Isolation and characterization of an aetiological agent in Whipple's disease.

Abstract

use of sensitive assays of digoxin in body fluids." This knowledge has recently been reviewed in detail by Smith and Haber.'2 Digoxin in serum is only 230' protein bound and is excreted primarily in the urine in unchanged form or as small amounts of metabolites which are both cardioactive and immunoreactive. Urinary excretion is directly proportional to the glomerular filtration rate, and serum levels in the elimination phase decline exponentially with an average serum half time of 36 hours in patients with normal renal function. Daily maintenance treatment without a loading dose results in a steady-state plateau concentration after four or five half lives or about seven days in patients with normal renal function. 13 Impairment of renal function is associated with higher serum digoxin concentrations at any dose level.Clearly, therefore, consistent differences in glomerular filtration rate in patients with thyroid disease, of the order observed in our patients, would influence comparative serum digoxin concentrations. In a recent review of renal function in patients with thyroid disease'4 inulin clearance was found to be raised (145-5±5-6 ml/min in 36 hyperthyroid patients reported by seven groups of workers), and in 17 hypothyroid patients G.F.R. fell to 71±+43 ml/min and then rose towards normal in six out of seven patients who received replacement therapy. In view of the close correlation between digoxin and creatinine clearance the finding of a short digoxin half time and lower serum concentrations of digoxin in the hyperthyroid patients was not unexpected. A similar interpretation is implicit in Doherty's data; mean digoxin clearance was 158 ml/min and 83 ml/min in hyperthyroid and hypothyroid subjects respectively. 5 Undoubtedly a difference in tissue distribution space for digoxin exists in patients with changed thyroid status, but this difference is not relevant to the serum concentrations after achievement of a steady-state plateau in clinical therapeutics.Serum digoxin concentrations in hyperthyroid subjects could also be low secondary to decreased absorption or increased metabolism or faecal excretion of the drug, factors which might explain our discrepant findings. The demonstration of a relative increase in cumulative urinary digoxin excretion in two hyperthyroid patients despite low serum concentrations argues against an important role for these alternative routes of metabolism or excretion.A rapid ventricular response to atrial fibrillation refractory to digitalis treatment is common in hyperthyroidism. Chamberlain's finding of a correlation between slowing of the ventricular rate in patients with atrial fibrillation and serum digoxin levels' 5 suggested that this apparent refractoriness may be partly due to the lower serum concentration in the hyperthyroid patient. Many clinical studies have established the correlation between serum digoxin levels and therapeutic or toxic effects of the drug, and our findings indicate that ideal digitalization of patients with altered thyroid function requires me...

Etiopathogenetic Studies in a Patient with Whipple’s Disease

“…Indeed his main immunological abnormality was a cutaneous anergy for various antigens which regressed spontaneously after antibiotic treatment. Similar observations were made also by Clancy et al (6) and many others. We therefore feel that abnormalities of the immune system, when present, are to be considered second ary in nature.…”

“…By Clancy et al (6) a Streptococcus dysgalactiae was isolated from a monolayer cell culture of a lymph node.…”

Clinoco-Pathological Correlation in Treated Whipple’s Disease

“…may be effective in therapy, further supporting the concept of sequential degradation in an o rganism which may be normally resident in the gut lumen. Clancy et al (1975) have recently reported growth of a cell wall deficient form of an a-haemolytic streptococcus from a prolonged mono layer cell culture of a lymph node taken from a patient with Whipple's disease. On biochemical criteria the organism was identified as Streptococcus dysgalacliae.…”

“…The duration of antibiotic therapy needed to establish a permanent cure, if indeed ihis is possible, has yet to be established (Trier et al 1965, Oliva et a1 1972. The suggestion, by Clancy et al (1975), that complete return to normal of T-Iymphocyte numbers and function occurs following antibiotic therapy raises the question of the possibility of use of transfer factor in these patients.…”

Chronic interstitial nephritis in Whipple's disease

“…The cause of the granulomatous inflammation of liver, kidney, and skeleton muscle, as well as the diffuse interstitial inflammation of the kidneys, may be the result of a disturbance of immune reaction (T cell defect) [23 26]. The immunologic disturbance may be the consequence of an infection with atypical -cell-wall deficientbacteria, in reverse [27][28][29].…”