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Biomedical subjects

D Lalloo

Publications and source records attributed to D Lalloo.

9 recordsLinked to original sources
PubMed1995

Immunogenic HIV variant peptides that bind to HLA-B8 can fail to stimulate cytotoxic T lymphocyte responses.

Cytotoxic T lymphocyte responses in HIV infection can be impaired through variation in the epitope regions of viral proteins such as a gag. We report here an analysis of variant epitope peptides in three gag epitopes presented by HLA B8. Fifteen variant peptides were examined for their binding to HLA-B8; all but one bound at concentrations comparable to known epitopes. All except two of those that bound could be recognized by CTL from an HLA-B8 positive HIV-1-infected patient and were therefore immunogenic. However, in a hemophiliac patient studied in detail, there was a failure to respond to two immunogenic peptide epitopes representing virus present as provirus in the patient's peripheral blood. In one case, the patient's CTL had previously responded to the peptide; in the other case, there was a good response to a peptide of closely related sequence. Thus there was a selective failure of the CTL response to some proviral epitopes. This impaired reaction to new variants could contribute to the loss of immune control of the infection.

Animals↗
PubMed1994

Cytotoxic T-cell activity antagonized by naturally occurring HIV-1 Gag variants.

Most asymptomatic individuals infected with HIV-1 have a cytotoxic T lymphocyte (CTL) response to the virus Gag proteins which can be demonstrated in vitro. Epitopes have been mapped in p17 Gag and p24 Gag restricted by HLA-B8 (p17-3 and p24-13) and -B27 (p24-14). Viruses isolated from patients who make CTL responses to these peptides vary within the genetic sequences encoding these epitopes and some mutations lead to reduction in killing activity in vitro. This was attributed to either failure of the variant epitope to bind major histocompatibility complex class I or failure of T-cell receptors to bind the presented peptide. But peptide variants of class I-restricted epitopes cause 'antagonism', that is, the presence of a variant epitope (in the form of peptide) inhibits normal lysis of targets presenting the original epitope. This mirrors similar findings in class II-restricted systems. Here we report that naturally occurring variant forms of p17-3, p24-13 and p24-14 may cause antagonism of CTL lines derived from the same individuals. The effect is present if the epitopes are derived from synthetic peptides and when they are processed from full-length proteins expressed by either recombinant vaccinia constructs or replicating HIV.

Amino Acid Sequence↗
PubMed1994

Neurotoxicity and haemostatic disturbances in patients envenomed by the Papuan black snake (Pseudechis papuanus).

Among 335 patients presenting with snakebites in Central Province, Papua New Guinea, nine were proved by enzyme immunoassay to have been bitten by Papuan black snakes (Pseudechis papuanus). Seven showed clinical evidence of envenoming. Early symptoms included vomiting and tender local lymph nodes. Five patients had neurotoxic signs and one required mechanical ventilation. Spontaneous systemic bleeding occurred in two patients. Coagulation studies in four patients showed thrombocytopenia, prolongation of prothrombin time, mild defibrination and depletion of other clotting factors with elevated fibrin(ogen) degradation products and other evidence of fibrinolysis. One patient developed mild renal dysfunction. There was no evidence of intravascular haemolysis or rhabdomyolysis. These clinical observations, which do not distinguish victims of P. papuanus from those of taipans (Oxyuranus scutellatus canni), suggest that the venom contains neurotoxic, haemorrhagic and mild procoagulant activities. Only two other cases of proven envenoming by this species have been reported. There appears to have been a decline in the abundance of this species, and hence its medical importance, over the last 25 years.

Adolescent↗
PubMed1994

Cryptococcal meningitis (C. neoformans var. gattii) leading to blindness in previously healthy Melanesian adults in Papua New Guinea.

Cryptococcal meningitis is a common cause of chronic meningitis in Papua New Guinea, affecting apparently immunocompetent people. The majority of infections are believed to be due to Cryptococcus neoformans var. gattii. We have reviewed the records of 49 Melanesian adults who presented with proven cryptococcal meningitis to the University teaching hospital in Port Moresby, and compare our findings with other published studies of cryptococcal meningitis in the tropics and sub-tropics. None of the patients had an obvious cause of immunosuppression. Visual disturbances and fundoscopic changes of papilloedema or papillitis were particularly common. The in-hospital case fatality rate for patients treated with amphotericin B and flucytosine was 22.4%. Of the fully treated patients, 31% became completely blind before being discharged from hospital. Therapy directly aimed at reducing intracranial pressure may improve outcome.

Adolescent↗
PubMed1992

The diagnosis of malaria: traditional and contemporary approaches.

There have been many recent developments in techniques for the diagnosis of malaria. The quantitative buffy coat (QBC) system and immunological and molecular biological methods are discussed, and compared with the present slide microscopic methods for the diagnosis of malaria. The suitability of each of these techniques for use in the field is reviewed.

DNA Probes↗
PubMed1992

A new look at an old drug: artemesinin and qinghaosu.

It is said that William Withering's discovery of digitalis arose out of curiosity engendered during a stage-coach journey, by witnessing an old woman collecting foxgloves by the side of the road. Whilst we are not aware of an analogous stroke of genius reported from ancient China, the story of qinghaosu has certain parallels. Just as foxgloves had been used traditionally for centuries to treat 'afflictions of the heart', the plant Artemesia annua has been used as a treatment for fever in China for almost two thousand years. Artemesia annua, also known as 'sweet wormwood', is found in many parts of the world, but it was not until the early 1970s that Chinese scientists recognized its potential for treating malaria and isolated the active principle, artemesinin or qinghaosu. This paper describes the evidence for the efficacy of this drug and some of its derivatives in the treatment of malaria and the potential of these drugs for the standard management of malaria in Papua New Guinea and elsewhere.

Antimalarials↗
PubMed1992

Quinine blindness.

A young women was treated with intravenous quinine and chloramphenicol for suspected severe malaria and/or typhoid fever. On the second day of quinine therapy (after 2.25 g of quinine) she suddenly developed total bilateral loss of vision. Both drugs were stopped and cyclandelate therapy was started. She showed slight improvement in vision but on referral her visual acuity was limited to seeing waving hand movement only; visual fields were constricted and colour vision was absent. Both pupils were fixed and dilated. The fundi showed macular oedema and attenuated retinal arteries. She was treated with dexamethasone, cyclandelate, vitamin B complex and vitamin C. Colour vision was completely recovered after 5 days of treatment. Full recovery of the direct light reflex occurred after 10 days. Visual acuity improved slowly over a period of one month to 6/15 vision in both eyes. At this time macular oedema and retinal arteriolar attenuation were still present but less severe. In the context of this case report the condition of quinine blindness is briefly reviewed and the management discussed.

Adult↗