Enhancement of a low-fidelity surgical simulator. Is it possible?

BACKGROUND: Simulation training has become a core component in the training of ENT surgeons. It provides the opportunity for the repetitive practice of a surgical technique. Simulators are broadly categorised into low- and high-fidelity simulators. A method using a home microprocessor to enhance a low-fidelity surgical simulator is introduced. METHOD: The Yorick tonsil tie trainer was enhanced using an Arduino microcontroller attached to the simulated inferior pole of the tonsil. The Arduino was coded to give a visual stimulus when linear motion exceeded parameters. The prototype simulator was tested to gain information on whether the enhancement could identify differences between novice and expert users. CONCLUSION: An enhanced low-fidelity tonsil trainer was produced using a low-cost, simple home microprocessing board. The enhanced simulator gives objective feedback allowing for self-directed learning. Further research is required to evaluate the benefits of these enhancements above non-enhanced simulation training.

Geographical barriers and climate influence demographic history in narrowleaf cottonwoods.

Studies of genetic variation can clarify the role of geography and spatio-temporal variation of climate in shaping demography, particularly in temperate zone tree species with large latitudinal ranges. Here, we examined genetic variation in narrowleaf cottonwood, Populus angustifolia, a dominant riparian tree. Using multi-locus surveys of polymorphism in 363 individuals across the species' 1800 km latitudinal range, we found that, first, P. angustifolia has stronger neutral genetic structure than many forest trees (simple sequence repeat (SSR) FST=0.21), with major genetic groups corresponding to large apparent geographical barriers to gene flow. Second, using SSRs and putatively neutral sequenced loci, coalescent simulations indicated that populations diverged before the last glacial maximum (LGM), suggesting the presence of population structure before the LGM. Third, the LGM and subsequent warming appear to have had different influences on each of these distinct populations, with effective population size reduction in the southern extent of the range but major expansion in the north. These results are consistent with the hypothesis that climate and geographic barriers have jointly affected the demographic history of P. angustifolia, and point the importance of both factors as being instrumental in shaping genetic variation and structure in widespread forest trees.

A decade of change in the uptake of parathyroidectomy in England and Wales.

INTRODUCTION: Since the late 1990s, a number of factors have reduced the threshold for parathyroidectomy in patients with primary hyperparathyroidism. This study examined whether this has translated into increased numbers of parathyroid operations over the last decade. METHODS: A retrospective analysis was performed of the Patient Episode Database for Wales and English Hospital Episode Statistics annual data from 2000 to 2010 for parathyroidectomy admissions per 100,000 population. Statistical analysis was by linear regression. RESULTS: Between 2000 and 2010 there were 24,247 parathyroid operations in England and Wales (0.005% of the population), with 3 times as many women treated as men. Overall, incidence of parathyroidectomy rose from 3.3/100,000 population in 2000 to 5.8/100,000 in 2010 (p<0.0001). In England, it increased from 3.3/100,000 population to 5.8/100,000 and in Wales, it increased from 2.4/100,000 population to 4.6/100,000. Despite similar population demographics, the difference in the rate of change between England and Wales was significant (p<0.05). Uptake also varied according to age; in those aged 0-14 years, incidence of parathyroidectomy remained static whereas in all other age groups, uptake of parathyroidectomy increased significantly from 2000 to 2010. Most notably, surgical intervention in those aged 60-74 and >75 years nearly doubled over the decade (p<0.0001). CONCLUSIONS: The incidence of parathyroidectomy in adults has increased significantly in the last decade in England and Wales. This likely reflects changes in population demography, available guidelines, lower threshold for referral, changing surgical approach and the realisation that surgical morbidity is now infrequent.

A national audit of current cardiac device policies from radiotherapy centres across the UK.

AIMS: The number of patients with cardiac implantable electronic devices (permanent pacemakers and implantable cardioverter defibrillators) undergoing radiotherapy treatment is increasing. The aims of this audit were to establish current UK practice regarding the management of patients with implanted cardiac devices undergoing radiotherapy and to compare this practice with current 'gold standard' evidence-based guidelines. MATERIALS AND METHODS: All UK radiotherapy departments were contacted and asked to provide their current cardiac implantable electronic device policy or to indicate if there was no current policy. A proforma was created to analyse these policies and to compare with current best practice. RESULTS: In total, 47/67 (70%) radiotherapy departments responded and 45 departmental policies were submitted; 31/45 (69%) policies defined the radiotherapy tolerance dose to permanent pacemakers and 14/45 (31%) defined the monitoring procedure for patients in line with current best practice. Only 5/45 (11%) policies defined the radiotherapy tolerance dose to implantable cardioverter defibrillators and 12/45 (27%) defined the monitoring procedure in line with current best practice. CONCLUSION: Most UK cardiac device policies do not reflect current best evidence. Policies are based on research carried out in 1994 by the American Association of Physicists in Medicine. This evidence does not account for advances in cardiac implantable electronic device technology. Further research is urgently needed to establish the effect of radiotherapy on these devices.

Temperature alters the relative abundance and population growth rates of species within the Dendroctonus frontalis (Coleoptera: Curculionidae) community.

Temperature has strong effects on metabolic processes of individuals and demographics of populations, but effects on ecological communities are not well known. Many economically and ecologically important pest species have obligate associations with other organisms; therefore, effects of temperature on these species might be mediated by strong interactions. The southern pine beetle (Dendroctonus frontalis Zimmermann) harbors a rich community of phoretic mites and fungi that are linked by many strong direct and indirect interactions, providing multiple pathways for temperature to affect the system. We tested the effects of temperature on this community by manipulating communities within naturally infested sections of pine trees. Direct effects of temperature on component species were conspicuous and sometimes predictable based on single-species physiology, but there were also strong indirect effects of temperature via alteration of species interactions that could not have been predicted based on autecological temperature responses. Climatic variation, including directional warming, will likely influence ecological systems through direct physiological effects as well as indirect effects through species interactions.

A longitudinal study into the new and long-term use of self-monitoring blood glucose strips in the UK.

AIMS: To determine the impact of self-monitoring blood glucose (SMBG) strip use in patients with type 2 diabetes in the UK. METHODS: The study period was April 1, 2004 to July 31, 2005. Data from primary care was extracted from The Health Improvement Network database. Patients identified with diabetes and matching the inclusion criteria were defined as new users of SMBG, prevalent users, or non-users. Patients were also defined as treated with insulin, with oral agents (OA), or not pharmacologically treated. Change in glycosylated hemoglobin (HbA(1c)) at baseline and after 12 months was compared. RESULTS: 2559 patients met the inclusion criteria. For new users, HbA(1c) fell by 0.59% (P=0.399) for those treated with insulin, 1.52% (P<0.001) for those treated with OA, and 0.51% (P<0.001) for no treatment. In prevalent users, changes were 0.31% (P<0.001), 0.34% (P<0.001), and 0.09% (P=0.456), respectively. In non-users, changes were 0.28% (P=0.618), 0.42% (P<0.001), and an increase of 0.05% (P=0.043), respectively. A significant decrease in mean HbA(1c) was associated with increasing strip use in OA patients newly initiated on strips. CONCLUSION: This observational study showed a significant decrease in HbA(1c) for new users of SMBG treated either non-pharmacologically or with OA, and for prevalent users treated with insulin or OA. Reduced HbA(1c) with increasing strip use was observed but was only significant for OA-treated new users. This suggests that SMBG use has a role in the treatment of non-insulin treated patients with type 2 diabetes.

Insulin therapy in type 2 diabetes: insulin analogue mix 50, a potential role in reducing postprandial hyperglycaemia and cardiovascular disease.

IMPORTANCE OF THE FIELD: Postprandial hyperglycaemia is becoming topical, with studies suggesting a link to cardiovascular disease. Recently, a number of new therapies for the treatment of type 2 diabetes have become available. AREAS COVERED IN THIS REVIEW: This review looks at the evidence for the potential role of insulin analogue mix 50 to reduce postprandial hyperglycaemia and cardiovascular disease. SEARCH STRATEGY: Medline and Embase databases were searched using the MeSH terms to identify relevant studies from 1980 to 2009. Both original articles and reviews were extracted. Published reference lists were also examined. MeSH terms used for literature searching: human insulins, insulin analogues, insulin analogue mix 50, glycaemia, postprandial glucose, fasting glucose, type 2 diabetes, type 1 diabetes, cardiovascular disease. WHAT THE READER WILL GAIN: The reader is presented with evidence discussing the importance of postprandial hyperglycaemia and studies comparing different insulin regimes and in particular insulin analogue mix 50 and its potential to reduce postprandial glucose surges and reduce cardiovascular disease. TAKE-HOME MESSAGE: Insulin analogue mix 50 is a viable therapeutic option in a sub-group of patients with type 2 diabetes.

Characterization and utilization of microsatellite loci in the New World screwworm fly, Cochliomyia hominivorax.

New World screwworm populations in North and Central America have been the targets of virtually continuous eradication attempts by sterile insect technique (SIT) since the 1950s. Nevertheless, in some areas, such as Jamaica, SIT control programmes have failed. Reasons for the failure of SIT-based control programmes in some locations are unknown, but it has been hypothesized that failure may be related to mating incompatibility between sterile and wild fly populations or to the existence of sexually incompatible cryptic species. This paper outlines the development of a suite of four new microsatellite loci which can be used to study intra-specific relationships between populations of Cochliomyia hominivorax from the Caribbean and South America, which represent those populations involved in, or earmarked for, forthcoming SIT control. Cross-amplification with the secondary screwworm, Cochliomyia macellaria, was also successful with three of the new loci. We present results which suggest that populations from Trinidad and Jamaica form distinct groupings of flies and that C. hominivorax from Trinidad appears particularly distinct.

Rosiglitazone produces a greater reduction in circulating platelet activity compared with gliclazide in patients with type 2 diabetes mellitus--an effect probably mediated by direct platelet PPARgamma activation.

AIMS: Type 2 diabetes mellitus (T2DM) is associated with enhanced platelet activation. We conducted a randomised double-blind study to compare the effects of combination metformin and rosiglitazone or metformin and gliclazide therapy on platelet function in persons with T2DM. METHODS: Fifty subjects on metformin monotherapy received either rosiglitazone 4 mg or gliclazide 80 mg. HbA1c, HOMA-R, markers of platelet activation, inflammation, endothelial activation and oxidative stress were measured at baseline and after 24 weeks of treatment. Separate in vitro platelet function studies were conducted on platelets pre-incubated with rosiglitazone and gliclazide. RESULTS: A significantly greater reduction in platelet aggregation was observed in the rosiglitazone treated group compared to gliclazide. HbA1c and markers of endothelial activation were reduced to a similar extent in both groups. A significant reduction in HOMA-R, markers of inflammation and oxidative stress was only observed with rosiglitazone. Reduction in platelet aggregation with rosiglitazone correlated with reduction in oxidative stress. In the in vitro study, rosiglitazone produced significantly greater reduction in platelet aggregation compared with gliclazide. CONCLUSION: Greater reduction in platelet activity observed with rosiglitazone may be related to reduced oxidative stress and a possible direct PPARgamma mediated effect on platelet function.

Peripheral cytokine expression in autoimmune thyroiditis: effects of in vitro modulation by rosiglitazone and dexamethasone.

BACKGROUND: In Hashimoto's thyroiditis (HT), there is evidence for activation of peripheral T-lymphocytes that predominantly express a T helper 1 (T(H)1) cytokine bias. However, the immunomodulatory factors involved in regulating this response have so far received scant attention. In this study, we examine the effects of the glucocorticoid, dexamethasone, and the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligand, rosiglitazone on the expression of interferon (IFN)-gamma (T(H)1) and interleukin (IL)-4 (T(H)2) by activated peripheral CD4(+) and CD8(+) lymphocytes in patients with HT (n = 10) and healthy control subjects (n = 12). METHODS: Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with phorbolmyristate acetate (PMA) and ionomycin in the presence or absence of varying doses of dexamethasone and rosiglitazone (0.01 microM, 1.0 microM, and 100 microM). Cytokine expression was determined by flow cytometry. RESULTS: CD4(+) and CD8(+) IFN-gamma expression was greater in HT than controls (14.87 versus 9.25; p < 0.05 and 21.34 versus 10.16; p < 0.01, respectively). A dose-dependent inhibition of IFN-gamma expression was seen with dexamethasone and rosiglitazone. Inhibition of CD4(+) and CD8(+) IFN-gamma expression with both dexamethasone and rosiglitazone was greater in control subjects than in patients (p < 0.05). There was no significant difference in IL-4 expression between patients and control groups and its expression remained unaffected by either compound. CONCLUSIONS: We show that CD4(+) and CD8(+) T lymphocytes from HT patients express a type 1 cytokine bias that is significantly more resistant to in vitro modulation by rosiglitazone and dexamethasone. Further studies are needed to clarify if this resistance plays a role in the pathogenesis of autoimmune thyroid disease (AITD).

Diuretic-induced hypokalaemia in patients with hypertension.

We describe a 55 year-old woman with longstanding hypertension who developed hypokalaemia following diuretic treatment. Investigations revealed primary hyperaldosteronism due to an adrenal adenoma, and normal blood pressure was restored after surgical removal of the tumour. Primary hyperaldosteronism is a potentially curable cause of hypertension and should be considered in hypertensive patients who present with diuretic - induced hypokalaemia.

Prolonged deterioration of endothelial dysfunction in response to postprandial lipaemia is attenuated by vitamin C in Type 2 diabetes.

BACKGROUND: Endothelial dysfunction (ED) has been described in Type 2 diabetes (T2DM). We have described previously a diminution of flow-mediated arterial dilatation and, by implication, further ED in T2DM in response to postprandial lipaemia (PPL) at 4 h. This is possibly mediated by oxidative stress/alteration of the nitric oxide (NO) pathway. T2DM subjects tend to exhibit both exaggerated and prolonged PPL. We therefore studied the relationship of PPL to the duration of ED in T2DM subjects and oxidative stress with or without the antioxidant, vitamin C. METHODS: Twenty subjects with T2DM with moderate glycaemic control (mean HbA1c 8.4%) were studied. After an overnight fast, all subjects consumed a standard fat meal. Endothelial function (EF), lipid profiles, and venous free radicals were measured in the fasting, peak lipaemic phase (4 h) and postprandially to 8 h. The study was repeated in a double-blinded manner with placebo, vitamin C (1 g) therapy for 2 days prior to re-testing and with the fat meal. Oxidative stress was assessed by lipid-derived free radicals in plasma, ex vivo by electron paramagnetic resonance spectroscopy (EPR) and by markers of lipid peroxidation (TBARS). Endothelial function was assessed by flow-mediated vasodilatation (FMD) of the brachial artery. RESULTS: There was a significant decrease in endothelial function in response to PPL from baseline (B) 1.3 +/- 1.3% to 4 h 0.22 +/- 1.1% (P < 0.05) and 8 h 0.7 +/- 0.9% (P < 0.05) (mean +/- sem). The endothelial dysfunction seen was attenuated at each time point with vitamin C. Baseline EF with vitamin C changed from (fasting) 3.8 +/- 0.9-2.8 +/- 0.8 (at 4 h) and 2.9 +/- 1.3 (at 8 h) in response to PPL. Vitamin C attenuated postprandial (PP) oxidative stress significantly only at the 4-h time point [301.1 +/- 118 (B) to 224.7 +/- 72 P < 0.05] and not at 8 h 301.1 +/- 118 (B) to 260 +/- 183 (P = NS). There were no changes with placebo treatment in any variable. PPL was associated with a PP rise in TG levels (in mmol/l) from (B) 1.8 +/- 1 to 2.7 +/- 1 at 4 h and 1.95 +/- 1.2 at 8 h (P = 0.0002 and 0.33, respectively). CONCLUSION: PPL is associated with prolonged endothelial dysfunction for at least 8 h after a fatty meal. Vitamin C treatment improves endothelial dysfunction at all time points and attenuates PPL-induced oxidative stress. This highlights the importance of low-fat meals in T2DM and suggests a role for vitamin C therapy to improve endothelial function during meal ingestion.

Long-term remission following withdrawal of dopamine agonist therapy in subjects with microprolactinomas.

OBJECTIVE: Reports suggest that up to 70% of patients with microprolactinomas treated with dopamine agonist therapy may achieve long-term normoprolactinaemic remission following drug withdrawal. Yet, there is no consensus on the duration of therapy nor is therapeutic interruption universally practised. We have assessed remission rates in a large cohort of treatment-naive subjects with microprolactinomas. Subjects received dopamine agonist (DA) therapy with either cabergoline or bromocriptine for a period of 2 to 3 years in the majority of cases, followed by a trial of treatment withdrawal. DESIGN: Retrospective analysis of clinic records of 89 patients (mean age 32.7 +/- 8.4 years, 84 women and 5 men) who had received either cabergoline (n = 67) (0.5-3 mg weekly) or bromocriptine (n = 22) (2.5-10 mg daily) for a mean duration of 3.1 years. RESULTS: Following withdrawal of therapy, 57 subjects developed recurrence (64%) and the mean time to recurrence was 9.6 months (range 1-44 months), while 32 subjects (36%) remained in remission beyond 1 year (mean 3.6 years, range 1-7 years). There was no difference in remission rates between subjects treated with cabergoline (n = 21) and bromocriptine (n = 11), but a direct relationship between pretreatment prolactin concentration and risk of recurrent symptomatic hyperprolactinaemia was observed. No subjects developed clinical features to suggest tumour expansion following therapeutic discontinuation. CONCLUSIONS: This study confirms that abrupt withdrawal of chronic dopamine agonist therapy, following 2 to 3 years of treatment is safe and associated with long-term remission in 30-40% of subjects with microprolactinomas. This therapeutic strategy is convenient and applicable in clinical practice.

"Osler's phenomenon": misdiagnosing Cushing's syndrome.

The clinical manifestations of Cushing's syndrome can be quite variable and are frequently mistaken, with consequent delayed diagnosis and significant morbidity and mortality. Harvey Cushing described the typical signs and symptoms of Cushing's syndrome but unfortunately attributed the features to myxoedema. The first typical description of a patient with Cushing's syndrome was probably made by Sir William Osler in 1898. Thus delay or misdiagnosis with consequent high morbidity and mortality exemplifies the history of Cushing's syndrome. Four cases of Cushing's syndrome are described that were associated with deteriorating morbidity because of the considerable delay from first presentation to a secondary care physician to eventual diagnosis. The clinical diagnosis was delayed in all the four patients, although they had symptoms and signs that were missed by a number of primary and secondary care physicians. Trans-sphenoidal surgery resulted in biochemical cure as well as improvement in the accompanying co-morbidity. Although still rare, the prevalence of Cushing's syndrome is increasing. Increasing clinical awareness and the use of appropriate screening tests should facilitate earlier diagnosis with reduced morbidity and mortality. Although the syndrome is named after Harvey Cushing, Sir William Osler was probably the first to describe it. Therefore, in deference to Osler's contribution to Cushing's syndrome and the work of Harvey Cushing, it is suggested that to the list of the other eponymous conditions of Osler-Weber-Rendu and Osler's nodes, should be added the delay or misdiagnosis of Cushing's syndrome-"Osler's phenomenon".

The TSH response to domperidone reflects the biological activity of prolactin in macroprolactinaemia and hyperprolactinaemia.

OBJECTIVE: To test the hypothesis that patients with hyperprolactinaemia due to biologically inactive macroprolactin will not show the characteristically increased dopaminergic inhibition of TSH release seen in patients with microprolactinomas secreting biologically active monomeric PRL. DESIGN: Comparison of the TSH and PRL responses to dopamine antagonism with domperidone (10 mg i.v.) in patients with hyperprolactinaemia due to macroprolactinaemia or microprolactinomas. PATIENTS: Twenty-two patients referred for the investigation of their hyperprolactinaemia were studied: 11 patients with macroprolactinaemia and 11 patients with hyperprolactinaemia due to microprolactinoma. MEASUREMENTS: TSH and PRL levels were measured at baseline and 30 min following domperidone in both groups. RESULTS: Patients with macroprolactinaemia showed normal TSH and PRL responses to dopamine antagonism whereas patients with microprolactinomas showed exaggerated TSH responses and reduced PRL responses. Although there was considerable overlap between the PRL responses in the two groups, there was very clear separation between the PRL/TSH response ratios (normal > 1.0) of 4.0 +/- 1.8 for the macroprolactinaemia group and 0.4 +/- 0.2 for the microprolactinoma group (P < 0.0001). CONCLUSIONS: These data support the hypothesis that elevated circulating levels of macroprolactin, as opposed to biologically active monomeric PRL, do not exert increased positive feedback on the hypothalamic dopaminergic inhibition of TSH release.

The effects of depot long-acting somatostatin analog on central aortic pressure and arterial stiffness in acromegaly.

Acromegaly is associated with increased cardiovascular risk. Although conventional risk factors such as glucose intolerance, hypertension, and dyslipidemia probably contribute, there may also be direct effects of GH/IGF-I excess on the vasculature. To study the effects of GH excess on the vasculature, we have assessed arterial stiffness in acromegalic subjects with and without active disease and have investigated the effects of Sandostatin LAR (OCT-LAR) on vascular function. Sixteen normotensive subjects with acromegaly (10 males and 6 females) and 8 healthy controls were studied. Of the acromegalic subjects, eight had active disease (group A), and eight were cured (GH < 2.5 mU/liter; group B). The three groups were age, sex, and blood pressure matched. Group A subjects were restudied after 3 and 6 months of OCT-LAR therapy. Arterial stiffness was assessed by analyzing central arterial pressure waveforms derived from measured radial artery waveforms. This allowed determination of the augmentation of central pressure and the augmentation index. Lipids, glucose, and IGF-I were also measured. Comparing the three groups (ANOVA; mean +/- SD), the augmentation index was higher in group A (28 +/- 12 vs. 12 +/- 13%; P < 0.01) but not in group B (22 +/- 7 vs. 12 +/- 13%; P = 0.60), compared with controls. IGF-I was higher in group A (50.3 +/- 21.2 nmol/liter; P < 0.01), compared with group B (22.5 +/- 8.9 nmol/liter) and controls (19.5 +/- 5.3 nmol/liter). On regression analysis, IGF-I concentration was identified as a strong independent predictor of the augmentation index (beta = 0.50; P = 0.007). There were no significant differences in aortic systolic pressure, aortic diastolic pressure, lipids, or glucose. Compared with baseline, OCT-LAR treatment resulted in a lowering of augmentation index at 3 months (20 +/- 15 vs. 28 +/- 12%; P < 0.05), but at 6 months (24 +/- 16%; P = 0.21) there was no significant change. IGF-I was reduced from 50.3 +/- 21.2 nmol/liter at baseline to 31.4 +/- 13.2 nmol/liter at 3 months (P < 0.05) and 26.6 +/- 15.8 nmol/liter at 6 months (P < 0.05). In conclusion, acromegaly is associated with changes in the central arterial pressure waveform, suggesting large artery stiffening. This may have important implications for cardiac morphology and performance in acromegaly as well as increasing the susceptibility to atheromatous disease. Large artery stiffness is reduced in cured acromegaly and partially reversed after pharmacological treatment of active disease.

Endothelial function and coagulant factors in growth hormone-treated hypopituitary adults receiving desmopressin.

Although GH deficiency may underlie the increased cardiovascular risk in adult hypopituitarism, other coexisting hormonal deficiencies and/or unphysiological hormone replacement may contribute. L-Deamino-8-D-arginine (DDAVP), when administered parenterally, potentiates hemostasis by increasing plasma procoagulant factors. We investigated whether chronic intranasal DDAVP therapy influences clotting factors (plasma fibrinogen, factor VIII, and von Willebrand factor antigen) and endothelial function (flow-mediated dilation of the brachial artery) in 30 GH-treated hypopituitary subjects, including both DDAVP-treated subjects (group A) (mean age, 46 +/- 11 yr) and vasopressin-sufficient subjects (group B) (mean age, 47 +/- 16 yr). Fifteen healthy controls (group C) (mean age, 48 +/- 12 yr) were also studied. All hypopituitary patients were receiving stable GH replacement (median duration, 19 months). Comparing the three groups, concentrations of fibrinogen (mean +/- SD) (A, 3.3 +/- 1.0 g/liter vs. B, 3.5 +/- 0.9 vs. C, 2.6 +/- 0.8, P < 0.05), factor VIII (A, 130% +/- 30% vs. B, 128% +/- 30% vs. C, 104% +/- 35%, P < 0.05) and von Willebrand factor antigen (A, 124% +/- 35% vs. B, 134% +/- 45% vs. C, 93% +/- 36%, P < 0.05) were higher in hypopituitary subjects, compared with controls. However, there were no differences in clotting factors between groups A and B. Flow-mediated dilation did not differ significantly between the two hypopituitary groups (A, 5.9% +/- 2.0% vs. B, 4.7% +/- 1.6%) and was similar to that in the control group (C, 5.7% +/- 2.1%). In conclusion, although endothelium-dependent vasodilation is intact in GH-treated hypopituitary adults, elevated concentrations of hemostatic markers suggest the persistence of a prothrombotic tendency and endothelial dysfunction. Intranasal DDAVP does not appear to influence this proatherogenic profile in hypopituitary adults with vasopressin deficiency.

Increased central arterial stiffness in hypothyroidism.

Hypothyroidism is associated with cardiovascular dysfunction. It is increasingly apparent that stiffening of central arteries may lead to increased afterload and cardiac dysfunction. We noninvasively studied the peripheral and central pressure waveforms in 12 untreated hypothyroid patients as well as in 12 age-, sex-, and body mass index-matched controls using the technique of pulse wave analysis from recordings at the radial artery. Indexes of arterial stiffness, augmentation index (AI) and augmentation of central arterial pressure (AG), were derived as well as time of travel of the reflected wave (TR), a direct estimate of aortic pulse wave velocity. At baseline, there were no significant differences between the 2 groups in brachial and aortic blood pressures. Hypothyroid patients had significantly higher AI than controls (mean +/- SEM[SCAP], 32.0 +/- 3.4% vs. 17.0 +/- 2.4%; P < 0.0005) even when corrected for heart rate (AI(C); 28.0 +/- 3.2% vs. 17.0 +/- 2.4%; P < 0.006) and AG (13.0 +/- 2.2 vs. 7.0 +/- 2.1 mm Hg; P < 0.03) together with a lower TR (132.0 +/- 4.1 vs. 142.0 +/- 1.5 msec; P < 0.03). After 6 months of therapy with T(4), all patients were euthyroid. AI(C) had decreased in the patient group (23.0 +/- 3.2% vs. 28.0 +/- 3.2%; P < 0.01) as had AG (9.0 +/- 1.5 vs. 13.0 +/- 2.2 mm Hg; P < 0.008), but TR was significantly higher (142.0 +/- 3.0 vs. 132.0 +/- 4.1 msec; P < 0.008). AI correlated with age in all groups (hypothyroid group: r = 0.937; P < 0.0005; control group: r = 0.804; P < 0.0005), but correlated with TSH level only among controls (r = 0.591; P < 0.05). This study confirms that hypothyroidism is associated with increased cardiovascular risk, as evidenced by increased augmentation of central aortic pressures and central arterial stiffness. Furthermore, these abnormalities are reversed after adequate T(4) replacement.

Effects of GH on lipid peroxidation and neutrophil superoxide anion-generating capacity in hypopituitary adults with GH deficiency.

OBJECTIVES: Untreated growth hormone deficiency (GHD) is implicated in the increased cardiovascular risk associated with adult hypopituitarism. Oxidative stress, predisposing to lipid peroxidation, may be an important mediator of endothelial dysfunction, a pro-atherogenic state associated with adult GHD. DESIGN AND PATIENTS: In a randomized, double-blind, placebo-controlled study we investigated the effects of GH replacement on low-density lipoprotein (LDL) oxidation and neutrophil superoxide (O(-)(2)) generating capacity in 32 GHD adults (19 males, 13 females; age range 19-64 years) over 3 months. Thirty age- and sex-matched healthy controls were also studied. MEASUREMENTS: Lipid hydroperoxides (HPOs) in plasma were measured using the ferrous oxidation with xylenol orange (FOX) assay. The susceptibility of LDL to oxidation was assessed by the copper-catalysed lag phase of LDL oxidation. Neutrophil O(-)(2)- generating capacity was assessed by a lucigenin-based chemiluminescent assay of NADPH oxidase activity. Body composition was assessed using bioelectrical impedance analysis. RESULTS: Compared to controls, GHD subjects had higher LDL cholesterol (4.0 +/- 0.8 vs. 3.5 +/- 0.9 mmol/l, P < 0.01) and higher triglyceride concentrations (2.3 +/- 1.5 vs. 1.1 +/- 0.7 mmol/l, P < 0.001) but lower HDL cholesterol (1.1 +/- 0.3 mmol/l vs. 1.4 +/- 0.4 mmol/l, P < 0.01), lower levels of HPOs (0.72 +/- 0.35 vs. 0.92 +/- 0.20 microm, P < 0.01) and lower basal (2.5 +/- 1.5 vs. 4.5 +/- 2.3 mV/5 x 10(5) neutrophils, P < 0.01) and peak post-activation levels (23.2 +/- 11.1 vs. 34.4 +/- 15.6 mV/5 x 10(5) neutrophils, P < 0.01) of neutrophil O(-)(2)- generation. GH replacement resulted in an increase in HPOs from 0.70 +/- 0.39 to 0.86 +/- 0.19 microm (P < 0.05), although there was no change in the lag time of LDL oxidation. Neutrophil O(-)(2)- generating capacity was enhanced with a rise in basal O(-)(2)- generation from 2.8 +/- 1.4 to 5.4 +/- 4.6 mV/5 x 10(5) neutrophils (P < 0.05) and in peak post-activation O(-)(2)- generation from 21.9 +/- 9.5 to 35.8 +/- 21.7 mV/5 x 10(5) neutrophils (P < 0.05). LDL cholesterol was reduced from 4.1 +/- 0.8 mmol/l to 3.5 +/- 0.8 mmol/l (P < 0.01). No significant changes in measured parameters occurred in the placebo group. CONCLUSIONS: Adult GHD is associated with reduced lipid peroxidation and impaired neutrophil O(-)(2)- generating capacity, both of which are reversible with GH replacement. Our data suggest that: (i) that oxidative stress is not a major feature of the pro-atherogenic state in hypopituitary adults with GHD and (ii) a role for GH in modulating neutrophil function and leucocyte-lipoprotein interactions.