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Investigation of protein metabolism with respect to amino acid administration.

A comparative study of the protein metabolism of two groups of patients having suffered major trauma (group I, n = 26, and group II, n = 16) and of two groups having undergone major surgery (group III, n = 10, and group IV, n = 9) was performed from the 2nd to the 11th day of treatment. All of the patients received approximately 35 kcal/kg body weight/day. In addition the patients in groups I and III received a 10% amino acid solution containing 0.24 g N/kg body weight/day whereas groups II and IV were administered a 5% solution containing only essential and semiessential amino acids amounting to 0, 12 g N/kg body weight/day. The 24-hr nitrogen output in urine, the serum free amino acid concentration as well as the serum protein fractions of transferrin and the C3c and C4 complements were contrasted. Significant differences between traumatised patients and those having had major surgery with respect to nitrogen balance and serum free amino acid concentrations were observed regardless of the pattern of nutrition. However, only slight differences in the concentrations of serum protein fractions of the two groups of patients were noted. Following amino acid solution the polytraumatized patients exhibited an average N balance of -11.9 g N/day, which is indicative of a severely catabolic metabolism. The average nitrogen loss observed in the postsurgical patients amounted to only half this amount. Following administration of the semiessential amino acid solution an appreciable difference in the nitrogen balance between comparable groups was not observed. However, the blood urea nitrogen was lower.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Chronic urticaria: a Canadian perspective on patterns and practical management strategies.

BACKGROUND: Chronic urticaria is a common condition and is a source of great frustration to patients. It has been suggested that there may be differences among physicians in their approach to this common clinical entity. OBJECTIVE AND METHOD: A questionnaire was distributed Canada-wide to allergists, dermatologists, and a selection of practitioners with an interest in alternative medicine. The survey included questions on demographics, epidemiology, causative factors, diagnostic methods, therapeutic strategies, follow-up advice, and efficacy of therapies, with emphasis on personal experience. RESULTS: The response rates of allergists and dermatologists were 31% and 36%, respectively. There was wide representation from all regions of Canada and from physicians from all age groups, both genders, different types of practice, and years in practice. The reported incidence per month was 13 and 4 patients for allergists and dermatologists, respectively. The prevalence was 199 and 44 patients by allergists and dermatologists, respectively. Comparison of causative factors showed differences in the experiences of the two groups. Diagnostic investigations were requested in a similar pattern with respect to timing. The specific tests ordered by the groups showing statistical difference were complete blood count (CBC), differential, C4 complement, antinuclear antibodies, and IgE antibody assay. Allergists chose the skin prick test (100%) as the most important allergy test. Dermatologists ranked skin prick (50%), radioallergosorbent test (RAST) (20%), and skin patch (30%) as the most important tests. The top six choices of pharmaceutical therapies chosen by the groups were similar, but in a slightly different order. The responders ranked their personal selection of antihistamines according to effectiveness. Hydroxyzine (Atarax) and cetirizine (Reactine, Allegra) were selected as first and second most effective agents by both groups. The results also show effective experience by both groups with nonsedating and sedating antihistamines. Also, doxepin, ketotifen, and cimetidine are used frequently by both groups. The experience of dermatologists in Canada with respect to other modalities including psoralen ultraviolet A (PUVA) therapy, danazol, chelation, calcium channel blockers, and acyclovir is limited and efficacy is ranked either neutral or ineffective. Allergists reported even less experience with these therapies. CONCLUSION: Allergists and dermatologists across Canada show interesting similarities and differences in their practical approach to the management of chronic urticaria. With the sharing of this information, these two specialties will be better equipped to effectively manage patients suffering from chronic urticaria.

Adult↗

Q fever endocarditis masquerading as Mixed cryoglobulinemia type II. A case report and review of the literature.

BACKGROUND: The clinical manifestations of Q fever endocarditis are protean in nature. Mixed cryoglobulinemia type II is rarely a facet of the presenting clinical manifestations of Q fever endocarditis. CASE PRESENTATION: We report a case of a 65-year-old pensioner with such an association and review the literature. As transesophageal echocardiograms are usually normal and blood cultures are usually negative in Q fever endocarditis, many of the manifestations (fever, rash, glomerulonephritis/evidence of renal disease, low serum C4 complement component, presence of mixed type II cryoglobulin, constitutional symptoms as arthralgias and fatigue) can be attributed to Mixed cryoglobulinemia type II per se. The use of Classic Duke Endocarditis Service criteria does not always suffice for the diagnosis of Q fever. CONCLUSION: The application of the modified criteria proposed by Fournier et al for the improvement of the diagnosis of Q fever endocarditis will help to reach the diagnosis earlier and thus reduce the high mortality of the disease. We would like to stress the importance of ruling out the diagnosis of Q fever endocarditis in cases of mixed type II cryoglobulinemia.

Aged↗

Effect of cannabinoid ingestion (in the form of bhang) on the immune system of high school and university students.

The discovery of cannabinoid receptors in the immune system and a family of endogenous ligands of these receptors provides a basis for understanding the cellular and molecular mechanisms of cannabis-induced immunotoxicity. The present study was conducted on 90 nonsmoker males of high school and university students living in Tanta city of matched age and socioeconomic lifestyle. They were divided into a control group (30 males) and a bhang user group (60 males), which used bhang by eating its sweet juice after boiling with a little water and drying in an oven, 'fola'. The bhang group was divided equally into two subgroups: subgroup 1 used bhang for 6-24 months (average 19 +/- 1.2) and subgroup 2 used bhang for 24-36 months (average 31 +/- 1.7). The immunotoxic effects of using bhang appeared in the form of a significant decrease in serum immunoglobulins (IgG and IgM), and C3 and C4 complement protein concentrations (P < 0.05). In addition, our results demonstrated a significant decrease in the absolute number of functionally different subsets of peripheral blood mononuclear lymphocytes, T and B lymphocytes and natural killer (NK) cells in bhang users as compared to controls (P < 0.05). Moreover, the fatty acid amide hydrolase (FAAH) showed significant decrease in bhang users as compared to controls and in subgroup 2 as compared to subgroup 1 (P < 0.05), indicating that the decrease in FAAH protein level is closely related to the duration of bhang use. Positive correlations were found between FAAH level and the absolute number of mononuclear cells (T, B lymphocytes and NK cells) among bhang user subgroups. The present study is the first study to report on the effect of bhang on complement proteins and immunoglobulins in humans. Our study revealed that bhang-induced immunotoxicity could be attributed to decrease in FAAH protein.

Adolescent↗

Large pericardial effusions due to systemic lupus erythematosus: a report of eight cases.

The aim of this study was to describe the clinical, echocardiographic and laboratory characteristics of large pericardial effusions and cardiac tamponade secondary to systemic lupus erythematosus (SLE). An ongoing prospective study was conducted at Tygerberg Academic Hospital, South Africa between 1996 and 2002. All patients older than 13 years presenting with large pericardial effusions (> 10 mm) requiring pericardiocentesis were included. Eight cases (out of 258) were diagnosed with SLE. The mean (SD) age was 29.5 (10.7) years. Common clinical features were Raynaud's phenomenon, arthralgia and lupus nephritis class III/IV. Echocardiography showed Libman-Sacks endocarditis (LSE) in all the mitral valves. Two patients developed transient left ventricular dysfunction; both these patients had pancarditis. Typical serological findings included antinuclear antibodies, anti-double stranded DNA antibodies, low complement C4 levels and low C3 levels. CRP was elevated in six cases. Treatment consisted of oral steroids and complete drainage of the pericardial effusions. No repeat pericardial effusions or constrictive pericarditis developed amongst the survivors (3.1 years follow up). This study concludes that large pericardial effusions due to SLE are rare, and associated with nephritis, LSE and myocardial dysfunction. Treatment with steroids and complete drainage is associated with a good cardiac outcome.

Adolescent↗

Phase I trial of a human-mouse chimeric anti-disialoganglioside monoclonal antibody ch14.18 in patients with refractory neuroblastoma and osteosarcoma.

PURPOSE: To evaluate the toxicity, immunogenicity, and pharmacokinetics of a human-mouse chimeric monoclonal antibody (mAb) ch 14.18 directed against disialoganglioside (GD2) and to obtain preliminary information on its clinical efficacy, we conducted a phase I trial in 10 patients with refractory neuroblastoma and one patient with osteosarcoma. PATIENTS AND METHODS: Eleven patients were entered onto this phase I trial. They received 20 courses of mAb ch 14.18 at dose levels of 10, 20, 50, 100, and 200 mg/m2. Dose escalation was performed in cohorts of three patients; intrapatient dose escalation was also permitted. RESULTS: The most prevalent toxicities were pain, tachycardia, hypertension, fever, and urticaria. Most of these toxicities were dose-dependent and rarely noted at dosages of 20 mg/m2 and less. Although the maximum-tolerated dose was not reached in this study, clinical responses were observed. These included one partial (PR) and four mixed responses (MRs) and one stable disease (SD) among 10 assessable patients. Biologic activity of ch 14.18 in vivo was shown by binding of ch 14.18 to tumor cells and complement-dependent cytotoxicity of posttreatment sera against tumor target cells. An anti-ch 14.18 immune response was detectable in seven of 10 patients studied. CONCLUSION: In summary, with the dose schedule used, ch 14.18 appears to be clinically safe and effective, and repeated mAb administration was not associated with increased toxicities. Further clinical trials of mAb ch 14.18 in patients with neuroblastoma are warranted.

Adult↗

Serum complement levels in infancy: age related changes.

Levels of eight complement components and two control proteins, were determined on cord serum from normal full term neonates and serum from healthy infants aged 1 and 6 months. For all proteins, the levels were below the adult normal at birth and rose toward the adult range by age 6 months. In a second group of 271 patients, ages 1-36 months, serum Clq and properdin levels were measured. For both proteins, the mean values in early infancy were more than two SD below the adult range and did not reach the adult range until 18-21 months of age. The Clq concentration was more variable than that for any other component studied. In infants from 11 months-3 yr of age, Clq levels correlated with serum IgG levels, but properdin levels did not.

Adult↗

Immune abnormalities in guinea pigs with asymptomatic congenital syphilis.

Spleens from 1-20-wk-old guinea pigs infected in utero with Treponema pallidum and age-matched controls, born to normal and heat-killed (56 degrees C, 2 h.) T. pallidum-injected mothers, were examined for their in vitro lymphoproliferative response to phytohemagglutinin, concanavalin A, and lipopolysaccharide. Additionally, T cell surface markers (mu-chain, pan T, CD4, and CD8) were determined in spleen, lymph node, and peripheral blood from 10-wk infected and normal pups by single and dual parameter fluorescence-activated cell sorter analysis. Compared with control animals, congenitally infected animals showed a remarkable prolonged naive-type of immune response as reflected by the higher (p < 0.01) proliferative responses to both T cell mitogens (up to 20 wk of age), and the weaker response to the B cell mitogen, significantly different (p < 0.01) at 10 wk of age. As opposed to controls, in all organs examined the level of CD8+ (cytotoxic/suppressor) T cells was significantly diminished (p < 0.01); consequently, the CD4/CD8 ratio was significantly elevated (p < 0.05). The role of C4 complement component and the nature and potential role of the immature T and B lymphocyte responses in asymptomatic congenital syphilis is discussed.

Animals↗

Pleural SC5b-9 in differential diagnosis of tuberculous, malignant, and other effusions.

A monoclonal antibody against soluble phase-terminal complement complex (SC5b-9) was used to try to differentiate pleural effusions of tuberculous vs malignant and other origin. Effusions of tuberculous origin showed a significantly higher SC5b-9 level than did plasma, suggesting activation of complement in the pleural space. All 26 patients with tuberculous effusions showed SC5b-9 levels in pleural fluid exceeding 2.0 mg/L, while 20 with malignant effusions had levels less than 2.0 mg/L. However, rheumatoid, some parapneumonic, and treated malignant effusions showed SC5b-9 levels above 2.0 mg/L. Considering a value exceeding 2.0 mg/L, the specificity and sensitivity of the SC5b-9 estimation in tuberculosis were 0.74 and 1.0, respectively. The mean values for C4d and Bb fragments of complement were significantly (p < 0.05) higher in the tuberculous than in the malignant effusions. However, the values for Bb in 16 (62 percent) of the 26 patients with tuberculous or malignant effusions were in the same range. The activity of adenosine deaminase (ADA) was higher in the tuberculous than in the malignant effusions. While 18 of 26 patients with tuberculous effusions showed an ADA value exceeding 50 mU/ml, the estimated cutoff point (sensitivity = 0.69), 35 of the 36 nontuberculous effusions showed a true negative value (specificity = 0.97). A correlation between ADA and SC5b-9 values was observed in pleural effusions. These observations suggest that the estimation of SC5b-9 in pleural fluid presents a new approach to differentiating tuberculous vs malignant effusions.

Adenosine Deaminase↗

Determination of reference intervals for 10 serum proteins measured by rate nephelometry, taking into consideration different sample groups and different distribution functions.

Reference intervals were established for 10 serum proteins (IgA, IgG, IgM, transferrin, haptoglobin, complement C3, complement C4, alpha 1-acid-glycoprotein, alpha 1-antitrypsin, alpha 2-macroglobulin) measured by rate nephelometry. The reference individuals - 200 blood donors - were divided into 5 subgroups: men aged 19-39 and 40-60 years, women aged 19-39 and 40-60 years and women aged 19-48 years using oral contraceptives. Where possible, two or more subgroups were combined to give reference sample groups. Criteria for this procedure are given. The reference limits of the sample groups were estimated by parametric methods. Assuming that for a specified serum protein the type of distribution is the same in each subgroup, the data were standardized with estimated group specific parameter values and combined into one big sample. This permitted an improved determination of the underlying type of distribution. As a possible form of distribution we also considered the normal distribution truncated on the left side at c greater than or equal to 0. In some cases, after determination of an optimal c, this unusual distribution fitted the data significantly better than the generally used normal or log-normal distribution.

Adult↗

A murine model for neuropsychiatric disorders associated with group A beta-hemolytic streptococcal infection.

A syndrome of motoric and neuropsychiatric symptoms comprising various elements, including chorea, hyperactivity, tics, emotional lability, and obsessive-compulsive symptoms, can occur in association with group A beta-hemolytic streptococcal (GABHS) infection. We tested the hypothesis that an immune response to GABHS can result in behavioral abnormalities. Female SJL/J mice were immunized and boosted with a GABHS homogenate in Freund's adjuvant, whereas controls received Freund's adjuvant alone. When sera from GABHS-immunized mice were tested for immunoreactivity to mouse brain, a subset was found to be immunoreactive to several brain regions, including deep cerebellar nuclei (DCN), globus pallidus, and thalamus. GABHS-immunized mice having serum immunoreactivity to DCN also had increased IgG deposits in DCN and exhibited increased rearing behavior in open-field and hole-board tests compared with controls and with GABHS-immunized mice lacking serum anti-DCN antibodies. Rearing and ambulatory behavior were correlated with IgG deposits in the DCN and with serum immunoreactivity to GABHS proteins in Western blot. In addition, serum from a GABHS mouse reacted with normal mouse cerebellum in nondenaturing Western blots and immunoprecipitated C4 complement protein and alpha-2-macroglobulin. These results are consistent with the hypothesis that immune response to GABHS can result in motoric and behavioral disturbances and suggest that anti-GABHS antibodies cross-reactive with brain components may play a role in their pathophysiology.

Animals↗

Hyperthyroidism following primary hypothyroidism in association with polyendocrine autoimmunity.

A 37 year old male with a strong family history of autoimmune disease presented with typical symptoms of hyperthyroidism. He had exophthalmos but no goitre. Hyperthyroidism was confirmed by failure of 131I neck uptake to suppress after 7 days treatment with triiodothyronine. Six years previously a diagnosis of primary hypothyroidism has been made. At diagnosis of hyperthyroidism, thyroglobulin antibodies, thyroidal microsomal antibodies and thyroid stimulating immunoglobulins were detected. The absence of thyroid growth stimulating immunoglobulins and presence of immunoglobulins blocking TSH-induced growth may account for the absence of goitre throughout. HLA -B8, -B, -DR3 and -DR4 genotypes, low C4 complement concentrations and islet cell autoantibodies were detected at the time of diagnosis and 1 year later diabetes mellitus developed.

Adult↗

'Nephritic factor' may be an autoantibody to C3b or C4b.

We attempted to clarify the character of 'Nephritic Factor' in the alternative (NeFA) and classical pathways (NeFC) of the complement, using an agglutinating and a hemolytic activity assay. The results suggested a possibility that NeFA and NeFC were different in their ability but might appear at the same time in some cases, and that NeFA was anti-C3b autoantibody and NeFC anti-C4b autoantibody.

Autoantibodies↗

Nephritic factor (NeF) of alternate pathway (NeFA) and of classical pathway (NeFc).

NeFA and NeFc were studied in various cases (115 cases). 5 cases were followed up for a long time. NeFA assay was done by the "microtest plate method". We detected the NeF activity for the first time in the cases of Sjögren syndrome (SjS) and SjS+SLE+Hashimoto's disease (Hashimoto). In some cases NeF activity disappeared after therapy, and in one case NeFA and NeFc were positive at first, but then only NeFA activity became negative following the adequate therapy. As to the antibody nature of NeF, the possibility was suggested that NeFA might be anti C3b autoantibody and NeFc might be anti C4b and/or C4b2a auto-antibody.

Complement Activation↗

Plasma anaphylatoxin concentrations in inflammatory skin diseases.

To study the possible involvement of the complement system in inflammatory skin disorders, we measured the concentrations of C3a and C4a anaphylatoxins in the peripheral blood of 148 patients with various inflammatory skin disorders and 48 healthy control subjects by radioimmunoassay. Significant increases in mean levels of both C3a and C4a anaphylatoxins were found in 59 patients with psoriasis. Remarkable increases in both C3a and C4a anaphylatoxins were also noted in some patients with leukocytoclastic vasculitis, urticarial vasculitis or unspecified toxic erythema. On the other hand, elevation of C4a alone was noted in a case of systemic lupus erythematosus. In contrast, using the mean of the normal control +/- 2 S.D., no significant anaphylatoxin elevation was found in 16 patients with pustulosis palmaris et plantaris, 7 with pityriasis rosea, 3 with erythema multiforme, and 3 with erythema nodosum or autoimmune bullous dermatoses.

Anaphylatoxins↗

Complement fragment C4d and Bb levels in inflammatory skin diseases (e.g. SLE, atopic dermatitis, erythroderma and pustulosis palmaris et plantaris) for assessment of complement activation.

The complement is one of the major effector system in the process of inflammation. Complement activation has been shown to occur in inflammatory dermatoses such as systemic lupus erythematosus, atopic dermatitis, erythroderma of unknown origin, and pustulosis palmaris et plantaris by the elevated blood levels of complement fragments. To clarify the complement activation, especially the alternative pathway involvement, we have measured the concentrations of classical pathway-specific C4d and alternative pathway-derived Bb in the plasma of patients with these inflammatory disorders at a mild to exacerbated stage. Only the SLE plasma showed significantly elevated Bb levels. These results suggest that assessments of plasma C4d and Bb levels may be of value in monitoring the involvement of the complement system in patients with inflammatory dermatoses with significant complement activation.

Adult↗

Renal thrombotic microangiopathy associated with anticardiolipin antibodies in hepatitis C-positive renal allograft recipients.

Hepatitis C virus (HCV) infection has been associated with de novo or recurrent membranoproliferative glomerulonephritis and acute transplant glomerulopathy in transplanted kidneys. Recently, anticardiolipin antibodies (ACA) have been linked with chronic HCV infection. A few reports have suggested an association between ACA and renal allograft thrombosis. This study examines the clinical and pathologic features of HCV-positive renal allograft recipients at our institution. From 1990 to 1996, 379 kidney transplants were performed. We identified 18 recipients (4.8%) with HCV-positive serology pretransplant. Determination of IgG and IgM ACA was performed by enzyme-linked immunosorbent assay, using pretransplant sera. Among the 18 patients, five patients presented with biopsy-proven de novo renal thrombotic microangiopathy (RTMA), occurring 5 to 120 d (median, 14 d) after transplant. No differences in pretransplant characteristics were observed between patients with (n = 5) or without (n = 13) RTMA. All five patients had a positive ACA test (either IgG or IgM titer > 2 SD above normal), compared with only one of 13 patients without RTMA. The mean value for IgG ACA was significantly higher in the RTMA patients than in patients without RTMA (22.9 +/- 14.1 versus 6.9 +/- 4.9 IgG phospholipid units, P = 0.02); however, there were no significant differences in IgM ACA titers. Rheumatoid factor and complement C4 levels were normal in pretransplant sera of patients with RTMA. Patients with RTMA had their cyclosporine withdrawn (four of five) or the dose was decreased (one of five), and one of five underwent plasmapheresis. Four of five patients died within 5 yr after transplant, compared with no deaths in the other 13 patients. Finally, as a control group, seven HCV-negative renal allograft recipients who presented with RTMA/hemolytic uremic syndrome during the same time period were found to have normal ACA values (IgG or IgM). RTMA associated with ACA in HCV-positive renal allograft recipients may represent a new clinical entity. The occurrence of this syndrome may have deleterious consequences for patient and graft survival.

Adult↗