Virtual surgeries in patients with congenital heart disease: a multi-scale modelling test case.

The objective of this work is to perform a virtual planning of surgical repairs in patients with congenital heart diseases--to test the predictive capability of a closed-loop multi-scale model. As a first step, we reproduced the pre-operative state of a specific patient with a univentricular circulation and a bidirectional cavopulmonary anastomosis (BCPA), starting from the patient's clinical data. Namely, by adopting a closed-loop multi-scale approach, the boundary conditions at the inlet and outlet sections of the three-dimensional model were automatically calculated by a lumped parameter network. Successively, we simulated three alternative surgical designs of the total cavopulmonary connection (TCPC). In particular, a T-junction of the venae cavae to the pulmonary arteries (T-TCPC), a design with an offset between the venae cavae (O-TCPC) and a Y-graft design (Y-TCPC) were compared. A multi-scale closed-loop model consisting of a lumped parameter network representing the whole circulation and a patient-specific three-dimensional finite volume model of the BCPA with detailed pulmonary anatomy was built. The three TCPC alternatives were investigated in terms of energetics and haemodynamics. Effects of exercise were also investigated. Results showed that the pre-operative caval flows should not be used as boundary conditions in post-operative simulations owing to changes in the flow waveforms post-operatively. The multi-scale approach is a possible solution to overcome this incongruence. Power losses of the Y-TCPC were lower than all other TCPC models both at rest and under exercise conditions and it distributed the inferior vena cava flow evenly to both lungs. Further work is needed to correlate results from these simulations with clinical outcomes.

Ethyl benzene-induced ototoxicity in rats: a dose-dependent mid-frequency hearing loss.

Rats were exposed to ethyl benzene at 0, 300, 400 and 550 ppm for 8 hours/day for 5 consecutive days. Three to six weeks after the exposure, auditory function was tested by measuring compound action potentials (CAP) in the frequency range of 1-24 kHz and 2f1-f2 distortion product otoacoustic emissions (DPOAEs) in the frequency range of 4-22.6 kHz. In addition, outer hair cell (OHC) loss was quantified by histological examination. The lowest concentration ethyl benzene had no effect on any of the above measures. At 400 ppm, auditory thresholds were increased by 15 and 16 dB at 12 and 16 kHz, respectively, and at 550 ppm by 24, 31, and 22 dB at 8, 12, and 16 kHz, respectively. DPOAE amplitude growth with stimulus level was affected only after 550 ppm at 5.6, 8, and 11.3 kHz. OHC loss was found in two of the five examined locations in the cochlea. At 400 ppm, 25% OHC loss was found at the 11- and 21-kHz region. The highest concentration evoked 40% and 75% OHC loss at the 11- and 21-kHz location, respectively. Thus, the mid-frequency region of rats is affected after exposure to relatively low concentrations of ethyl benzene (400-550 ppm). These results indicate that ethyl benzene is one of the most potent ototoxic organic solvents known today.

The sigmoidal parathyroid hormone-ionized calcium curve and the set point of calcium in hemodialysis and continuous ambulatory peritoneal dialysis.

A high incidence of adynamic bone disease not related to aluminum intoxication has been reported in continuous ambulatory peritoneal dialysis (CAPD). Since reduced parathyroid hormone (PTH) secretion may predispose to adynamic bone, we investigated whether parathyroid gland sensitivity may be depressed in CAPD in comparison with hemodialysis (HD). Thus we determined parathyroid function by the evaluation of the PTH-ionized calcium (ICa) relationship, which was obtained inducing hypocalcemia and hypercalcemia in 19 CAPD and 18 HD patients with biochemical and histological evidence of mild (MILD) or severe (OF) hyperparathyroidism, but negative stainable bone aluminum. Either CAPD or HD patients with OF showed a shift to the right of the sigmoidal PTH-ICa curve in comparison with patients with MILD, greater set point of calcium, and maximal PTH stimulation and inhibition. The PTH-ICa curve and the other parathyroid function parameters were not different in CAPD and HD patients within the same bone histological group. In conclusion, our data document that parathyroid gland activity is stimulated either in CAPD and HD patients with OF, but is not depressed in CAPD patients in comparison with HD patients.

Short-term effects of low-calcium dialysis solutions on calcium mass transfer, ionized calcium, and parathyroid hormone in CAPD patients.

Patients on CAPD using calcium carbonate (CaCO3) as phosphate binder might benefit from low-calcium (Ca) concentration dialysis solutions; however, no data are available for the effects of this regimen on Ca metabolism. We studied 10 patients on stable CAPD regimens with standard dialysis solutions (Ca 7 mg/dL) who were taking CaCO3 to control hyperphosphatemia (mean daily doses 4.5 +/- 2.4 g). Hypercalcemic episodes had been recorded in 6 patients. Standard dialysis solutions were replaced with solutions containing 5 mg/dL of Ca. Calcium and phosphate peritoneal mass transfer (MT), serum concentrations of total Ca, ionized Ca (Ca++), phosphate, intact PTH, and mid-molecular PTH, were evaluated before and 48 hours after change of dialysate. The switch to low-Ca solutions was accompanied by significant changes in calcium mass transfer (Ca MT) (+9.84 +/- 48.22 versus -96.74 +/- 48.32 mg/day, p less than .001). Ca MT was significantly (p less than .05) correlated with the serum/dialysate Ca gradient. There was no difference in phosphate MT. Serum Ca++ significantly (p less than .05) decreased from 5.20 +/- 0.32 to 4.88 +/- 0.36 mg/dL, and intact PTH significantly increased (81.5 +/- 139 versus 112.4 +/- 168 pg/mL, p less than .05). It is concluded that dialysis solutions with Ca 5 mg/dL result in a negative peritoneal Ca MT and can be useful to prevent and treat hypercalcemia in CAPD patients taking CaCO3 as phosphate binder. A careful monitoring of ionized calcium, PTH, and phosphate is suggested when an extensive and long-term use of this solution is considered.

Acquired immunodeficiency syndrome transmitted by transplanted kidney: clinical course during maintenance haemodialysis.

We describe the clinical course of a 39-year-old man who developed AIDS during maintenance haemodialysis. The infection had been transmitted by cadaveric kidney transplantation from a donor with a history of i.v. drug abuse. Fever, splenomegaly, hypergammaglobulinaemia and thrombocytopenia were the first signs, and appeared when haemodialysis was resumed 26 months after transplantation. Twenty-eight months later the patient developed a cerebral abscess due to toxoplasma infection. A striking improvement was obtained with cotrimoxazole, but the treatment had to be stopped because of severe leukopenia. The patient died due to relapse of the cerebral abscess. End-stage renal failure does not seem to have modified the clinical course of AIDS in our patient.