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S Tuma

Publications and source records attributed to S Tuma.

At least 19 recordsLinked to original sources
PubMed2002

Chances and shortcomins of adenovirus-mediated ATP7B gene transfer in Wilson disease: proof of principle demonstrated in a pilot study with LEC rats.

BACKGROUND & AIMS: Wilson disease (WD) is an autosomal recessively inherited copper storage disease due to mutations in the ATP7B gene. It results in impaired biliary copper excretion followed by liver injury leading to cirrhosis. In parallel, copper accumulates in other tissues e. g. basal ganglia of the brain inducing motoric disorders. Phenotypical cure of Wilson disease by liver transplantation raised the question whether gene therapy may represent a successful alternative treatment procedure. To examine the principle feasibility of this approach we investigated the effects of gene transfer using an adenoviral vector construct expressing the human ATP7B cDNA in an established rodent model for WD, the Long-Evans Cinnemon rat (LEC). METHODS: Transduction efficiency was assessed by RT-PCR, Western blot and immunofluorescence analysis. The therapeutic effect was estimated by analyzing holoceruloplasmin and its ferroxidase activity in serum, and the copper content of excrements. Changes in copper homeostasis were determined by positron emission tomography (PET). RESULTS: Successful, but temporary gene transfer was clearly detectable on RNA and protein levels. In parallel the temporary therapeutic effect was documented by restoration of serum holoceruloplasmin and of its ferroxidase activity. Additionally the Ad-ATP7B treated LEC rat revealed a higher (64)Cu content in stool. PET was able to visualize differences in (64)Cu distribution between wild type and LEC rats, indicating its principle usefulness as analytical tool. CONCLUSION: The data demonstrate proof of principle of successful gene therapy in an experimental model of WD. As a consequence of successful but only transient therapeutic effect of adenoviral gene transfer we can now focus more efficient and permanent gene transfer strategies.

Adenosine Triphosphatases↗
PubMed1995

Influence of bidirectional superior cavopulmonary anastomosis on pulmonary arterial growth.

Right-sided BSCA provides for satisfactory pulmonary arterial growth in infants and children with complex congenital heart defects, and it could enhance the growth of a small right pulmonary artery. The growth of the left pulmonary artery, particularly in younger patients, needs close attention to confirm the safe role of BSCA in long-term palliation.

Anastomosis, Surgical↗
PubMed1992

Intermediate to late results of surgical relief of vascular tracheobronchial compression.

Since 1979, a total of 69 infants and children aged 0.1 to 11.9 (median 0.7) years required surgical intervention for: double aortic arch (26), anomalous origin of innominate artery (26), right aortic arch with left ligamentum arteriosum (9), pulmonary artery sling (5), retroesophageal right subclavian artery (3). Before operation, the morbidity was high: 84% of children were symptomatic in the first trimester of life with 24 patients requiring mechanical ventilation. Seven children had an accompanying heart defect. Left thoracotomy was the preferred approach. There were 2 early (asphyxic brain damage, postoperative pneumonia) and 2 late (tracheomalacia, complex heart defect) deaths. Five patients (2 originally operated elsewhere) needed reoperation for persistent symptoms. All 65 survivors are well 1 month to 11.9 (mean 3.9 +/- 3.62) years after surgery. Tracheobronchoscopy, magnetic resonance imaging, and lung function testing were helpful for postoperative evaluation. Minor tracheal compression was revealed in 4 patients despite their good clinical condition.

Airway Obstruction↗
PubMed1985

Unilateral dilatation of the internal mammary artery as a sign of an intrathoracic lesion.

Nineteen children had unilateral dilatation of the internal mammary artery associated with an intrathoracic lesion on the same side. Dilatation of one internal mammary artery to a calibre more than twice that of the artery on the other side is a sign of an intrathoracic pathological finding on the same side. However, when the arteries have the same calibre an intrathoracic pathological process is not excluded. Dilatation occurs independently of the vascular supply of the pathological process by systemic collaterals. A share in the collateral supply from the pulmonary circulation is specially characteristic.

Adolescent↗
PubMed1984

Intact and carboxyterminal PTH do not cross the blood-cerebrospinal fluid barrier.

In order to examine whether parathyroid hormone (PTH) enters the cerebrospinal fluid (CSF), the blood levels of the hormone were acutely elevated either by infusion of parathyroid extract or by stimulation of the parathyroid glands by hypocalcemia. Despite marked elevations in the blood levels of the hormone, PTH could not be detected in the CSF. The data indicate the intact PTH or its carboxyterminal fragment do not cross the blood-CSF interface of the blood-brain barrier. The results, therefore, suggest that the action of PTH on brain must be mediated by an effect on the blood-brain interface of the blood-brain barrier.

Animals↗
PubMed1979

Reversal of skeletal resistance to parathyroid hormone in uremia by vitamin D metabolites: evidence for the requirement of 1,25(OH)2D3 and 24,25(OH)2D3.

This study evaluates the role of vitamin D metabolites in the genesis of the skeletal resistance to the calcemic action of PTH in uremia. The changes in serum calcium after infusion of 2 U of PTE per kilogram per hour for 8 hr were evaluated in thyroparathyroidectomized dogs before and after 1 and 3 days of acute uremia produced by bilateral nephrectomy. The animals received vitamin D metabolites during the 3 days of uremia. Supplementation of 0.68 microgram/day 1,25(OH)2D3 and 24R,25(OH)2D3 restored the calcemic response to PTE to normal. This is in contrast to only partial correction of the response to PTE by 1,25(OH)2D3 alone. Administration of 1.36 microgram/day 24R,25(OH)2D3 did not improve the calcemic response to PTE. The results indicate that (1) both 1,25(OH)2D3 and 24R,25(OH)2D3 are necessary for the complete reversal of the impaired calcemic response to PTE, (2) this effect is not due to the increase in the amount of the dihydroxylated compounds of vitamin D, since equivalent amounts of these compounds in the form of 24R,25(OH)2D3 alone had no effect, and (3) the better effect of the combination of 1,25(OH)2D3 and 24R,25(OH)2D3 is most probably due to an interaction between these two metabolites of vitamin D permitting an intact calcemic action of PTH.

Animals↗
PubMed1975

Hypertensive crisis, erythrocytosis, and uraemia due to renal-artery stenosis of kidney transplants.

Two patients with kidney transplants had hypertensive encephalopathy and rapidly progressive kidney failure 10 weeks and 18 months postoperatively. In one patient renal failure was associated with erythrocytosis. Absence of proteinuria, despite progressive renal insufficiency in both patients, suggested that these abnormalities were not due to rejection episodes. Subsequently, angiography proved that each of these patients had renal-artery stenosis. Surgical repair of this lesion increased creatinine clearance at least threefold, and the hypertension and erythrocytosis disappeared. Apparent "rejection" episodes in which there is no proteinuria should alert clinicians to the possiblity of renal-artery stenosis of the graft. Restoration of kidney function and amelioration of hypertension may follow revascularisation, even after many months of renal ischaemia producing severe uraemia.

Adult↗
PubMed1975

Exaggerated phosphaturic response to volume expansion in patients with essential hypertension.

1. Tubular handling of sodium in hypertensive patients has been evaluated with urinary phosphate excretion used as a marker for proximal tubular reabsorptive capacity. 2. Nine hypertensive patients and nine normal control subjects were studied during sustained water diuresis and the intravenous infusion of isotonic sodium chloride solution to produce volume expansion. 3. In the hypertensive patients there was exaggerated phosphaturia, natriuresis and enhanced distal delivery of sodium. Sodium reabsorption in the diluting segment was normal. 4. The enhanced distal delivery and augmented phosphaturia suggest that a decreased reabsorption of sodium in the proximal tubule is the most likely explanation for the exaggerated natriuretic response to volume expansion in hypertensive patients.

Adolescent↗
PubMed1975

Enhanced tubular reabsorption of phosphate.

Individual kidney functions were studied during water diuresis in eight patients, following the relief of unilateral ureteral obstruction. Fractional excretion of phosphate was diminished in four of the patients, presumably due to enhanced tubular reabsorption of phosphate in the diseased side. Glomerular underperfusion may be the main factor responsible for the hypophosphaturia in the postobstructive kidney. Fractional excretion of sodium and water was increased in the obstructed side in six of the eight patients. In two of the four patients with hypophosphaturia, there was enhanced fractional sodium excretion, suggesting a dissociation of renal handling of sodium and phosphate in some patients with this condition.

Absorption↗