Total thyroidectomy for differentiated thyroid cancer: primary compared with completion thyroidectomy.

OBJECTIVE: To analyse morbidity after completion total thyroidectomy compared with primary total thyroidectomy in a specialist thyroid surgery centre. DESIGN: Retrospective study. SETTING: Tertiary referral hospital, India. PATIENTS: Medical records of 143 patients who had total thyroidectomy between January 1990 and December 1999. 95 had primary thyroidectomies and 48 were completion thyroidectomies. MAIN OUTCOME MEASURES: Complication rate in both groups. RESULTS: The groups were comparable in respect of clinicopathological variables. Residual tumour was found in 19/48 (40%). After completion thyroidectomy, transient hypoparathyroidism and transient recurrent laryngeal nerve palsy were recorded in 8/48 (17%) and 2/48 (4%), respectively. No permanent hypoparathyroidism or permanent recurrent laryngeal nerve palsy was recorded in the completion thyroidectomy group. CONCLUSIONS: Completion thyroidectomy can be done with acceptable morbidity in a specialist thyroid surgery centre. Fear of increased morbidity after the procedure should not deter surgeon from doing this operation or referring the patients to a specialist centre.     

The effects of chymase on matrix metalloproteinase-2 activation in neointimal hyperplasia after balloon injury in dogs.

Chymase is known to generate angiotensin II in the vascular wall. In this study we investigated a novel role for chymase other than angiotensin II production in vascular proliferation after balloon injury. Chymase promoted the migration of vascular smooth muscle cells in the matrix-coated invasion chambers and activated promatrix metalloproteinase-2 obtained from the culture medium of vascular smooth muscle cells. Two weeks after balloon injury, significant neointimal formation was found in dog carotid arteries. After injury, active matrix metalloproteinase-2 was increased in parallel with the augmentation of chymase activity that was seen in the proliferating region of the vascular wall. The oral administration of NK3201 (1 mg/kg per day), a chymase inhibitor, prevented neointimal formation and significantly suppressed both active matrix metalloproteinase-2 and chymase activities 2 weeks after injury. These results suggest that chymase inhibitors can prevent the development of intimal hyperplasia via the inhibition of matrix metalloproteinase-2 activation in balloon-injured arteries.     

Inhibitory action of Ca2+ on spontaneous transmitter release at motor nerve terminals in a high K+ solution

The inhibitory effect of a high external Ca²⁺ ([Ca²⁺]_o) on spontaneous transmitter release in a high K⁺ solution (Gage and Quastel 1966; Birks et al. 1968) was studied at the frog neuromuscular junction, based on the hypothesis that an increased intracellular free Ca²⁺ ([Ca²⁺]_i) in the nerve terminal plays a key role in the depression. Three procedures were employed to increase [Ca²⁺]_i; increasing [Ca²⁺]_o, application of caffeine and tetanic nerve stimulation. All of these procedures increased m.e.p.p. frequency in normal Ringer. However, as the basic m.e.p.p. frequency was increased by raising the external K⁺ concentration (7–15 mM), their facilitatory effects on m.e.p.p. frequency decreased, disappeared and eventually reversed to depressant actions. Since a rise in the external K⁺ concentration would increase the steady state level of [Ca²⁺]_i, it is suggested that when the [Ca²⁺]_i is preset at a high level, manipulations so as to further increase [Ca²⁺]_i depress spontaneous release of transmitter. Possible mechanisms for this inhibition was discussed in relation to a question whether or not the rate of spontaneous transmitter release is a monotonic function of [Ca²⁺]_i.     

Rhythmic hyperpolarizations and depolarization of sympathetic ganglion cells induced by caffeine.

Superfusion of the isolated sympathetic ganglion of the bullfrog with a caffeine-containing (1-6 mM) solution caused in many cells an initial slow hyperpolarization which was followed by a subliminal depolarization interruped by rhythmic hyperpolarizations. A hyperpolarization, similar to one of the rhythmic hyperpolarizations, could be triggered by an action potential in the presence of caffeine. The action potential itself was not markedly affected by caffeine except for its afterhyperpolarization which was prolonged. All these caffeine-induced hyperpolarizations were associated with a marked reduction of the membrane resistance, their amplitude was increased in a K+-free solution and decreased in a high-K+ solution, and their polarity was reversed at the same level at which the afterhyperpolarization was also inverted. This reversal level was not altered by omission of Na+ or C1- from the external medium. These hyperpolarizations were reversibly abolished by depletion of external Ca2+ or replacement of external Ca2+ by Mg2+. Excess of external Ca2+ caused a shortening of the interval between rhythmic hyperpolarizations. Furthermore, iontophoretic injection of EDTA into the cytoplasm markedly depressed the initial caffeine hyperpolarizatin and abolished both the rhythmic and evoked caffeine hyperpolarizations. The caffeine-induced depolarization was not affected by omission of external Cl-. It was decreased in a Na+-free medium, but completely eliminated by omission of both Na+ and Ca2+ from the external medium. Tetrodotoxin did not impair the production of the initial and the rhythmic hyperpolarizations. A strong depolarizing pulse could evoke a typical hyperpolarizing response in the presence of this compound. Dibutyryl cyclic AMP, d-tubocurarine, atropine, and phenoxybenzamine were without effect on the caffeine-induced hyperpolarizations and depolarization. It was concluded that each caffeine-induced hyperpolarization is the result of an increased K+ permeability, which is probably caused by a rise in the internal Ca2+ concentration. It was also concluded that the caffeine-induced depolarization is due to an increased membrane permeability to Ca2+ and Na+.     

Formation of granulomas in liver of silica-treated rats

Hepatic silicosis was induced in rats by an intravenous injection of saline-suspended silica, 40 mg/kg of body weight. Changes in the liver were examined by biochemical, histological and histochemical methods. Infiltration of the liver parenchyma by polymorphonuclear leucocytes was observed only on the first day after silica treatment. Formation of silicotic nodules began on the first day by clustering of liver macrophages. A 22% increase in liver weight and a 67% increase in total liver DNA reflected accumulation of cells in the liver by day 28 after silica injection. Local cell division contributed to this increase. Almost all cells in the nodules contained carbon when the rats had been given ink before silica. Macrophages showed high activity of lysosomal esterases on the first few days after silica treatment; the activity disappeared later. Large granulomas containing hundreds of cells including lymphocytes were seen 226 days after treatment. Hydroxyproline content per gram of liver tissue increased by 35% and 58% by day 80 and 162, respectively. Connective tissue formed capsules around the nodules and grew to their inside. Activities of lysosomal enzymes, beta-D-galactosidase and acid proteases, in serum were increased by 20% and 300%, respectively, 35 days after treatment. Neither malondialdehyde concentration nor superoxide dismutase activity was elevated in silicotic liver.     

Expression of mRNAs related to connective tissue metabolism in rat hepatic stellate cells and myofibroblasts

Hepatic stellate cells (HSC) and liver myofibroblasts (MFB) are two cell populations most likely responsible for the synthesis of most connective tissue components in fibrotic liver. They differ in their origin and location, and possibly in patterns of gene expression. Normal and carbon tetrachloride-cirrhotic livers from rats were used to isolate HSC. Liver was perfused with pronase and collagenase solutions, followed by centrifugation of the cell suspension on a density gradient. HSC were quiescent 2 days after plating on plastic but they became activated after another 5 days in culture. When the culture was passaged 5 times, its character changed profoundly as HSC were replaced by MFB. Microarray analysis was used to determine gene expression in quiescent HSC, activated HSC and MFB. The expression of 49 genes coding for connective tissue proteins, proteoglycans, metalloproteinases and their inhibitors, growth factors and cellular markers was determined. The pattern of gene expression changed during HSC activation and there were distinct differences between HSC and MFB. Little difference between normal cells and cells isolated from cirrhotic liver was found.     

Properties of visual evoked potentials to onset of movement on a television screen

In 80 subjects the dependence of movement-onset visual evoked potentials on some measures of stimulation was examined, and these responses were compared with pattern-reversal visual evoked potentials to verify the effectiveness of pattern movement application for visual evoked potential acquisition. Horizontally moving vertical gratings were generated on a television screen. The typical movement-onset reactions were characterized by one marked negative peak only, with a peak time between 140 and 200ms. In all subjects the sufficient stimulus duration for acquisition of movement-onset-related visual evoked potentials was 100ms; in some cases it was only 20ms. Higher velocity (5.6°/s) produced higher amplitudes of movement-onset visual evoked potentials than did the lower velocity (2.8°/s). In 80% of subjects, the more distinct reactions were found in the leads from lateral occipital areas (in 60% from the right hemisphere), with no correlation to handedness of subjects. Unlike pattern-reversal visual evoked potentials, the movement-onset responses tended to be larger to extramacular stimulation (annular target of 5°–9°) than to macular stimulation (circular target of 5° diameter).Abbreviation PREP pattern-reversal visual evoked potentials