Non-specific symptoms in adult patients referred to a Lyme centre.

OBJECTIVES: There is controversy whether non-specific symptoms can be related to previous Lyme borreliosis (LB). Positive serology can be considered a proxy for previous or persistent LB. We assessed non-specific symptoms and serology in patients suspected of LB referred to a Lyme centre. METHODS: Included were adult patients who visited a Lyme centre between 2008 and 2014. Before medical consultation, serum samples were taken and questionnaires on non-specific symptoms completed. The prevalence of non-specific symptoms was calculated for patients with positive and negative IgG serology. Logistic regression was used to obtain odds ratios (ORs) with 95% confidence interval (CI) for an association between positive serology and non-specific symptoms. RESULTS: Of 1439 included patients, 31.6% (455/1439) had positive serology. The most common non-specific symptoms were severe fatigue (61.4%, 883/1439), sleep disturbances (54.8%, 789/1439) and stiffness of neck/back (52.6%, 757/1439). The prevalence of severe fatigue was 53.0% (241/455) in patients with positive serology vs. 65.2% (642/984) in patients with negative serology (OR = 0.74; 95% CI, 0.58-0.94). The prevalence of sleep disturbances was respectively 46.2% (210/455) vs. 58.8% (579/984) (OR = 0.73; 95% CI, 0.58-0.93). The prevalence of stiffness of neck/back was respectively 47.7% (217/455) vs. 54.9% (540/984) (OR = 0.85; 95% CI, 0.67-1.06). CONCLUSIONS: In patients referred to a Lyme centre, non-specific symptoms did not occur more frequently in patients with positive serology compared to patients with negative serology. Hence, a questionnaire on non-specific symptoms cannot be used for identifying patients with possible post-LB symptoms in clinical practice.

Acute pyelonephritis: a cause of acute renal failure?

Two patients with acute renal failure due to acute pyelonephritis are described. Examination of the renal biopsy showed normal glomeruli, severe interstitial neutrophilic infiltration and edema with no signs of acute tubular necrosis. Until now, only twelve biopsy-proven proven cases have been reported. A review of the literature on acute renal failure due to acute pyelonephritis is presented.

Effect of intravenous saline, albumin, or hydroxyethylstarch on blood volume during combined ultrafiltration and hemodialysis.

It is generally advocated to use saline or albumin infusions during symptomatic hypotension during dialysis. However, because of their side effects and/or costs, they are of limited use. Hydroxyethylstarch (HES), a synthetic colloid with a long-standing volume effect, is used in the management of hypovolemia. In this study, the efficacy of three fluids (isotonic saline [0.9%], albumin [20%], and HES [10%]) was assessed during three treatment sessions with combined ultrafiltration and hemodialysis, which differed in the type of fluid given intravenously. Changes in relative blood volume (BV), systolic BP (SBP), and vascular reactivity (venous tone [VT]) were compared. An intravenous infusion of 100 ml of fluid was given when the decrease in BV versus baseline was more than 10% as measured by a continuous optical reflection method. The ultrafiltration was continued. BV decreased significantly versus baseline independent of the intravenous fluid administration in all three treatment sessions. However, when we compared BV values at the end of the dialysis session with those at the time of infusion, BV continued to decrease significantly with saline (change in BV -4.56 +/- 2.75%; P < 0.05) and albumin (change in BV -2.13 +/- 2.51%; P < 0.05), but not with HES (change in BV -0.15 +/- 2.17%; NS). Between albumin and HES there were no significant differences in changes in BV (NS), whereas between HES and saline (P < 0.05) and between albumin and saline (P < 0.05) the differences in BV changes were significant. SBP remained unchanged within each session. Although SBP tended to decrease more with saline compared to albumin and HES, the difference was not significant. The higher decrease in BV and SBP with saline was counterbalanced by a significantly higher increase in VT, while VT remained unchanged in the other two sessions. It is concluded that HES is a promising fluid in preserving blood volume, comparable to albumin, but superior to saline.

Increased urinary excretion of monocyte chemoattractant protein-1 during acute renal allograft rejection.

BACKGROUND: Acute rejection is characterized histologically by infiltration of the interstitium by mononuclear cells. Monocyte chemoattractant protein 1 (MCP-1) has recently been identified as a monocyte chemotactic factor. This study examined the possible role of MCP-1 in renal transplantation. METHODS: The concentration of MCP-1 in urine and serum of 19 renal transplant patients was investigated using an inhibition radioimmunoassay. The patients were divided into a non-rejection (NRj) and a rejection (Rj) group. Normal healthy volunteers were included as controls. Immunoperoxidase staining for MCP-1 and CD14, as a marker for macrophages, was performed in renal biopsies of transplant patients with rejection and six biopsies from histologically normal kidneys, as controls. The size of urinary MCP-1 was determined by gel filtration chromatography and in a number of fractions assessed for monocyte chemotactic activity using a modified Boyden chamber assay. RESULTS: Urinary excretion of MCP-1 in the Rj group ranged between 250 ng/mmol Cr and 3148 ng/mmol Cr with a median of 612 ng/mmol Cr. This is significantly higher than the results in the NRj group, ranging between 47 ng/mmol Cr and 288 ng/mmol Cr with a median of 229 ng/mmol Cr. In the normal control group, urinary MCP-1 levels ranged between 38 ng/mmol Cr and 74 ng/mmol Cr with a median of 50 ng/mmol Cr. The fractional excretion of MCP-1, calculated on the basis of MCP-1 and creatinine clearances, was found also to be significantly higher in the Rj group as compared to the NRj group. However, there was no significant difference in the serum levels of MCP-1 between the Rj, NRj, and normal control group. The intensity of MCP-1 staining in tubular epithelial cells and the degree of CD14+ cells in the interstitium was significantly higher in renal allograft biopsies than in the normal kidneys. In addition, MCP-1 isolated from urine of renal transplant patients with rejection was filtered with apparent molecular weight of 13 kDa and 11 kDa. Both sizes are chemotactically active for monocytes. CONCLUSIONS: These data suggest that urinary excretion of MCP-1 can be used as a marker for the episodes of acute rejection. The increase of urinary excretion of MCP-1 most likely is the result of local production by tubular epithelia cells. MCP-1 produced locally may, at least in part, be responsible for the influx of macrophages into the interstitium during rejection.

Intrarenal production of dopamine and natriuresis following DOPA and saline infusions in healthy human volunteers.

The interactions of intrarenal dopamine (DA) synthesis and natriuresis were studied in 11 healthy volunteers by giving a low and high sodium diet (LoSo, 50 mmol Na+; HiSo, 250 mmol Na+). On 2 days in both dietary phases an acute saline load was given, without or with an infusion of the DA precursor 3, 4-dihydroxyphenylalanine (DOPA) 0.15 microgram kg-1 min-1. Urinary excretion rates of sodium (UNa V), DOPA (UDOPA V), DA (UDA V) and noradrenaline (NA; UNA V), hormonal parameters, blood pressure (BP), glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured. On HiSo UDOPA V increased by 35% (P < 0.05) while UDA V remained unchanged. Only weak correlations were found between 24h UNa V and UDA V (r = 0.23) or UDOPA V (r = 0.39). On both diets and without the DOPA infusions, the saline infusions enhanced UNa V but did not increase UDA V. The DOPA infusions caused no significant change of UNa V, in spite of five- to eight-fold increases in UDA V. During LoSo the DOPA infusion only caused a slightly larger increase of UNa V after the saline infusion, when expressed as percentage change to the pre-saline UNa V (119 +/- 25% without DOPA infusion, 244 +/- 56%, P < 0.05 with DOPA infusion). On HiSo the DOPA infusion did not affect UNA V. The dietary sodium intake and the DOPA infusions did not influenced BP, GFR, or ERPF. In conclusion, dietary sodium intake or acute sodium loads did not clearly modulate UDA V.(ABSTRACT TRUNCATED AT 250 WORDS)

Borderline hypertensive autosomal dominant polycystic kidney disease patients have enhanced production of renal dopamine. Normalization of renal haemodynamics by DOPA infusion.

BACKGROUND: In autosomal dominant polycystic kidney disease (ADPKD) the pathophysiology of hypertension, which is frequently observed before loss of renal function, is not well understood. We investigated intrarenal dopamine, the renin-angiotensin-aldosterone system (RAAS), and plasma endothelin in relation to sodium homeostasis as potential hypertensive factors in this disease. METHODS: Eight borderline hypertensive ADPKD patients with (near) normal renal function and seven matched healthy control subjects were investigated at three levels of daily dietary sodium intake: 150, 50 and 450 mmol. In the 450-mmol sodium intake period we studied the effects of renally formed dopamine by infusing its precursor DOPA (DOPAi.v., 7 micrograms kg-1 min-1). In the 50-mmol sodium intake period we studied the influence of the RAAS by administering enalaprilate (42 micrograms kg-1), followed by angiotensin II (12 ng kg-1 min-1) intravenously. GFR and ERPF were measured by continuous infusion of inulin and PAH. RESULTS: At all levels of sodium intake sodium balances were equal, but daily urinary excretions of dopamine and DOPA were higher (P < 0.01) in the ADPKD patients than in the controls. Renal vascular resistance, filtration fraction and blood pressure were higher in the ADPKD patients (all P < 0.05) while plasma renin activity was similar. DOPAi.v. normalized renal haemodynamics and increased plasma endothelin in ADPKD patients (all P < 0.05), while stimulation of natriuresis was equal in both groups. Enalaprilate increased plasma endothelin in the ADPKD patients and only partially normalized renal haemodynamics. CONCLUSIONS: In borderline hypertensive ADPKD patients: (1) urinary dopamine excretion is increased at all levels of sodium intake, suggesting that this may be needed to maintain sodium balance; (2) stimulation of renal dopamine production is able to normalize renal haemodynamics, making dopamine receptor agonism a potential therapeutic option; (3) the activity of the RAAS is not clearly enhanced; (4) renal vasodilatation increases plasma endothelin levels.

Interactions between sodium balance, intrarenal dopamine synthesis, and sympathetic activity in HLA-identical kidney donors and recipients.

Intrarenal dopamine (DA) synthesis, sympathetic activity and sodium homeostasis were studied in eight HLA-identical kidney recipient and donor pairs at 50, 150, and 300 mmol sodium intake. Trimethaphan was given intravenously (i.v.), to mimic acute denervation, tyramine i.v. to induce noradrenaline (NE) release, and the DA precursor DOPA i.v. to study DOPA to DA conversion. Blood pressure was higher in the recipients (P < 0.05) and was not influenced by sodium intake. Cumulative sodium balances were not different between the groups. Sodium intake did not affect DA excretion in either group. The recipients had higher DA (P < 0.05) and DOPA (P < 0.01) excretions and lower urinary DA over DOPA ratio (UDA/DOPA, P < 0.01) and lower NE excretion (P < 0.05) during the whole study. High sodium intake suppressed the UDA/DOPA in both groups (P < 0.05). Trimetaphan decreased renal vascular resistance (RVR) and increased sodium excretion only in the donors (P < 0.05), while GFR increased in both groups. During HiSo tyramine increased RVR in the recipients (P < 0.01) and UDA/DOPA in the donors (P < 0.05). DOPA infusion increased DA excretion four to fivefold but did not change sodium excretion in either group. It is concluded that the recipients maintained sodium homeostasis well but seem to have an impaired functional innervation of the transplanted kidney. NE release seem to stimulate intrarenal DOPA to DA conversion. In both groups a direct relation between DA and sodium excretion was lacking.

Modulation of natriuresis and renal dopamine excretion by sympathetic activity and the renin-angiotensin-aldosterone system.

The involvement of the sympathetic nervous system and the renin-angiotensin-aldosterone system in renal dopamine (DA) synthesis and sodium excretion (UNaV) were studied in 11 healthy volunteers. On a low sodium diet (LoSo, 50 mmol Na+) saline infusions were given without pretreatment or after oral intake of 50 mg captopril or 300 micrograms clonidine. On a high sodium diet (HiSo, 250 mmol Na+) saline was infused without or after intake of 300 micrograms clonidine. UNaV, the excretion rates of the DA precursor 3,4-dihydroxyphenylalanine (DOPA; UDOPAV), DA (UDAV), and noradrenaline (NA; UNAV), hormonal parameters, blood pressure (BP), glomerular filtration parameters, blood pressure (BP), glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured. Saline infusion alone during LoSo increased natriuresis without changes in catechol excretion or suppression of plasma renin activity (PRA) or plasma aldosterone (PALD). Sympatho-inhibition by clonidine resulted in marked antinatriuresis, decrease in BP and decrease in UDOPAV and UDAV, whereas plasma DOPA, GFR, and ERPF remained unchanged. PRA and PALD rose as indication of activation of the RAA system, probably by the reduced renal perfusion pressure after clonidine. Captopril significantly stimulated the saline-induced natriuresis without affecting UDOPAV and UDAV. On HiSo, when sympathetic tone is relatively suppressed, saline infusion alone stimulated natriuresis but did not affect catechol excretion or PRA. In the first and second hour after saline infusion PALD was suppressed. Clonidine again reduced BP and natriuresis, while PRA, PALD, and UDOPAV and UDAV were unaffected. These results suggest that sympathetic nerve activity may stimulate the intrarenal DA production.(ABSTRACT TRUNCATED AT 250 WORDS)

Glomerular filtration rate measurement by "single-shot" injection of inulin.

In 14 ADPKD patients the total body clearance and the urinary clearance of inulin using the constant infusion method were compared with the "single-shot" technique. Triplicate measurements of both clearances by each infusion method were obtained in 12 out of 14 patients. A high correlation was found between the total body clearance and the urinary clearance for both the constant infusion method (r = 0.96) and the single injection technique (r = 0.96). The coefficient of variation for the total body clearance of inulin was significantly lower for the constant infusion method and the single injection technique (7.8% and 7.1%) than for the urinary clearance of inulin (11.3% vs. 9.7%, P < 0.05). A constant overestimation of the urinary clearance by the total body clearance was observed with both methods (constant infusion method 8.3 ml.min-1 x 1.73 m-2 and single injection technique 13.4 ml.min-1 x 1.73 m-2). No concentration-dependent clearance was present. Determination of plasma inulin, especially at low levels, showed substantial interference by glucose. We conclude that, taking into account a constant overestimate of urinary clearance by the total body clearance of inulin, the single injection total body clearance possesses the best reproducibility and shows a good agreement with the conventional urinary clearance, which can be calculated by: GFR = TBCLss-13.1 ml.min-1 x 1.73 m-2 (in the range of 28 to 124 ml.min-1 x 1.73 m-2).

Ketanserin pharmacokinetics in patients with renal failure.

1. The pharmacokinetics of ketanserin and its major metabolite ketanserin-ol were investigated after a single oral dose of 40 mg and after chronic oral administration of 20 or 40 mg twice daily for 10 days in 12 patients with chronic renal insufficiency of whom six were on intermittent haemodialysis. Plasma protein binding of ketanserin was measured in these 12 patients and in eight healthy volunteers. 2. In both dialysis and non-dialysis patients the terminal half-life of ketanserin (mean +/- s.d.) was prolonged compared with that reported previously for healthy volunteers (28 +/- 4 h vs 18 +/- 4 h). This may be explained by a lowered renal clearance of ketanserin-ol from which ketanserin is partly regenerated. 3. In patients with chronic renal insufficiency plasma ketanserin concentrations were similar to those found in healthy subjects after the same dose. Plasma ketanserin-ol concentrations were elevated, resulting in a raised AUC ratio of ketanserin-ol to ketanserin as compared with healthy individuals (7.3 +/- 4.0 vs 3.2 +/- 0.7). 4. Urinary excretion of ketanserin was negligible in both dialysis and non-dialysis patients, and ketanserin-ol excretion was markedly lowered. 5. The plasma protein binding of ketanserin was slightly reduced in comparison with healthy volunteers (93.7 +/- 1.0% vs 95.0 +/- 0.2%). 6. A dose regimen of 20 mg twice daily appeared to be well tolerated in spite of less plasma binding in renal failure.

Legionella infection with acute renal failure and thrombocytopenia mimicking allograft rejection. A pitfall in post-transplantation diagnosis.

A patient is described who developed cavitary Legionella pneumonia 2 weeks after kidney transplantation. The initial pulmonary symptoms were followed by severe thrombocytopenia and acute renal failure. Although acute irreversible graft rejection was suspected, this was not supported by the pathology findings in the resected kidney, which were compatible with tubular damage. We presume that the extrapulmonary symptoms were caused by Legionellosis.

[Subcapsular hematoma of the liver in an eclamptic crisis]. / Hématome sous-capsulaire du foie au cours d'une crise d'éclampsie.

A patient is described who showed signs of eclampsia in the 31st week of first pregnancy. The cause of shock proved to be a subcapsular hematoma in the liver and it was accompanied by a hematothorax. The diagnosis was made by CT-scanning. The pathogenesis is discussed.

Thrombocytopenia and leucopenia with mianserin-dependent antibodies.

By indirect immunofluorescence specific mianserin-dependent antibodies were detected against platelets but not against granulocytes in the serum of a patient with thrombocytopenic purpura and mild leucopenia. A complement-mediated cytotoxicity assay demonstrated 70% lysis of granulocytes but no lysis of platelets, only when mianserin was added to the medium. We suggest that, at least in some patients, mianserin may cause blood disorders by an immunologically-mediated mechanism.