Acquired neuro-secretory defect in growth hormone secretion due to Imatinib mesylate and the efficacy of growth hormone therapy in children with chronic myeloid leukemia.

Imatinib results in growth retardation in children with chronic myeloid leukemia (CML). The study was planned to assess the GHRH-GH-IGF1 axis in children with CML, receiving Imatinib and to evaluate the efficacy of human growth hormone (hGH) therapy. Twenty children with CML, receiving Imatinib for a period exceeding 6 months, with resultant growth retardation were included. The GHRH-GH-IGF1 axis was assessed using growth hormone stimulation tests. IGF-1 generation test was performed for the evaluation of GH insensitivity. The mean age at inclusion was 15.2 years. The mean duration of treatment with Imatinib was 5.7 years. The mean decrease in height SDS since the start of Imatinib was -0.95 (p = 0.008). IGF-1 SDS was <-2 in all the patients. 71.4% of patients had a suboptimal GH response following stimulation with GHRH-Arginine. All patients had stimulable, although a delayed GH response with glucagon stimulation. 20% of patients had GH insensitivity. Four patients were treated with hGH for a mean duration of 5.75 months, achieved normalization of IGF-1 levels and improvement in growth velocity improved from 0.21 to 0.86 cm/month. Imatinib results in an acquired neurosecretory defect in GH secretion. Treatment with growth hormone leads to an improvement in growth velocity and normalization of IGF-1.

Fabry's disease presenting as ventricular tachycardia and left ventricular 'hypertrophy'.

Fabry's disease (FD) is a genetic disorder leading to deficiency of alpha-galactosidase A. Enzymatic replacement therapy has recently become available. Patients with classical FD develop multi-system involvement; however, there is an increasingly recognized cardiac variant that presents as unexplained left ventricular hypertrophy. We describe a patient with Fabry's disease who presented with ventricular tachycardia.

Corrigendum to "Amiodarone Induced Hyponatremia Masquerading as Syndrome of Inappropriate Antidiuretic Hormone Secretion by Anaplastic Carcinoma of Prostate".

[This corrects the article DOI: 10.1155/2014/136984.].

Sternal fracture and osteomyelitis: an unusual complication of a precordial thump.

Out of hospital cardiac arrest is generally managed by cardiopulmonary resuscitation (CPR) and defibrillation. The precordial thump can also be used in the initial management of witnessed cardiac arrest whilst awaiting direct current cardioversion. However, complications are associated with a precordial thump. We report a case of an out-of-hospital cardiac arrest due to ventricular fibrillation that was treated initially with a precordial thump, which resulted in a sternal fracture and the development of sternal osteomyelitis.

Effect of perindopril on large artery stiffness and aortic root diameter in patients with Marfan syndrome: a randomized controlled trial.

CONTEXT: Aortic stiffness is increased in Marfan syndrome contributing to aortic dilatation and rupture, the major cause of premature death in this population. Angiotensin-converting enzyme inhibitors have been shown to reduce arterial stiffness. OBJECTIVE: To determine whether perindopril therapy reduces aortic stiffness and attenuates aortic dilatation in patients with Marfan syndrome. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled trial of 17 patients with Marfan syndrome (mean [SD], 33 [6] years) taking standard beta-blocker therapy, initiated in January 2004 and completed in September 2006, at Alfred Hospital Marfan Syndrome Clinic, Melbourne, Australia. INTERVENTION: Patients were administered 8 mg/d of perindopril (n = 10) or placebo (n = 7) for 24 weeks. MAIN OUTCOME MEASURES: Indices of arterial stiffness were assessed via systemic arterial compliance, and central and peripheral pulse wave velocities. Aortic root diameters were assessed at 4 sites via transthoracic echocardiography. RESULTS: Perindopril reduced arterial stiffness as indicated by increased systemic arterial compliance (mean [SEM], 0.33 [0.01] mL/mm Hg at baseline to 0.54 [0.04] mL/mm Hg at 24 weeks in perindopril group vs 0.30 [0.01] mL/mm Hg to 0.29 [0.01] mL/mm Hg in placebo group, P = .004), and reduced central (7.6 [0.4] m/s to 5.9 [0.3] m/s in perindopril group, P < .001 vs placebo) and peripheral (10.9 [0.4] m/s to 8.7 [0.4] m/s in perindopril group, P < .001 vs placebo) pulse wave velocities. In addition, perindopril significantly reduced aortic root diameters relative to placebo in both end-systole and end-diastole (P<.01 to P < .001 for all comparisons between groups). Although perindopril marginally reduced mean arterial pressure (from 81 [2] mm Hg to 80 [1] mm Hg in perindopril group vs 83 [2] mm Hg to 84 [3] mm Hg in placebo group, P = .004), the observed changes in both stiffness and left ventricular outflow tract diameter remained significant when mean arterial pressure was included as a covariate. Transforming growth factor beta (TGF-beta), which contributes to aortic degeneration in Marfan syndrome, was reduced by perindopril compared with placebo in both latent (59 [6] ng/mL to 45 [3] ng/mL in perindopril group, P = .01 vs placebo) and active (46 [2] ng/mL to 42 [1] ng/mL in perindopril group, P = .02 vs placebo) forms. CONCLUSIONS: Perindopril reduced both aortic stiffness and aortic root diameter in patients with Marfan syndrome taking standard beta-blocker therapy, possibly through attenuation of TGF-beta signaling. Large clinical trials are needed to assess the clinical benefit of angiotensin II blockade in Marfan syndrome. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00485368.

Closure of patent Potts shunt with aortic endoluminal stent graft.

Pulmonary hypertension secondary to residual Potts shunt is not an uncommon phenomenon. A 59-year-old male with a history of tetralogy of Fallot was noted, on a full heart study, to have persistent pulmonary hypertension, normal left ventricular function, severe aortic regurgitation, and a residual Potts shunt. A previous surgical attempt at closure of the shunt during definitive repair was unsuccessful. An aortic endoluminal stent graft was deployed to definitively close the shunt. There was a subsequent normalization of pulmonary pressures following Potts shunt closure. The patient will now proceed with surgical aortic root repair and aortic valve replacement.

Norepinephrine turnover is increased in suprabulbar subcortical brain regions and is related to whole-body sympathetic activity in human heart failure.

BACKGROUND: Although it is established that heightened sympathetic drive exists in congestive heart failure (CHF), the reflex processes by which this may occur and the sites in the central nervous system that may be responsible for mediating this process are not yet fully elucidated. METHODS AND RESULTS: Eight patients with moderate to severe CHF and 8 healthy control subjects underwent simultaneous arterial and bilateral internal jugular venous blood sampling and cerebral venous blood pool scanning for anatomical determination of the origin of internal jugular venous blood flow. We estimated sympathetic nervous activity by measuring total body norepinephrine (NE) spillover using radiotracer methodology and determined brain NE turnover by measuring the internal jugular overflow of NE and its lipophilic metabolites, 3-methoxy-4-hydroxyphenylglycol and 3,4-dihydroxyphenylglycol. Suprabulbar subcortical turnover of NE was significantly greater in CHF patients than in the healthy group (2.77 +/- 0.75 versus 0.66 +/- 0.40 nmol/min, P<0.05). There was a significant positive correlation between suprabulbar subcortical turnover of NE and total body NE spillover (r=0.62, P=0.01). CONCLUSIONS: This study, for the first time, demonstrates elevated suprabulbar subcortical noradrenergic activity in human CHF and identifies a positive correlation between this and the level of whole-body NE spillover. The findings suggest that the activation of noradrenergic neurons projecting rostrally from the brain stem mediates sympathetic nervous stimulation in CHF.

Factors that impact upon the time to hospital presentation following the onset of chest pain.

INTRODUCTION: Although morbidity and mortality associated with chest pain are related to time to intervention, many patients have delayed ED presentations. We aimed to assess the extent of and reasons for prehospital delay, and identify patient subgroups more at risk of delayed presentation. METHODS: This was an analytical, cross-sectional survey of patients with undifferentiated, potentially ischaemic chest pain, at a tertiary referral ED. Data were collected on the circumstances surrounding the chest pain incident (including components of total prehospital time) and the proportion of delayed presentations (defined as >3 h). Multiple linear regression determined variables significantly associated with prehospital time. RESULTS: One hundred and fifty patients were enrolled. Mean age was 51.9+/-15.9 years and 90 (60.0%, 95% CI 51.7-67.8) were male. The mean total prehospital time was 6.38 h (median 3.17). Seventy-nine (52.7%, 95% CI 44.4-60.8) patients had a delayed presentation (>3 h) and those most at risk of this were those at home at pain onset and those with a history of AMI. The decision time (from onset of pain to decision to present) comprised the majority (82.8%) of total prehospital time. Factors positively associated with decision time were: waiting to see if symptoms resolved (P<0.0001), seeking GP advice (P<0.0001), fluctuating symptoms (P=0.02), embarrassment (P=0.01) and attributing symptoms to muscle problems (P=0.04). Nine patients diagnosed with AMI had a mean total prehospital time of 10.2 h. CONCLUSION: Intensified efforts are required to promote awareness of the need to present directly to the ED upon the onset of chest pain. The factors associated with decision delay may help to inform revisions in public education initiatives.

Management of new onset atrial fibrillation in previously well patients less than 60 years of age.

OBJECTIVE: This study reviewed the ED management of new onset atrial fibrillation (AF) in previously well patients aged less than 60 years. METHODS: We undertook a retrospective review of ED patients from 1998 to 2002 inclusive. The main outcome measures were approaches to rate or rhythm control and anticoagulation, the use of echocardiography, the value of diagnostic testing and the frequency of hospital admission. RESULTS: Fifty-two patients were identified. In general, all patients were haemodynamically stable. One patient had mild cardiac failure and one was clinically thyrotoxic. Serum potassium was measured in 51 (98%) patients, magnesium in 23 (44%) and cardiac enzymes in 30 (58%); results were generally unhelpful. Thyroid function tests were carried out in 40 (77%) patients; results were unremarkable except for the clinically thyrotoxic patient. No patient had echocardiography in the ED; however, 6 patients (12%) were later found to have major cardiac abnormalities. Forty-four (85%) patients received a variety of medications; 37 (71%) received an anti-arrhythmic and 24 (46%) an antithrombotic. Overall, 17 (33%) patients received theoretically effective therapy for conversion to sinus rhythm. Twenty-two (42%) patients were admitted to hospital. CONCLUSIONS: This study reveals variation in the management of acute AF in previously well, haemodynamically stable, young patients. Pathology testing was frequently carried out with a low yield. There were high rates of attempts to cardiovert, use of antithrombotics and of admission to hospital. Although cardioversion attempts appeared to be contrary to existing guidelines, decisions may have been based primarily on patient symptoms. Echocardiography should be considered prior to anti-arrhythmic therapy.

Spontaneous diabetic myonecrosis: report of four cases from a tertiary care institute.

UNLABELLED: Spontaneous diabetic muscle infarction (DMI) is a rare and under diagnosed complication of diabetes mellitus. Clinically it presents with acute to subacute onset swelling, pain and tenderness of muscle(s) without systemic manifestations. MRI is helpful in diagnosis, exclusion of other causes and for localization of affected muscle for biopsy in atypical cases. Muscles of the thighs are commonly affected in diabetic myonecrosis (DMN). Here we present the summary of four cases seen in the last 3 years in a tertiary care centre with simultaneous or sequential involvement of multiple groups of muscles or involvement of uncommon sites. All these patients had advanced duration of diabetes with microvascular complications and poor glycemic control. Conservative management including rest and analgesics is the treatment of choice. Short-term prognosis is good but there may be recurrence. LEARNING POINTS: A high index of suspicion is required for the diagnosis of DMN which can avoid inadvertent use of antibiotics.Acute-subacute onset severe focal muscle pain in the absence of systemic symptoms in a female patient with long-standing diabetes with microvascular complications suggests DMI.MRI is the most sensitive test for diagnosis.Muscle biopsy should be reserved for atypical cases.Conservative management including rest and analgesics has good outcome.Improvement usually occurs within 6-8 weeks, but there may be recurrence.

Amiodarone induced hyponatremia masquerading as syndrome of inappropriate antidiuretic hormone secretion by anaplastic carcinoma of prostate.

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is one of the most common causes of hyponatremia. The usual causes are malignancies, central nervous system, pulmonary disorders, and drugs. Amiodarone is a broad spectrum antiarrhythmic agent widely used in the management of arrhythmias. The different side effects include thyroid dysfunction, visual disturbances, pulmonary infiltrates, ataxia, cardiac conduction abnormalities, drug interactions, corneal microdeposits, skin rashes, and gastrointestinal disturbances. SIADH is a rare but lethal side effect of amiodarone. We describe a 62-year-old male who was suffering from advanced prostatic malignancy, taking amiodarone for underlying heart disease. He developed SIADH which was initially thought to be paraneoplastic in etiology, but later histopathology refuted that. This case emphasizes the importance of detailed drug history and the role of immunohistochemistry in establishing the diagnosis and management of hyponatremia due to SIADH.

Disseminated cryptococcosis with hepatic dysfuction as the initial manifestation in an immunocompetent adult.

Disseminated cryptococcosis is rare in immunocompetent hosts and hepatic manifestations as the presenting feature is further rare. We report a case of disseminated cryptococcosis with hepatic involvement as an initial manifestation in a previously healthy, immunocompetent adult. A young married female presented with progressive jaundice, anorexia, weightloss, cough with expectoration, and hepatosplenomegaly. Biochemical profile showed liver function derangement with increased transaminases, alkaline phosphatase, bilirubin with deranged coagulation assay, and decreased albumin. The patient was treated initially for disseminated tuberculosis with associated sepsis, but she succumbed on the third day. Diagnosis of cryptococcosis was made on the basis of sputum culture, serology, and liver histopathology.

Non-islet cell tumor-induced hypoglycemia: a report of five cases and brief review of the literature.

UNLABELLED: We describe the clinical presentation, diagnostic and management issues in five cases of non-islet cell tumor hypoglycemia (NICTH), diagnosed at a tertiary care institute over a period of 15 years. The clinical, laboratory, and histopathological findings of these patients along with diagnostic utility of IGF2:IGF1 ratio are discussed. The mean age of presentation was 52 years, with a male predominance (3:2). Three patients presented with recurrent episodes of fasting hypoglycemia and it was detected in other two patients during hospitalization. Two patients had acromegaloid features that regressed following treatment. One patient had hypokalemia. Low levels of insulin, C-peptide, GH, and IGF1 were invariably found in all. The IGF2 level was elevated in only one patient; however, IGF2:IGF1 ratio was more than 10 in four of the five patients. The mean tumor size was 16.4 cm and mean weight was 3.6 kg. Four patients had mesenchymal tumors and one had epithelial tumor. NICTH is a rare cause of hypoglycemia. Hypoinsulinemic hypoglycemia with low IGF1 and IGF2:IGF1 ratio more than 10 is suggestive of this entity. LEARNING POINTS: NICTH should be considered in patients presenting with tumor of mesenchymal origin and hypoglycemia.Hypoinsulinemic hypoglycemia with low IGF1 is a strong biochemical evidence of NICTH.IGF2:IGF1 ratio of more than 10 is a complementary investigation in the absence of an assay facility for IGF2.

Can losartan and blood pressure control peri arteriovenous fistula creation ameliorate the early associated left ventricular hypertrophic response a randomised placebo controlled trial.

BACKGROUND: Haemodialysis results in a left ventricular hypertrophic response. It is unclear whether tight blood pressure control or particular medications might attenuate this response. We sought to determine, in a pre-dialysis cohort on atenolol, whether Losartan might attenuate left ventricular hypertrophy post arteriovenous fistula creation in end stage kidney disease. MATERIALS AND METHODS: Placebo controlled double blind randomisation of 26 patients to fixed dose atenolol plus fixed dose losartan or placebo occurred 1 day prior to fistula creation. Pre-randomisation echocardiography was repeated at 1 week and 1-month. Measurement was undertaken of blood pressure, heart rate, brain natriuretic peptide, serum creatinine and estimated glomerular filtration rate. The primary pre-specified endpoint was the change in left ventricular mass at 1 month. Non-parametric statistical comparison was performed within and between groups. RESULTS: There was no difference in left ventricular mass between our groups 1-month post fistula creation. In the entire cohort, change in left ventricular mass was driven by changes in blood pressure and volume loading. Blood pressure changes correlated with left ventricular mass changes seen shortly post arteriovenous fistula creation, suggesting blood pressure control during this time period may be an important part of the management of end stage kidney disease. CONCLUSIONS: We did not see an advantage with the use of losartan with respect to diminution of the LVM response. However, our demonstrated change in LVM was relatively small compared to previous literature and suggests a possible role for beta blockade as a neurohormonal modulator around the time of arteriovenous fistula creation. TRIAL REGISTRATION: Clinical trials.gov (NCT00602004).

A role for plasma transforming growth factor-beta and matrix metalloproteinases in aortic aneurysm surveillance in Marfan syndrome?

BACKGROUND: We have previously shown that the angiotensin-converting enzyme (ACE) inhibitor perindopril reduced aortic diameter by 3-7mm in Marfan syndrome (MFS) patients. Excessive signalling by the transforming growth factor-beta (TGF-beta) has been implicated in the development of aortic dilatation. We hypothesised that reduction in aortic diameter would correlate with reduction in plasma TGF-beta and matrix metalloproteinase (MMP) levels. METHODS: 17 MFS patients (aged 33+/-5 (mean+/-SD)) on standard beta-blocker therapy were randomised to also receive perindopril (n=10) or placebo (n=7) for 24 weeks in a double blind study. Aortic root diameters were assessed at four sites via transthoracic echocardiography. Venous blood samples were analysed for latent and active TGF-beta, MMP-2 and MMP-3 levels. RESULTS: Perindopril significantly reduced aortic root diameters relative to placebo in both end-systole and end-diastole (by 1.2-3mm/m(2), p<0.001). In addition, compared to placebo perindopril significantly reduced latent TGF-beta levels by 14.0+/-4.5ng/ml (p=0.01), active TGF-beta levels by 4+/-1ng/ml (p=0.02), MMP-2 levels by 22+/-6ng/ml (p<0.001), and MMP-3 levels by 5+/-1ng/ml (p<0.001). There were moderately strong correlations between the pre/post intervention change in aortic diameters and the change in both latent (r=0.49-0.76, p=0.001-0.04) and active TGF-beta (r=0.59-0.73, p=0.002-0.02), MMP-2 (r=0.63-0.75, p=0.001-0.007), and MMP-3 plasma levels (r=0.81-0.83, p<0.0001). CONCLUSIONS: Plasma TGF-beta, MMP-2 and MMP-3 should be further explored in longitudinal trials as potential prognostic indicators of progression of aortic dilatation and response to therapy in MFS.

Marantic endocarditis presenting as recurrent arterial embolisation.

Marantic endocarditis is a non-infective cause of valvular masses. It is most commonly associated with advanced malignancy. We report a case of rapidly progressive marantic endocarditis, complicated by valve destruction and recurrent systemic embolisation, in a patient whose cancer was occult.

Carvedilol reduces aldosterone release in systolic heart failure.

BACKGROUND: Treatment of advanced systolic heart failure (HF) with the aldosterone antagonist spironolactone on the background of angiotensin converting enzyme inhibition (ACEI) is well established. However, the only large prospective trial to investigate this therapy (RALES) predated the routine use of beta-blockade in HF. The widespread practice of combining ACEI, beta-blockers and spironolactone in HF management has led to serious concerns regarding hyperkalemia. Beta-blockade has been shown to reduce circulating angiotensin (Ang) II levels in HF patients established on ACEI therapy, possibly by renin suppression. OBJECTIVES: To measure the effects of addition of the beta-blocker carvedilol to optimal ACEI therapy on aldosterone release in HF. METHODS: Seventeen patients with NYHA Class II-III HF, left ventricular ejection fraction <35%, were stabilised on diuretic and ACEI therapy. Plasma was collected for measurement of Ang II, Ang I, aldosterone and amino-terminal-pro-B-type natriuretic peptide (NT-proBNP). A 24h urine collection was obtained for measurement of aldosterone/creatinine ratio. Carvedilol was then commenced and up titrated over the next 6-8 weeks and all samples were again obtained. RESULTS: Plasma Ang II levels decreased from 8.6 (0.8-94.6)fmol/mL, geometric mean (95% confidence interval) to 2.0 (0.1-61.9)fmol/mL, P=0.001, Ang I levels decreased from 96 (13-702)fmol/mL to 23 (0-1050)fmol/mL, P=0.002, and urine aldosterone/creatinine ratio decreased from 3.7 (0.9-14.8)nmol/mmol to 1.8 (0.4-8.9)nmol/mmol, P=0.01, with addition of carvedilol therapy. CONCLUSION: It is concluded that carvedilol suppresses aldosterone production in HF patients receiving ACEI therapy. However, the clinical importance of this finding needs to be further tested from the point of view both of the likelihood of clinical benefit from aldosterone antagonists as well as the risk of hyperkalemia and whether aldosterone levels are of predictive value.