Increased urinary excretion of carnitine in patients treated with cisplatin.

OBJECTIVE: To study the effect of cisplatin on plasma concentrations and urinary excretion of carnitine in ten patients with different malignancies treated with chemotherapy. METHODS: Carnitine concentrations were determined using a radioenzymatic assay and other metabolites by routine methods of clinical chemistry. Renal clearances were calculated by dividing urinary excretions by the respective plasma concentrations. RESULTS: Before treatment, all patients had a normal plasma carnitine concentration. During treatment with cisplatin, the plasma total carnitine concentration increased by approximately 30% and normalized 7 days after stopping therapy. Urinary excretion of total carnitine increased by a factor of 10 during cisplatin administration and also normalized 7 days after cessation of chemotherapy. This increase was due to excretion of both free carnitine and acylcarnitine and averaged approximately 1 mmol carnitine per day. Similarly, urinary clearance of total carnitine was increased during therapy with cisplatin by a factor of approximately 8 and returned to normal 7 days after chemotherapy. In comparison, patients with similar malignancies treated with radiotherapy showed no significant increase in renal carnitine excretion. Similar to urinary excretion of carnitine, excretion of glucose and phosphate, two metabolites also reabsorbed by the proximal tubule of the nephron, was increased during therapy with cisplatin. There was a strong linear correlation between urinary excretion of free carnitine and acylcarnitines. CONCLUSIONS: Treatment with cisplatin is associated with a tenfold increase in renal carnitine excretion, most likely due to inhibition of carnitine reabsorption by the proximal tubule of the nephron. Well-nourished patients support this loss of carnitine even after repeated cycles of chemotherapy without developing hypocarnitinaemia. However, cachectic patients with decreased dietary carnitine uptake may develop carnitine deficiency when treated repeatedly with chemotherapies including cisplatin.

Thyrotropin-releasing hormone has stimulatory effects on ventilation in humans.

Thyrotropin-releasing hormone (TRH) stimulates pituitary thyrotropin synthesis and release and also regulates autonomic nervous system functions by acting as a neuromodulator and neurotransmitter. In experimental animals a stimulation of ventilation by thyrotropin-releasing hormone was shown when applied at central nervous system sites that affect respiratory motor output. It was the goal of our study to investigate the respiratory properties of thyrotropin-releasing hormone on basal and stimulated (i.e. CO2-rebreathing) conditions following systemic thyrotropin-releasing hormone application in healthy humans. Thyrotropin-releasing hormone (200 micrograms, 400 micrograms intravenous) initiated a rapid short lasting rise of minute volume, ventilatory air-flow and alveolar oxygen tension under steady state breathing (P less than 0.001). Breathing frequency was less affected, heart rate rose concomitantly (P less than 0.001). While breathing with increasing concentrations of carbon dioxide, minute volume was higher under thyrotropin-releasing hormone than under placebo alone. Further effects (e.g. nausea, dizziness, palpitations) mostly appeared later than respiratory changes and thus may not be responsible for their initiation. Our findings prove systemic thyrotropin-releasing hormone to be a strong respiratory stimulant in man. Response in respiratory output was also accompanied by central nervous system-effects (e.g. dizziness, restlessness, augmented vigilance). The mode of thyrotropin-releasing hormone effects on respiration after peripheral administration is still speculative. An augmented sympathetic output or a direct receptor mediated action at central nervous system sites may be responsible, while a peripheral effect cannot be excluded.

[Further studies of the respiratory stimulating effect of thyrotropin releasing hormone in the human]. / Weitere Untersuchungen über die atemstimulierende Wirkung von Thyreotropin Releasing Hormon (TRH) beim Menschen.

The results of animal experiments, neuroanatomical and neurophysiological investigations reported in the literature suggest a central influence of TRH on respiration. In a group of 18 test subjects receiving 400 micrograms of thyrotropin releasing hormone i. v., we were able to demonstrate a clear stimulation of respiration on the basis of lung function parameters. We observed a highly significant increase (p less than 0.001) in minute volume from 8.2 to 10.6 l/minute, and in the PETO2 from 101.5 to 109.8 mmHg. TRH administered via a peripheral vein can reach areas of the brain via preformed passages in the tissue around the ventricles, and thus exercise an effect on the central respiration centres. Additional peripheral influences may be assumed.

[The "so-called" spontaneous cerebrospinal fluid rhinorrhoea (CFR) (author's transl)]. / Uber die "sogenannte" spontane Rino-Liquorrhoe.

Sometimes it is very difficult to decide whether or not a CFR is spontaneous. This is why it has been termed "so-called" CFR. Trying ot find a new definition we think that a little change in the classic definition by Coleman and Troland (1947) will meet the requirements best. "Spontaneous CFR if the drainage of cerebrospinal fluid through the nose without definite demonstrable cause of origin. Three cases of spontaneous CFR are presented.