Forty-four subjects with classic or definite rheumatoid arthritis who were on individualized chrysotherapy were observed for changes in serum protein electrophoresis, immunoglobulins, and circulating lymphocyte counts. By paired variate analysis, significant declines from pretreatment values were recorded for the following--electrophoretic protein fractions: gamma, alpha-1, alpha-2, (P less than 0.05); immunoglobulins: IgM--53% (P less than 0.001), IgG--37% (P less than 0.01), IgA--34% (P less than 0.001). Rheumatoid factor decreased in 29 of 39 subjects, 15 becoming seronegative (P less than 0.001); circulating lymphocytes decreased by 27% (P less than 0.001). The maximal suppressive effect on IgG and IgM was not achieved until the third and fourth years of therapy by sustained weekly administration of gold sodium thiomalate (one year cumulative dosage, mean 2106 mg, range 1065-2,885; greater than or equal to 4 year cumulative dosage, mean 8747 mg, range 5,385-15,160 mg). An immunosuppressive effect is suggested by these results.

Adult↗

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Average national payments.

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Arthritis, Rheumatoid↗

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Recommended methods for conducting radiolabeled platelet survival studies.

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Blood Platelets↗

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Uneventful administration of plasma products in a recipient with T-activated red cells.

A patient with T-polyagglutinable red cells and a severe coagulopathy provided an opportunity to observe the results of plasma transfusion in the face of T-activation. The patient was a 52-year-old Navajo Indian with a perforated gall bladder and related sepsis due to Clostridium perfringens. The gall bladder was removed surgically. Postoperatively, he had severe thrombocytopenia, and prolonged partial thromboplastin and prothrombin times. The patient's red cells were agglutinated by Arachis hypogaea and Glycine soja lectins but were unagglutinated by extracts of Salvia horminum, Salvia sclarea, and Bandeiraea simplicifolia. No untoward reactions or any evidence of hemolysis were observed when the patient was given platelet concentrates and 4 units of single-donor plasma. Serial plasma hemoglobin and haptoglobin levels documented that there was no hemolysis. His coagulopathy responded, and he had a successful surgical re-exploration and recovery. This case documents that serious adverse consequences do not necessarily follow transfusion of plasma in a recipient with T-activated red cells. T-activation is a relative but not absolute contraindication to plasma transfusion.

Blood Coagulation Disorders↗

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The incidence of hearing impairment after successful treatment of neuroblastoma.

BACKGROUND: Platinum compound based chemotherapy has contributed to improved survival rates in neuroblastoma patients. We studied the association of hearing loss with the use of platinum based drugs. METHODS: Data of children from the two German neuroblastoma study cohorts, NB90 and NB97, were analyzed for the incidence of hearing impairments greater than WHO grade 2. Data from patients surviving more than 1 year after diagnosis without progression or recurrence were used. RESULTS: Of these 1,170 patients, 146 (12.5 %) had persisting hearing impairments. The incidence was low after localized neuroblastoma INSS stage 1 - 3 with 35/650 (5 %) and stage 4S with 2/113 (2 %), but high in stage 4 disease with 109/405 (27 %). Ototoxicity depended on the cumulative cisplatin dose. For doses of 1 - 200 mg/m (2), 201 - 400 mg/m (2), 401 - 600 mg/m (2) and 601 - 800 mg/m (2) we found hearing impairments in 5/39 (12 %), 28/221 (13 %), 61/230 (26 %) and 50/225 (22 %) patients, respectively. The incidence of hearing impairment was not age dependent. In stage 4 patients, there was an additional effect of high dosed carboplatin. 65/188 (40 %) patients developed hearing impairments after carboplatin containing (1,500 mg/m (2)) high dose chemotherapy with autologous stem cell reinfusion compared to only 33/217 (15 %) in patients receiving platinum free maintenance chemotherapy. Substitution of cisplatin (40 mg/m (2) x d, d 1 - 4, 96 h infusion) with carboplatin (100 mg/m (2) x d, d 1 - 4, 1 - 2 h infusion) due to otoxicity during induction chemotherapy did not reduce event free survival. CONCLUSION: One fourth of high risk neuroblastoma survivors suffer from treatment induced hearing impairments. The substitution of cisplatin with carboplatin was not associated with an increased rate of tumor recurrences.

Antineoplastic Combined Chemotherapy Protocols↗

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Neuroblastoma preoperatively treated as nephroblastoma: does inadequate therapy worsen the prognosis?

BACKGROUND: The current standard in the treatment of nephroblastoma is preoperative chemotherapy based on radiological appearance. After subsequent surgical removal few tumours proved histologically to be neuroblastoma. We asked whether initial chemotherapy according to nephroblastoma trials would change the prognosis for those neuroblastoma patients. RESULTS: Out of 1603 patients registered in the German neuroblastoma trials, 29 patients (1.8 %) have preoperatively been treated according nephroblastoma protocols. Advanced stages (11 stage 3, 12 stage 4) were dominant. Diagnostic work up of those patients revealed elevation of catecholamine metabolites in only 39 % (compared to 80 % of the control patients) and mIBG uptake in only 71 % (compared to 89 % of the control patients). Elevation of NSE was observed in 92 % of patients (control group 72 %). Patients with preoperative nephroblastoma treatment were older than the patients of the control group. Risk factors like MYCN amplification or elevation of LDH were more often detected. The outcome of the patients with preoperative chemotherapy according nephroblastoma trials was worse than that of the control group, but risk group adapted survival analysis revealed no disadvantage. CONCLUSION: The prognosis of children with neuroblastoma tumours, which have been radiologically classified as nephroblastoma, is inferior compared to the prognosis of patients without preoperative nephroblastoma therapy. The difference appears to be associated rather with more unfavourable biology than with the element "preoperative chemotherapy".

Adolescent↗

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[Efficiency and side effects of antiretroviral treatment of HIV infected pregnant women].

OBJECTIVE: Antiretroviral treatment (ART) of pregnant women and newborn reduces the vertical HIV transmission below 2 % but long term effects are still not clear. METHOD: We analyzed the data of 59 children born to HIV infected women. RESULTS: The median observation time was 404 (14-740) days. There was no vertical HIV transmission (95 %-confidence interval [CI] 0-5.1 %). Among 6 children without prenatal ART one child with congenital diaphragmatic hernia was born. In 53 infants with prenatal ART we observed 19 congenital malformations (35.8 %, 95 %-CI 23.2-50.6 %). Three were severe malformations (5.7 %, 95 %-CI 1.2-15.5 %): one supraorbital hemangioma (after zidovudine), one athetoid cerebral palsy without evidence of mitochondrial dysfunction (after zidovudine), and one unilateral femoral hypoplasia (after short term zidovudine, lamivudine, and efavirenz in late pregnancy). Sixteen minor malformations were found (30.1 %, 95 %-CI 21.2-43.8 %): ventricular septal defect (closed spontaneously after 6 months), atrial septal defect, transient and persistent pulmonary stenoses, hexadactylies, unilateral hearing impairment, dystopic kidney, subependymal bleeding cysts, and mild dilation of ventricles. CONCLUSIONS: ART prevents vertical HIV transmission. All women should be advised ART during pregnancy and delivery. The prevalence of malformations after prenatal/perinatal ART appears considerably high. Therefore, detailed information for the parents and long term follow-up of all children exposed to antiretroviral drugs are crucial.

Anti-HIV Agents↗

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Stressful events, pessimism, natural killer cell cytotoxicity, and cytotoxic/suppressor T cells in HIV+ black women at risk for cervical cancer.

OBJECTIVE: This study examines whether stressful negative life events and pessimism were associated with lower natural killer cell cytotoxicity (NKCC) and T cytotoxic/suppressor cell (CD8+CD3+) percentage in black women co-infected with human immunodeficiency virus Type 1 (HIV-1) and human papillomavirus (HPV), a viral initiator of cervical cancer. METHOD: Psychosocial interviews, immunological evaluations, and cervical swabs for HPV detection and subtyping were conducted on 36 HIV+ African-American, Haitian, and Caribbean women. RESULTS: Greater pessimism was related to lower NKCC and cytotoxic/suppressor cells after controlling for presence/absence of HPV Types 16 or 18, behavioral/lifestyle factors, and subjective impact of negative life events. CONCLUSIONS: A pessimistic attitude may be associated with immune decrements, and possibly poorer control over HPV infection and increased risk for future promotion of cervical dysplasia to invasive cervical cancer in HIV+ minority women co-infected with HPV.

AIDS-Related Opportunistic Infections↗

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Comparison of omeprazole, metronidazole and clarithromycin with omeprazole/amoxicillin dual-therapy for the cure of Helicobacter pylori infection.

In this randomized, multicenter trial, we evaluated the effectiveness and side effect profile of a modified omeprazole-based triple therapy to cure Helicobacter pylori infection. The control group consisted of patients treated with standard dual therapy comprising omeprazole and amoxicillin. One hundred and fifty-seven H. pylori infected patients with duodenal ulcers were randomly assigned to receive either a combination of omeprazole 10 mg, clarithromycin 250 mg and metronidazole 400 mg (OCM) given three times daily for 10 days (n = 81), or a combination of omeprazole 20 mg and amoxicillin 1 g (OA) given twice daily for 14 days (n = 76). Prior to treatment and after 2 and 6 weeks, gastric biopsies from the antrum and corpus were obtained for histology and H. pylori culture. H. pylori infection was cured in 97.4% after OCM and in 65.8% after OA in the per-protocol analysis (p < 0.001) (intention-to-treat analysis: 93.4% and 63.2%, respectively). H. pylori was successfully cultured in 122 patients (77%). The overall rate of metronidazole resistance was 19.7% (24/122), no primary resistance to clarithromycin or amoxicillin was found. In the OCM group, all patients infected with metronidazole-sensitive H. pylori strains (n = 51) and those infected with strains of unknown susceptibility to metronidazole (n = 14) were cured (100%), while 77% (10/13) of those harboring metronidazole-resistant strains were cured of the infection (p = 0.36). Side effects leading to premature termination of treatment occurred in 2.5% of the patients in the OCM group and in 1.4% of the OA group. We conclude that combined treatment with omeprazole, clarithromycin and a higher dose of metronidazole is highly effective in curing H. pylori infection, and that this regimen remains very effective in the presence of metronidazole-resistant strains.

Adolescent↗