A thoracic approach is more frequently needed for treatment of intrathoracic thyroid carcinoma as it offers a greater chance of radical excision and better control of intraoperative bleeding. Histologically, thyroid carcinoma in intrathoracic goiter is often anaplastic or rare and has a poor long-term survival rate when compared to cervical forms.

Mechanisms are a way of explaining how biological phenomena work rather than why single elements of biological systems are there. However, mechanisms are usually described as physiological entities, and little or no attention is paid to malfunction as an independent theoretical concept. On the other hand, malfunction is the main focus of interest of applied sciences such as medicine. In this paper I argue that malfunctions are parts of pathological mechanisms, which should be considered separate theoretical entities, conceptually having a priority over physiological sequences. While pathological mechanisms can be described in terms of a Cummins-like mechanistic explanation, they show some unnoticed peculiarities when compared to physiological ones. Some features of pathological mechanisms are considered, such as outcome variability, ambivalence and dependence on a range.

1. Salbutamol as a beta 2-adrenergic agonist used in the treatment of lung obstructive disease and premature labour. It has a bioavailability of 50% and sulphation is the main route of its metabolism. (-)-Salbutamol retains most of the beta 2-adrenergic activity and, thereby, we describe the interindividual variability in the sulphation rate of (-)-salbutamol in 100 specimens of human liver and duodenal mucosa. 2. The mean rate (pmol/min/mg of salbutamol sulphation was 498 in the duodenum and 141 in the liver with 4-fold variation within +/-2 SD units in both tissues. 3. A modelling approach based on the comparison of the best fittings obtained using a gaussian and the sum of two gaussian curves revealed the presence of two subgroups in the hepatic rate of salbutamol sulphation and their means were 69.5 and 105 pmol/min/mg (p < 0.05). In the duodenum, the rate of salbutamol sulphation approached normality. 4. The rates of salbutamol and 4-nitrophenol sulphation correlated highly (r = 0.853; p < 0.001) in the liver whereas in duodenum the rates of salbutamol and dopamine correlated highly (r = 0.914; p < 0.001), 4-Nitrophenol and dopamine are the diagnostic substrates of phenol- and catechol-sulphotransferases respectively. These findings are consistent with the view that the rate of salbutamol sulphation is higher in the gut than in liver and it varies considerably in both tissues.

The beta2-adrenoceptor agonist ritodrine has a bioavailability of 30% due to its presystemic metabolism and sulphation is an important metabolic route. The interindividual variability in the rate of ritodrine sulphation in 100 specimens of human liver and duodenum is reported. The final concentrations of ritodrine were 2 mM (duodenum) and 20 mM (liver). The mean estimates of ritodrine sulphation rate were 490 pmol x min(-1) x mg(-1) (duodenum) and 140 pmol x min(-1) x mg(-1) (liver). There was a 4-5-fold variation within +/- 2 SD units in the hepatic and duodenal rates of ritodrine sulphation. Statistical analysis revealed the presence of at least two subgroups of ritodrine sulphation. In the liver, 30% and 70% of the population fell into two subgroups with the mean estimates of ritodrine sulphation rate of 114 and 149 pmol x min(-1) x mg(-1), respectively (P < 0.05). In the duodenum, 25% and 75% of the population fell into two subgroups and the mean estimates of ritodrine sulphation rate were 332 and 538 pmol x min(-1) x mg(-1), respectively (P < 0.05). The rates of ritodrine and 4-nitrophenol sulphation correlated highly in the liver (r = 0.865; P < 0.001) and the rates of ritodrine and dopamine sulphation correlated highly (r = 0.914; P < 0.001) in the duodenum. In both tissues, the rates of ritodrine and (-)-salbutamol sulphation underwent a similar extent of variation and correlated highly. The intrinsic clearance of ritodrine sulphation was over one order of magnitude higher in the duodenum than in the liver suggesting that the duodenum is an important site of ritodrine sulphation.

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