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Biomedical subjects

A Gaafar

Publications and source records attributed to A Gaafar.

At least 19 recordsLinked to original sources

[Clinical and epidemiological study of disease caused by Mycobacterium kansasii in the metropolitan area of Bilbao, Spain].

OBJECTIVE: Epidemiological description of individuals from whom Mycobacterium kansasii isolates were obtained in respiratory samples, and analysis of the isolates using molecular biological techniques. MATERIAL AND METHODS: A descriptive retrospective/ prospective study was carried out from January 1994 to April 2002 in Basurto Hospital and Santa Marina Hospital and from January 2000 to April 2002 in Cruces Hospital, Galdakao Hospital, and San Eloy Hospital. Diagnosis of the disease was performed according to American Thoracic Society criteria; other definitions were also applied to allow inclusion of all cases. Disease caused by M. kansasii in patients who were not infected with the human immunodeficiency virus (HIV) was compared with disease caused by Mycobacterium tuberculosis in a control group. Polymerase chain reaction was applied with analysis of restriction fragment length polymorphisms to differentiate between species of mycobacteria and classify them into genotypes. Amplified fragment length polymorphisms were used to recognize clones within each genotype. RESULTS: The patient charts of 334 patients in which an isolate of M. kansasii had been recorded were reviewed. We considered 220 patients to be suffering from disease caused by M. kansasii (American Thoracic Society criteria along with probable disease according to established definitions). The disease was more frequent in male patients (n=185; 84.1%) and in individuals who were not HIV positive (n=184; 83.6%). The highest incidence of disease in the Bizkaia region was found in Margen Izquierda-Encartaciones, where the rate was 8.05 per 100 000 inhabitants. In the Bilbao area, the highest rate was found in the districts lying on the outskirts. The underlying diseases were tuberculosis (20.5%), chronic obstructive pulmonary disease (25.9%), pulmonary neoplasia (7.7%), silicosis (0.9%), chronic liver disease (11.4%), and duodenal ulcer (8.6%). The most frequent constitutional symptoms were fever (39.1%), loss of appetite (23.2%), and weight loss (33.3%). Among the respiratory symptoms, the most outstanding were cough (70.9%) and expectoration (62.3%). The most frequent radiographic patterns were cavitation and pulmonary infiltration. The most common treatment regimen was rifampicin, isoniazid, and ethambutol (43.4%), and the average duration was 12 months in patients who were HIV negative. Analysis of antibiotic sensitivity, performed on 56 strains, revealed that 100% were resistant to isoniazid, while none displayed rifampicin resistance. Thirty-four cases of disease caused by M. kansasii were compared with 68 cases of tuberculosis, all of them without HIV infection. The comparison revealed a predominance of smokers, respiratory symptoms, and cavitation in patients with disease caused by M. kansasii. The majority of the isolates (98.5%) corresponded to genotype I. A total of 8 clones were obtained; the clones designated 1 and 3 were more common in HIV-positive and HIV-negative individuals respectively. CONCLUSIONS: In recent years, there has been an increase in the number of patients with disease caused by M. kansasii in the province of Bizkaia. The disease is more frequent in male patients, individuals who are HIV negative, and in urban areas. In addition, more respiratory symptoms and a higher incidence of cavitation were found in patients with disease caused by M. kansasii than in those with tuberculosis. Genotype I is the most common isolate, and clones 1 and 3 affect 80% of patients suffering from the disease.

Adult↗

Segmental tracheal replacement in mongrel dogs.

OBJECTIVE: To evaluate the use of alcohol- and detergent-preserved tracheal allografts in dogs. MATERIAL AND METHODS: Experimental segmental tracheal replacement was performed in 18 adult mongrel dogs. Three different techniques were tried in three groups of dogs. In the first group, a four-ring cervical tracheal segment was dissected out and implanted in the trachea of another dog. In the second group, the procedure was performed using a tracheal allograft that had been preserved in 70% ethyl alcohol for 20 days. In the third group, tracheal grafts were previously impregnated in 10% povidone iodine for 72 h before being implanted. Allografts were harvested 60 days after transplantation and assessed both histologically and in terms of the percentage patency. Dogs that died within 60 days were also included in the analysis. RESULTS: The best results were found in the group in which the tracheal allograft had been preserved in ethyl alcohol and this was explained by the reduced antigenicity of the graft in this group. CONCLUSIONS: The use of alcohol-preserved allografts is a practical method of tracheal transplantation, and the alcohol-preservation technique markedly reduces the immunogenicity of the grafts.

Animals↗

Characterization of the local and systemic immune responses in patients with cutaneous leishmaniasis due to Leishmania major.

In this study skin biopsies and peripheral blood samples were obtained from patients with cutaneous leishmaniasis caused by Leishmania major. Samples were obtained at diagnosis and during healing when the lesions had regressed to half the original size. At diagnosis most of the cells expressed HLA-DR. The numbers of CD8+ cells in the lesions were higher at diagnosis than during healing. By contrast, a lower percentage of PBMC expressed CD8+ cells at diagnosis probably due to sequestration in the lesion. In the lesion, in situ staining for IFN-gamma, IL-10, and IL-4 showed marked variation between all patients in the number of positive cells for a particular cytokine. The proliferative response of PBMC to leishmanial antigens and IFN-gamma production tended to increase during healing. Cytokine patterns in the PBMC in response to Leishmania antigen was more specific than in the lesion and correlated better with the clinical manifestations. Possible reasons for this are discussed.

Animals↗

T-cell response in human leishmaniasis.

In the present communication we provide evidence for the existence of a Th1/Th2 dichotomy in the T-cell response to Leishmania antigens in human leishmaniasis. Our data suggest that the pattern of IL-4 and IFN-gamma response is polarised in these patients. Lymphocytes from individuals recovered from cutaneous leishmaniasis (CL) responded by IFN-gamma production following stimulation with Leishmania antigens whereas cells from patients recovered from visceral leishmaniasis (VL) showed a mixed pattern of IFN-gamma and IL-4 responses. The cells producing these cytokines were predominantly CD4+. Furthermore, IL-10 plays an important role in the development of post kala azar dermal leishmaniasis (PKDL) from VL. The balance between the parasitic-specific T-cell response plays an important regulatory role in determining the outcome of Leishmania infections in humans.

Antigens, Protozoan↗

Palliative treatment for tracheal stenoses using carbon dioxide laser and the Gianturco stent. Long-term results.

Between September 1992 and March 1998, the self-expandable Gianturco prosthesis was inserted in 23 patients suffering from tracheal stenosis. After radial incision and dilation of the stenosis as described by Shapshay, the positioning of the stent was performed during an endoscopic procedure under optical control. The prosthesis used was a double-ring stent 50 mm long and 20 mm in diameter. The follow-up period ranged between 0.5 and 67 months with an average of 31 +/- 18 months. Pulmonary function tests showed an average improvement of the peak expiratory flow (50%) from preoperative results of 1.06 +/- 0.60 L/s to short-term postoperative results of 2.08 +/- 0.78 L/s and long-term postoperative results of 2.11 +/- 0.78 L/s. The mean peak inspiratory flow (50%) improved from 1.43 +/- 0.85 L/s to 2.40 +/- 1.29 L/s at short term and to 2.56 +/- 1.20 L/s at long term. Eight patients out of the 23 had to undergo a second endoscopic procedure: 3 patients for granuloma vaporization; 1 patient to change a malpositioned stent; 2 patients to add a second stent because of insufficient tracheal enlargement; and 2 patients to resect mucosal membranes between the 2 stent rings and to place a second stent. Optical control of the accurate positioning and use of this model of Gianturco prosthesis helped to avoid the severe complications described in the literature (migration, extrusion, fracture, wall erosion. and hemorrhage). The follow-up must particularly target the prevention of granulomas. The self-expandable Gianturco prosthesis can be advocated for long-term palliative treatment of tracheal stenoses that are inoperable by an external surgical approach.

Aged↗

Humoral and cellular immune responses to synthetic peptides of the Leishmania donovani kinetoplastid membrane protein-11.

Native kinetoplastid membrane protein-11 (KMP-11), purified from crude extracts of Leishmania donovani parasites, activates T cells from individuals who have recovered from visceral leishmaniasis. In this work we used three 38-mer peptides spanning the amino acid sequence of the L. donovani KMP-11 as solid-phase ligands in enzyme-linked immunosorbent assays (ELISAs) and as stimulating antigens in lymphoproliferative assays in order to evaluate humoral and cellular immune responses to well-defined sequences of the protein. Antibody reactivity against the three peptides was measured in plasma from 63 Sudanese visceral leishmaniasis patients (VL) and the percentage of patients with anti-KMP-11 antibodies in ELISA were 37% (KMP-11-1), 30% (KMP-11-2) and 58% (KMP-11-3). The fraction of VL patients with measurable antibody reactivity in one or more of the three ELISAs was 79%. Cross-reactivity to the KMP-11 peptides was detected in plasma from Sudanese patients suffering from Leishmania major infections and in plasma from Sudanese and Danish patients infected with Plasmodium falciparum. In lymphoproliferative assays, 10 of 17 PBMC isolates from donors previously infected with L. donovani showed a response to one or more of the three KMP-11 peptides.

Adolescent↗

Necrotizing and suppurative lymphadenitis in Leishmania major infections.

The pathology of lymph nodes and subcutaneous nodules in 6 patients with cutaneous leishmaniasis (Oriental sore) due to Leishmania major is described in this paper. In 3 patients enlarged epitrochlear lymph nodes were found to be associated with primary skin lesions in the forearm. The lymph node in one patient showed a necrotizing granulomatous reaction that simulated tuberculous lymphadenitis. Leishmania parasites were, however, found in sections of the node, and staining for mycobacteria was negative. The second patient presented with an abscess and a discharging sinus in the epitrochlear region. Parasites were found in smears of the pus and cultures for bacteria were negative. The lesion healed with antimonial therapy. In the third patient the lesion resembled cat-scratch disease and showed stellate abscesses and granulomas. Leishmania parasites were also identified in the sections. Sections of a subcutaneous nodule from the fourth patient showed a necrotizing granuloma. The lesion healed spontaneously and the patient became leishmanin-positive. In two other patients fine needle aspiration of the subcutaneous nodules showed parasites, granuloma and necrosis. We concluded that L. major disseminates from the primary cutaneous lesion via the lymphatics to the subcutaneous tissues and the regional lymph nodes. The subcutaneous nodules and lymphadenopathy may persist long after the primary lesion had healed. The primary lesion is sometimes inconspicuous. Necrotizing and suppurative lymphadenitis due to L. major have to be distinguished from other causes of necrosis and suppuration such as tuberculosis and cat-scratch disease.

Adolescent↗

Serodiagnosis of cutaneous leishmaniasis: assessment of an enzyme-linked immunosorbent assay using a peptide sequence from gene B protein.

An enzyme-linked immunosorbent assay (ELISA) using a 28 amino acid sequence of the repetitive element of gene B protein (GBP) from Leishmania major was developed for serodiagnosis of cutaneous leishmaniasis (CL). The assay was compared to ELISAs using crude amastigote and promastigote antigens from L. donovani and the major surface glycoprotein (Gp63) from either L. donovani or L. major as a solid-phase ligand. The sensitivity of the assays was tested in 33 patients suffering from CL caused by L. major. The sensitivity of the GBP peptide (GBPP) ELISA was 82%. This was higher than in the assays using crude amastigote (67%) or promastigote (67%) antigens, but the difference was not statistically significant. The sensitivity in the assays using Gp63 from L. donovani (52%) or L. major (39%) was significantly lower than in the assay using GBPP (P = 0.019 and P < 0.001, respectively). Plasma samples from healthy Sudanese individuals living in an area endemic for malaria but free of leish-maniasis were negative in all the assays. Significantly higher levels of antibodies were found in the patients who had suffered from the disease for more than eight weeks than in patients with a shorter clinical history (GBPP ELISA; P = 0.038; amastigote ELISA; P = 0.004; and promastigote ELISA; P = 0.017). In the former group, the sensitivities of the five ELISAs were 100% (GBPP), 87% (amastigote), 93% (promastigote), 67% (L. donovani), and 53% (L. major), respectively.

Adolescent↗

Dichotomy of the T cell response to Leishmania antigens in patients suffering from cutaneous leishmaniasis; absence or scarcity of Th1 activity is associated with severe infections.

The T cell response was studied in 25 patients suffering from cutaneous leishmaniasis caused by Leishmania major with severe (n = 10) and mild (n = 15) disease manifestations. Peripheral blood mononuclear cells (PBMC) from the patients were activated by sonicates of Leishmania promastigotes (LMP) and amastigotes (LDA), and the surface protease gp63. The proliferative responses to Leishmania antigens were lower in patients with severe disease than in patients with mild disease (P = 0.01-0.05), and such a difference was not observed in the response to purified protein derivative of tuberculin (PPD) or tetanus toxoid (TT). LMP-induced interferon-gamma (IFN-gamma) production was lower in patients with severe than in patients with mild disease (P < 0.05). When the IL-4 and IFN-gamma responses of each patient were considered, two response patterns were observed in the cultures activated by the Leishmania sonicates. One response pattern was characterized by high production of IFN-gamma without production of IL-4 (a Th1-like pattern), the other was characterized by low IFN-gamma levels which in most cases were associated with IL-4 production (not a Th1-like pattern). These patterns could not be distinguished when the cells from the same donors were stimulated by TT and PPD. The percentages of patients with a Th1-like response pattern after stimulation by LMP in patients with severe and mild disease manifestations were 30% and 80%, respectively. This difference was statistically significant (P = 0.034).

Animals↗

Antigen-presenting cells in human cutaneous leishmaniasis due to Leishmania major.

In this study biopsies from skin lesions and draining lymph nodes of patients suffering from cutaneous leishmaniasis caused by Leishmania major were examined by immunohistochemistry, and by light and electron microscopy to identify the types of antigen-presenting cells (APC) and their location. APC, identified morphologically and by their expression of specific cell markers, included Langerhans cells, macrophages, follicular dendritic cells, and interdigitating reticulum cells of the paracortex of lymph nodes. These cells expressed MHC class II antigens and contained Leishmania antigen. Since some keratinocytes and endothelial cells also showed these characteristics, they may also act as APC. By examining tissue samples from skin lesions and draining lymph nodes it was possible to follow the probable route of trafficking of various inflammatory cells between the skin lesion and lymph nodes. Leishmania antigen containing Langerhans cells were found in the epidermis, dermis and the regional lymph nodes. We believe these cells translocate from the epidermis to the dermis, where they take up antigen and migrate to the paracortex of the regional lymph nodes. There they are intimately associated with cells of the paracortex, and could be involved in the generation of Leishmania-specific T memory cells. LFA-1-positive T cells of the CD45RO phenotype were found in the skin lesion. Venular endothelium in the skin lesions expressed intercellular adhesion molecule-1 (ICAM-1), which is the ligand for LFA-1. The migration of lymphocytes from the vascular lumen to the site of inflammation is possibly a result of the interaction of these two adhesion molecules.

Animals↗

The pathology of cutaneous leishmaniasis due to Leishmania major in Sudan.

The pathology of cutaneous leishmaniasis in Sudan, where the disease is caused by Leishmania major, was studied by light and electron microscopy. Lesions were classified into four distinct groups based on the ratio of different cell types, especially lymphocytes, macrophages, and plasma cells in the inflammatory infiltrate, and the formation of compact epithelioid granulomas or the presence of necrosis. In the lesions, there was a positive correlation between the number of lymphocytes and the number of activated macrophages and epithelioid cells. We suggest that the parasites are eliminated from the lesion by two processes: 1) a lytic mechanism in which parasites are lysed within activated macrophages and 2) necrosis of parasitized macrophages. Morphologic evidence for these two mechanisms of parasite elimination was detected by both light and electron microscopy. The evolution of the pathology of the lesions was followed by rebiopsy when the lesion had regressed in size under antileishmanial therapy.

Adult↗

Dichotomy of the human T cell response to Leishmania antigens. I. Th1-like response to Leishmania major promastigote antigens in individuals recovered from cutaneous leishmaniasis.

The T cell response to antigens from Leishmania major promastigotes was investigated in peripheral blood mononuclear cells from Sudanese individuals with a history of cutaneous leishmaniasis (CL), Sudanese individuals with positive DTH reaction in the leishmanin skin test but with no history of skin lesions, and in Danes without known exposure to Leishmania parasites. Proliferation and production of interferon-gamma (IFN-gamma) and IL-4 in antigen-stimulated cultures was measured. Lymphocytes from individuals with a history of CL proliferated vigorously and produced IFN-gamma after stimulation with either a crude preparation of L. major antigens or the major surface protease gp63. These cultures produced no or only little IL-4. Also cells from leishmanin skin test-positive donors with no history of CL produced IFN-gamma and no IL-4 in response to L. major antigens. Cells from the unexposed Danes were not activated by gp63. The cells from Danish donors produced either IFN-gamma or IL-4, but not both cytokines after incubation with the crude preparation of L. major antigens. The data show that the T cell response to Leishmania antigens in humans who have had uncomplicated CL or subclinical L. major infection is an IFN-gamma-producing Th1-like response.

Animals↗

Prevalence of cutaneous leishmaniasis along the Nile River north of Khartoum (Sudan) in the aftermath of an epidemic in 1985.

Based on a pilot clinical study of the prevalence of cutaneous leishmaniasis (CL) among school children in villages on both banks of the Nile River north of Khartoum, Sudan in the aftermath of a 1985 epidemic, we studied a random sample (303 individuals) from one of these villages to determine the prevalence of infection and exposure to CL. Four percent of the population had active CL lesions, 47% had healed lesions, and another 43% reacted positively to sensitization with leishmanin in the absence of past or active CL lesions. Ninety-one percent of the total population reacted positively to leishmanin. The present status of CL in the area and possible reasons for the emergence of the epidemic are discussed, and gaps in our knowledge about the epidemic are identified.

Adolescent↗

The relaxant property of local prostaglandin E-2 on the non-pregnant uterus - a cyclic triphasic response.

The response of the non-pregnant human uterus to intravenous (i.v.) injections and intra-uterine instillation of various doses of prostaglandin E-2 (PGE-2) was evaluated at the different phases of the menstrual cycle in 13 fertile regularly menstruating women who were neither lactating nor using any hormonal therapy. Uterine contractility was recorded by the microballoon technique in at least three sessions(proliferative, mid-cycle and secretory) in a single cycle with endometrial biopsy performed immediately following the last session to ascertain that the particular cycle was an ovulatory one. Single i.v. injections of PGE-I had a consistent stimulatory effect on the contractility throughout the cycle with a tendency towards a decreased uterine response at mid-cycle and luteal phase as compared to the proliferative part of the cycle. Intra-uterine instillation of the compound induced a peculiar and interesting type of response. In the proliferative and secretory phases of the cycle the response was one of stimulation; being more pronounced in the former period. However, around ovulation time, the local administration induced an evident uterine relaxation in most cases without any instance of stimulation. The possible implication of this triphasic response behaviour on the non-pregnant uterus within certain physiological events and pathological conditions is discussed.

Adult↗

Sporotrichoid cutaneous leishmaniasis due to Leishmania major of different zymodemes in the Sudan and Saudi Arabia: a comparative study.

Sporotrichoid cutaneous leishmaniasis is due to dissemination of amastigotes via the lymphatics to the subcutaneous tissues. A comparison was made between the potential to disseminate by this route of 2 parasites of different zymodemes in Sudan and Saudi Arabia. In Sudan cutaneous leishmaniasis is caused by Leishmania major zymodeme LON-1, and in Saudi Arabia by L. major LON-4. Sporotrichoid leishmaniasis was significantly more common in Sudan, occurring in 23% of patients compared with 10% in Saudi Arabia. Lymph node involvement was slightly more prevalent in the Sudan. Clinical and pathological differences between subcutaneous nodules, particularly when they ulcerate, and multiple primary cutaneous lesions are described and treatment of localized and sporotrichoid leishmaniasis is discussed. The pathological features of the primary lesions in the Sudan and Saudi Arabia were similar.

Adolescent↗