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Lysozyme as a measure of cellular dynamics in the lesions of leprosy.

The levels and distribution of lysozyme-positive cells and exudate were studied in leprosy lesions through the spectrum, in untreated and treated patients, in relapse and in reactions. Altogether 124 skin biopsies were examined by the immunoperoxidase technique. Monocytes, neutrophil-polymorphs and mast cells were the most conspicuous cells seen. Lysozyme proved to be a useful means of indexing renewal of these cells in the lesions. Peak numbers of monocytes were seen in lesions of active lepromatous leprosy (LL) and of tuberculoid leprosy (TT), at poles of opposite immunological performance. In TT the stimulus for recruitment was delayed hypersensitivity (DH). A decline in DH from TT towards the middle of the spectrum, mid-borderline, was accompanied by a fall in monocyte level. Furthermore, reacting lesions due to enhanced DH also had increased numbers of monocytes. On the other hand reactions associated with immunological deterioration were similar to active lepromatous leprosy (LL) and monocyte influx was raised in response to the stimulus of free multiplication of bacilli in both cases. In TT delayed hypersensitivity acted also to promote the rapid transformation of monocytes to epithelioid and giant cells all of which were strongly positive for lysozyme. This was in contrast to much lower levels in histologically similar macrophage-epithelioid cells of BT granulomas. Lysozyme synthesis was not seen in macrophages after ingestion of M. leprae. Early foamy change was made conspicuous by lysozyme deposited in phagocytic vacuoles, but old foam cells in regressing lepromas were negative. Lysozyme bound to dead extracellular M. leprae but not to viable or intracellular organisms. Dead bacilli or immune complexes appeared to be the stimulus for neutrophil-polymorph recruitment, mainly in reactions.

Granuloma↗

Immunoglobulins in leprosy.

Serum immunoglobulins were estimated by the single radial immunodiffusion technique and the results were compared among various groups of leprosy patients. Most of the serum immunoglobulin classes are increased in lepromatous leprosy patients. Controls from different regions in Thailand and even from two populations in the same region show different results. This can lead to different interpretations of results in leprosy patients and may explain apparent discrepancies in earlier studies of serum immunoglobulins in leprosy.

Adolescent↗

Minimum temperature felt as hot (MTH)--a new concept for grading the loss of temperature sensation in leprosy patients.

In order to grade the loss of the temperature sensation in the skin of leprosy patients, a newly designed instrument called the Temperature-Sensation-Testing-and-Grading device has been employed to determine the minimum temperature felt as hot (MTH) at the skin area. The MTH in normal subjects was observed to vary from one region of the body to another; it was generally higher on the distal parts of the extremities compared to the proximal parts; and it was also higher on the lower extremities compared to the upper ones. The abdomen and the back generally had the lowest values. There were no variations according to age (11-80 years) or sex and no differences on symmetrical sites of the body. The MTH value, however, showed a dependence on the environmental temperature, the values being lower at low environmental temperatures and higher at high environmental temperatures. But at the same site and the same environmental temperature, the MTH value was found to be almost constant. Different individuals had different MTH values at the same body site and even at the same environmental temperature. The unaffected skin of leprosy patients showed values comparable to the controls. At the leprosy lesions, however, the degree of sensory loss could easily be determined in comparison with the MTH at the contralateral/adjoining unaffected skin. Out of 54 leprosy patients, 7 patients had no sensory loss; in 27 patients the loss varied between 1 degree C and 20 degrees C; while in 20 patients the loss was complete--they could not perceive even 50 degrees C as hot.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Experimental leprosy in the mangabey (Cercocebus atys): necropsy findings.

A mangabey monkey (Cercocebus atys) was inoculated intravenously and intracutaneously with acid-fast bacilli (AFB) from a mangabey with spontaneously acquired leprosy. It developed generalized lepromatous leprosy and died 46 months after inoculation. Necropsy revealed severe lepromatous infiltrates in the skin, nasal mucosa, peripheral nerves, and testicles. Internal organs were only minimally involved. The lesions seen at necropsy were very similar to those seen in untreated cases of human lepromatous leprosy. These findings further substantiate the mangabey monkey as a suitable animal model for the study of lepromatous leprosy.

Animals↗

[Research in the campaign against leprosy (author's transl)].

"Leprosy Relief through Leprosy Research" means that the results of research are made available for curing and eradicating the disease. The "Marinum Model" and the "planter test in mice" are, along with determination of serum activity in healthy test subjects, part of a complex of experiments for the assessment of the therapeutic value of an antimycobacterial substance. This replaces the "controlled studies" which, in their proper form, are scarcely possible for leprosy. With the recently developed forms of combination therapy, the duration of leprosy treatment is reduced to a few years. Because of the relationship of Mycobacterium leprae to Mycobacterium tuberculosis, certain types of combination therapy can be used in both diseases at the same time.

Animals↗

Leprosy in children one year of age and under.

Information obtained from a review of the literature, the United States Armed Forces Institute of Pathology files, and from a correspondence survey revealed a total of 91 infants one year of age and under in whom leprosy was diagnosed. Biopsy confirmation was available on 19 infants, and in an additional 32 patients the diagnosis of leprosy was considered certain even though biopsy confirmation was not obtained. Although the mother was probably the most common source of the infection (29 infants), it was of interest to note that the father, another relative, or an unknown contact was the source of the infection in at least 43% of the infants. The youngest infant was 2-3 months old and had no known familial contact. The role of intrauterine exposure to Mycobacterium leprae, or to antigens of M. leprae, in infection and pathogenesis is discussed. The diagnosis of leprosy in infants under one year may frequently be missed or early signs disregarded because of a mistaken belief that leprosy is exceedingly rare or non-existent in the very young.

Biopsy↗

Hepatitis B antigen in a leprosy hospital.

A survey of hospital patients with lepromatous and with tuberculoid leprosy showed 5% of the former and 6.3% of the latter to be carriers of hepatitis B antigen. These findings contradict the hypothesis of a genetically determined predisposition; opportunity for infection appears rather to be the determining factor. It was also found that (1) the number of carriers was higher among patients staying longer in hospital; (2) titres of antigen in patients with lepromatous leprosy were higher than in those with tuberculoid leprosy or in controls; and (3) antigen titres measured twice at an interval of 4 months indicated that the carrying of hepatitis B antigen in patients with leprosy is stable and persistent.

Adolescent↗

BCG vaccination of children against leprosy. Preliminary findings of the WHO-controlled trial in Burma.

The use of BCG vaccine in the prevention of leprosy has been one of the most important subjects of investigation in the field of leprology in the last 25 years. The action of the vaccine was for many years investigated by determining its effect on the lepromin reaction. Field studies were later considered essential to determine whether BCG vaccination would be useful to leprosy contacts, to the child population probably exposed to infection, or to persons persistently lepromin-negative.The interest of the World Health Organization in this matter began in 1952 and, following the recommendations of certain advisory committees, it was decided to institute a field trial in Singu township in Burma. The main purpose of the investigation was to observe, in a highly endemic area, the protective effect, if any, of BCG vaccine against leprosy in the child population not exposed to Mycobacterium leprae at home but possibly exposed to the infection elsewhere.Field operations began at the end of August 1964 and the preliminary findings obtained up to the end of June 1968 relate to 3 annual re-examinations. So far, from the material studied, it appears that, under the conditions prevailing in Singu township, no significant effect of BCG vaccine can be seen within a period of 3 years. When children in both trial groups are followed-up for much longer periods, mainly children aged 0-4 years at intake, it is possible that a significant difference may emerge. However, to be operationally desirable, a merely significant difference is not enough; the protective effect of BCG should be substantial to warrant its large-scale use as an immunization procedure against leprosy.

Adolescent↗

Some epidemiological data on leprosy collected in a mass survey in Burma.

In the WHO Leprosy BCG Trial in Burma a mass survey was undertaken to determine whether children had been exposed to patients with leprosy and, if so, the form of the index case. This paper presents the most important epidemiological data collected in this survey. The prevalence rate was 31.6 per 1 000. It seems that even if the prevalence rate is very high the L rate does not increase accordingly. The high T rates in areas of high endemicity seem to be related mainly to the degree of spreading of leprosy, even to persons who react to lepromin. Comparison of the results with data available for the area before the survey was made shows that 87% of the L cases had already been detected and that 54% of the T cases had not. There was a tendency for high L rates to be associated with high prevalence rates. The results do not suggest that any particular age group has greater susceptibility or resistance; the prevalence rates seemed to be related mainly to the age when exposure occurred. A higher prevalence of leprosy in males started to appear in the 10-14-year age group, and after the age of 15 the difference became impressive. Biological, socio-economic, and environmental factors seem to be responsible for the level of endemicity, which does not seem to be essentially or primarily related to ethnic origin.

Adolescent↗

Acid mucopolysaccharide metabolism in leprosy. 2. Subcellular localization of hyaluronic acid and beta-glucuronidase in leprous infiltrates suggestive of a host-Mycobacterium leprae metabolic relationship.

Electron- and light microscopic analyses were conducted on leprosy skin biopsies relative to the origin of hyaluronic acid, which has previously been observed to be distributed inversely in ratio to the degree of cell- mediated immunity. The present study investigated the subcellular localization of hyaluronic acid and its degrading enzyme in various types of leprosy. Hyaluronic acid in some lepromatous leprosy cases was shown to be accumulated in the limiting membranes of the phagosomes of lepra cells and Myco-bacteria leprae have beta-glucuronidase which plays a role in the degradation of hyaluronic acid. Contrariwise, in tuberculoid leprosy, beta-glucuronidase was detected in the lysosomes of epithelioid cells and giant cells. This result suggests that the origin of hyaluronic acid is in histiocytes and at the same time it might suggest that M. leprae is in competition with enzymes of epithelioid cells for hyaluronic acid, whereas reduced or absent beta-glucuronidase in lepra cells enable bacilli to utilize the AMPS as a nutrient.

Acetylglucosaminidase↗

Secondary amyloidosis and the serum amyloid precursor in leprosy: geographical variation and association with leukocytosis.

The prevalence of the amyloid-related serum component, protein SAA, was investigated in two groups of leprosy patients from different areas of Papua New Guinea. Protein SAA was more prevalent in coastal leprosy patients (49% positive) than in highland patients (21% positive). Paradoxically, many more cases of amyloidosis were diagnosed in the highland group (17 of 199) than in the coastal group (3 of 112). In the highland patient group, SAA was found to correlate with the leprosy disease spectrum, being more prevalent in patients toward the lepromatous pole. Borderline and tuberculoid patients who had detectable SAA usually had neurotrophic ulcers. No such relationships were observed in the coastal patient group, probably because other infections, more common on the coast, were also responsible for causing increased concentrations of SAA which is known to behave as an acute phase reactant. A correlation was observed between SAA positivity and neutrophil leukocytosis. This suggests that various inflammatory stimuli such as erythema nodosum leprosum reactions, neurotrophic ulcers and intercurrent infections, all contribute to the prevalence of SAA in leprosy patients.

Amyloid↗

A histopathologic study of renal biopsies in fifty cases of leprosy.

Renal biopsies from 50 cases of leprosy, including 45 cases of lepromatous and 5 cases of tuberculoid, have been studied in detail histopathologically with special reference to any specific leprosy lesion such as the presence of leproma or granuloma, the presence of acid-fast bacilli and the occurrence of amyloid deposit. Leproma or granuloma, acid-fast bacilli and amyloid deposit could not be detected in any of these cases. Pathologic features of nephritis of various types were seen in only 40% of cases. Similar observations made by previous authors have been reviewed. The question is raised as to why kidney tissue should escape from developing specific leprosy lesions in either type of leprosy when other tissues such as liver, striated muscles and lymph nodes are known to develop such lesions. A greater immunologic resistance of the renal tissue to lepra bacilli or local physiochemical factors which may render renal tissue an unfavorable site for the settling and multiplication of lepra bacilli are considered as possible related factors.

Adult↗

Ocular immunoglobulins in lepromatous leprosy.

Immunoglobulin levels in the ocular fluids have been estimated in normal subjects and lepromatous leprosy patients. In the normal tear, IgA is the major immunoglobulin while IgG is the only immunoglobulin detected in the aqueous humor. The immunoglobulin profiles in the tear and the aqueous humor in normal subjects are different. The mean IgA level in the tears of the lepromatous leprosy group is significantly lower than in the control patients. IgA and IgG levels are raised in the aqueous humor of some leprosy cases who had suffered from uveitis in the past and also in all cases with active endogenous uveitis. Therefore, in lepromatous leprosy the pattern of immunoglobulin alteration in the tear and the aqueous humor is not parallel.

Adolescent↗

Serum proteins and immunoglobulins in leprosy.

Serum proteins and immunoglobulins were studied in patients suffering from various types of leprosy. A significant increase in total protein and decrease in albumin was found in all types of leprosy except borderline-tuberculoid. Gamma globulin was found to be increased in all types. An increase of alpha-2-globulin in lepromatous, a decrease of beta globulin in borderline-lepromatous, and a decrease of alpha-2 and increase of beta globulin in borderline-tuberculoid were observed. These changes do not seem to be of diagnostic importance. A statistically significant increase of IgG in borderline-lepromatous and lepromatous, IgM in all types of leprosy and IgA only in lepromatous was found. The increase of different immunoglobulins in leprosy, especially the lepromatous type, suggests a humoral response which was found to be directly proportional to the severity of the lesion.

Blood Proteins↗

Untreated lepromatous leprosy: histopathological findings in cutaneous blood vessels.

Skin biopsies from 100 patients with untreated lepromatous leprosy from Malaysia, India, Africa, and South America were examined with particular regard to pathological changes in intima, media, or adventitia of blood vessels and to the presence of leprosy bacilli in these layers. Bacilli were found in capillaries, venules, or arterioles in all cases, and in many instances they were present in endothelial lining cells or smooth muscle in large masses (globi). In several cases, solid-staining bacilli in endothelial lining cells were especially prominent. The findings are discussed in relation to a) the continuous bacteremia of lepromatous leprosy, b) the role of endothelial cells in phagocytosis, c) smooth muscle cells of the media as a site in which bacilli may persist, and d) the transmission of human leprosy by biting arthropods.

Blood Vessels↗

Nutritional aspects of leprosy.

Desoxyfructo-serotonin (DFS) being a naturally occurring metabolite, which, like serotonin, has its origin in tryptophane in the food, one can ask about the role of nutrition in leprosy. The unique situation, that a human metabolite shows antileprosy activity, confirmed in vitro and in vivo, makes it possible to develop a "build in" antileprosy therapy. This is now realised through a so-called "Anti-Leprosy Nutriment" (NAL). The effectiveness of this diet was confirmed by the fact, that a daily dose of 0.5 g NAL per mouse has a similar effect, like 20 mg/kg body weight Dapsone per day in the conventionnal mouse foot-pad test. The biosynthesis of DFS in man has been demonstrated by high performance liquid chromatography (HPLC), spectrofluorometry and mass spectrometry. The activity of NAL (rich in tryptophane, unsaturated fatty acids and glucose) is due to an increased biosynthesis of DSF. The latter may be considered as a "physiological protecting agent" against leprosy. This type of food may play a role in the prevention of leprosy in endemic area.

5-Hydroxytryptophan↗

In situ demonstration of T lymphocyte subsets in granulomatous inflammation: leprosy, rhinoscleroma and sarcoidosis.

T lymphocyte subpopulations in frozen tissue sections of four granulomatous conditions (five patients with tuberculoid leprosy, five with lepromatous leprosy, seven with sarcoidosis and four with rhinoscleroma) were studied using monoclonal antibodies and a modified immunoperoxidase technique. Two immunohistological patterns were observed. In tuberculoid leprosy and sarcoidosis, lymphocytes expressing the helper/inducer phenotype were present within the aggregates of mononuclear phagocytes (epithelioid cells); however, cells with the suppressor/cytotoxic phenotype were predominantly in the lymphocytic mantle surrounding each granuloma. In lepromatous leprosy and rhinoscleroma the helper/inducer T cells and suppressor/cytotoxic T cells were both diffusely distributed among the mononuclear phagocytes (histiocytes) without any discernible mantle. The segregation of the helper/inducer and suppressor/cytotoxic phenotypic subsets was associated with an epithelioid cell differentiation of mononuclear phagocytic cells, bacterial elimination and a delayed type hypersensitivity response. The intimate admixture of helper/inducer and suppressor/cytotoxic subsets was associated with undifferentiated mononuclear phagocytes, bacterial proliferation and the absence of a delayed type hypersensitivity response. Thus the different distributions of T cell subpopulations in granulomas may be associated with differences in the host's immune response in several forms of granulomatous reactions.

Granuloma↗

Suppressor cell activity and phenotypes in the blood or tissues of patients with leprosy.

Suppressor cell activity has been demonstrated in the peripheral blood of patients with leprosy. Cells bearing the suppressor/cytotoxic phenotype have been enumerated in both peripheral blood and tissues, and microanatomical differences in tissue distribution have been observed. This first generation of studies has been characterized by considerable disagreement, a not unusual circumstance in the study of leprosy. In the case of blood suppressor cell activity, there appears to be no doubt as to its existence, but much uncertainty regarding its distribution. Concerning peripheral blood phenotypic suppressor cells, the observed differences in lepromatous and ENL patients may well reflect differences in methods used. Concerning phenotypic suppressor cells in tissue, there is no agreement as to their numbers or microanatomical distribution across the spectrum of leprosy or in its reaction states. Although these observational differences make firm conclusions impossible, this first generation of studies has provided new ways of considering old problems. For example, lepromin unresponsiveness might be a consequence of active cellular suppression. Differences in the numbers (or percentages) of the suppressor phenotype in blood or tissues of lepromatous patients with or without ENL reopens the door to the possibility of cell-mediated immune mechanisms in the pathogenesis of ENL. The identification of defective suppressor cells as important in the pathogenesis of hypergammaglobulinaemia is of interest in and of itself, but also gives rise to the possibility that other kinds of phenomena may be a consequence of defective or effete suppressor mechanisms. The observation of microanatomical differences in the distribution of the suppressor phenotype in tuberculoid and lepromatous leprosy indicates that effective or ineffective immunity might be a sequela of particular interactions between the suppressor/cytotoxic and helper/inducer phenotypes, and that these interactions merit further study. These new perspectives may be subject to experimental testing by the next generation of studies, which will surely include the techniques of clonal expansion and limiting dilution, as well as the study of interleukins 1 and 2.

Humans↗