Fatigue in sarcoidosis: American versus Dutch patients.

BACKGROUND: Fatigue is a major problem in sarcoidosis. Fatigue has mainly been examined in patients from The Netherlands. OBJECTIVE: The aims of the study were to establish the prevalence of fatigue in US and Dutch patients and to determine whether fatigue was related to the common demographic and clinical parameters. DESIGN: Two patients groups were studied: Dutch outpatients at Maastricht University Medical Center in The Netherlands (n = 121) and US patients at the University of Cincinnati Medical Center in the USA (n = 126). Both groups completed the Fatigue Assessment Scale. Clinical data were gathered from the patients' medical files. RESULTS: The prevalence of fatigue was similar in the US and Dutch patients, but more severe in the latter group. Fatigue was unrelated to demographic and clinical parameters in the total group. However, when examining the US and Dutch patients separately, fatigue was associated with age, extrapulmonary involvement and drug use in the US group. CONCLUSIONS: Dutch patients report more severe fatigue compared with US patients. Interestingly, fatigue was related to clinical and demographical parameters in the US patients, although no such relationships was found in the Dutch patients.

Allergen challenge primes for IL-5 mRNA production and abrogates beta-adrenergic function in peripheral blood T lymphocytes from asthmatics.

BACKGROUND: In previous studies, we have found a dysfunctional adenylyl cyclase (AC) system in patients with asthma after allergen provocation, which resulted in a 40-50% decreased generation of intracellular cAMP. In addition, in activated T helper lymphocyte clones, it has been demonstrated that IFN-gamma (TH1-like cytokine) and IL-5 (TH2-like cytokine) are differentially regulated by the AC system. Therefore, we postulate that an increased IL-5/IFN-gamma ratio as observed in asthmatics might be due to a dysfunctional AC system. OBJECTIVE: To assess whether a dysfunctional AC system as observed in asthmatics after allergen provocation, is responsible for an increased IL-5/IFN-gamma cytokine ratio. METHODS: Peripheral blood T lymphocytes of seven asthma patients were stimulated with anti-CD3 plus anti-CD28 MoAbs in the absence and presence of isoproterenol (ISO) and prostaglandin E2 (PGE2) to activate the AC system. Before, 3 h and 24 h after allergen provocation, IFN-gamma and IL-5 mRNAs were detected by semiquantitative RT-PCR. RESULTS: Before allergen provocation, ISO (10-5 mol/L) significantly downregulated IFN-gamma mRNA (P < 0.03, n = 6), and showed a trend to upregulate IL-5 mRNA (P = 0.138, n = 5). Three and 24 h after allergen provocation, ISO was not longer able to modulate IFN-gamma and IL-5. In contrast with the observations with ISO, PGE2 still dose-dependently inhibited IFN-gamma mRNA, both before, 3 h and 24 h after allergen provocation (n = 7). IL-5 mRNA, but not IFN-gamma mRNA, was significantly upregulated in anti-CD3 plus anti-CD28-activated T cells (P < 0.05, n = 5) 24 h after allergen provocation, compared with before allergen provocation. CONCLUSION: Twenty-four hours after allergen provocation, a significant reduction of beta-adrenergic control on IFN-gamma and IL-5 mRNA expression was observed in peripheral blood T lymphocytes, which coincides with a selective priming of IL-5 mRNA production.

Changes in renal function induced by ACE-inhibition in the conscious two-kidney, one-clip Goldblatt hypertensive dog.

In order to study why the diagnostic sensitivity of 123I-hippurate renography for a renal artery stenosis is improved by angiotensin converting enzyme (ACE-) inhibition we used the model of the conscious chronically instrumented two-kidney, one-clip Goldblatt hypertensive dog. Urine flow (UV), renal blood flow (RBF), glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured (with constant infusion of 125I-iothalamate and 131I-hippurate, respectively) for both kidneys separately before and after a bolus injection of a mild unilateral renal artery stenosis (approximately 30% reduction of RBF). During ACE-inhibition, there were remarkable falls in poststenotic GFR (from 37 +/- 5 to 4 +/- 2 ml/min, p less than 0.05), ERPF (from 111 +/- 13 to 21 +/- 10 ml/min, p less than 0.05) and UV (from 0.86 +/- 0.15 to 0.075 +/- 0.045 ml/min, p less than 0.05), whereas RBF of the poststenotic kidney slightly increased (from 193 +/- 18 to 237 +/- 27 ml/min, p less than 0.05). The concentration of hippurate and thalamate in the blood remained remarkably constant while the excretion of the tracers by the poststenotic kidney diminished and renal retention of 123I-hippurate was seen on the renogram. In 2 dogs, the experiments were repeated during mannitol infusion. In that situation, there was a much smaller decrease of poststenotic UV and GFR whereas ERPF even showed a small increase comparable to the RBF changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Disseminated actinomycosis due to Actinomyces meyeri and Actinobacillus actinomycetemcomitans.

A 44-year-old man presented with pulmonary lesions and neurological symptoms suggestive of lung carcinoma with cerebral metastases. He had non-specific chest X-ray findings since 6 years and he also suffered from relapsing purulent skin lesions which resolved spontaneously or by short courses of antibiotic treatment. When corticosteroids were given, multiple subcutaneous swellings developed that spontaneously ruptured. The pus contained Actinomyces meyeri and Actinobacillus actinomycetemcomitans. On operation, the intracerebral lesions appeared to be abscesses and the same bacteria were cultured as from the skin lesions. Bronchoscopical examination did not reveal a diagnosis. Amoxicillin was given for 12 months and the patient recovered.

The mechanism and diagnostic value of angiotensin I converting enzyme inhibition renography.

The effect of angiotensin converting enzyme (ACE) inhibition on the sensitivity of radionuclide renography in the diagnosis of a unilateral renal artery stenosis was tested both in a conscious dog model and in the human situation. ACE inhibition (10 mg enalaprilic acid, intravenously) markedly improved the sensitivity of [123I]hippuran renography in 10 renovascular hypertensive dogs with a mild to moderate unilateral renal artery stenosis from 50 to 100%. This improved sensitivity was due to an ACE-inhibition-induced delayed tracer handling at the stenotic side without an appreciable change in the renographic curve at the contralateral side. A similar phenomenon was observed in 15 hypertensive patients with an angiographically proved unilateral renal artery stenosis. Both [123I]hippuran and 99mTc-diethylenetriaminepentaacetic acid (DTPA) handling was delayed on the stenotic side after oral enalapril treatment. However, only a moderate increase in sensitivity was observed comparing control renograms to ACE-inhibition renograms: from 87 to 93% for hippuran, and from 60 to 86% for DTPA. Eight of these 15 patients underwent either surgery or angioplasty resulting in a successful correction of the stenosis. Hypertension was more or less cured in five patients. Each of these patients had shown an ACE-inhibition-induced change in the renogram at the stenotic side, suggesting that such a response may predict the curability of the hypertension. However, of the three patients that showed no blood pressure change upon successful revascularization, two showed a positive ACE-inhibition renogram. In conclusion, in an ideal setting as obtained in animal experiments, ACE inhibition improves the sensitivity of renographic studies to 100%. However, its value in the clinical setting needs more standardization.

Angiotensin converting enzyme inhibition induces alterations to hippuran renography despite unchanged ipsilateral renal blood flow in conscious two-kidney, one clip Goldblatt hypertensive dogs.

We performed experiments in the two-kidney, one clip Goldblatt hypertensive dog to see whether angiotensin converting enzyme (ACE) inhibition could improve the sensitivity of hippurate renography in detecting renal artery stenosis. Ten dogs on a sodium-restricted diet were studied before and after induction of a renal artery stenosis. In the absence of renal artery stenosis nine dogs showed normal renograms before ACE inhibition, and one was false positive. During ACE inhibition all 10 renograms were normal. With a renal artery stenosis 50% of the renograms were false negative, whereas a 100% sensitivity was reached during ACE inhibition. The alterations induced by the ACE inhibition on the renograms were not related to changes in renal blood flow. In conclusion, ACE inhibition markedly improved the sensitivity of hippurate renography in the two-kidney, one clip dog.

Angiotensin converting enzyme inhibition improves diagnostic procedures for renovascular hypertension in dogs.

In renovascular hypertension adaptive mechanisms in the poststenotic kidney are a probable cause of the 20 to 25% false-negative findings during rapid sequence urography or [123I]o-iodohippurate renography. We blocked the renin-angiotensin system in an effort to increase the yield of these diagnostic procedures. Chronically instrumented, salt-depleted conscious dogs were used in which a light (n = 5), moderate (n = 4), or severe (n = 2) renal artery stenosis was induced. Before stenosis 10 of the dogs showed no left-right differences with either diagnostic procedure, and angiotensin converting enzyme (ACE) inhibition did not change this result. Two to 3 weeks after induction of a renal artery stenosis, all dogs showed signs of renovascular hypertension. However, only 50% of the renograms and 22% of the urograms showed differences between the two kidneys indicative of the presence of stenosis. After ACE inhibition, all previously negative test results became positive (abnormal) and previously existing left-right differences became more evidence. Electromagnetically measured renal blood flow on the stenotic side did not change during ACE inhibition (146 +/- 13 vs 145 +/- 21 ml/min), whereas contralateral blood flow showed a distinct increase (207 +/- 18 vs 282 +/- 20 ml/min, p less than 0.01). In conclusion, ACE inhibition markedly improves the sensitivity of rapid sequence urography and hippurate renography in the diagnosis of renovascular hypertension in the two-kidney, one clip Goldblatt hypertensive dog. The effects of ACE inhibition on the handling of the different tracers do not appear to be related to its effects on renal blood flow or systemic blood pressure.

A new constrictor device for external induction of a long-term stable and irreversible renal artery stenosis in the dog.

A new externally adjustable constrictor device for renal artery stenosis in the dog is described. The constrictor combines hydraulic and mechanical characteristics, and is connected to the exterior of the animal by a thin catheter. Applying hydraulic pressure via the catheter causes the plunger in the device to compress the renal artery to any desired degree of stenosis. A mechanical catch prevents backward movement of the plunger, thus ensuring a stable, irreversible renal artery constriction. This constrictor was implanted in 13 dogs, together with an electromagnetic blood flow sensor around a renal artery. In twelve dogs the constriction procedure was performed 3-12 weeks after implantation, and in all 12 cases the intended degree of stenosis [defined as percentage renal blood flow reduction (RBF)] was achieved within a range of 10%. In 5 dogs the long-term stability of the stenosis was studied and the RBF reduction appeared to be stable up to at least 6 weeks after constriction. In conclusion, the presented constrictor device is easily externally adjustable, and allows induction of a stable renal artery stenosis of various degrees in the conscious dog.

Pharmacological zero for electromagnetic renal blood flow measurement.

Measurement of blood flow in chronically instrumented laboratory animals using electromagnetic flow probes depends on a reference "zero flow" value. The latter is usually obtained by mechanical vessel occlusion. We tested an alternative method: a bolus of angiotensin II was injected in the abdominal aorta resulting in an immediate decrease of renal blood flow. Diastolic blood flow at this stage appeared to be identical to the zero level obtained by mechanical occlusion. Thus, pharmacological interruption of renal blood flow may serve as a zero reference in the dog.