LERPOSY
(Diagnosis, Diagnostics,
Immunodiagnosis, Immunodiagnostics, Pathogenesis, Vaccines
& Drugs)
ABSTRACTS
1306. Arora
SK. Kumar B. Sehgal S. Development of a polymerase chain reaction dot-blotting
system for detecting cutaneous tuberculosis. British Journal of Dermatology. 142(1):72-6, 2000 Jan.
Abstract
For a definitive diagnosis of cutaneous tuberculosis the
demonstration of mycobacteria is
essential, but this is generally not possible in skin lesions. Routinely available techniques have poor sensitivity and
are time consuming, therefore, delaying
the institution of timely therapy. The high
sensitivity and speed of polymerase chain reaction (PCR) for the
detection of infectious agents has
prompted investigators to use this technique for the detection of Mycobacterium tuberculosis in body fluids such
as cerebrospinal fluid or pleural
fluid. In the present study, PCR was used
to examine punch biopsy specimens from the affected skin of 10
patients with clinical diagnoses of
tuberculosis verrucosa cutis, lupus vulgaris,
scrofuloderma, papulonecrotic tuberculide and erythema induratum. A control group of 20 patients included
individuals having skin manifestations
with definite clinical diagnoses other than cutaneous tuberculosis, such as leprosy, fungal mycetoma, chronic bullous
disease of childhood and pemphigus
vulgaris. The PCR amplified products were dot
hybridized with a probe which was random prime labelled with 32P.
The results were compared with routine
microbiological and histological findings. Among the test group, six of 10
(60%) were positive for M. tuberculosis by PCR, although their histopathology showed
non-specific chronic inflammation with no definite diagnosis. Microbiological
investigations, including acid-fast bacillus smear and culture, were positive
in a single case of scrofuloderma. All patients in the control group were
negative by PCR for M. tuberculosis. The data indicate that the combination of
dot hybridization with PCR markedly increased the sensitivity and specificity of PCR. This may be a useful tool in
the diagnosis of tuberculosis when conventional methods fail.
1307. Chen
S. Han C. Li B. Zheng R. Zhang L. A survey on knowledge and skills in
the early diagnosis of leprosy in general health services at different levels
in Shandong Province, The People's Republic of China. Leprosy Review. 71(1):57-61, 2000 Mar.
Abstract
In the late phase of a leprosy control programme, problems arise
with regard to the early detection and treatment of a small number of new
incident cases. We describe a study in the province of Shandong, People's
Republic of China, on the knowledge and skills regarding leprosy of general
health service staff, including rural doctors, paramedical doctors at township
level, doctors from county general and provincial hospitals and dermatologists.
The results showed that there is a continuing need for suitable training
programmes for medical staff in the general health services. Most
dermatologists had good levels of knowledge and skills and more than 80% of new
cases have been diagnosed in skin clinics in this province since 1990. Their
participation in early diagnosis and training of staff should be strengthened.
1308.
No Abstract
1309.
No Abstract
1310. Halliday
G. Robinson SR. Shepherd C.
Kril J. Alzheimer's disease and inflammation: a review of cellular and
therapeutic mechanisms. [Review] [75 refs] Clinical & Experimental
Pharmacology & Physiology.
27(1-2):1-8, 2000 Jan-Feb.
Abstract
1. Of the neurodegenerative diseases that cause dementia,
Alzheimer's disease (AD) is the most
common. Three major pathologies characterize the disease: senile plaques, neurofibrillary tangles and
inflammation. We review the literature
on events contributing to the inflammation and the treatments thought to target this pathology. 2. The senile plaques
of AD consist primarily of complexes of
the beta-amyloid protein. This protein
is central to the pathogenesis of the disease. 3. Inflammatory microglia
are consistently associated with senile plaques in AD, although the classic
inflammatory response (immunoglobulin and leucocyte infiltration) is absent.
beta-Amyloid fragments appear to mediate such inflammatory mechanisms by
activating the complement pathway in a similar fashion to immunoglobulin. 4.
Epidemiological studies have identified a reduced risk of AD in patients with
arthritis and in leprosy patients treated with anti-inflammatory drugs.
Longitudinal studies have shown that the
consumption of anti-inflammatory medications reduces the risk of AD
only in younger patients (< 75
years). 5. There is a considerable body of in
vitro evidence indicating that the inflammatory response of
microglial cells is reduced by
non-steroidal anti-inflammatory drugs (NSAID).
However, no published data are available concerning the effects of these medications on brain pathology in AD. 6.
Cyclo-oxygenase 2 enzyme is
constitutively expressed in neurons and is up-regulated in
degenerative brain regions in AD.
Non-steroidal anti-inflammatory drugs may reduce this expression. 7. Platelets are a source of beta-amyloid and
increased platelet activation and
increased circulating beta-amyloid have been
identified in AD. Anti-platelet medication (including NSAID) would
prevent such activation and its
potentially harmful consequences. 8. Increased
levels of luminal beta-amyloid permeabilizes the blood-brain barrier
(BBB) and increases vasoconstriction of
arterial vessels, paralleling the
alterations observed with infection and inflammation. Cerebral
amyloidosis is highly prevalent in AD,
compromising the BBB and vasoactivity.
Anti-inflammatory medications may alleviate these problems. [References:
75]
1311. Hoffner RJ. Esekogwu V.
Mallon WK. Leprosy in the emergency department.
Academic
Emergency Medicine. 7(4):372-6, 2000
Apr.
Abstract
OBJECTIVES: Los Angeles County-University of Southern California
Medical Center, like many large urban
hospitals, has a large immigrant population
from regions of the world where leprosy is endemic. Emergency
physicians (EPs) in these settings can
expect to encounter leprosy patients. This
study reviewed the emergency department (ED) course of patients
with confirmed leprosy in an attempt to
describe the most common presenting
patterns so that future cases can be more easily recognized. METHODS:
This was a retrospective chart review
of all patients followed in the Hansen's
disease clinic. Demographics, leprosy type, clinical presentations to
the ED, and medications were recorded.
RESULTS: Of the total number of
patients (415), most were of Mexican (52%), Filipino (15%),
Vietnamese (14%), and Chinese (5%)
origin. Leprosy was classified as lepromatous
(56%), borderline (40%), and tuberculoid (4%). There were a total of
118 ED visits by 74 patients. The mean
age was 46 years, with 51% male and 49%
female. Dermatologic (68%), neurologic (23%), and ophthalmologic
(9%) complaints were the most common
reasons for ED presentation related to
leprosy. The EP did not elicit a history of leprosy in 34% of those patients followed in the leprosy clinic. The
ED diagnosis of leprosy was made in 3
of 15 (20%) undiagnosed cases. Of the 63 patients prescribed medications in the leprosy clinic at the
time of their ED visits, 22 (35%) ED
charts did not report leprosy drugs. CONCLUSION: Patients with leprosy present to U.S. EDs, and new cases can be
identified. Early recognition is
important given leprosy's devastating consequences, major drug side effects of medications used for treatment,
and improved prognosis with multidrug therapy. A history of leprosy and
associated medications are often not documented in the ED chart, which may
reflect a continued fear of stigmatization among these patients.
1312. Kajihara
H. Paturusi IA. Saleh RM.
Rasyad C. Ikuta Y. Light and
electron microscopic study of peripheral nerve damage in patients with
lepromatous leprosy (LL) and borderline lepromatous leprosy (BL). Hiroshima
Journal of Medical Sciences.
49(1):83-92, 2000 Mar.
Abstract
Cutaneous branches of radial nerves in patients with lepromatous
leprosy (LL) and borderline lepromatous (BL) were studied by light and electron
microscopy. Foamy macrophages were found more or less in the nerve fibers of
all leprosy patients and distributed in the epineurial, perineurial and endoneurial areas. In the endoneurium, the
foamy macrophages were mainly located
in the subperineurial and perivascular spaces. Vacuolated Schwann cells were also found in the nerve
fasciculus. In electron microscopy,
these foamy macrophages and vacuolated Schwann cells contained numerous small dense materials, irregular in size and
shape, considered to be degenerated and
fragmented mycobacterium leprae. These dense materials were found also in the cytoplasm of vascular
endothelial cells. These findings
suggest that mycobacteria enter into the endoneurium via the blood vessels. In our present study, on the
other hand, it was very difficult to
find the intact mycobacteria in the cytoplasm of the foamy macrophages, Schwann cells or endothelial
cells, as well as in the Ziehl-Neelsen
staining of paraffin sections. The disappearance of intact bacilli in our present study might have been
caused by multi drug therapy. The
myelinated nerve fibers were degenerated and disappeared in variable degrees. Degenerative changes of the myelin
sheath developed from the outer layer
to the inner layer with disarrangement of the lamellar structure. These findings were different
from myelin destruction of peripheral
nerves in Wallerian degeneration. The degenerative changes of the myelin sheath
are caused by degeneration and destruction of Schwann cells in leprosy patients.
Fibrosis surrounding myelinated and unmyelinated nerve fibers, i.e., periaxonal
fibrosis, was found to a greater or lesser extent in the endoneurium. In the
present study, it is still unclear whether the periaxonal fibrosis was due to
necrosis of the Schwann cells by infection of mycobacteria or to an autoimmune
mechanism such as antiperipheral nerve
antibody. However, lamellated concentric
fibrosis surrounding regenerative myelinated and unmyelinated nerve fibers with the disappearance of mycobacteria
suggests that degenerations and regenerations
of nerve axons were repeated during clinical cause. These findings indicated that autoimmune
mechanisms play an important role in
the pathogenesis of periaxonal fibrosis.
1313. Mahaisavariya
P. Jiamton S. Manonukul J. Khemngern
S.Mast cells in leprosy and leprosy reaction. International Journal of
Dermatology. 39(4):274-7, 2000 Apr.
Abstract
BACKGROUND: Mast cells can be visualized in routine,
acid-fast-staining, paraffin tissue
section as metachromatic staining cells, and can be activated to release inflammatory mediators which play a role in
the cell-mediated immune response.
METHODS: Skin biopsy tissues were taken
from the most active skin lesion of each leprosy patient at the time
of diagnosis (nonreactional group) and
at the time of reaction (reactional
group) during the years 1994-1997 in the leprosy clinic at the
Department of Dermatology, Faculty of
Medicine, Siriraj Hospital, Mahidol University, Thailand. Mast cells were identified by metachromatic staining
(purple) in Fite's stain sections and
reported as the average number of cells per high power field in three compartments: at the center and periphery of
the granuloma and in the interstitium.
The data were analyzed in three groups:
nonreactional group, type I, and type II leprosy reactions. The mast
cell count of each group and each
compartment of the section, expressed as the
mean standard error, was
compared. RESULTS: A total of 95 persons were
included in the study, but 108 tissue sections were obtained due to nine cases having more than one section. Of these
patients, 63 cases (66.32%) had no reaction, 19 cases (20%) had type I
reaction, and 13 cases had type II reaction. There was no difference in age and
sex among these groups. The mast cell
count in the interstitium was higher than that within the granuloma, both at the center and at the
periphery, in every type, and the count
in this area reduced significantly in leprosy reactions, both type I and type II, compared with the nonreactional
group. CONCLUSIONS: The change in the
average mast cell number in nonreactional leprosy and leprosy reactions may indicate the important role of mast cells
in dynamic changes in the cell-mediated
immune response in leprosy and leprosy
reactions.
1314. Maslov
AK. Phagocytic myeloperoxidase in leprosy pathogenesis [letter]. International Journal of Leprosy & Other
Mycobacterial Diseases. 68(1):71-3,
2000 Mar.
1315. Patil
SA. Ramu G. Prasad R. Detection of disease related immune complexes in the
serum of leprosy patients. A novel single step method. Journal of
Neuroimmunology. 105(1):64-8, 2000 Jun
1.
Abstract
Mycobacterium leprae antigen and antibody complexes could be
detected in the serum of leprosy patients using monoclonal antibody ML34 and
anti-BCG antibodies by enzyme-linked immunosorbent assay. This simplified
system detects disease related
complexes without the need for isolating and purifying them from the serum.
Immune complexes captured using monoclonal
antibody ML34 revealed positivity in seven out of eight neuritic, two
out of nine tuberculoid (TT), five out
of ten borderline tuberculoid (BT),
four out of ten borderline lepromatous (BL) and four out of ten lepromatous (LL), leprosy cases. One of the
controls also showed immune complex of
an IgM type. Anti-BCG based IgG immune complexes assay revealed positivity in
six out of eight neuritic, one out of nine TT, four out of ten BT, two out of
ten BL, four out of ten LL leprosy cases, and two out of 24 healthy controls.
IgM type of mycobacterial immune complexes were almost negligible. Capture of
complexes using monoclonal antibody ML34 which is against lipoarabinomannan of
M. leprae seems to work better than
polyclonal anti-BCG antibody. The probable role of immune complexes in
nerve damage needs to be evaluated, as very high levels of immune complexes are
found in neuritic leprosy by both the assays. The above test would be useful in
immunodiagnosis of neuritic leprosy and also in cases where antibody response
is not detectable because of the formation of immune complexes.
1316. Ramesh V.
Beena KR. Mukherjee A.
Sporotrichoid presentations in leprosy. Clinical & Experimental
Dermatology. 25(3):227-30, 2000 May.
Abstract
Two adult patients of leprosy, one woman and
one man, presented with a
clinical picture simulating sporotrichosis.
The skin and regional nerve
trunk was affected in one, and in the other
the disease was confined to
the nerve. Both had features of an upgrading
reaction following
anti-leprosy therapy; this was seen as
erosion and scarring of the plaque,
and acute onset of abscesses along the
easily palpable and thickened nerve
that ruptured through the skin. The
diagnosis was supported by
histopathology. In the light of other
infections that give rise to a
sporotrichoid pattern of infection it is
concluded that leprosy should
also be included in this category so that
early diagnosis and use of
corticosteroids can be implemented quickly
to prevent nerve destruction.
1317. Young RJ 3rd. Gilson RT. Elston DM. Generalized
annular borderline tuberculoid leprosy and update in management of Hansen's disease. Cutis. 65(4):203-6, 2000 Apr.
Abstract
We describe a patient with widespread borderline tuberculoid
leprosy and significant peripheral
nerve involvement. Despite the presence of
widespread lesions, Fite stains and polymerase chain reaction studies
were initially negative. We discuss the
diagnosis and treatment of leprosy
including recent changes in treatment regimens and duration.
1746. Authors
Haimanot RT. Melaku Z.
Title
Leprosy. [Review] [63
refs]
Source
Current Opinion in
Neurology. 13(3):317-22, 2000 Jun.
Abstract
Leprosy is a unique
infectious disease with a prolonged incubation period
and a predilection for
skin and nerves. The involvement of nerves by the
primary infection as well
as the immunologically mediated reversal
reactions result in
impairment of nerve function and severe disabilities.
The introduction of the
World Health Organization Multi Drug Therapy over
the last two decades has
produced dramatic changes in the management and
control programmes of
leprosy. A recent important contribution to the
understanding of leprosy
pathogenesis has been the elucidation of the
molecular basis for the
entry of Mycobacterium leprae into the Schwann
cell and the peripheral
nerve. Leprosy still remains the commonest cause
of peripheral neuropathy
in developing countries. [References: 63]
1747. Authors
Hermon-Taylor J. Bull TJ.
Sheridan JM. Cheng J. Stellakis ML. Sumar N.
Title
Causation of Crohn's
disease by Mycobacterium avium subspecies
paratuberculosis [see
comments] [comment]. [Review] [369 refs]
Source
Canadian Journal of
Gastroenterology. 14(6):521-39, 2000
Jun.
Abstract
Mycobacterium avium
subspecies paratuberculosis (MAP) is a member of the M
avium complex (MAC). It
differs genetically from other MAC in having 14 to
18 copies of IS900 and a
single cassette of DNA involved in the
biosynthesis of surface
carbohydrate. Unlike other MAC, MAP is a specific
cause of chronic
inflammation of the intestine in many animal species,
including primates. The
disease ranges from pluribacillary to
paucimicrobial, with
chronic granulomatous inflammation like leprosy in
humans. MAP infection can
persist for years without causing clinical
disease. The herd
prevalence of MAP infection in Western Europe and North
America is reported in
the range 21% to 54%. These subclinically infected
animals shed MAP in their
milk and onto pastures. MAP is more robust than
tuberculosis, and the
risk that is conveyed to human populations in retail
milk and in domestic
water supplies is high. MAP is harboured in the
ileocolonic mucosa of a
proportion of normal people and can be detected in
a high proportion of full
thickness samples of inflamed Crohn's disease
gut by improved culture
systems and IS900 polymerase chain reaction if the
correct methods are used.
MAP in Crohn's disease is present in a
protease-resistant
nonbacillary form, can evade immune recognition and
probably causes an immune
dysregulation. As with other MAC, MAP is
resistant to most
standard antituberculous drugs. Treatment of Crohn's
disease with combinations
of drugs more active against MAC such as
rifabutin and
clarithromycin can bring about a profound improvement and,
in a few cases, apparent
disease eradication. New drugs as well as
effective MAP vaccines
for animals and humans are needed. The problems
caused by MAP constitute
a public health issue of tragic proportions for
which a range of remedial
measures are urgently needed. [References: 369]
1748. Authors
Jones PB. Parrish NM.
Houston TA. Stapon A. Bansal NP.
Dick JD.
Townsend CA.
Title
A new class of
antituberculosis agents.
Source
Journal of Medicinal
Chemistry. 43(17):3304-14, 2000 Aug 24.
Abstract
Long-chain lipid
envelopes are characteristic of mycobacteria such as
those that cause
tuberculosis and leprosy. Inhibition of fatty acid
synthesis or elongation
is a strategy demonstrated to be clinically
effective against M. tuberculosis. A new class of compounds
designed to
inhibit the beta-ketoacyl
synthase reaction of fatty acid synthesis has
been developed. Of >30
compounds described, the most active were
acetamides containing
alkylsulfonyl substituents. Inhibitory activities
were acutely sensitive to
net charge, chain length, and degree of
unsaturation. The most
active compound 5 (alkyl = C(10)) contained a
single methylene spacer
between the sulfone and carboxamide and exhibited
an MIC of 0.75-1.5
&mgr;g/mL, comparable to first-line antituberculosis
drugs. These compounds
are species-specific, exhibiting no significant
activity against
bacterial species other than M. tuberculosis and closely
related strains. The
synthesis, biological activity, and specificity of
these compounds are
described.
1749. Authors
Pennini SN. Pedrosa L.
Rebello PF.
Title
Early diagnosis and
treatment of leprosy in intradomiciliary contacts in a
high prevalence area:
Amazon region.
Source
Indian Journal of
Leprosy. 70 Suppl:73S-77S, 1998.
Abstract
The importance of
dermato-neurological examination of intradomiciliary
contacts is well known as
an important secondary preventive measure in
leprosy control, due to
the fact that it allows early diagnosis and
treatment. This is an
intervention trial in an area of high leprosy
prevalence
(Manaus/Brazil) where the proportion of contacts examined is
low. The aim of the study
is to assess whether a simple educational
session conducted among patients
increases contacts examination and leads
to early case detection.
The intervention group had examined more contacts
(p < 0.05) but,
paradoxically, presented fewer new cases than the control
group. The authors
discuss the probable causes for this unexpected
outcome, the advantages
of the intervention and other related issues.
1750. Authors
Singh HB. Katoch K.
Natrajan M. Sharma RK. Gupta UD.
Sharma VD.
Singh D. Chauhan DS.
Srivastava K. Katoch VM.
Title
Effect of treatment on PCR
positivity in multibacillary leprosy patients
treated with conventional
and newer drugs ofloxacin and minocycline.
Source
Acta Leprologica. 11(4):179-82, 1999.
Abstract
In order to develop
objective criteria to monitor trends of therapeutic
responses positivity of
PCR signals and ATP assay methods has been
compared in
multibacillary (MB) leprosy patients. Biopsies from lesions of
95 BL/LL patients before
and after one year of treatment with a new drug
regimen comprising of
conventional and newer drugs ofloxacin and
minocycline have been
studied. These biopsies were processed for bacillary
ATP assay and PCR
positivity for a 36 kDa gene target by earlier published
methods. In the untreated
patients bacillary ATP levels were detectable in
all specimens and ranged
from 0.02 to more than 36 pg/millions organisms.
After one year of
treatment ATP levels were not detectable in any of the
57 biopsies specimens
available for analysis. However, PCR signals were
detectable in 3 out of 57
biopsies. In two specimens signals were very
weak detectable only by
hybridization. It may be concluded that DNA based
PCR assay may be useful
in monitoring the trends of therapeutic responses
in MB patients under
treatment.
1751. Authors
Spierings E. De Boer T.
Zulianello L. Ottenhoff TH.
Title
Novel mechanisms in the
immunopathogenesis of leprosy nerve damage: the
role of Schwann cells, T
cells and Mycobacterium leprae. [Review] [64
refs]
Source
Immunology & Cell
Biology. 78(4):349-55, 2000 Aug.
Abstract
The major complication of
reversal (or type 1) reactions in leprosy is
peripheral nerve damage.
The pathogenesis of nerve damage remains largely
unresolved. In situ
analyses suggest an important role for type 1 T cells.
Mycobacterium leprae is
known to have a remarkable tropism for Schwann
cells that surround
peripheral axons. Reversal reactions in leprosy are
often accompanied by
severe and irreversible nerve destruction and are
associated with increased
cellular immune reactivity against M. leprae.
Thus, a likely
immunopathogenic mechanism of Schwann cell and nerve damage
in leprosy is that
infected Schwann cells process and present antigens of
M. Leprae to
antigen-specific, inflammatory type 1 T cells and that these
T cells subsequently
damage and lyse infected Schwann cells. Previous
studies using rodent CD8+
T cells and Schwann cells have revealed evidence
for the existence of such
a mechanism. Recently, a similar role has been
suggested for human CD4+
T cells. These cells may be more important in
causing leprosy nerve
damage in vivo, given the predilection of M. leprae
for Schwann cells and the
dominant role of CD4+ serine esterase+ Th1 cells
in leprosy lesions.
Antagonism of molecular interactions between M.
leprae, Schwann cells and
inflammatory T cells may therefore provide a
rational strategy to
prevent Schwann cell and nerve damage in leprosy.
[References: 64]
1752. Authors
Suarez RE. Lombardi C.
Title
Leprosy elimination at
sub-national level.
Source
Leprosy Review. 71(2):206-11, 2000 Jun.
Abstract
New strategies for the
countries that have already achieved the
elimination goal, which
includes the great majority of the endemic
countries, are needed.
There is current concern in these countries about
the reduction in the
political-technical commitment when the goal is
achieved and the
possibility of the re-emergence of the disease. A review
of the literature on the
leprosy post-elimination strategy is done. The
proposal to estimate the
true prevalence using hidden prevalence based on
late diagnosis of the new
cases is made. Suggestions are explored for
strategies of the work
after elimination at national level is attained
such as the
stratification at the first sub-national level, using
estimated true
prevalence. It is considered necessary to define strategies
for the post-elimination
phase with the aim of continuing to the long-term
objective of the
interruption of transmission and the consequent leprosy
eradication.
2221. Cho SN. Cellona RV. Villahermosa LG. Fajardo TT Jr. Balagon MV. Abalos RM. Tan EV. Walsh GP. Kim JD. Brennan PJ. Detection of phenolic glycolipid I of Mycobacterium leprae in sera from leprosy patients before and after start of multidrug therapy. Clinical & Diagnostic Laboratory Immunology. 8(1):138-42, 2001 Jan.
Abstract
A total of 100 untreated new leprosy patients were recruited prospectively and examined for the presence of phenolic glycolipid I (PGL-I) antigen in their serum specimens by dot enzyme-linked immunosorbent assay (ELISA) using rabbit anti-PGL-I antiserum. The presence of circulating PGL-I antigen was closely related to the bacterial indices (BI) of the patients. The PGL-I antigen was detectable in 27 (93.1%) of 29 patients with a BI of 4.0 or above and in 15 (68.2%) of 22 patients with a BI of 3.0 to 3.9. However, none of the 37 patients with a BI of less than 1.9 had detectable PGL-I antigen by the methods used in this study. The level of PGL-I in serum declined rapidly by about 90% 1 month after the start of multidrug therapy. This study showed clearly that anti-PGL-I IgM antibodies and circulating PGL-I antigen levels reflect the bacterial loads in untreated leprosy patients. The serological parameters based on the PGL-I antigen may therefore be useful in the assessment of leprosy patients at the time of diagnosis and possibly in monitoring patients following chemotherapy.
2222. Donoghue HD. Holton J. Spigelman M. PCR primers that can detect low levels of Mycobacterium leprae DNA. Journal of Medical Microbiology. 50(2):177-82, 2001 Feb.
Abstract
There are several specific PCR-based methods to detect Mycobacterium leprae DNA, but the amplicons are quite large. For example, primers that target the 36-kDa antigen gene and are in common diagnostic use yield a 530-bp product. This may be a disadvantage when examining samples in which the DNA is likely to be damaged and fragmented. Therefore, two sets of M. leprae-specific nested primers were designed, based on existing primer pairs which have been shown to be specific for M. leprae. Primers that targeted the 18-kDa antigen gene gave an outer product of 136 bp and inner product of 110 bp. The primers based on the RLEP repetitive sequence yielded a 129-bp outer product and 99-bp nested product. With dilutions of a standard M. leprae killed whole-cell preparation as the source of DNA, both single-stage and nested PCR were performed after optimisation of the experimental conditions. Compared with the 36-kDa antigen gene primers, the 18-kDa antigen gene outer primers were 100-fold more sensitive and the RLEP outer primers were 1000-fold more sensitive. As an illustration of two possible applications of these new primers, positive results were obtained from three skin slit samples from treated lepromatous leprosy patients and three archaeological samples from human remains showing typical leprosy palaeopathology. It was concluded that these new primers are a useful means of detecting M. leprae DNA which is damaged or present at a very low level.
2223. John TJ. Muliyil J. Care after cure in leprosy. Lancet. 357(9252):313, 2001 Jan 27.
2224. Kalantri SP. Dr K. V. Desikan gets the Damien-Dutton Award. National Medical Journal of India. 14(1):61, 2001 Jan-Feb.
2225. Kim SK. Dohlman CH. Causes of enlarged corneal nerves. [Review] [81 refs] International Ophthalmology Clinics. 41(1):13-23, 2001 Winter.
2226. Marques MA. Ant nio VL. Sarno EN. Brennan PJ. Pessolani MC. Binding of alpha2-laminins by pathogenic and non-pathogenic mycobacteria and adherence to Schwann cells. Journal of Medical Microbiology. 50(1):23-8, 2001 Jan.
Abstract
The ability of Mycobacterium leprae to specifically bind alpha2-laminins of Schwann cells has been described recently as being an important property of the leprosy bacillus, which could explain the neural tropism of M. leprae. Therefore, the extent of the expression of alpha2-laminin-binding properties among mycobacteria was investigated. In an ELISA-based assay, all three species of Mycobacterium tested (M. tuberculosis, M. chelonae and M. smegmatis) expressed laminin-binding capacity, suggesting that the ability to bind alpha2-laminins is conserved within the genus Mycobacterium. This report also demonstrated that not only M. leprae but all the mycobacterial species tested readily interacted with the ST88-14 cells, a human schwannoma cell line, and that the addition of soluble alpha2-laminins significantly increased their adherence to these cells. These results failed to demonstrate the presence in M. leprae of a unique system based on alpha2-laminins for adherence to Schwann cells.
2227. Moraes MO. Sampaio EP. Nery JA. Saraiva BC. Alvarenga FB. Sarno EN. Sequential erythema nodosum leprosum and reversal reaction with similar lesional cytokine mRNA patterns in a borderline leprosy patient. British Journal of Dermatology. 144(1):175-81, 2001 Jan.
Abstract
We compare the clinical and histological data with the immunological status of a borderline leprosy patient who experienced an erythema nodosum leprosum (ENL) reaction followed by a reversal reaction (RR) after 12 weeks of anti-inflammatory treatment (pentoxifylline, PTX, 1200 mg daily). Skin biopsies, serum and blood samples were collected sequentially during the reactional episodes. At the outset of RR, the patient's lymphocytes secreted interferon (IFN) -gamma and there was a positive lymphoproliferative test in response to Mycobacterium leprae, which had been absent during ENL. The lepromin reaction reversed from negative (0 mm) at diagnosis, to positive (3 mm) 3 months after the development of RR. Tumour necrosis factor (TNF) -alpha levels in the serum decreased after 1 week of treatment and increased slightly thereafter. The immunohistochemical data for ENL showed a diffuse dermal and hypodermal infiltrate composed of mononuclear cells and neutrophils, while RR was characterized by an epithelioid granulomatous infiltrate with a marked presence of gammadelta T cells. Reverse transcription-polymerase chain reaction showed a mixed cytokine profile characterized by the expression of TNF-alpha, IFN-gamma, interleukin (IL) -6, IL-10 and IL-12 mRNA in the skin, which persisted throughout the development of ENL and RR lesions. IL-4 mRNA, first detected after 7 days of PTX treatment, was still present during RR. The results suggest the emergence of an initial Th0-like cytokine profile in ENL, typical of a state of immunoactivation, before conditions optimal for the appearance of an antigen-specific cell-mediated immune response and gammadelta T-cell migration are created.
2228. Mvogo CE. Bella-Hiag AL. Ellong A. Achu JH. Nkeng PF. Ocular complications of leprosy in Cameroon. Acta Ophthalmologica Scandinavica. 79(1):31-3, 2001 Feb.
Abstract
PURPOSE: This study aimed to identify the main ocular complications of leprosy in Cameroon. PATIENTS AND METHODS: It is a prospective cross-sectional study which took place from July 1998 to January 1999 in five leprosaria in Cameroon. The ophthalmological examination of all patients was performed by the same team. RESULTS: Of the 218 patients examined, 60.1% were males and 39.9% females. 72.5% had a paucibacillary leprosy and 27.5% a multibacillary form. 77.5% of patients had at least one ocular lesion and 38.3% of eyes had visual acuity < or = 1/10. Madarosis and anterior uveitis were more frequent in multibacillary forms while lagophthalmos and cataract were so in paucibacillary forms. CONCLUSION: Ocular complications are frequent in leprosy in Cameroonians. It is a true public health problem and it is important to prevent these lesions by early diagnosis and adequate treatment.
2229. Nunez-Gussman J. Hwang L. Hsu S. Guess what! Targetoid erythematous plaques: an unusual morphological presentation of multibacillary Hansen's disease. European Journal of Dermatology. 11(1):65-7, 2001 Jan-Feb.
2230. Ochoa MT. Stenger S. Sieling PA. Thoma-Uszynski S. Sabet S. Cho S. Krensky AM. Rollinghoff M. Nunes Sarno E. Burdick AE. Rea TH. Modlin RL. T-cell release of granulysin contributes to host defense in leprosy. Nature Medicine. 7(2):174-9, 2001 Feb.
Abstract
A novel mechanism by which T cells contribute to host defense against microbial pathogens is release of the antimicrobial protein granulysin. We investigated the role of granulysin in human infectious disease using leprosy as a model. Granulysin-expressing T cells were detected in cutaneous leprosy lesions at a six-fold greater frequency in patients with the localized tuberculoid as compared with the disseminated lepromatous form of the disease. In contrast, perforin, a cytolytic molecule that colocalizes with granulysin in cytotoxic granules, was expressed at similar levels across the spectrum of disease. Within leprosy lesions, granulysin colocalized in CD4+ T cells and was expressed in CD4+ T-cell lines derived from skin lesions. These CD4+ T-cell lines lysed targets by the granule exocytosis pathway and reduced the viability of mycobacteria in infected targets. Given the broad antimicrobial spectrum of granulysin, these data provide evidence that T-cell release of granulysin contributes to host defense in human infectious disease.
2231. Rambukkana A. How does Mycobacterium leprae target the peripheral nervous system? [see comments]. [Review] [44 refs] Trends in Microbiology. 8(1):23-8, 2000 Jan.
Abstract
Mycobacterium leprae has the capacity to invade the peripheral nervous system and cause neuropathy. The molecular mechanisms responsible have remained unknown until recently. Identification of the endoneurial laminin-2 isoform and its receptor alpha-dystroglycan as neural targets of M. leprae has not only opened up a new area of scientific inquiry into the pathogenesis of neurological damage in leprosy, but has also revealed unexpected biological properties of these important host molecules. [References: 44]
2232. Salvadori M. Index of suspicion. Case 2. Diagnosis: Leprosy. Pediatrics in Review. 22(1):22-31, 2001 Jan.
2233. Santos DO. Santos SL. Esquenazi D. Nery JA. Defruyt M. Lorre K. Van Heuverswyn H. Evaluation of B7-1 (CD80) and B7-2 (CD86) costimulatory molecules and dendritic cells on the immune response in leprosy. Nihon Hansenbyo Gakkai Zasshi. Japanese Journal of Leprosy. 70(1):15-24, 2001 Feb.
Abstract
The cell activation depends on T cell antigen receptor binding to antigen plus MHC and costimulation. The binding of CD28, expressed on the T cell surface to B7 (B7-1 or CD80/B7-2 or CD86) present on the antigen--presenting cells (APCs), determines, in several T cell function models, if activation or anergy follows antigenic stimulation. In leprosy, the role of CD80 and CD86 as costimulatory signal in M. leprae-specific cellular immunity has not yet been defined. We investigated the role of B7-CD28 pathway of T cell activation in the in vitro response to M. leprae, following stimulation in the presence of monocytes or dendritic cells (DCs) as APCs. Monocytes were purified, by cold aggregation, from peripheral blood mononuclear leukocytes (PBMC), isolated from leprosy patients. In order to obtain DCs, the monocytes were cultured in the presence of IL-4 and GM-CSF. T cells were purified from PBMC by negative selection with mABs and C'. The phenotype of the cell populations was monitored by FACS. Lymphoproliferative assays were performed with T cells, in the presence of monocytes or DCs. The cells were stimulated by M. leprae in the presence of anti-CD80 antibody (Ab) and/or anti-CD86 antibody (Ab) (Innogenetics). In some experiments Il-10, Il-12 and anti-Il-12 Ab were also added to the culture. We observed a significantly more efficient APC function for DCs when compared to monocytes in T cell in vitro responses to M. leprae. Regardless of the clinical form of Leprosy, the M. leprae-specific immune response was markedly reduced in the presence of anti-CD86 Ab. Il-12 increase the immune response to M. leprae while IL-10 or anti-IL-12 Ab reduce this response when monocytes or DCs were used as APCs.
2234. Stockel S. Meurer M. Wozel G. Dapsone-induced photodermatitis in a patient with linear IgA dermatosis. [Review] [17 refs] European Journal of Dermatology. 11(1):50-3, 2001 Jan-Feb.
Abstract
Dapsone (4, 4'
diaminodiphenylsulfone) is an efficient antiinflammatory agent. Its therapeutic
use may result in a variety of adverse effects. The most frequent unwanted
reactions are hemolytic anemia and methemoglobinemia. By oral route dapsone is
mainly metabolized to monoacetyldapsone (MADDS) and hydroxylamine dapsone
(DDS-NOH). We report a 76-year-old female patient with linear IgA dermatosis
who developed a dapsone-induced photosensitivity 8 weeks after initiation of
sulfone therapy. She showed a widespread erythematous eruption in UV-exposed
skin area. After clearing of skin lesions the photopatch test revealed positive
reactions to dapsone, MADDS and DDS-NOH. Dapsone-induced photosensitivity to
date has been described only in leprosy patients. We demonstrate for the first
time that this adverse reaction is not restricted to leprosy and that dapsone
metabolites may also contribute to the mechanism of photosensitivity like the parent sulfone. Dapsone-induced
photosensitivity is a rare, not dose-related adverse effect of the sulfone and
can also occur in patients with inflammatory skin disorders. [References: 17]
2819. Bhake AS.
Desikan KV. Jajoo UN.
Cytodiagnosis of histoid leprosy. Leprosy Review. 72(1):78-82, 2001 Mar.
2820. Charlab R.
Sarno EN. Chatterjee D. Pessolani MC. Effect of unique Mycobacterium
leprae phenolic glycolipid-I (PGL-I) on tumour necrosis factor production by
human mononuclear cells. Leprosy Review.
72(1):63-9, 2001 Mar.
2821. Coleman MD. Dapsone-mediated agranulocytosis:
risks, possible mechanisms and prevention. [Review] [51 refs] Toxicology.
162(1):53-60, 2001 Apr 12.
2822. Curtiss R 3rd. Blower S. Cooper K. Russell D.
Silverstein S. Young L. Leprosy
research in the post-genome era. [0 refs]
Leprosy Review. 72(1):8-22, 2001
Mar.
2823. de la Barrera S. Fink S. Finiasz M. Aleman M.
Helena Farina M. Pizzariello
G. del Carmen Sasiain M. Lysis of
autologous macrophages pulsed with hsp10 from Mycobacterium leprae is
associated to the absence of bacilli in leprosy. Immunology Letters. 76(1):55-62, 2001 Feb 1.
2824. Lockwood DN.
Reid AJ. The diagnosis of leprosy is delayed in the United Kingdom.
QJM. 94(4):207-12, 2001 Apr.
2825. Ooi WW.
Moschella SL. Update on leprosy in immigrants in the United States:
status in the year 2000. [Review] [38 refs] Clinical Infectious Diseases. 32(6):930-7, 2001 Mar 15.
2826. Ramadan W.
Mourad B. Fadel W. Ghoraba E. Clinical, electrophysiological,
and immunopathological study of peripheral nerves in Hansen's disease. Leprosy
Review. 72(1):35-49, 2001 Mar.
2827. Tovar-Rivera T. Sanchez-Colon S.
Padierna-Olivos L. Masso-Rojas
F. Estrada-Parra S. Mondragon-Gonzalez R. Jimenez-Martinez MC. Sanchez-Garcia FJ. Connectivity patterns in
tuberculosis and leprosy patients are indistinguishable from that of healthy
donors. Scandinavian Journal of Immunology.
53(5):520-7, 2001 May.
2828. Walsh DS.
Prieto-Go D. Abalos RM. Tuur-Saunders SM. Villahermosa LG. Jabien
Z. Walsh GP. Fajardo TT. Malignant T-cell lymphoma mimicking lepromatous
leprosy. Clinical & Experimental Dermatology. 26(2):173-5, 2001 Mar.
2829. Zijlstra EE.
el-Hassan AM. Leishmaniasis in Sudan. Post kala-azar dermal
leishmaniasis. Transactions of the Royal Society of Tropical Medicine &
Hygiene. 95 Suppl 1:S59-76, 2001 Apr.