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Biomedical subjects

D L Leiker

Publications and source records attributed to D L Leiker.

At least 19 recordsLinked to original sources

Agreement between histopathological results in clinically diagnosed cases of indeterminate leprosy in São Paulo, Brazil.

Histopathological slides from skin biopsies of fifty-seven self-reporting patients diagnosed as indeterminate leprosy by the Leprosy Control Programme in São Paulo, were sent to three independent histopathologists. Agreement between the reports were based on the following diagnosis: "indeterminate leprosy", "suggestive leprosy" or "no leprosy". A great variation was observed in the interpretation of the histopathological examination. The three pathologists reported "indeterminate leprosy" respectively in 7.0%, 54.4% and 84.2%, of the cases studied. A kappa index of agreement between any two pathologists ranged from 0.08 to 0.32, showing poor agreement between observers. Agreement improved by pooling together the reports "suggestive leprosy" and "indeterminate leprosy". The three pathologists agreed in the results of 24 biopsies of the 27 classified as leprosy by any one of the three observers. Eight cases were considered as "no leprosy" by all pathologists. Higher agreement indices were obtained for positive and negative proportionate concordance between any two examiners. The implications of the variation in the diagnosis of indeterminate leprosy and early leprosy are discussed in the context of public health and case-management.

Brazil

Follow-up of multibacillary leprosy patients using a phenolic glycolipid-I-based ELISA. Do increasing ELISA-values after discontinuation of treatment indicate relapse?

With the introduction of reproducible serological tests it was hoped that relapses in leprosy patients, after discontinuing treatment, could be detected before damaging reactions occurred and before the patients became infectious. The possible value of an ELISA using a semisynthetic analogue of phenolic glycolipid-I to detect antibodies to this antigen in order to predict a relapse in multibacillary patients was investigated. In contrast to that reported for paucibacillary patients, this test was useful to detect early relapses in multibacillary patients. In 3 out of 4 multibacillary patients who relapsed, the ELISA-values were increased. The decreased ELISA-values in the one relapsed patient could be attributed to the corticosteroid therapy. In the multibacillary patients who did not relapse after RFT, the ELISA-values were consistently low or decreased. In only one patient did the ELISA-values increase following his release from treatment and this patient was clinically suspected of developing a relapse.

Adult

Reversal by interleukin-2 of the T cell unresponsiveness of lepromatous leprosy to Mycobacterium leprae.

In some subjects Mycobacterium leprae causes disseminated (lepromatous) disease. Such subjects show both in vivo and in vitro deficient T cell responses to M. leprae, but not to other antigens. We have recently shown that lepromatous peripheral blood mononuclear cells (PBMC) failed to produce interleukin 2 (IL-2) in response to M. leprae and that T cell-conditioned media (TCM) can reverse the T cell unresponsiveness in a majority of lepromatous leprosy patients (Haregewoin et al. 1983). Here we show that highly purified and recombinant IL-2 had effects similar to TCM. On the other hand, lepromatous PBMC produced IL-1, and IL-1 had no restorative effect. These findings provide further evidence that the unresponsiveness in lepromatous leprosy often results from a deficiency in IL-2 production. After initial stimulation with TCM + M. leprae, lepromatous PBMC could be restimulated with M. leprae alone, providing clear evidence that M. leprae-reactive lymphocytes were generated in the presence of TCM. The present findings are discussed in relation to the possible mechanisms involved in the failure of IL-2 production. If our findings can be reproduced in vivo, IL-2 may offer a novel approach to therapy in lepromatous leprosy.

Antigens, Bacterial

Low T lymphocyte responsiveness to Mycobacterium leprae antigens in association with HLA-DR3.

The type of leprosy which develops after infection with Mycobacterium leprae is influenced by the presence or absence of HLA-DR3, as has been demonstrated in an ethnic group originating from Surinam. In the present study we investigated in this same ethnic group the role of HLA-DR, and of HLA-DR3 in particular, in monocyte-T cell interactions during leprosy specific proliferative responses in vitro. HLA-DR3 heterozygous T cells from tuberculoid leprosy patients were cultured with antigen and either HLA-DR3 positive or HLA-DR3 negative homozygous HLA-DR compatible allogeneic monocytes as antigen presenting cells (APCs). T cell proliferative responses with DR3 homozygous monocytes as APCs, were observed to be decreased as compared to T cell proliferative responses with DR3 negative homozygous monocytes as APCs. Furthermore, although the leprosy specific monocyte-T cell interactions were shown to be restricted for HLA-DR, in the anti-MLW-1 response HLA-DR3 appeared to function as a restricting element poorly or not at all. These observations may imply, that an in vitro correlate has been found for an (HLA associated) genetic control of leprosy in vivo.

Antigens, Bacterial

A survey on eye involvement among leprosy patients in The Netherlands.

A survey of 121 leprosy patients in the Netherlands showed eye involvement in 20% of the patients, rising to 27% if madarosis and the adnexae are included. Iris atrophy was the main lesion encountered in BL and LL patients. One typical lepromatous fundus lesion was seen. No bilateral blindness occurred. Two eyes had a visual acuity of 3/60 due to intractable scleritis and acute iritis in LL with ENL. Seven eyes of 5 patients had a visual acuity of 0.2 to 3/60, mainly due to iris atrophy in lepromatous leprosy. Prevalence of blindness in our series was low as compared with the literature.

Adolescent

HLA-DR-associated genetic control of the type of leprosy in a population from surinam.

The relationship between HLA phenotype and leprosy classification was studied in 73 unrelated patients and 92 healthy controls from a mixed Negroid-Caucasoid population originating from Surinam, South America. Heterogeneity in the distribution of HLA-DR (but not A, B, and C) was detected between tuberculoid (TT* + BT*) leprosy and lepromatous (BL* + LL*) leprosy patients (p = 0.024). This heterogeneity appeared to be caused almost exclusively by DR3. Most significantly, the frequency of DR3 was increased among polar tuberculoid (TT) leprosy patients as compared to the rest of the patients (p = 0.0003). Compared with healthy controls the frequency of DR3 was increased among TT patients (p = 0.006), unchanged in BT patients, and decreased among lepromatous (BL + LL) patients (p = 0.027). These data indicate that in this population an DR3-associated factor controls the type of the disease that develops after infection with Mycobacterium leprae.

Antigens, Heterophile

Intramuscular injection of dapsone in therapy for leprosy: a new approach.

Dapsone is the drug of first choice in the treatment of leprosy. Although the oral route of administration has been mostly used, recent studies of patient compliance revealed that only about 50% of the tables received by the patients are actually taken. It is generally assumed that irregular self-medication favors the development of dapsone resistance. The need for a more reliable route of administration led us to investigate the possibility of an i.m. dapsone depot injection. To achieve effective blood levels for 3-4 weeks, suspensions of large dapsone particles in an aqueous vehicle were made. In a trial with 20 leprosy patients in Nigeria, injection of 900 mg dapsone i.m. as a mixture of particle sizes less than 90 micrometer (20%) and 90-125 micrometer (80%) resulted in a serum level above 0.5 microgram/ml for 18 +/- 5 days with a mean peak concentration of 3.1 +/- 0.9 microgram/ml (n = 10). Injection of 1200 mg of the same particle-size mixture led to peak concentrations of 2.7 +/- 1.0 microgram/ml and maintenance of the level above 0.5 microgram/ml for 25 +/- 3 days (n = 5). After injection of 1200 mg (particle size less than 90 micrometer), serum levels were kept above 0.5 microgram/ml for 21 +/- 5 days with a maximum concentration of 3.9 +/- 1.2 microgram/ml (n = 5). Serum levels were measured using a rapid non-extractive HPLC method. The injections were very well tolerated. Due to these encouraging results, the dosage and formulation will be further optimized.

Adult