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Biomedical subjects

P D Marsden

Publications and source records attributed to P D Marsden.

At least 55 records · Page 3Linked to original sources

Mucosal leishmaniasis ("espundia" Escomel, 1911).

One of the more serious clinical forms of leishmaniasis occurs in espundia when the mucosae of the upper respiratory passages are inflamed. This complication is a metastasis from a skin lesion caused by Leishmania braziliensis braziliensis (Lbb) although cases have been described associated with other leishmanial species. Epidemiological data suggest that a detectable mucosal metastasis occurs in fewer than 5% of patients infected with Lbb in our study area. The determinants of this complication are still largely obscure. The granuloma usually commences on the nasal septum. In about two-thirds of our patients the lesion remained restricted to the nose. In the rest the pharynx, palate, larynx and lips were involved, in this order. It is often difficult to isolate the parasite and for routine diagnosis the leishmanin skin reaction and serological tests are helpful. Although a serious condition, with possible mutilation and even death as subsequent complications, treatment is still mainly with pentavalent antimonials, introduced 40 years ago. These are most unsatisfactory for field use, being given parenterally and relatively toxic. In mucosal leishmaniasis, if sufficient antimony can be administered in a regular daily dose, the relapse rate is small (3 of 42 patients followed for a mean of 5 years). Also, antimony treatment of the initial skin ulcer due to Lbb followed for a mean of 4 years of 83 patients resulted in subsequent mucosal metastasis in only 2. Since espundia is relatively rare, specific treatment targeted to this specific problem is the efficient short term solution. At present there is no satisfactory alternative drug to those in current use.

Antimony Sodium Gluconate↗

A new prognostic index in surgery and parenteral feeding: the ratio of triiodothyronine to reverse triiodothyronine in serum (T3/rT3 ratio).

Serum concentrations of albumin, triiodothyronine (T3), and reverse triiodothyronine (rT3) were measured in 46 patients on the first day after routine gastrointestinal surgery, and the molar ratio T3/rT3 was calculated. The median value of this ratio, but not of albumin, was significantly lower in 11 who subsequently suffered major septic complications than in the remainder. Measurement of the ratio correctly predicted the outcome of 80% of individuals. The T3/rT3 ratio, midarm muscle circumference (MAMC), triceps skin fold (TSF) and serum concentrations of albumin and transferrin were measured in 23 patients at referral for parenteral feeding. Median values of T3/rT3 ratio, MAMC and transferrin, but not of the other parameters, were significantly lower in nine who died than in survivors. Measurements of the ratio, MAMC and transferrin correctly predicted the outcome of 87%, 78% and 74% of individuals, respectively.

Journal Article↗

Disseminated cutaneous leishmaniasis in a field clinic in Bahia, Brazil: a report of eight cases.

Eight Bahian patients with cutaneous leishmaniasis who had 20 or more ulcerative lesions of short duration are described. Of five identifications of isolated parasites, four were Leishmania braziliensis braziliensis and one was L. mexicana amazonensis. All but one had positive Montenegro tests initially, and all did after treatment. All had circulating anti-leishmanial antibodies and five responded well to glucantime therapy suggesting a functioning immune response. This is quite different to the anergic hansenoid leishmaniasis seen with L. mexicana amazonensis infections in Brazil. Possible reasons for the occurrence of this type of leishmaniasis are briefly discussed.

Adolescent↗

A focus of mucocutaneous leishmaniasis in Três Braços, Bahia, Brazil: characterization and identification of Leishmania stocks isolated from man and dogs.

The characterization and identification to species and subspecies of 20 stocks of Leishmania isolated from the region of Três Braços, Bahia, Brazil, are described: 17 stocks were from patients and three from dogs. The following techniques were used (i) biological (growth in culture, hamster tissues and phlebotomine gut), (ii) biochemical (isoenzyme and kinetoplast DNA analysis) and (iii) immunological (using monoclonal antibodies). All except two stocks belong to the L. braziliensis complex. One of these two corresponded to L. mexicana amazonensis but the other, while clearly in the mexicana complex, showed slight differences from the L. mexicana amazonensis reference strain on isoenzyme analysis. Two stocks from different lesions in the same patient and with different growth characteristics in hamster tissues were both identified as L. braziliensis braziliensis. All the fully characterized stocks of the L. braziliensis complex were identified as L. braziliensis braziliensis. L. braziliensis guyanensis was not identified. Dog and human stocks of L. braziliensis braziliensis were indistinguishable. From these findings and other evidence, L. braziliensis braziliensis seems to be the predominant species transmitted in Três Braços.

Animals↗

Clinical presentations of Leishmania braziliensis braziliensis.

Leishmania braziliensis braziliensis (Lbb) is probably the most serious, leishmanial infection of the New World. Although epidemiological information is incomplete, its distribution is believed to extend from Belize in Central America to northern Argentina, involving all countries east of the Andes. Lbb causes a variety of clinical lesions and is one of the most difficult forms of leishmaniasis to treat. We still do not know how many patients suffer from mucosal disease requiring treatment. In this review of 10 years field experience in an endemic area of Brazil, Philip Marsden shows that parasitologists have much to contribute, especially in improving diagnostic methods, developing better animal models, and providing new drugs suitable for routine treatment on a large-scale.

Journal Article↗

High continuous antimony therapy in two patients with unresponsive mucosal leishmaniasis.

The treatment of two patients with severe mucosal leishmaniasis due to Leishmania braziliensis braziliensis is described. Both patients had received much prior antimonial therapy and one had relapsed after a total dose of 2.5 g of Amphotericin B. Both patients responded to prolonged continuous Pentostam therapy at a daily dose of 20 mg Sbv/kg/day for 62 days in one case and for 85 days in the other. Pentavalent antimonials can be curative in such protracted courses in selected patients unresponsive to standard chemotherapy.

Adult↗

Pentavalent antimonial inhibition of the osmotic effect of oxytocin on the isolated toad bladder.

The inhibition of osmotic stimulated water flow in the isolated toad bladder by 0.1 mM sodium stibogluconate (pentavalent antimony) is described. Pentavalent antimony on the serosal surface significantly inhibited oxytocin-induced water flow but when the drug was added to the mucosal surface only the effect of low oxytocin concentrations was reduced. The phosphodiesterase inhibitor pentoxifylline, when present on the serosal side, blocks the effect of pentavalent antimony on stimulated water flow. No effect was detected when indomethacin was present on the serosal side. It is suggested that phosphodiesterase activation might play a role in the mechanism of pentavalent antimonial inhibition of oxytocin-induced water flow in the isolated toad bladder. The effect obtained when sodium stibogluconate on the serosal side was replaced with antimony pentachloride (SbCl5) supports the view that the metal in the molecule is responsible for the inhibition of the effect of oxytocin.

Animals↗

[Current aspects of endemic mucocutaneous leishmaniasis in Brazil].

Mucocutaneous leishmaniasis has a large incidence in Brazil. Biochemical, immunological and biological studies have characterized three disease agents: Leishmania mexicana amazonensis, Leishmania brasiliensis guyanensis and Leishmania brasiliensis brasiliensis; these have distinct geographical distributions. The last one is the most common and is the most difficult to treat. Destructive mucosal lesions can occur days, months or years after the cutaneous lesions. The Montenegro intradermal test, biopsy, smears of the border of ulcers and indirect immunofluorescence are the auxiliary diagnostic methods currently in use. The only effective drugs for the treatment of this disease are pentavalent antimonials and amphotericin B. After clinical cure, relapses can occur, and there are rare cases with mucosal lesions that are resistant to all forms of treatment.

Biopsy↗

Cell mediated immunity in American cutaneous and mucosal leishmaniasis.

Cellular immune responses were studied in 35 Brazilian patients with either active cutaneous leishmaniasis (CL), active mucosal leishmaniasis (ML), or healed cutaneous leishmaniasis. The mean age and duration of illness in the two groups were as follows: 14 CL patients, age 28 +/- 13 yr, disease 5 +/- mo; and 16 ML patients, age 34 +/- 15 yr, disease 86 +/- 117 mo. Patients with CL and ML responded well to leishmania antigen in blastogenesis assays. However, the response of ML patients was over three times greater than the response of CL patients. There was a significant correlation between the magnitude of the lymphoproliferative response and the duration of disease activity. There were no significant differences between CL and ML patients in terms of the following parameters: lymphoproliferative responsiveness to mitogens (phytohemagglutinin, concanavalin A, and pokeweed mitogen) and peripheral blood lymphocyte subpopulations (T and B cells, oKT8+ and OKT4+ cells, OKT4:OKT8 ratio). Peripheral blood mononuclear cells from ML patients also generated interferon-gamma containing lymphokine in response to stimulation with leishmania antigen. This lymphokine was capable of inducing macrophages from ML patients to inhibit the intracellular multiplication of leishmania in vitro. These studies have determined that the parameters of lymphocyte and macrophage functions evaluated in ML and CL patients are comparable, except for an enhanced lymphoproliferative response, with leishmania antigen in ML patients. This later finding may be a function of the long duration of active disease in this population and unrelated to the pathogenesis of their mucosal lesions.

Adolescent↗