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Biomedical subjects

N Francis

Publications and source records attributed to N Francis.

At least 73 records · Page 4Linked to original sources

Malaria chemoprophylaxis, infection of the placenta and birth weight in Gambian primigravidae.

A randomized, double blind, placebo-controlled community based trial of Maloprim (pyrimethamine 12.5 mg+dapsone 100 mg) administered to primigravid pregnant women by Traditional Birth Attendants was carried out in a rural area of The Gambia, West Africa. Placental histology showed less malaria infection in women who received chemoprophylaxis than in those who received placebo. The birth weight of children born to women who received chemoprophylaxis was increased by an average of 153 g. Within the treatment groups, there were no significant differences in the birthweights of babies born to women who had histological evidence of malaria infection of the placenta compared to those who had no malaria infection. This study confirms the beneficial effect of malaria prophylaxis for primigravid pregnant women but questions the mechanism by which malaria affects foetal development.

Acute Disease↗

Placental malaria. I. Pathological classification.

Pregnant women are more likely to contract malaria than their non-pregnant counterparts. The aim of this study was to develop a simple classification system for the histopathological diagnosis of placental malaria infection applicable to placentas collected in field conditions. The placentas were classified into four groups depending on the presence and distribution of parasites and malaria pigment: active infection, active-chronic infection, past-chronic infection, not infected. The frequency of parasitized placentas (26.4%) was in keeping with the prevalence of placental parasitaemia documented in epidemiological studies. An additional 29.8% placentas showed pigment in fibrin only, indicating past-chronic infection. Chronic placental malaria infection was most common in primigravidae, possibly reflecting ineffective clearance of parasites from the placenta. Seasonal fluctuations between infection categories support progression of placental infection with delayed clearance of pigment from fibrin. The proposed classification system has allowed diagnosis of different categories of placental malaria infection by two independent observers. A standardized method of diagnosis may enhance understanding of placental pathology and reduced birth weight in malaria infection during pregnancy.

Adolescent↗

Placental malaria. II. A semi-quantitative investigation of the pathological features.

Malaria in pregnancy is associated with reduced birth weight. Most pathological studies of placental malaria infection have focused on severe Plasmodium falciparum infection. In the present study of 121 placentas delivered in a rural area of The Gambia, malaria infection was diagnosed in tissue sections using a simple classification system and severity of pathology was ranked semiquantitatively. Deposition of malaria pigment in circulating cells was associated with active infections whereas pigment in fibrin was a feature of active-chronic infections. Primigravidae had higher levels of pigment at all sites, although these observations were not always significant. Thickening of the trophoblast basement membrane occurred in all infection categories but fibrinoid necrosis of chorionic villi was a feature of active and active-chronic infection. Both birth weight and placental weight were increased in infected placentas but widespread trophoblast basement membrane thickening was associated with decreased birth weight. Both birth weight and placental weight decreased with increased fibrinoid necrosis and cytotrophoblast prominence but the results were not significant. By this approach it has been possible to correlate placental pathology with different infection categories and to analyse the pathological features associated with decreased birth weight.

Adolescent↗

The contribution of Gambian traditional birth attendants to field research.

One thousand, one hundred and forty-seven pregnant women from a rural area of The Gambia were followed throughout pregnancy. In order to determine the incidence of malaria infection of the placenta, traditional birth attendants (TBAs) from 18 villages were trained to collect placental biopsies and to prepare thick smears of placental blood at delivery. Nine hundred and eighty-eight of 1112 term deliveries (89%) occurred at home. Eight hundred and fifty-nine (87%) of these home deliveries were assisted by a TBA. TBAs collected 829 placental biopsies and 800 thick blood smears from the 859 women whom they assisted. Seven hundred and forty-seven thick blood films (93%) and 807 placental samples (97%) were satisfactory. TBAs are an important resource for clinical research; in this case they made a major contribution to a community study of the impact of malaria on pregnancy.

Biopsy↗

Adenovirus infection of the large bowel in HIV positive patients.

AIMS: To describe the microscopic appearance of adenovirus infection in the large bowel of human immunodeficiency virus (HIV) positive patients with diarrhoea. METHODS: Large bowel biopsy specimens from 10 HIV positive patients, eight of whom were also infected with other gastrointestinal pathogens, with diarrhoea were examined, together with six small bowel biopsy specimens from the same group of patients. Eight of the patients had AIDS. The biopsy specimens were examined by light microscopy performed on haematoxylin and eosin stained and immunoperoxidase preparations, the latter using a commercially available antibody (Serotec MCA 489). Confirmation was obtained with electron microscopy. RESULTS: The morphological appearance of cells infected with adenovirus showed characteristic nuclear and cellular changes, although the inflammatory reaction was non-specific. Immunoperoxidase staining for adenovirus was sensitive and specific, and the presence of viral inclusions consistent with adenovirus was confirmed by electron microscopy. CONCLUSIONS: The light microscopic features of adenovirus infection are distinctive and immunocytochemistry with a commercially available antibody is a sensitive and specific means of confirming the diagnosis. Further studies of the role of adenovirus in causing diarrhoea in these patients are indicated.

Acquired Immunodeficiency Syndrome↗

Monoclonal immunofluorescence compared with silver stain for investigating Pneumocystis carinii pneumonia.

Two hundred and eighty two specimens from 220 patients positive for HIV with respiratory tract symptoms, or febrile illness, or both, were examined for the presence of Pneumocystis carinii. Specimens were either induced sputum samples or bronchoalveolar lavage fluids. To establish the optimal method for laboratory diagnosis a comparison was made of detection of the organism by use of monoclonal antibody and immunofluorescence with conventional silver staining methods. Three commercially available reagents for immunofluorescence were also compared. Immunofluorescence was significantly more sensitive than the silver stain and the best results for immunofluorescence were obtained using. Northumbria Biologicals Ltd reagents.

Bronchoalveolar Lavage Fluid↗

Prediction of the delayed complications of intestinal and mesenteric injuries following experimental blunt abdominal trauma.

Injuries to the intestine and mesentery are often found in patients undergoing laparotomy for blunt abdominal trauma. Although treatment of perforations is relatively straightforward, the same is not true for contusions. Few guidelines exist at present to aid the surgeon in deciding which injuries require resection in order to avoid the complications of delayed perforation and late stricture formation. The natural history of these non-perforating intestinal and mesenteric injuries has been examined in an experimental model to identify possible criteria on which future management can be based. In the immediate postinjury period peristalsis and local mesenteric pulsation were absent in the majority of injuries which went on to full recovery and these observations are thus of little predictive value in predicting outcome. The initial size of contusion (length of contusion along longitudinal axis of bowel) relative to bowel wall circumference (BWC) was related to complications as follows: contusion less than BWC (n = 47)--one complication; contusion greater than BWC (n = 8)--three complications (P = 0.02). Similarly, six mesenteric injuries which produced an initial ischaemia (assessed by fluorescein) less than twice the BWC did not result in any complications, compared with four complications which occurred in ten cases when the initial ischaemia was greater than twice the BWC. These results go some way towards providing a better understanding of these injuries and in turn may help the emergency surgeon in deciding which injuries require resection.

Abdominal Injuries↗

Contribution of focal haemorrhage and microvascular fibrin deposition to fatal envenoming by Russell's viper (Vipera russelli siamensis) in Burma.

In Burma, clinicopathological studies were carried out in three young farmers who died 15, 52 and 36 h after being bitten by Russell's vipers. Clinical features included local swelling, spontaneous systemic bleeding, defibrination, shock, cardiac arrhythmia, hypoglycaemia, coma and oliguria. On admission to hospital, 15, 48 and 21 h after the bites, serum venom antigen concentrations ranged from 50 to 130 ng/ml. Autopsies revealed widespread congestion and bleeding in the lungs, gastrointestinal and renal tracts, adrenals, heart, brain and anterior pituitary. There was histopathological evidence of focal haemorrhage and fibrin deposition at the site of the bite and in the pituitary, lungs and kidneys and acute tubular necrosis. Deposition of fibrin microthrombi results from the action of venom procoagulants. Shock was attributed to increased capillary permeability, revealed clinically by conjunctival oedema. Acute pituitary/adrenal failure in one case was explained by fibrin deposition and haemorrhage in the anterior pituitary--resembling Sheehan's syndrome. Acute tubular necrosis resulted from ischaemia caused by fibrin deposition and to prerenal factors. An intractable cardiac tachyarrhythmia may have been caused by subendocardial and myocardial haemorrhages.

Adolescent↗

Scanning transmission electron microscopic study of alpha-ketoglutarate dehydrogenase complex from Escherichia coli.

The alpha-ketoglutarate dehydrogenase complex was resolved into its three component enzymes: alpha-ketoglutarate dehydrogenase (E1), dihydrolipoyl transsuccinylase (E2), and dihydrolipoyl dehydrogenase. Subcomplexes were prepared in vitro by incubating the resolved E2, a 24-subunit cube-shaped molecule, with E1 (dimeric). The morphology and mass of the subcomplexes were determined by scanning transmission electron microscopy of negatively stained and of freeze-dried specimens. Images of both negative stained and freeze-dried subcomplexes were consistent with E1 binding at or near the midpoints of the edges of the E2 molecule. Mass analysis of the freeze-dried specimen showed that at least 95% of E1 remains in the dimeric state (or as two closely juxtaposed monomers) when it binds to E2.

Escherichia coli↗

Role of excess lipoyl dehydrogenase in reconstituted alpha-ketoglutarate dehydrogenase complex of Escherichia coli.

The alpha-ketoglutarate dehydrogenase complex of Escherichia coli can bind up to 12 dimers of dihydrolipoyl dehydrogenase (E3) besides those already present. Maximal activity does not increase, however, when surplus E3 is present. This observation was previously interpreted to mean that the excess enzyme is inactive. We have now determined that if the reactions catalyzed by E3 are made rate-limiting, the excess E3 functions equivalently to that in the native complex.

Dihydrolipoamide Dehydrogenase↗

Helical disorder and the filament structure of F-actin are elucidated by the angle-layered aggregate.

Angle-layered aggregates of F-actin are net-like structures induced by Mg2+ concentrations below that used to form paracrystals. These aggregates incorporate the angular disorder of subunits, which has been described elsewhere for isolated actin filaments. Because this disorder is incorporated into the aggregates in solution at the time they are formed, the possibility of negative stain preparation being responsible for the disorder is excluded. The simple two-layered geometry of the angle-layered aggregate provides information about the shape of the component actin filaments free from the superposition of large numbers of layers. A model for the filament shape, derived from single filaments and confirmed by the angle-layered aggregate, is different from those that have previously emerged from paracrystal studies. An understanding of the interfilament bond in both the angle-layered aggregate and the paracrystal allows one to reconcile these different models. We have found a bipolar bonding rule, with staggered crossover points in the angle-layered aggregate, which we suggest is also responsible for Mg2+ paracrystals. This bonding rule can explain the apparent alignment of crossover points in adjacent filaments in paracrystals as a consequence of the superposition of staggered filaments.

Actins↗

alpha-Ketoglutarate dehydrogenase complex may be heterogeneous in quaternary structure.

The quaternary structure of the alpha-ketoglutarate dehydrogenase complex (KGDC) from Escherichia coli has been investigated by electron microscopy. KGDC consists of an octahedral cube-shaped structural core, lipoyl transsuccinylase (E2), to which 12 polypeptide chains each of alpha-ketoglutarate dehydrogenase (E1) and dihydrolipoyl dehydrogenase (E3) are non-covalently bound. The analysis was greatly simplified by analyzing subcomplexes of KGDC prepared by assembly of the purified component enzymes in vitro; the subcomplexes consisted of the E2 component to which only a few E1 or E3 subunits were attached. We find that both the E1 and E3 bind on the surface of the E2 molecule approximately midway between the 4-fold and 2-fold symmetry axes of E2. There are 24 such positions per E2 molecule but, based upon the observed stoichiometries of the component enzymes, it is clear that at least half of these sites are unoccupied in KGDC. If KGDC possesses symmetry, then a mechanism must exist for selecting a symmetrically distributed subset of the potential binding sites for the E1 and E3. However, analysis of images of subcomplexes in which two E1 or E3 subunits are present suggests that binding to the E2 occurs through random selection of the potential binding sites. If native KGDC is assembled by such a mechanism, then KGDC would not have a unique quaternary structure, but instead would consist of a family of structural isomers having up to approximately 125,000 members. Consideration of independent structural and biochemical data regarding the mechanism of action of the E2 indicates that the kind of structural heterogeneity being proposed is consistent with a functional KGDC.

Acyltransferases↗