Rheumatic heart disease: how big is the problem?
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Biomedical subjects
Publications and source records attributed to A Ibrahim.
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This is a prospective study on 123 randomly selected patients admitted with the diagnosis of acute appendicitis. The value of rebound tenderness as a clinical diagnostic tool was statistically compared to those of some other physical signs; namely guarding, rigidity and Rovsing's sign. Rebound tenderness was found to carry the highest sensitivity (94.7%), negative predictive value (81.3%), reliability (49.1%), and association with histological diagnosis (P < 0.05). However, its specificity and positive predictive value was not significantly different from those of other physical signs. It is concluded that, in contradistinction to some previously published reports, our study emphasizes the role of rebound tenderness in the clinical diagnosis of acute appendicitis.
A 19 year old student was admitted with generalised lymphadenopathy, paraplegia, double incontinence and weight loss in our hospital (Abuth Zaria). A histological diagnosis of lymphocytic (non-Hodgkin's) lymphoma was made on lymph node biopsy. Before treatment could be started the patient developed increasing difficulty in breathing. He was transferred to our ICU where he was noted to have developed no sustained VT. Subsequent repeated episodes did not respond to resuscitative measures (i.v. lignocaine 100 mg for five minutes, oxygen and assisted respiration). The patient died.
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Butyric acid increases fetal hemoglobin synthesis in adult animals and in erythroid cells in culture and induces the gamma-globin gene promoter in transient expression experiments in K562 cells (McDonagh KT, Nienhuis AW, Blood 78:255a, 1992 [abstr, suppl 1]). We compared the effect of butyrate and other short-chain carboxylic acids in transient expression studies with K562 cells using an expression plasmid bearing a luciferase reporter gene driven by the normal human A gamma-globin gene promoter. Butyrate (4 carbons) increased the activity of the human A gamma-globin gene promoter up to 123 times. Marked augmentation of the normal gamma-promoter activity was also noted with 5-carbon valeric acid (up to 394 times) and 3-carbon propionic acid (up to 129 times). The branched isobutyric acid as well as phenylacetate showed less ability to increase promoter activity. Addition of the tandemly repeated AP-1/NF-E2 (AP) enhancer sequences from hypersensitive site 2 (HS2) of the locus control region (LCR) increased gamma-promoter activity up to 24 times. Addition of a nearby 16-bp conserved motif (CM) in HS2 (Safaya S, Rieder RF, Blood 78:146a, 1992 [abstr, suppl 1]) to the AP-containing plasmid construct further increased gamma-promoter activity. In the presence of butyrate, the plasmid bearing both the AP and CM sequences showed gene expression up to 477 times greater than that of the basal gamma-promoter-driven luciferase plasmid in the absence of inducer. A plasmid bearing the herpes simplex thymidine kinase promoter was also tested and gene expression was markedly increased by the same organic acids. MEL cells responded to butyrate, valerate, and propionate with induction of hemoglobin synthesis. Responses to isobutyrate and 6-carbon caproate required higher concentrations of the compounds. Thus, other short-chain organic acids as well as butyrate increase gamma-promoter activity in the transient expression system, and this activity can be further augmented by incorporating LCR elements into the expression vector. Nonglobin promoters also respond to the same carboxylic acids.
The inter- and intrageneric relationships of the genus Yersinia were investigated by sequence analysis of the 16S rRNA gene. A stretch of approximately 1450 nucleotides was sequenced from representatives of ten of the eleven validly described species. Phylogenetic analysis revealed that yersinae form a coherent cluster within the gamma subgroup of Proteobacteria. The intrageneric relationship was characterized by five sublines with Y. enterocolitica, Y. rohdei, and Y. ruckeri forming separate sublines each represented by a single species. A separate subline was formed by Y. pestis, Y pseudotuberculosis and Y. kristensenii, while Y. mollaretii, Y. intermedia, Y. bercovieri, Y. aldovae, and Y. kristensenii formed a fifth subline. The phylogenetic distinctness of the yersiniae sublines is compared to published phenotypic properties and results of DNA-DNA similarity studies.
Schistosomiasis parasitic infection (Schistosoma haematobium) is associated in some patients with bladder cancer. The production of cytokines such as tumor necrosis factor alpha (TNF alpha) is a key event of inflammation in human infectious disease and malignancy. TNF alpha has not been previously investigated from schistosomiasis infection and bladder malignancy. In this report we demonstrate that serum levels of TNF alpha are highly elevated in patients with schistosomiasis of urinary bladder (SB), schistosomiasis with carcinoma of urinary bladder (SCB), and carcinoma of urinary bladder without schistosomiasis (CB). Purified monocytes from bladder malignancy (SCB and CB) cultured without exogenous stimuli release TNF alpha in the culture supernatants. However, lipopolysaccharides and concanavalin A stimulation of monocytes from these patients produced highly elevated levels of TNF alpha compared with normal controls. The findings that monocytes are the potent producers of TNF alpha in this malignancy may be a key observation implicating these cells in the pathophysiology of this disease. Furthermore, it was shown that serum TNF alpha levels correlated with the clinical staging of disease in both SCB and CB, with higher levels in T3 and T4 advanced-stage patients and low levels in T1 and T2 early-stage patients. These results suggest that monocyte abnormality and serum TNF alpha levels might be one of the factors contributing to the progression of disease.
25 patients with poor-prognosis malignancies were treated with a combination of fixed-dose etoposide (1750 mg/m2), cyclophosphamide (6400 mg/m2) and escalating doses of carboplatin (from 800 to 1600 mg/m2) followed by autologous bone marrow transplantation (ABMT). The median duration of granulocytopenia (< 500/mm3) and thrombocytopenia (< 20,000/mm3) was 23 days and 20.5 days, respectively. The main non-haematological toxicity was gastro-intestinal, with moderate to severe diarrhoea in 15 patients. No significant renal toxicity was observed. 2 patients died early due to toxicity. The overall response rate was 58% including 42% having complete responses. 4 of the 25 patients are alive with no evidence of disease at 22, 27, 40 and 43 months after ABMT. The encouraging antitumoral activity of this regimen makes it a good candidate for intensified chemotherapy in patients with various malignancies. Toxicity is acceptable and may be reduced in the near future with the widespread use of haematopoietic growth factors.
Twenty-seven patients with poor-prognosis malignancies were treated with a combination (CARBOPEC) of fixed-dose etoposide (1,750 mg/m2), cyclophosphamide (6,400 mg/m2), and escalating doses of carboplatin (from 800 to 1,600 mg/m2) followed by autologous bone marrow transplantation (ABMT). All patients had previously received platinum derivatives. The diagnoses were as follows: germ cell tumors (GCTs; n = 15); ovarian carcinomas (n = 8); rhabdomyosarcomas (n = 3), and Hodgkin's disease (n = 1). All 27 patients were fully evaluated for toxicity. The median duration of granulocytopenia (leukocytes < 0.5 x 10(9)/l) and thrombocytopenia (platelets < 20 x 10(9)/l) was 23 and 20 days, respectively. Hematologic growth factors were used in 3 cases. The main nonhematologic toxicity was gastrointestinal, with moderate to severe diarrhea in 18 patients. No significant renal toxicity was observed. The overall response rate to this high-dose chemotherapy was 55%, with a complete response (CR) rate of 45% (9 patients). The median duration of CR was 9 months. Five of the 27 patients are alive with no evidence of disease (NED) at 5, 22, 27, 40, and 43 months after ABMT. Four of the 11 patients with refractory GCTs have NED at 5, 22, 27, and 40 months, together with 1 of the 3 responders (43 months). Our study shows the encouraging antitumor activity of this regimen. Similar chemotherapy schedules have also been used with high response rates in GCT, ovarian cancer, breast cancer, and soft tissue sarcoma in children. The CARBOPEC protocol seems to be a good candidate for therapy intensification in patients with various malignancies. A European trial for salvage therapy in GCT will be activated in the near future. Moreover, results should improve with the widespread use of hematopoietic growth factors and optimization of carboplatin administration that takes pharmacokinetic parameters into account.
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Thrombotic episodes represent the second cause of mortality in cancer patients. These complications are more frequent with some adenocarcinomas and hematologic malignancies. The mechanisms of pathogenesis are complex inducing an unbalanced function of the antithrombotic system. According to the type of tumor and the underlying mechanism, clinical manifestations are generally severe. The diagnosis of these thromboses are essentially clinical or radiological. The treatment is based on heparinotherapy, thrombolytic agents or eventually on surgery, which is not discussed here.
A primer set designed to amplify the enterotoxin (yst) gene of pathogenic Yersinia enterocolitica strains generated two different electrophoretic profiles of the target sequence when a collection of strains of worldwide origin was screened. Serovars O:1,3; O:2a,3; O:3; O:5,27 and O:9, known as European strains, produced a 200-bp fragment that matched the size of the target sequence. However, serovars O:4,32; O:8; O:13a,13b; O:20 and O:21, known as American strains, generated two fragments of 1.4 and 1.6 kb. The amplified products of one American strain were sequenced and the presence of the yst gene was confirmed in both fragments. Thus, the potential of the polymerase chain reaction to be used as an epidemiological tool in differentiation between the two clusters of pathogenic strains of Y. enterocolitica could be demonstrated.
In humans the majority of the CD3+ T cells usually express an alpha/beta T cell receptor (TcR) and a minority express a gamma/delta TcR. The CD3+ TcR alpha/beta and CD3+ TcR gamma/delta cells from blood of the patients with schistosomiasis with carcinoma of the urinary bladder (SCB) were analyzed for phenotype, activation, secretion of interleukin 2 (IL 2). B cell growth factor (BCGF) and B cell differentiation factor (BCDF), as well as for autologous (AMLR) and allogeneic (MLR) mixed lymphocyte reaction. Patients with SCB had a highly increased percentage of CD3+ TcR gamma/delta and a decreased percentage of CD3+ TcR alpha/beta T cells in their circulation. These CD3+ TcR gamma/delta T cells expressed the CD25 (IL 2 receptor), CD38, CD71 (transferrin receptor) and HLA-DR activation antigens at a higher intensity after in vitro stimulation with recombinant IL 2, phytohemagglutinin and soluble egg antigen (from Schistosoma haematobium). The SCB patients' CD3+ TcR gamma/delta T cells were highly deficient in secretion of IL 2 but produced highly elevated levels of BCGF and BCDF. On the contrary, both BCGF and BCDF activities of the CD3+ TcR alpha/beta T cells were decreased. Moreover, CD3+ TcR gamma/delta T cells demonstrated highly deficient AMLR and MLR activity. These observations suggest a possible role of CD3+ TcR gamma/delta T cells in the immune response and the disease pathogenesis in human schistosomiasis infections.
The Polymerase Chain Reaction (PCR) method was used to generate a vector-free digoxigenin-dUTP labelled probe that targets the Yersinia enterocolitica gene encoding the heat stable enterotoxin (yst). The probe was used in DNA-DNA colony hybridization to screen 113 strains of Y. enterocolitica and related species for the presence of the enterotoxin gene. In Y. enterocolitica, the probe clearly discriminated between pathogenic and non-pathogenic strains even those belonging to the same serotype. Of the other Yersinia species, only three strains of Y. kristensenii possessed DNA sequences homologous to the yst gene. The probe was further checked for its specificity in artificially inoculated fecal samples and could easily detect the target sequence of the yst gene. The digoxigenin-labelled probe proved to be a reliable epidemiological tool to discriminate between pathogenic and non-pathogenic strains in pure and mixed culture, thus offering the advantage of using a non-radioactive detection system in clinical laboratories with the possibility of reusing the same hybridization solution several times and obtaining results within a relatively short time.
We have investigated tumor necrosis factor-alpha levels in serum samples of patients before and after allogenic (16 patients) or autologous (8 patients) bone marrow transplantation. A sensitive immunoradiometric assay for monitoring levels of endogenous tumor necrosis factor-alpha was used. The serum levels of tumor necrosis factor-alpha were found to be relatively low (ranging from less than 15 to 77 pg/ml). Among 13 patients having graft-versus-host disease following allogeneic bone marrow transplantation 8 patients did not have detectable tumor necrosis factor-alpha (less than 15 pg/ml) while 4 out of 8 patients undergoing autologous bone marrow transplantation had detectable tumor necrosis factor-alpha levels (15 pg/ml), indicating a lack of correlation between tumor necrosis factor-alpha serum levels and the occurrence of graft-versus-host disease. Because the tumor necrosis factor-alpha levels detected in patient sera could be regulated by TNF-receptor expression, the presence of TNF-receptor on patients' peripheral blood mononuclear cells was also studied using fluorescent liposome-conjugated tumor necrosis factor-alpha and immunofluorescence analysis. Our data indicate that peripheral blood mononuclear cells of some patients receiving either autologous or allogeneic bone marrow transplantation expressed significant levels of TNF-receptors, suggesting a lack of correlation between TNF-receptor expression and graft-versus-host disease development.
Soluble interleukin-2 receptor (sIL-2R) level in serum is a marker of immune regulation and lymphocyte activation. Highly elevated levels of sIL-2R in serum were observed in patients of schistosomiasis with carcinoma of the bladder (SCB) and carcinoma of the bladder without schistosomiasis (CB) compared with patients with carcinoma of the prostate with or without schistosomiasis and normal healthy controls. Patients with SCB, who had an elevated percentage of cells expressing CD38+ activation antigen and CD71+ transferrin receptors in circulation, also had elevated levels of sIL-2R in serum. There were few interleukin-2 receptor (CD25+) positive cells in circulation in some patients with SCB. Despite this, the sIL-2R levels were extremely elevated. Our data suggest that in SCB, CD38+ and CD71+ cells may be the source of secretion of sIL-2R in serum. This relationship was confirmed by phenotypic characterizations of mononuclear cells and sIL-2R levels in individual patients. Measurements of sIL-2R levels in serum may provide a sensitive method of immune activation in patients with SCB.
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