a normocytic anaemic state (p < 0.01) and a degree of lympho-thrombocytosis (p < 0.05). The observed changes were similar to those expected following the well-characterized endotoxin-challenge model of inflammation. CONCLUSIONS: Intensive periodontal treatment produced an acute systemic inflammatory response of 1 week duration and might represent an alternative to classic endotoxin-challenge or drug-induced models to study acute inflammation in humans.

Acute-Phase Reaction↗

Fatal familial cholestatic syndrome in Greenland Eskimo children.

A syndrome of intrahepatic cholestasis leading to death in early childhood was studied in 16 Greenland Eskimo children. The pedigrees are compatible with autosomal recessive inheritance. Jaundice, bleeding, pruritus, malnutrition, steatorrhoea, osteodystrophy and dwarfism were typical clinical features. Eight had died between the ages of six weeks and three years due to bleeding or infections. Hyperbilirubinaemia, profound hypoprothrombinaemia, thrombocytosis and elevated alkaline phosphatase levels were evident. Serum calcium, phosphate and parathyroid hormone levels indicated a secondary hyperparathyroidism. Hepatic fibrosis developed with increasing age. Follow-up of the surviving patients was 4 to 30 months. The aetiology of the disease is unknown. The syndrome has some features in common with previously described patients with familial intrahepatic cholestasis. No specific treatment is available. Genetic counselling is essential.

Celiac Disease↗

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