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Biomedical subjects

R E Phillips

Publications and source records attributed to R E Phillips.

At least 145 records · Page 8Linked to original sources
PubMed1986

Antigen-specific immunosuppression in human malaria due to Plasmodium falciparum.

Proliferative responses of T lymphocytes to antigens specific and not specific for malaria were investigated in 32 adult patients in eastern Thailand during acute infection with Plasmodium falciparum malaria and during their convalescence. Immune unresponsiveness to malarial antigen, which persisted for more than four weeks in 37.5% of the individuals, was present in all patients, irrespective of parasitemia or severity of clinical illness. Suppression of responses to nonspecific antigens was less profound and observed only in patients with moderately severe or cerebral malaria. The depressed functional responses were associated with a loss of T lymphocytes--both helper and suppressor subsets--from the peripheral blood; these responses were recovered once parasites were cleared. These results indicate that blood-stage plasmodial infections may suppress responses important for immunity to malaria and so allow the parasite to survive. They further suggest that patients acutely or even recently infected with P. falciparum may not respond as well to a malaria vaccine as would uninfected individuals.

Adolescent↗
PubMed1986

The activity of drugs against Giardia intestinalis in neonatal mice.

The activities of 12 5-nitroimidazoles and ten other compounds have been compared against Giardia intestinalis stock BRIS/83/HEPU/106 in a suckling mouse model. Ronidazole, satranidazole and fexinidazole were the most active compounds being 2.8, 2.0 and 2.0 times more active than tinidazole respectively and warrant further investigation as potential chemotherapeutic agents. The results obtained in mice are consistent with the known activity of nitroimidazoles in man. There was a strong positive correlation between these results and previous in-vitro studies obtained using a 3H-thymidine uptake assay, indicating that in-vitro studies are of value in predicting in-vivo responses.

Animals↗
PubMed1986

Quinine pharmacokinetics and toxicity in pregnant and lactating women with falciparum malaria.

Quinine dihydrochloride (10 mg or, in two patients, a loading dose of 20 mg kg-1) was infused intravenously over 4 h in ten severely ill but conscious women with falciparum malaria complicating the third trimester of pregnancy. Plasma quinine concentrations, measured spectrophotofluorimetrically after benzene extraction, fitted closely a single exponential decline after the intravenous infusion. These data were therefore fitted to a one compartment model: total apparent volume of distribution, V, 0.96 +/- 0.27 l kg-1 (+/- s.d.), elimination half-time (t1/2,z), 11.3 +/- 4.3 h, total clearance, 1.22 +/- 0.77 ml min-1 kg-1. There was no relationship between arterial blood pressure and plasma quinine concentrations. Eight women delivered of live infants while taking quinine, had placental cord plasma quinine concentrations from 1.0 to 4.6 mg l-1 (mean 2.4) which correlated significantly with maternal plasma quinine concentrations (r = 0.78, t = 3.06, P less than 0.05). The mean (+/- s.d.) ratio of cord plasma to maternal plasma quinine concentration was 0.32 +/- 0.14. Heart blood from a foetus aborted at term had a plasma quinine concentration of 2.8 mg l-1; simultaneous maternal plasma quinine was 7.1 mg l-1 (ratio 0.39). Breast milk quinine concentrations and milk to plasma ratios were 0.5-3.6 mg l-1 (mean 2.6) and 0.11-0.53 (mean 0.31) in twenty-five women who were breast-feeding and had taken oral quinine sulphate for 1-10 days (mean 4.0). Five women with more serious infections received intravenous quinine; breast milk quinine concentrations ranged between 0.5 and 8.0 mg l-1 (mean 3.4).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Evidence against immune haemolysis in falciparum malaria in Thailand.

Evidence of immune mediated haemolysis was sought in 83 patients with P. falciparum malaria in eastern Thailand. Amongst 73 patients with uncomplicated infection 12 (16.4%) had a weakly positive direct antiglobulin test (DAT). The incidence in 32 children aged 8-16 years was similar to that in adults. Of 10 patients with cerebral malaria, six adults, all of whom were in unrousable coma, had a positive DAT. Erythrocyte-bound IgG1 accounted for the positive DAT in all cases; sensitization with complement or other IgG subclasses was not found. Patients with uncomplicated malaria had a median value of 70 IgG molecules per erythrocyte compared with 65 molecules per cell in 67 healthy controls. This difference was not statistically significant but could account for the lower incidence of a positive DAT in control subjects (4.5%). There was no correlation between the number of IgG molecules per cell and the degree of anaemia during the acute or convalescent phases of the infection. There is no evidence from this study that an immunohaemolytic process contributes to the anaemia of falciparum malaria in eastern Thailand.

Adolescent↗
PubMed1986

A central venous temperature sensing lead.

Pacemaker rate responsiveness derived from changing central venous blood temperature requires the development of sensor leads that are stable and reliable. The relevant characteristics of one such design are described. Temperature response time, data acquisition time, temperature sensitivity, and long-term sensor shunt impedance have been studied both in vitro and in vivo. These parameters are analyzed with respect to the intrinsic temperature signal and to pacemaker implementation problems.

Blood↗
PubMed1986

Effects of ethaverine hydrochloride on the walking tolerance of patients with intermittent claudication.

The effect of ethaverine hydrochloride on exercise tolerance of patients with intermittent claudication was evaluated in a double-blind, placebo-controlled study conducted at three sites. Forty-five patients with symptoms of occlusive arterial insufficiency of the lower extremities were randomly assigned to receive ethaverine 200 mg or placebo four times daily. The patients were evaluated biweekly for 12 weeks with treadmill claudication tests, patient and investigator assessments of symptom severity, and reports of adverse reactions. Doppler ankle/brachial pressure ratios were recorded for 26 patients. Walking tolerance improved for patients in both groups during the course of the study. Increases in distance-to-claudication were significantly greater for patients receiving ethaverine after 6, 8, 10, and 12 weeks of therapy. Ankle/brachial pressure index after exercise was unchanged in both groups. Incidence of adverse reactions was similar for the two groups. Although patients were generally unaware of any improvement in symptoms, the investigators judged significant relief of claudication among those receiving ethaverine compared to those receiving placebo. It was concluded that ethaverine safely increased distance-to-claudication in patients with intermittent claudication.

Ankle↗
PubMed1986

Randomized comparative trial of three monospecific antivenoms for bites by the Malayan pit viper (Calloselasma rhodostoma) in southern Thailand: clinical and laboratory correlations.

Three monospecific antivenoms for Malayan pit viper (MPV) (Calloselasma rhodostoma) were compared in Southern Thailand, where this species is the most common cause of snake bite morbidity. Forty-six patients with proved MPV bites and incoagulable blood, indicating systemic envenoming, were randomly allocated for treatment with Thai Red Cross (TRC), Thai Government Pharmaceutical Organization (GPO), or Twyford Pharmaceutical monospecific antivenoms. Both GPO and Twyford antivenoms produced rapid and permanent restoration of blood coagulability, but TRC antivenom failed in 2/15 cases. Patients in the GPO group showed the greatest increase in plasma fibrinogen concentration during the first 24 hr and had fewer early anaphylactic reactions (6/15) compared with Twyford 8/16 and with TRC 13/15. Pyrogenic reactions occurred more frequently after TRC antivenom (8/15) than GPO (1/15) or Twyford (0/16). Patients requiring more than one dose of antivenom were identifiably more severely envenomed on admission. In an accompanying laboratory study the antivenoms were assessed in rodents using five WHO standard tests of neutralizing activity. Compared with the other two antivenoms TRC was significantly inferior in anti-lethal potency, GPO was superior in anti-hemorrhagic and anti-necrotic potency and Twyford was superior in anti-procoagulant and anti-defibrinogenating potency. The clinical efficacy of these antivenoms against local necrosis remains equivocal. GPO and Twyford antivenoms are recommended for the treatment of systemic envenoming by MPV in an initial dose of 5 ampoules.

Adult↗
PubMed1986

Clinical significance of venom antigen levels in patients envenomed by the Malayan pit viper (Calloselasma rhodostoma).

Serial venom antigen levels were measured by enzyme-linked immunosorbent assay (ELISA) in 46 patients with systemic envenoming by the Malayan pit viper (Calloselasma rhodostoma), a major cause of snake bite in Southeast Asia. The principal effects of the venom are defibrination, hemorrhage and local tissue necrosis. Admission venom levels, which varied between 0 and 595 ng/ml, correlated with the incidence of spontaneous systemic bleeding, blood incoagulability and concentrations of plasma fibrinogen and serum fibrin degradation products. The presence or absence of nonclotting blood also correlated with the time elapsed between the bite and hospital admission. The development of nonclotting blood may be delayed by up to 72 hr after the bite even though circulating venom and raised FDP may be detected at presentation. This is probably explained by a temporary equilibrium between synthesis and consumption of fibrinogen. Venom antigenemia recurred in 12 patients (26%) suggesting continuous absorption of venom from the wound or saturation of extravascular binding sites. Admission venom levels also correlated with the extent of local swelling and the occurrence of tissue necrosis at the site of the bite. Venom was detected in 87% of wound aspirates and 88% of urine specimens taken on admission. Tourniquets, of the type used in rural Thailand, did not delay the absorption of venom into the circulation.

Adolescent↗
PubMed1986

Function of the blood-cerebrospinal fluid barrier in human cerebral malaria: rejection of the permeability hypothesis.

We tested the hypothesis that cerebral malaria is caused by blood-brain barrier inflammation and cerebral edema. In a group of 157 Thai patients with strictly defined cerebral malaria, cerebrospinal fluid (CSF) opening pressures were normal in 79% and were lower in fatal cases than in survivors (means +/- 1 SD, 144 +/- 58 and 167 +/- 51 mm CSF, respectively, P = 0.051). CSF: serum albumin ratios (X 10(3)) in 39 of them were significantly higher than in 61 British controls (medians 8.5 and 5.5, respectively, P = 0.04), but were no higher in 7 fatal cases. In a group of 12 patients this ratio was not significantly higher during coma than after full recovery (means +/- 1 SD, 9.0 +/- 6.2 and 6.7 +/- 4.2, respectively, P greater than 0.1). CSF alpha 2-macroglobulin concentrations were always normal. CSF : serum 77Br- ratios were elevated in 11/19 comatose cases but fell to normal 4 to 9 days later in 11/11 cases. Dexamethasone treatment had no significant effect on bromide partition. The percentage of an intravenously administered dose of 125I-human serum albumin detectable per ml of CSF 6 hr after intravenous injection was 2.4 +/- 1.3 X 10(-5) in 14 comatose patients and 4.4 +/- 4.0 X 10(-5) in 9 of them during convalescence (P greater than 0.1). These results demonstrate that the blood-CSF barrier is essentially intact in patients with cerebral malaria and give no support to the idea that cerebral edema is the cause of coma.

Blood-Brain Barrier↗
PubMed1986

The importance of anaemia in cerebral and uncomplicated falciparum malaria: role of complications, dyserythropoiesis and iron sequestration.

Ninety-four per cent of 169 patients with cerebral malaria developed anaemia (haematocrit less than 35 per cent) and 30 per cent required blood transfusion to maintain the haematocrit at more than 21 per cent. Anaemia was at its worst on admission in 58 patients (34 per cent); in the rest the haematocrit fell further, reaching its nadir one to 17 days later (mean 2.3 days). The mean lowest haematocrit was 24.3 +/- 7.2 per cent (+/- 1 SD) and the mean maximum fall was 7.9 +/- 5.6 per cent. Anaemia was more severe in patients with bacterial infection, retinal haemorrhages, schizontaemia and in pregnancy. The lowest haematocrit correlated with admission parasitaemia (r = -0.33, p less than 0.001), total serum bilirubin (r = -0.25, p less than 0.01) and serum creatinine (r = -0.22, p less than 0.01). In 23 patients with uncomplicated falciparum malaria the mean serum iron on admission was 53 micrograms/dl (range 16-157) and the mean serum ferritin 1773 ng/ml (range 170-10 000). There was a significant (p less than 0.001) rise in serum iron 96 h after starting antimalarial treatment; the serum ferritin declined slowly over several weeks. Stainable iron was present in all marrows examined and in eight patients the characteristic pattern of the anaemia of chronic disorders was seen. Seventy-three per cent of patients had dyserythropoiesis which was moderate to gross in 36 per cent. Dyserythropoiesis and erythrophagocytosis were often present on admission but sometimes appeared after the parasitaemia had cleared and persisted for at least three weeks into convalescence. These disturbances in iron metabolism and haemopoiesis are not completely explicable by red blood cell parasitisation. They may contribute more to the anaemia than has previously been recognised.

Adolescent↗
PubMed1985

Bites by Russell's viper (Vipera russelli siamensis) in Burma: haemostatic, vascular, and renal disturbances and response to treatment.

Of 123 patients with proved Russell's viper bite, 28% showed no evidence of envenoming, 28% had local swelling alone, but 44% had systemic envenoming manifested by incoagulable blood (100% of those admitted before treatment), thrombocytopenia (26%), spontaneous systemic bleeding (20%), hypotension (35%), evidence of increased capillary permeability (24%), and oliguria (44%). Patients with systemic envenoming usually had more local swelling than those without, but 5 had no local signs. Snake length correlated with the amount of local swelling, but snakes causing systemic envenoming were no longer than those causing local or no envenoming. Burma Pharmaceutical Industry monospecific antivenom was rapidly effective in restoring blood coagulability but did not prevent the development of renal failure even when given within 4 h of the bite. Hypotension responded to volume expanders (11/19 cases) and dopamine (6/7 cases) but not to naloxone (0/3) or high-dose methylprednisolone (0/5). The 10 deaths (8%) were attributed to hypotension, pituitary haemorrhage, and renal failure.

Adolescent↗
PubMed1985

Intravenous amodiaquine and oral amodiaquine/erythromycin in the treatment of chloroquine-resistant falciparum malaria.

In eastern Thailand, 14 adults with moderately severe falciparum malaria were treated with intravenous amodiaquine dihydrochloride, loading dose 10 mg base/kg infused over 4 h followed by three further intravenous infusions of 5 mg base/kg at 24, 48, and 72 h. All patients were clinically cured--mean fever clearance time 37.8 h (range 24-60), mean parasite clearance time 64.9 h (18-164). There were no serious toxic effects. 33 patients aged over 5 years with uncomplicated falciparum malaria were given oral amodiaquine dihydrochloride (mean total dose 41 mg base/kg over 3 days) combined with erythromycin estolate (mean dose 48 mg base/kg daily for 5 days). 2 patients failed to respond. In the other 31 patients mean fever clearance time was 55.9 h (range 10-104) and mean parasite clearance time was 65.4 h (40-120). In both studies, more than half the patients followed-up had recurrent parasitaemia but reinfection could not be excluded. Parasites isolated from 18 patients were highly resistant to chloroquine in vitro.

Administration, Oral↗
PubMed1985

Quinine and severe falciparum malaria in late pregnancy.

Quinine dihydrochloride was given intravenously to 12 women with severe falciparum malaria in the third trimester of pregnancy. The initial dose consisted of 10 or 20 mg salt/kg over 4 h and was followed by 10 mg salt/kg every 8 h until patients were fit to swallow, when quinine sulphate tablets were given. Uterine activity showed little or no change despite rising quinine concentrations. Of 3 patients in labour, 2 proceeded normally while a third had a successful caesarean section for fetal distress. Late (type II) decelerations of the fetal heart rate were recorded in 6 patients before treatment but in most patients signs of fetal distress diminished as the maternal temperature fell. Hypoglycaemia and hyperinsulinaemia developed in 7 patients, in 2 before quinine was started. The important toxic effect of quinine in late pregnancy is not an oxytocic action but rather its capacity to release insulin.

Adolescent↗
PubMed1985

Intravenous quinidine for the treatment of severe falciparum malaria. Clinical and pharmacokinetic studies.

Quinidine has proved more effective than quinine against chloroquine-resistant Plasmodium falciparum both in vitro and in patients with uncomplicated disease. To examine the effectiveness and pharmacokinetics of quinidine for this use, we treated 14 patients who had severe falciparum malaria with intravenous quinidine gluconate; a loading dose of 15 mg of the base per kilogram of body weight was followed by 7.5 mg per kilogram every eight hours. Two of the five patients with cerebral malaria died, but parasitemia was eliminated in the 12 survivors. Two patients had recurrent parasitemia on Days 25 and 28. Times required for parasite clearance and elimination of fever (49.4 +/- 17.8 and 69.5 +/- 18.7 hours, respectively) were comparable to those in earlier studies with a loading dose of quinine. Quinidine appears to have a larger volume of distribution than quinine. The elimination half-life was 12.8 hours, the volume of distribution was 1.68 liters per kilogram, total clearance was 1.75 ml per kilogram per minute, and urinary clearance was 0.62 ml per kilogram per minute. Electrocardiographic changes were common but there were no dysrhythmias. In two patients, blood pressure fell during the initial infusion of quinidine. Quinidine gluconate is more widely available than quinine in many countries, and our findings show that it is effective in severe falciparum malaria.

Adolescent↗
PubMed1985

Pathophysiological and prognostic significance of cerebrospinal-fluid lactate in cerebral malaria.

Cerebrospinal-fluid (CSF) lactate concentrations were elevated in all but 1 of 45 patients with cerebral malaria. They were significantly higher in patients who died (9.0 +/- 5.3 mmol/l, mean +/- SD) than in survivors (3.4 +/- 1.1 mmol/l, p = 0.0002) and had returned to normal values in each of 9 patients studied after recovery of consciousness. There was a significant negative correlation between CSF lactate and CSF glucose. All 11 patients with CSF lactate concentrations above 6 mmol/l died. CSF lactate is thus an important prognostic indicator in cerebral malaria and these findings suggest that hypoxia contributes to the pathogenesis of this disorder.

Adolescent↗
PubMed1985

A comparison of the in-vitro activity of some 5-nitroimidazoles and other compounds against Giardia intestinalis.

The activities of 11 5-nitroimidazole compounds have been compared against Giardia intestinalis in vitro using a 3H-thymidine incorporation assay. All the compounds were at least equipotent to, or more active than metronidazole with the exception of panidazole. Satranidazole, ronidazole and S75 0400 A were all about five times more active than metronidazole and warrant further study as potential chemotherapeutic agents for man. No major differences in the response to these compounds was found between two stocks of Giard. intestinalis with the exception of flunidazole. Several other antiprotozoal drugs showed activity against Giard. intestinalis. Berberine sulphate, paromomycin sulphate, erythromycin estolate and sulphasalazine, all of which have been used to treat human patients, showed no activity in vitro.

Giardia↗
PubMed1985

Pharmacokinetics of primaquine in man. II. Comparison of acute vs chronic dosage in Thai subjects.

We have investigated the pharmacokinetics of primaquine after acute and chronic administration of the drug to five healthy Thai volunteers. After acute dosage (15 mg p.o.) mean (+/- s.d.) peak plasma concentrations of 65.0 +/- 34.7 ng ml-1 were achieved within 2 +/- 1h. Thereafter plasma drug concentrations declined monoexponentially with a mean elimination half life of 4.4 +/- 1.4 h. The mean (+/- s.d.) oral clearance was 37.6 +/- 15.5 1 h-1. These values are in broad agreement with values obtained in healthy Caucasians after administration of an equivalent dose of primaquine. Repeated dosing with primaquine had no effect on the mean pharmacokinetic parameters calculated for this drug. In contrast, individual pharmacokinetic parameters for some subjects exhibited gross and unpredictable changes after chronic dosage. The carboxylic acid metabolite of primaquine accumulated in plasma after repeated dosing such that by day 14 of chronic dosing the mean AUC (0,24) for this metabolite was 74% greater than that obtained after acute administration of primaquine.

Humans↗