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Biomedical subjects

J F Doherty

Publications and source records attributed to J F Doherty.

At least 19 recordsLinked to original sources
PubMed2004

Falciparum malaria in malaria-naive travellers and African visitors.

BACKGROUND: Patients from malaria-endemic areas who present in non-endemic countries with Plasmodium falciparum malaria are often assumed to have some degree of immunity. If this were reliably true, it would simplify their management. AIM: To determine whether being born and resident in a malaria-endemic country is a predictor of clinical course in UK admissions for malaria. DESIGN: Prospective observational study. METHODS: We compared clinical and laboratory parameters between two groups of adult patients with acute P. falciparum malaria, admitted to the Hospital for Tropical Diseases in London: one born and resident in non-endemic countries (n=167); the other born and resident in malaria-endemic countries of Africa (n=93). Patients were excluded if they had taken prophylaxis or prior treatment. RESULTS: There were no differences between these two groups in terms of peak parasitaemia or time to parasite clearance. There was a significantly higher risk of malaria-naive patients having peak parasitaemia >5% (OR 4.5, 95%CI 1.5-13.2). Of those usually resident in Africa, 31% required parenteral treatment compared to 41% of the malaria-naive group. Of the visitors from Africa, 4.3% needed admission to the Intensive Therapy Unit (ITU), although there was a tendency for more malaria-naive patients to require ITU care (OR 2.69, 95%CI 0.9-8.1). DISCUSSION: While there are differences in presentation between those who are malaria-naive and those who live in malaria-endemic African countries, making assumptions about the immunity or clinical course of an individual patient with malaria presenting in the UK on the basis of presumed history of exposure is unwise.

Adolescent↗
PubMed1999

A phase I safety and immunogenicity trial with the candidate malaria vaccine RTS,S/SBAS2 in semi-immune adults in The Gambia.

RTS,S is a novel pre-erythrocytic malaria vaccine based on the circumsporozoite surface protein (CSP) of Plasmodium falciparum linked to hepatitis B surface antigen (HBs) and combined with a novel adjuvant system (SBAS2). We have conducted a Phase I trial with three doses of this vaccine given at 0, 1, and 6 months to 20 semi-immune, adult, male volunteers in The Gambia to assess its safety and immunogenicity. Eighteen of the 20 volunteers completed the study. There were no clinically significant local or systemic adverse events following each vaccination. Hematologic and biochemical indices before and two weeks after each vaccination showed no evidence of toxicity. Antibody titers to both CSP and HBs showed a significant increase after vaccination; these were the largest after the third dose. We conclude that the RTS,S/SBAS2 vaccine induces no significant toxicity in this semi-immune population and produces significant increases in antibody titers to CSP.

Adolescent↗
PubMed1998

Short report: hematologic changes in acute, imported Plasmodium falciparum malaria.

We conducted a retrospective analysis of hematologic changes in 89 patients with imported Plasmodium falciparum malaria. Thirteen (15%) were anemic at presentation, 60 (67%) had thrombocytopenia, and 63% had lymphopenia. There was a significant inverse relationship between parasitemia and platelet count. Anemia is rare among patients with imported malaria, while thrombocytopenia and lymphopenia are common.

Acute Disease↗
PubMed1997

As the world of managed care turns.

Health maintenance organizations have become predominant in the health care industry and continue to evolve as expectations for quality and affordability change. Although initially limited, managed care options have grown extensively and will continue to develop as America's needs change. The author describes the early impetus for the growth of MCOs and the legislation that guided the maturation of managed care.

Capitation Fee↗
PubMed1995

Fever as the presenting complaint of travellers returning from the tropics.

We investigated prospectively the cause of fever in patients requiring hospitalization after returning from the tropics. All consecutive admissions (n = 195) with oral temperature > 37.0 degrees C at the time of admission were enrolled. Final diagnosis as recorded on the discharge summary by the attending physician and results of any relevant laboratory or radiological investigations were recorded on standard proforma. Malaria accounted for 42% of admissions; two patients had returned to Britain more than 6 months before presentation. The second largest group was assumed to have a non-specific viral infection (25%). Cosmopolitan infections (urinary tract infection, community-acquired pneumonia, streptococcal sore throat, etc.) accounted for 9%. Coincidental infections (schistosomiasis, filariasis, intestinal helminths) were found in 16%. Serology was positive for HIV infection in 3%. The most useful investigation was a malaria film, which was positive in 45% of cases in which it was performed. The combination of thrombocytopaenia (platelet count < 100 x 10(9)) and hyperbilirubinaemia (bilirubin > 18 IU/ml) were useful predictive markers of malaria: all 23 patients with both abnormalities had positive malaria films. Malaria must be excluded in any febrile patient returning from the tropics. In the absence of a positive malaria film, the combination of a low platelet count and raised bilirubin may suggest the need for an empirical course of therapy.

Acute Disease↗
PubMed1994

Production of interleukin-6 and tumour necrosis factor-alpha in vitro is reduced in whole blood of severely malnourished children.

1. Cytokine production in vitro was assessed in 16 malnourished children, before and after nutritional recovery. 2. Tumour necrosis factor-alpha and interleukin-6 were measured in whole blood after lipopolysaccharide stimulation. 3. The total amount of both cytokines was significantly less after 24 h incubation among malnourished children when compared with the same children after nutritional rehabilitation. 4. Cytokine production in vitro is impaired in severely malnourished children.

Female↗
PubMed1994

Peroxisomes and the hepatic pathology of childhood malnutrition.

Liver specimens obtained immediately after death from eight severely malnourished children were examined by electron microscopy, and compared with seven liver biopsy specimens from children who had recovered from malnutrition. The liver cells from the fatal cases showed mitochondrial swelling, with coarse densities in the matrix, cholestasis, depletion of the endoplasmic reticulum and Golgi apparatus, diminished glycogen stores, prominent lipid deposits and focal cytoplasmic degradation. The nucleoli were enlarged. There was marked reduction in peroxisomes. In contrast, the biopsies from recovering children showed good cellular organisation, and a normal frequency of peroxisomes. Multiple factors, including sepsis, may lead to depletion of peroxisomes. Loss of peroxisomes may interrupt beta-oxidation of long-chain fatty acids and accentuate the accumulation of lipid. Moreover, a reduction in the concentration of catalase may remove one avenue for the detoxification of free radicals. As the concentration of other anti-oxidants, notably glutathione, is also reduced, free radical damage may occur, leading to lipid peroxidation of membranes, mitochondrial damage, pump failure and influx of water and electrolytes into the cell.

Biopsy↗
PubMed1993

Is there an acute-phase response in steady-state sickle cell disease?

Metabolic and serum changes during steady-state homozygous sickle cell (SS) disease are consistent with an acute-phase response and raise the possibility that inflammation occurs in SS disease even during the steady state. To test this hypothesis, we measured concentrations of acute phase reactants in patients with SS disease, in patients with sickle cell haemoglobin C (SC) disease, and in normal (AA) control subjects. The concentrations of C-reactive protein and serum amyloid A were increased above 10 mg/L and 5 mg/L, respectively (our definition of an acute-phase response) in 18% (26/143) of subjects with SS disease even when they were symptom free, in 17% (6/35) of subjects with SC disease, and in 1% (1/80) of AA controls (p < 0.001). We suggest that subclinical vaso-occlusion may generate a covert inflammatory response and that the cytokine mediators of this response may contribute to the metabolic abnormalities and growth failure in sickle cell disease.

Acute-Phase Proteins↗
PubMed1993

Acute-phase protein response is impaired in severely malnourished children.

1. The responses of plasma levels of C-reactive protein and serum amyloid A were assessed in two groups of malnourished children. 2. Sixty-six severely malnourished children were studied at admission. Fifty of these had clinical and/or laboratory evidence of infection. C-reactive protein was not elevated in 23 (46%) and serum amyloid A was not raised in 29 (58%) of these 50 children. 3. Surviving children (n = 62) received two doses of diphtheria-pertussis-tetanus vaccine, to which the C-reactive protein and serum amyloid A responses were measured. The first was given early in recovery, the second after nutritional rehabilitation. Ten mildly malnourished children acted as controls, receiving a single dose of diphtheria-pertussis-tetanus vaccine. 4. The responses of both C-reactive protein and serum amyloid A to diphtheria-pertussis-tetanus vaccine were significantly less in early recovery than after nutritional recovery. The response of the mildly malnourished group was no different from that of the severely malnourished group in early recovery, but was less than their response on discharge. 5. The acute-phase protein response of malnourished children is impaired. This may have prognostic implications as the response plays a central role in promoting healing.

Acute Disease↗
PubMed1992

Ultrasonographic assessment of the extent of hepatic steatosis in severe malnutrition.

Ultrasonographic, blinded assessment was made of the extent of hepatic steatosis in 55 children with severe malnutrition: undernutrition (n = 6), marasmus (n = 18), marasmickwashiorkor (n = 17), and kwashiorkor (n = 14). The children were examined on admission, in early recovery (considered as baseline), and again at discharge. Eleven healthy control children and eight of the previously malnourished children were studied as comparison groups. Both oedematous and non-oedematous malnourished children had significantly more steatosis than the comparison groups at each time. Children with oedematous malnutrition had significantly greater steatosis than non-oedematous children at admission. Half of the non-oedematous malnourished children had appreciable hepatic steatosis at both admission and at baseline. Hepatic fat was only slowly mobilised. The rate constant was 1.4 +/- 0.3%/day. One quarter of the children did not change steatosis grades during the period they were in hospital. There was no overall correlation between the extent of steatosis and liver size. Hepatic steatosis in childhood malnutrition is not confined to oedematous children: it is frequently present in marasmic and undernourished children. Its extent is not necessarily related to the degree of hepatomegaly and accumulated lipid is only slowly mobilised.

Child, Preschool↗