Using bevacizumab in the fight against malignant glioma: First results in Asian patients

Objectives To investigate the efficacy and safety profile of bevacizumab in combination with irinotecan in Hong Kong Chinese patients with recurrent malignant glioma and to determine whether their response differed from that reported in other populations. Design Retrospective study. Setting Two private clinics and a public hospital in Hong Kong. Patients Fourteen individuals who presented with recurrent glioma presenting to the hospital between November 2005 and November 2009. Intervention Salvage therapy with bevacizumab (10 mg/kg) and irinotecan (125 mg/m 2 [340 mg/m 2 for those taking enzyme-inducing antiepileptic drugs]) on a 14-day schedule. Results A radiological response was observed in 12 (86%) of the patients, four (33%) of whom had a complete response. The median progression-free survival was 6 (range, 1-15) months; 71% remained progression-free at 6 months. The median overall survival was 18 (range, 9-61) months. The most common adverse events during the bevacizumab and irinotecan treatment period were haematological; five patients had grade 2/3 adverse events. Pulmonary embolism occurred in two patients, one of whom died. Intracranial haemorrhage was not detected in any of the 14 treated patients. Conclusions Bevacizumab plus irinotecan was at least as effective at treating Chinese patients with recurrent glioma as previously reported in clinical trials in different patient populations.published_or_final_versio

High-density lipoprotein cholesterol, hepatic lipase and lipoprotein lipase activities in thyroid dysfunction - Effects of treatment

The have investigated the effects of hyper- and hypothyroidism (clinical and subclinical) on lipid metabolism, with special emphasis on serum high-density lipoprotein cholesterol, post-heparin plasma hepatic lipase and lipoprotein lipase activities. In 16 patients with hyperthyroidism, increased post-heparin plasma hepatic lipase activity, decreased serum total cholesterol and serum high-density lipoprotein cholesterol were found while lipoprotein lipase activity and serum triglyceride were normal. In six patients with overt hypothyroidism serum total cholesterol and triglyceride were increased, post-heparin plasma hepatic lipase and lipoprotein lipase were decreased while serum high-density lipoprotein cholesterol was normal. In six patients with subclinical hypothyroidism, serum total cholesterol was increased, serum high-density lipoprotein cholesterol was decreased was decreased, while serum triglyceride, post-heparin plasma hepatic lipase and lipoprotein lipase were normal. When the three groups of patients became euthyroid, serum total cholesterol, serum triglyceride, post-heparin plasma hepatic lipase, lipoprotein lipase, and serum high-density lipoprotein cholesterol reverted to normal except for serum high-density lipoprotein cholesterol in the hyperthyroid group which showed no significant change with treatment. A positive correlation was found between serum T3 and post-heparin plasma hepatic lipase while negative correlations were found between serum total cholesterol and serum T3, post-heparin plasma hepatic lipase and serum total cholesterol, lipoprotein lipase and serum triglyceride respectively. Thus in these patients with thyroid dysfunction, significant reversible alterations in serum total cholesterol, triglyceride and high-density lipoprotein cholesterol were found and could be correlated with the observed changes in the activities of hepatic lipase and lipoprotein lipase.link_to_subscribed_fulltex

Effects of gliclazide and glibenclamide on platetet function, fibrinolysis and metabolic control in diabetic patients with retinopathy | EFFETS DU GLICLAZIDE ET DU GLIBENCLAMIDE SUR LES FONCTIONS PLAQUETTAIRES, LA FIBRINOLYSE ET L'EQUILIBRE GLYCEMIQUE CHEZ DES DIABETIQUES PRESENTANT UNE RETINOPATHIE

In order to compare the metabolic and hemobiological properties of two sulfonylureas, thirty-five non-insulin-dependent diabetics were randomly assigned to two groups. Each group was given either gliclazide (n = 20) or glibenclamide (n = 15) for six months. Metabolic control was improved in both groups, as evidenced by the decrease in HbA1 concentrations. A significant fall in ADP (1 and 4 μM) induced platelet aggregation was recorded in the gliclazide group, while antithrombin III levels remained normal throughout the trial and plasminogen activator levels increased. These hemobiologic changes may be effective in preventing the vascular complications of diabetes. In contrast, glibenclamide did not alter platelet aggregation. Furthermore a significant decrease in both antithrombin III levels and basal and venostasis-stimulated plasminogen activator levels were seen in glibenclamide patients. The beneficial changes in hemostasis seen in gliclazide patients probably result from a direct effect of the drug since hemobiological parameters and metabolic control parameters were not correlated.link_to_subscribed_fulltex

Effects of heroin addiction on thyrotrophin, thyroid hormones and prolactin secretion in men

Pituitary-thyroid function in male heroin addicts and addicts after abstinence (ex-addicts) was studied and compared with that of healthy euthyroid men. In heroin addicts the increases in circulating total thyroxine and triiodothyronine levels were accompanied by an increase in the thyroid hormone uptake test. These changes may reflect a quantitative increase in thyroxine binding globulin. Reverse triidothyronine concentrations in heroin addicts were normal. The thyrotrophin-releasing hormone elicited a diminished thyrotrophin response in heroin addicts which was significantly different from that in control subjects and ex-addicts. An elevation of serum prolactin was noted in heroin addicts, while ex-addicts had normal levels. Gradual recovery of pituitary-thyroid function occurred after heroin withdrawal.link_to_subscribed_fulltex

Pituitary-thyroid responses to surgical stress

The effect of surgery on pituitary-thyroid function was studied in 1 euthyroid patients. There was a sharp early increase in total thyroxine level, causing displacement of triiodothyronine from thyroid hormone binding proteins resulting in the elevation of the biologically more potent free triiodothyronine fraction. The serum triiodothyronine concentration fell rapidly during and after the operation, with a concomitant rise in reverse triiodothyronine level. Increased prolactin levels were found during and after surgery. With no post-operative complication, recovery of normal pituitary-thyroid function occurred after 4 to 7 days of convalescence.link_to_subscribed_fulltex

Effect of surgical stress on pituitary-testicular function

The effect of surgical stress on the secretions of LH, FSH, testosterone (T) and oestradiol (E2) were studied in twelve male patients. During surgery LH rose significantly; post-operatively, LH fell but remained persistently elevated a week after operation. However, T and E2 fell progressively to a nadir on the second and fifth post-operative day respectively and remained suppressed. Serum FSH showed no significant change. Despite a post-operative decrease in sex hormone binding globulin (SHBG) binding capacity, non-SHBG bound T showed a decrease parallel to T. Multiple sampling studies showed that the secretions of LH were increased and that of T were decreased post-operatively. Following surgery, LH responses to LHRH were magnified, FSH and T responses showed no significant change when compared with the pre-operative responses. These data suggest that secretions of LH were increased during surgery. Following surgical stress, T and E2 concentrations were suppressed resulting in a compensatory elevation of LH concentrations.link_to_subscribed_fulltex

The effect of heroin addiction on pituitary-testicular function

The effect of heroin addiction on pituitary-testicular function was studied in 54 active and 19 abstinent addicts and their results were compared with those of 43 age-matched controls. Abnormal sexual function was frequently found in heroin addicts and this persisted after drug withdrawal. The mean total (mean ± SE, 18.1 ± 1.0 nmol/l) and free (0.17 ± 0.03 nmol/l) testosterone (T) levels in heroin addicts were significantly lower than those in healthy controls (total T 22.8 ± 1.1 nmol/l, P<0.005; free T 0.30 ± 0.03 nmol/l, P<0.005). The mean sex hormone binding globulin binding capacity was higher in heroin addicts (60.1 ± 5.2 nM) than in healthy controls (35.5 ± 2.1 nM). These hormonal changes returned promptly to normal after withdrawal. The basal LH and FSH and the responses to LHRH were comparable in the 3 groups studied. The finding of significantly lower total and free T together with higher SHBG indicates an abnormal testicular function in heroin addiction. Normal basal and LHRH-stimulated LH and FSH levels suggest that chronic heroin abuse depressed testicular function via the hypothalamus or higher centers.link_to_subscribed_fulltex

Dissociated thyroxine, triiodothyronine and reverse triiodothyronine levels in patients with familial goiter due to iodide organification defects

The thyroid function of patients with three different types of organification defect was studied. All patients were characterized by a high thyroidal 131I uptake and a positive perchlorate discharge. Patients with Pendred's syndrome who had goitre and congenital nerve deafness were mostly euthyroid with normal circulating thyroid hormone levels. Only two of them had compensated euthyroidism with elevated total T3, high basal TSH and delayed return to basal value after TRH. The patients who were euthyroid with large goitres and normal hearing had elevated total T3 and an exaggerated TSH response to TRH. The thyroid function of these two groups of patients contrasted with that of goitrous cretins, who were clinically hypothyroid with low circulating total T4, increased T3 and decreased rT3 levels. The data suggest that in patients with intrathyroidal iodine deficiency secondary to organification defect, there is preferential T3 production in an effort to maintain euthyroid state, and this is further substantiated in the case of gross thyroid insufficiency either by enhanced peripheral conversion of T4 to T3, or reduced metabolic clearance of T3 and increased clearance of rT3, resulting in elevated T3 and decreased rT3 levels.link_to_subscribed_fulltex

Thyrotropin: α- and β-subunits of thyrotropin, and prolactin responses to four-hour constant infusions of thyrotropin-releasing hormone in normal subjects and patients with pituitary-thyroid disorders

TRH was administered as a 4-h constant rate iv infusion (0.4 μg/min) to eight healthy euthyroid volunteers, three euthyroid females on estrogen, eight hyperthyroid patients, eight patients with primary hypothyroidism, and five patients with hypothalamic and pituitary disorders. Blood was collected at regular intervals for the measurements of TSH, α- and β-TSH subunits, T3 and PRL. Healthy euthyroid subjects exhibited biphasic increases in intact TSH as well as in α- and β-TSH subunits. Circulating TSH levels rose rapidly within 10 min of infusion to a peak in 45 min. Levels were then stable or decreasing until 90 min, when a second phase of increase occurred which was maximal at 160 min. Greater responses were observed in females than in males. Primary hypothyroid patients exhibited similar biphasic increases in TSH and its subunits as did euthyroid subjects. Patients with hypothalamic and pituitary disorders had delayed and diminished responses, while thyrotoxic patients did not respond at all. In euthyroid subjects, significant increases in serum T3 levels as a result of thyroidal stimulation by TSH occurred within 60-120 min and continued steadily until the end of infusion when they declined. In patients with hypothalamic and pituitary disorders, T3 levels began to rise at 180 min and continued for 2 h after stopping the infusion. The PRL response in normal subjects showed a rapid increase to maximum levels within 30-45 min, followed by a gradual decrease despite continued TRH stimulation. This pattern was maintained in women on estrogen who had higher basal PRL levels. The biphasic response pattern of TSH and its subunits to TRH reflects the probable existence of two pools of TSH in the pituitary. The first is a readily releasable pool of presynthesized hormone, and the second, which required longer stimulation before release, represented newly synthesized hormone. The pattern of PRL secretion differs from that of TSH. The biphasic response of PRL is not clearly differentiated. This may be explained by an initial release phase greater than the second biosynthetic phase.link_to_subscribed_fulltex

Treatment of acromegaly with bromocriptine

Five men and three women with active acromegaly were treated with bromocriptine. After three months' therapy (30 mg/day) mean GH during the day decreased by 50% in six out of eight subjects. In the remaining two subjects (non-responders) GH was persistently over 100 μg/l. Mean GH during glucose tolerance test were not significantly decreased in three out of the eight subjects, of whom two were the non-responders. The minimum dose of bromocriptine required to achieve maximum GH suppression ranged from 7.5 to 20 mg/day. In contrast, serum prolactin (PRL) throughout the day suppressed significantly in all subjects after 5 mg/day bromocriptine. Decreases in clinical symptoms, hand volume, urinary hydroxyproline and calcium excretion were seen in about half of the subjects. Three of the four subjects with diabetes mellitus showed improvement in glucose tolerance. Although minor side effects were uncommon, one patient died because of massive gastrointestinal haemorrhage from a duodenal ulcer.link_to_subscribed_fulltex