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Biomedical subjects

M A James

Publications and source records attributed to M A James.

At least 55 records · Page 3Linked to original sources
PubMed1996

Assessment of baroreceptor-cardiac reflex sensitivity using time domain analysis in patients with IDDM and the relation to left ventricular mass index.

Autonomic dysfunction in insulin-dependent diabetic (IDDM) patients has been associated with abnormalities of left ventricular function and an increased risk of sudden death. A group of 30 patients with IDDM and 30 age, sex and blood pressure matched control subjects underwent traditional tests of autonomic function. In addition, baroreceptor-cardiac reflex sensitivity (BRS) was assessed using time domain (sequence) analysis of systolic blood pressure and pulse interval data recorded non-invasively using the Finapres beat-to-beat blood pressure recording system. 'Up BRS' sequences-increases in systolic blood pressure associated with lengthening of R-R interval, and 'down BRS' sequences-decreases in systolic blood pressure associated with shortening of R-R interval were identified and BRS calculated from the regression of systolic blood pressure on R-R interval for all sequences. We also assessed heart rate variability using power spectral analysis and, after expressing components of the spectrum in normalised units, assessed sympathovagal balance from the ratio of low to high frequency powers. IDDM subjects underwent 2-D echocardiography to assess left ventricular mass index. Standard tests of autonomic function revealed no differences between IDDM patients and control subjects, but dramatic reductions in baroreceptor-cardiac reflex sensitivity were detected in IDDM patients. 'Up BRS' when supine was 11.2 +/- 1.5 ms/mmHg (mean +/- SEM) compared with 20.4 +/- 1.95 in control subjects (p < 0.003) and when standing was 4.1 +/- 1.9 vs 7.6 +/- 2.7 ms/mmHg (p < 0.001). Down BRS when supine was 11.5 +/- 1.2 vs 22 +/- 2.6 (p < 0.001) and standing was 4.4 +/- 1.9 vs 7.3 +/- 2.5 ms/mmHg (p < 0.003). There were significant relations between impairment of the baroreflex and duration of diabetes (p < 0.001) and poor glycaemic control (p < 0.001). From a fast Fourier transformation of supine heart rate data and using a band width of 0.05-0.15 Hz as low-frequency and 0.2-0.35 Hz as high frequency total spectral power of R-R interval variability was significantly reduced in the IDDM group for both low-frequency (473 +/- 62.8 vs 746.6 +/- 77.6 ms2 p = 0.002) and high frequency bands 125.2 +/- 12.9 vs 459.3 +/- 89.8 ms2 p < 0.0001. When the absolute powers were expressed in normalised units the ratio of low frequency to high frequency power (a measure of sympathovagal balance) was significantly increased in the IDDM group (2.9 +/- 0.53 vs 4.6 +/- 0.55, p < 0.002 supine: 3.8 +/- 0.49 vs 6.6 +/- 0.55, p < 0.001 standing). Thus, time domain analysis of baroreceptor-cardiac reflex sensitivity detects autonomic dysfunction more frequently in IDDM patients than conventional tests. Impaired BRS is associated with an increased left ventricular mass index and this abnormality may have a role in the increased incidence of sudden death seen in young IDDM patients.

Adult↗
PubMed1996

Characteristics of patients with hypoplastic thumbs.

The records of 98 patients with 160 hypoplastic thumbs seen between 1923 and 1993 were reviewed to determine the salient characteristics of this population. Physical findings, photographs, and x-ray films were studied. Sixty-three percent of patients were male, and 63% had bilateral thumb hypoplasia, 59% had radial dysplasia, and 86% had other anomalies. An associated syndrome, most commonly the vertebral, anal, tracheosophageal, renal, and radial limb anomalies association or Holt-Oram syndrome, was present in 44%. Patients with spine, genitourinary, or gastrointestinal anomalies were most likely to have the vertebral, anal, tracheosophageal, renal, and radial limb anomalies association, those with cardiac anomalies were most likely to have Holt-Oram syndrome, and those with lower extremity anomalies were most likely to have a different syndrome. One hundred thirty-nine thumbs were classifiable, using a modification of Blauth's classification; 19% were types 1 and 2, 23% were type 3, and 58% were types 4 and 5. One hundred seven operations were performed on 63 upper limbs, including 24 thumb reconstructions and 35 pollicizations. These patients must be carefully examined for bilaterality, other anomalies, and syndromes. Classification using a modification of Blauth's criteria is useful and helps the surgeon determine a treatment plan.

Abnormalities, Multiple↗
PubMed1996

Abnormal baroreceptor-cardiac reflex sensitivity is not detected by conventional tests of autonomic function in patients with insulin-dependent diabetes mellitus.

1. Autonomic neuropathy is a common complication of diabetes mellitus and is a major risk factor for sudden death. 2. A group of 30 patients with insulin-dependent diabetes mellitus and 30 age-, sex- and blood pressure-matched control subjects underwent traditional tests of autonomic function. Resting supine R-R interval and systolic blood pressure variability were assessed using spectral analysis methods. In addition, we assessed the baroreceptor-cardiac reflex from the linear relation of the change in R-R interval to the increasing systolic blood pressure measured non-invasively with the Finapres monitor during phase 4 of the Valsalva manoeuvre and from resting heart rate and systolic blood pressure power spectra. 3. Whereas standard tests of autonomic function revealed no differences between patients with insulin-dependent diabetes mellitus and control subjects, there was a significant reduction in power spectral density of heart rate variability around the high-frequency region (125.2 +/- 112.9 versus 459.3 +/- 189.8 ms2, mean +/- SD). Furthermore, reductions in baroreflex sensitivity calculated from the Valsalva manoeuvre were detected in diabetics compared with controls (3.3 +/- 1.6 versus 9.5 +/- 2.5 ms/mmHg, mean +/- SD, P < 0.00001). There were significant relations between impairment of the baroreflex and duration of diabetes (P < 0.001) and poor diabetic control (P < 0.05). 4. In summary, autonomic dysfunction occurs much more frequently in diabetic patients than conventional tests would suggest. Abnormal baroreceptor-cardiac reflex sensitivity in patients with insulin-dependent diabetes mellitus may in part be explained by abnormal parasympathetic function. This unrecognized abnormality may have a role in the increased incidence of sudden death seen in young diabetic subjects.

Adult↗
PubMed1996

Arterial baroreceptor-cardiac reflex sensitivity in the elderly.

Uncertainty still remains regarding the differing effects of blood pressure and age on baroreceptor-cardiac reflex sensitivity in elderly individuals; these differences are at least partly due to the differing methods and subject groups used in previous studies. We sought to resolve these issues by examining baroreflex sensitivity in 54 subjects aged 70 +/- 1 years (mean +/- SE; range, 60 to 81) divided into groups with combined systolic-diastolic hypertension (CH group, n = 16), isolated systolic hypertension (ISH group, n = 16), or normotension (NT group, n = 22). Baroreflex sensitivity was quantified from the pulse interval and blood pressure responses to the Valsalva maneuver and pressor (phenylephrine) and depressor (sodium nitroprusside) stimuli. Baroreflex sensitivity was significantly reduced in the two hypertensive groups but did not differ between them (Valsalva maneuver: CH group, 1.9 +/- 0.3 ms/mm Hg; ISH group, 2.8 +/- 0.5; NT group, 4.4 +/- 0.4; phenylephrine: CH group, 3.1 +/- 0.6; ISH group, 3.5 +/- 0.7; NT group, 7.7 +/- 1.0; sodium nitroprusside CH group, 2.1 +/- 0.3; ISH group, 3.6 +/- 0.8; NT group, 5.4 +/- 0.3; all P < .05 for comparison with the NT group). Thus, this study demonstrated reductions in baroreflex sensitivity with hypertension in elderly subjects consistent across all methods but with no difference between subjects with combined hypertension and isolated systolic hypertension matched for similar systolic pressure. Baroreflex sensitivity was related only to the level of systolic pressure independent of diastolic pressure or age. If elderly subjects with isolated systolic hypertension have a greater reduction in large-artery compliance than combined hypertensive subjects with similar systolic pressure, this does not appear to lead to further reductions in baroreflex sensitivity in these individuals.

Aged↗
PubMed1996

Comparison of diurnal systolic blood pressure change as defined by wrist actigraphy, fixed time periods and cusum.

AIMS: To assess whether differences exist in nocturnal blood pressure (BP) levels and the diurnal BP change when using fixed time and wrist actigraphy methods to define the night-time period. METHODS: Untreated hypertensive (n = 48) and normotensive (n = 33) subjects (mean age 67 years: range 29-90) underwent simultaneous 24-h ambulatory BP monitoring and wrist actigraph monitoring. The diurnal BP change and nocturnal BP levels were assessed using two fixed night-time definitions-a reference period of 22.00-06.59 and also 00.00-05.59, as well as unedited and edited actigraph values and cumulative sums (cusums) analysis. RESULTS: The reference definition of night-time 22.00-06.59 resulted in the highest values for night-time BP compared to other definitions (p < 0.05), although actigraph defined night-time BP values were not significantly different from the more restrictive definition of night-time (00.00-05.59). Restrictive night-time, edited and unedited actigraph and cusums values for the day-night difference were all significantly greater than the value calculated using the reference night-time period. Dipping status changed significantly depending on which definition of night-time was used. CONCLUSIONS: Significant differences exist in nocturnal BP levels and circadian change between the various methods for defining night-time. The routine use of wrist actigraphy does not however appear to alter the value of night-time BP levels when compared to a more restrictive fixed-time definition of night-time.

Adult↗
PubMed1995

Is ventricular wall stress rather than left ventricular hypertrophy an important contributory factor to sudden cardiac death?

Sudden cardiac death comprises a significant proportion of cardiac mortality in Western society. Left ventricular hypertrophy has been identified by many authors as a possible risk factor for sudden cardiac death, however, left ventricular hypertrophy develops in response to external stimuli on the heart as a means of normalizing wall stress. It is possible that the fundamental abnormalities in wall stress, rather than the left ventricular hypertrophy itself, pose the increased risk of sudden death. Left ventricular hypertrophy, the consequence of raised wall stress, is easy to measure and easy to study and it is understandable why this parameter should have received more attention. Wall stress by contrast is difficult to measure, and worse, is variable throughout the ventricle so that it cannot be measured in a single quantifiable figure. As a consequence, only a limited amount of attention has been paid to wall stress as a possible trigger mechanism for cardiac arrhythmia. However, there is evidence from both basic and clinical research to suggest that raised wall stress may be a risk factor for sudden cardiac death and cardiac arrhythmia. This review discusses the evidence for and against left ventricular hypertrophy and wall stress as risk factors for sudden cardiac death, and also presents recent evidence that left ventricular hypertrophy in isolation can protect the heart against the arrhythmogenic effects of raised wall stress.

Death, Sudden, Cardiac↗
PubMed1995

Screening tests for microalbuminuria in non-diabetic elderly subjects and their relation to blood pressure.

1. Microalbuminuria in non-diabetic elderly subjects is predictive of vascular disease and mortality, and related to levels of blood pressure. 2. This study was designed to examine whether more restricted periods of urine collection retained the relation to the prevailing level of blood pressure and successfully identified subjects with microalbuminuria. 3. Fifty elderly subjects (aged over 60 years) made two consecutive 24-h urine collections for measurement of urinary albumin excretion, divided between daytime and night-time periods. Thirty-three subjects also provided a random 'spot' urine sample. Clinic and 24-h ambulatory blood pressure were also recorded. 4. Median 24-h urinary albumin excretion was 15.75 mg; 17 subjects had microalbuminuria. The median 24-h albumin-creatinine ratio was 1.91 mg/mmol. A threshold albumin-creatinine ratio of > or = 3.0 mg/mmol in a random urine sample predicted microalbuminuria with 92% sensitivity and 90% specificity. Alternatively, threshold values of 2.5 mg/mmol for men and 4.5 mg/mmol for women in an overnight urine collection predicted microalbuminuria with 88% sensitivity and 100% specificity. 5. The closest relation between albumin-creatinine ratio and blood pressure was that between spot albumin-creatinine ratio and clinic systolic blood pressure (r = 0.64, P < 0.001). Albumin-creatinine ratio was generally related to clinic systolic blood pressure, diastolic blood pressure and ambulatory systolic blood pressure. Microalbuminuric subjects had significantly higher levels of clinic and ambulatory systolic blood pressure than non-microalbuminuric subjects. 6. Microalbuminuria in the elderly is most related to clinic systolic blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Reproducibility of the circadian systolic blood pressure variation in the elderly.

OBJECTIVES: To establish the reproducibility of the nocturnal systolic blood pressure (SBP) change in elderly subjects and to examine the use of cumulative sums (cusums) analysis in the assessment of circadian SBP variation. SUBJECTS: Forty-two untreated elderly subjects (35 hypertensive, 7 normotensive) of mean age 75.5 years from the hypertension clinic at a large teaching hospital participated in a reproducibility study. METHODS: Twenty-four-hour ambulatory blood pressure monitoring was performed and repeated at a median interval of 2 months (range 2 weeks to 9 months). OUTCOME MEASURES: Reproducibility of circadian SBP variation from fixed time analysis of day-night SBP difference and from cusums-based parameters. RESULTS: Twenty-four-hour SBP values were highly reproducible with a coefficient of variation of 5.8%. However, the day-night SBP difference for fixed time periods was poorly reproducible, with a coefficient of variation > 130%. A substantial proportion of subjects (36-43%) altered their 'dipping status' between visits. The use of cusums analysis improved the reproducibility of measures of circadian SBP change (cusums plot height and maximum circadian variation) with coefficients of variation falling to 40 and 38%, respectively. CONCLUSIONS: The use of fixed time definitions results in poor reproducibility of the circadian SBP change in the elderly, which will lead to regression dilution bias when studying the relationship of circadian SBP variation to outcome measures in hypertension. The notion of dipping and non-dipping circadian blood pressure patterns should be abandoned in favour of more reproducible cusums-based measures of circadian blood pressure variation.

Aged↗
PubMed1995

Pulse pressure and resistance artery structure in the elderly.

There has been recent interest in the possibility that resistance vessel structural adaptation in hypertension may be more closely related to pulse pressure than to other blood pressure parameters. We investigated the relation between blood pressure and resistance vessel structure in a group of subjects from an age group (older than 60 years) in which a widening of pulse pressure is a typical finding and characterized blood pressure parameters using 24-hour ambulatory blood pressure monitoring. We studied resistance vessels retrieved from biopsies of skin and subcutaneous fat taken from the gluteal region of 32 subjects under local anesthesia (age, 70 +/- 1 years [mean +/- SEM], 21 of whom were hypertensive and 11 normotensive. Media-lumen ratio was higher in the hypertensive than the normotensive subjects (18.6 +/- 1.6% versus 12.8 +/- 1.2%, P < .01) and correlated with age (r = .44, P < .05), clinic systolic pressure (r = .35, P < .05), 24-hour systolic pressure (r = .40, P < .05), and 24-hour pulse pressure (r = .56, P < .001). Stepwise multivariate regression analysis identified clinic and 24-hour pulse pressure as the only significant predictors of media-lumen ratio independent of age, other parameters of clinic blood pressure, and blood pressure variability (R2 = 41%, P < .05). These findings confirm those from animal models of hypertension in demonstrating the importance of pulse pressure in relation to cardiovascular structural adaptation and have important implications for the goals of treatment of hypertension in the elderly.

Aged↗
PubMed1995

Relationship of antibodies to soluble Plasmodium falciparum antigen (Pf70) and protection against malaria in a human population living under intense transmission in Kinshasa, Zaire.

The rapid acquisition of resistance by Plasmodium falciparum to antimalarial drugs has focused worldwide efforts on vaccine development. The definition of critical antigens involved in the induction of protective immunity against disease is essential. Our previous studies have characterized a synthetic peptide complex (SPf70), derived from a 70 kDa P. falciparum exoantigen, in terms of its immunogenicity and antigenic reactivity. In the present study total anti-P. falciparum asexual blood-stage antibodies and antibodies to the Pf70 antigen were measured by immunofluorescence (IFA) and ELISA, respectively, in children and adults (n = 160) of Kinshasa, Zaire, an area with continuous and intense malaria transmission. All of the subjects tested had IFA antibodies and 90% (143/160) had antibodies to Pf70 antigen. Antibody levels against Pf70 were significantly higher among children with low parasitemias (p < 0.05). These results suggest that antibodies to Pf70 antigen may have a protective role against P. falciparum infection. Further studies are needed to define the functional nature of the protective mechanism(s).

Adolescent↗
PubMed1994

Beta-adrenoceptor blockers in atrial fibrillation: the importance of partial agonist activity.

1. The ideal drug treatment for atrial fibrillation will control resting heart rate, blunt exercise induced tachycardia whilst not exacerbating nocturnal bradycardia. Monotherapy with digoxin may not be ideal. We have compared the effect of combining digoxin (0.25 mg daily) with atenolol 50 mg and 100 mg or pindolol 5 mg twice daily and 15 mg twice daily in a cross-over randomised single-blind trial in eight symptomatic patients (six male; mean age 62 years) with poorly controlled atrial fibrillation. 2. Heart rate control was measured by 24 h ECG at baseline on digoxin therapy and after 2 weeks with each treatment. Symptom scores for breathlessness and palpitation were measured using visual analogue scales. 3. The addition of both beta-adrenoceptor blockers significantly reduced mean diurnal maximum heart rate from baseline (all P < 0.001 ANOVA). Atenolol at both doses caused a greater reduction than either dose of pindolol (P < 0.001 ANOVA). Nocturnal maximum heart rate was not significantly reduced from baseline by either beta-adrenoceptor blocker, but both doses of pindolol caused increases in nocturnal maximum heart rate compared with atenolol (P < 0.001 ANOVA). 4. Atenolol caused a reduction in diurnal minimum heart rate compared with baseline and caused a reduction in nocturnal minimum heart rate whereas pindolol caused an increase (P < 0.001 ANOVA). 5. Atenolol 100 mg caused longer nocturnal pauses compared with baseline but pindolol 15 mg twice daily reduced the number of nocturnal pauses > 1.5 s (P = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1994

Microalbuminuria in elderly hypertensives: reproducibility and relation to clinic and ambulatory blood pressure.

OBJECTIVE: To examine the short-term reproducibility of urinary albumin measurements and the relation of urinary albumin excretion to the clinic and ambulatory blood pressure levels in elderly untreated hypertensive subjects. SETTING: Outpatient hypertension clinic of a District General Hospital. MAIN OUTCOME MEASURES: The within-patient reproducibility of 24-h urinary microalbumin and electrolyte excretion and relation to 24-h and clinic blood pressure levels. PATIENTS: Sixty-four untreated elderly hypertensives (mean age 74.7 years, range 64-82) with systolic blood pressure > or = 160 mmHg or diastolic blood pressure > or = 95 mmHg, or both, were recruited from general practitioner clinics and current outpatient attenders. The patients had not received antihypertensive treatment for at least 4 weeks. METHODS: The clinic and 24-h non-invasive ambulatory blood pressures were recorded with a simultaneous 24-h urine collection for measurement of the urinary albumin and electrolyte excretion. Thirty-seven subjects performed two consecutive 24-h urine collections for an assessment of the short-term reproducibility of the albumin and electrolyte excretion. RESULTS: The coefficient of variation of 24-h urinary albumin excretion was 62%, and for the albumin:creatinine ratio 52%, compared with 19% for sodium and 15% for potassium excretion. The urinary albumin excretion correlated with clinic systolic blood pressure (r = 0.33, P = 0.01) and with 24-h ambulatory systolic (r = 0.48, P < 0.001) and diastolic (r = 0.32, P = 0.01) blood pressure. The subjects with microalbuminuria (24-h urinary albumin excretion in the range 30-300 mg) had higher clinic and ambulatory blood pressures than those with lower levels of albumin excretion. CONCLUSIONS: The low day-to-day intrasubject reproducibility in the 24-h urinary albumin excretion considerably reduces the potential value of single collections in the assessment of microalbuminuria in elderly hypertensives. The urinary albumin excretion correlates with the clinic and 24-h ambulatory blood pressures in elderly hypertensives.

Aged↗
PubMed1994

Clinical correlates of left ventricular mass in elderly hypertensives.

We set out to examine the prevalence of echocardiographically-determined left ventricular hypertrophy (LVH) in a hospital-based population of untreated elderly hypertensives and to study the relationship between left ventricular mass index and clinic and 24h ambulatory BP, urinary electrolyte and microalbumin excretion and ECG changes. We studied 52 untreated elderly hypertensives, mean age 76 years, with no evidence of stroke or heart disease. Subjects underwent 24h ambulatory BP recording together with 24h urine collection for electrolytes and microalbumin estimation. A standard ECG was examined for LVH by commonly used criteria. Subjects were examined by 2-dimensional guided M-mode echocardiography; left ventricular mass was calculated from the formula of Devereux and Riechek and corrected for body surface area (left ventricular mass index, LVMI). Mean LVMI was 168 +/- 39 g/m2 for men and 153 +/- 36 g/m2 for women; 43 (83%) subjects had LVH. LVMI was significantly related to clinic SBP (r = 0.27, P = 0.05), ambulatory daytime SBP (r = 0.27, P = 0.05), nighttime SBP (r = 0.41, P = 0.003) and nighttime DBP (r = 0.29, P = 0.04). LVMI was also related to the difference in mean SBP between day and night (r = -0.32, P = 0.02) and subjects with a day-night SBP difference of > or = 10 mmHg (n = 27) had significantly lower LVMI than those with a day-night SBP difference < 10 mmHg (141 +/- 32 g/m2 vs. 176 +/- 35 g/m2, respectively; P = 0.0005). Fifteen subjects had LVH by ECG criteria giving a sensitivity of 28% and specificity of 66%. LVMI was not related to urinary sodium, potassium or albumin excretion. This study shows that in elderly hypertensives it is measures of nighttime BP which are most closely related to LVMI and subjects with a greater nocturnal fall in BP have lower LVMI, presumably reflecting differences in 24h BP load.

Aged↗
PubMed1993

Immunogenicity and antigenic reactivity of a carrier-free synthetic peptide complex derived from a 70-kDa Plasmodium falciparum exoantigen.

A 70-kDa Plasmodium falciparum exoantigen was purified from supernatant fluids of continuous in vitro P. falciparum cultures using sequential cation-exchange and high performance liquid chromatographic procedures. The purified protein was then digested with chymotrypsin and amino-acid sequences were determined for the resulting fragments. Four peptides (termed C2, C3, C5, and C10) were subsequently selected for synthesis based on their predictability for antigenic sites. The peptides were effectively used as a synthetic immunogen (SPf70) when they had been copolymerized with glutaraldehyde in the absence of a carrier. When given with Freund's adjuvant, the synthetic peptide complex was found to be highly immunogenic in rabbits. Serologic reactivity to the peptide complex and peptides C2 and C5 was uniformly high, followed by the responses to peptides C3 and C10. Peptide antigenicity was also assessed with human anti-P. falciparum sera from malaria-endemic regions of Uganda and Venezuela. Enzyme-linked immunosorbent assay (ELISA) data showed that anti-P. falciparum antibodies were specific for and reactive to the peptides. The specificity of the rabbit anti-SPf70 antibodies for P. falciparum antigen was shown by immunoprecipitation of metabolically labeled proteins and by immunoblotting. Herein we describe the peptide sequences of a 70-kDa P. falciparum exoantigen (Pf70) that, when synthesized and constructed as a copolymer (SPf70), are capable of inducing the formation of antibodies that are reactive with the native malarial protein. The high immunogenicity and antigenic reactivity of SPf70 indicate the potential use of this synthetic peptide polymer as an immunogen and a diagnostic reagent.

Amino Acid Sequence↗
PubMed1993

Detection of antibodies to a 70 kDa Plasmodium falciparum exoantigen in malarious subjects using synthetic peptides.

Indirect fluorescent antibody (IFA) tests and enzyme-linked immunosorbent assays (ELISA) were used to measure antibodies to Plasmodium falciparum in patients with acute malaria from Bolivar State, Venezuela. Antibody titers increased significantly with repeated malarial episodes. IgG antibody responses to 4 synthetic peptides (termed C2, C3, C5, C10) derived from a 70 kDa P. falciparum (Indochina I/CDC strain) exoantigen were evaluated by a peptide-ELISA with overall positivity rates of 20%, 40%, 20% and 58%, respectively. Seropositivity to peptide C10 was consistently over 50% (range 53-75%) among patients of different ages. Overall IgM reactivity to the respective peptides was 53%, 30%, 83% and 70%. IgM reactivity was generally greater in patients with primary malarial infections. The ELISA is a useful adjunct to the IFA in measuring naturally-occurring antibodies to specific parasite proteins.

Acute Disease↗