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Background: Lesch-Nyhan disease (LND) is a disease of purine metabolism linked to chromosome X due to the absence or near-absence of enzyme hypoxanthine-guanine phosphoribosyltransferase. Patients with LND have a compulsive autoaggressive behavior that consists of self-mutilation by biting., Methods: The objective of this study was to explore the safety and efficacy of botulinum toxin (BoNT) injected into the masticatory muscles and biceps brachii to reduce self-mutilation in patients with LND. We retrospectively analyzed six patients with LND who were treated with BoNT to prevent automutilatory behavior., Results: The patient ages when started on treatment with BoNT were 4, 4.5, 6.6, 7.9, 13.9, and 32.3 years. Patients received a mean number of injections of 20, ranging from 3 to 29, over a period that ranged from 1.5 to 7.1 years. The maximum total dose of Botox was 21.3 units/kg mean and the maximum total dose of Dysport was 37.5 units/kg mean. A total of 119 injections were performed. Of these 113 (95%) were partially or completely effective. Only three of 119 injections (2.5%) produced adverse effects., Conclusions: Botulinum toxin is useful and safe for the treatment of self-biting behavior in patients with LND., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Bakground and Objective: To compare the efficacy of two strategies of blood pressure (BP) measurement-based follow-up in hypertension and albuminuria control., Patients and Methods: Multicentre, prospective, randomised, open trial with a parallel-group design. Nineteen primary care centres and a hospital clinic participated. Adult type 2 diabetics with systolic BP ≥140mmHg without relevant renal disease were randomised to one of two follow-up strategies: 1) standard follow up, with a clinic BP target <140/90mmHg and 2) self-monitoring home BP (SMHBP)-based follow up, with a BP target <135/85mmHg. Biochemical standard blood variables, albuminuria, and 24-h ambulatory BP monitoring were performed at entry, 12 and 24 months. The main outcome measurement was 24-h ambulatory systolic BP variation. Albuminuria change was analysed as a secondary outcome., Results: 116 patients were analysed (mean age: 66.8 years). Mean systolic ambulatory 24- h BP change in two years was 3.9mmHg (95% CI 1.8-6.1). We did not find significant differences between both groups (p=0.706). Similarly, no differences were found when we compared other ambulatory BP values. Initial albuminuria was similar in both groups and did not significantly changed throughout the follow-up period., Conclusion: In type 2 diabetics without relevant nephropathy a SMHBP- based follow up was equivalent to a standard clinic-based BP follow up in BP and albuminuria control., (Copyright © 2017 Elsevier España, S.L.U. All rights reserved.)

Objectives: To explore whether the increase in the intima-media thickness (IMT) in arteriosclerotic disease correlates with the increase in the IMT in temporal arteries (TAs) and if that could mimic the US GCA halo sign., Methods: Consecutive patients ⩾50 years old with high vascular risk and without signs or symptoms of GCA were included. The carotid US IMT measurements were obtained using a standardized software radiofrequency-tracking technology. Colour Doppler US and grey-scale measurements of the IMT in the branches of both TAs were performed by a second sonographer using a 22 MHz probe., Results: Forty patients were studied (28 men) with a mean age of 70.6 years. The carotid IMT exhibited significant correlation with the TA IMT. A carotid IMT >0.9 mm was associated with a temporal IMT >0.3 mm. Only one patient had an IMT >0.34 mm in two branches., Conclusions: Atherosclerotic disease with a carotid IMT >0.9 mm increases the TA IMT and might mimic the halo sign. As atherosclerosis is common in this age group, we propose a cut-off of TA IMT >0.34 mm in at least two branches to minimize false positives in a GCA diagnosis., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Combination antihypertensive therapies are recommended to attain blood pressure (BP) targets especially in high-risk patients in whom rapid and pronounced BP control is essential. This 28- to 54-week, open-label, multicenter study evaluated the safety and efficacy of a triple combination, aliskiren with amlodipine and hydrochlorothiazide (HCTZ), in patients with moderate to severe hypertension. Following a washout period of up to 4 weeks, patients received aliskiren/HCTZ 300/12.5 mg for 1 week, followed by add-on amlodipine 5 mg for 1 week. Thereafter, the doses of amlodipine and HCTZ were doubled. The first 206 of 564 patients who completed 28 weeks of study continued for an additional 26 weeks. Safety was assessed by recording all adverse events. Efficacy variables included changes in BP from baseline to endpoint and BP control rate. Of 564 patients, 493 completed the study. Peripheral edema (9.4%), headache (5.7%), nasopharyngitis (4.1%), and bronchitis (3.7%) were reported frequently. Clinically significant reductions in mean sitting systolic BP/mean sitting diastolic BP from baseline (-34.2/-20.3 mm Hg and -37.3/-21.8 mm Hg at weeks 28 and 54, respectively) were observed. Corresponding BP control rates were 69.1% and 77.1%. The aliskiren/amlodipine/HCTZ combination in patients with moderate to severe hypertension was well tolerated and provided clinically significant BP reductions and effective BP control., (© 2012 Wiley Periodicals, Inc.)

Aim: This 52-week, randomized, double-blind, parallel-group study was designed to compare rosiglitazone/metformin fixed-dose combination therapy with combination sulphonylurea plus metformin therapy in overweight individuals with inadequately controlled type 2 diabetes mellitus., Method: Individuals with inadequate glycaemic control (HbA (1c)> or =7%) while on metformin monotherapy (> or =0.85 g/day) entered a 4-week run-in period during which they received metformin 2 g/day. At the end of the run-in, individuals with fasting plasma glucose > or =7.0 mmol/l were randomized to treatment with metformin (2 g/day) and either rosiglitazone (4 mg/day; RSG+MET [N=294]) or a sulphonylurea (glibenclamide 5 mg/day or gliclazide 80 mg/day; SU+MET [N=302]). Medications were up-titrated to maximum tolerated doses (rosiglitazone 8 mg, glibenclamide 15 mg or gliclazide 320 mg plus metformin 2 g/day) during the first 12 weeks of double-blind treatment. The primary efficacy end point was the change in HbA (1c) from baseline after 52 weeks of treatment., Results: RSG+MET was non-inferior to SU+MET with respect to changes in HbA (1c) after one year of treatment (DeltaHbA (1c)= -0.78% and -0.86%, respectively; treatment difference =0.09%, 95% CI=-0.08, 0.25). The HbA (1c) reductions with RSG+MET, but not SU+MET, were accompanied by significant improvements in measures of beta-cell function including proinsulin:insulin ratio. The degree of beta-cell failure was significantly greater with SU+MET compared to RSG+MET as measured by the coefficient of failure (0.543 vs. 0.055 HbA (1c)%/year, respectively, p=0.0002). The proportion of individuals who experienced hypoglycaemic events was significantly (p<0.0001) lower with RSG+MET (6%) than with SU+MET (30%). Diastolic ambulatory blood pressure and cardiovascular biomarkers (high-sensitivity C-reactive protein and plasminogen activator inhibitor-1) were also reduced following one year of treatment with RSG+MET but not SU+MET. Both treatments were generally well tolerated., Conclusion: Fixed-dose combination therapy with rosiglitazone/metformin is non-inferior to sulphonylurea plus metformin combination therapy in reducing HbA (1c) over one year of treatment. Improvements in measures of beta-cell function suggest that the improvements in glycaemic control may be better maintained in long-term therapy with the rosiglitazone/metformin combination.

Background: Ambulatory blood pressure (BP) is more sensitive than office BP and is highly correlated with the left ventricular mass (LVM) of hypertensive patients with left ventricular hypertrophy (LVH)., Methods: In this prospectively designed ancillary study of the PICXEL trial, the effects of first-line combination perindopril/indapamide on ambulatory BP were compared with those of monotherapy with enalapril in 127 patients. Hypertensive patients with LVH received once daily either perindopril 2 mg/indapamide 0.625 mg (n = 65) or enalapril 10 mg (n = 62) for 52 weeks. Dose adjustments were allowed for uncontrolled BP. Twenty-four-hour ambulatory BP and echocardiographic parameters were measured at baseline, week 24, and week 52., Results: At study end, both treatments significantly improved ambulatory BP compared with baseline (p < or = 0.01). Perindopril/indapamide treatment reduced 24-hour and daytime systolic BP (SBP) and pulse pressure (PP) significantly more than enalapril treatment (p < 0.01). No significant between-group differences were noted for diastolic BP (DBP) or for night-time measurements. Trough/peak ratios were higher with perindopril/indapamide than with enalapril (88.5 vs 65.8 for SBP and 86.7 vs 63.9 for DBP, respectively). The global smoothness index was higher with perindopril/indapamide than with enalapril (6.6 vs 5.2 for SBP and 5.6 vs 4.9 for DBP, respectively). With perindopril/indapamide treatment, LVM index was significantly reduced (-9.1 g/m2 from baseline; p vs baseline <0.001). More patients required dose increases with enalapril (87%) than with perindopril/indapamide (71%). No unusual safety elements were noted., Conclusions: First-line perindopril/indapamide combination decreased ambulatory SBP and PP, and LVM more effectively than enalapril.

Hypothesis: The efficacy of a treatment in a clinical trial depends in part on where the cut-off point is placed for the test result used to select patients for the trial, and this applies to irbesartan in the Irbesartan Microalbuminuria II (IRMA II) trial for preventing nephropathy., Patients and Methods: Patients in the IRMA II trial were stratified into different pre-treatment albumin excretion rate (AER) ranges to compare the proportion of patients starting in these different ranges (i) that progressed to develop nephropathy within 24 months and (ii) whose AER was over 40 microg/minute at three months., Results: The proportion of patients with pre-treatment AER values between 20 and 40 microg/minute progressing to develop nephropathy was 1.25% in the placebo group and 0.78% in the irbesartan group, while for pre-treatment AER values between 41 and 200 microg/minute, 24.4% and 11.2% develop nephropathy respectively in the placebo and irbesartan groups. In patients with a pre-treatment AER of 20 to 30 microg/minute, 32.5% and 13.6% respectively in the placebo and irbesartan groups had a value exceeding 40 microg/minute at three months., Conclusions: The data demonstrate that irbesartan is effective in reducing the onset of nephropathy within two years when the pre-treatment AER is above 40 microg/minute, but if the AER is below this level it progresses unusually to nephropathy within two years. Irbesartan also slows progression of AER to over 40 microg/minute for patients with pre-treatment AER values at or above 20 microg/minute and these patients should be treated.

In type 2 diabetic hypertensive patients, microalbuminuria can be due to hypertension and/or diabetic nephropathy. Angiotensin-converting enzyme (ACE) inhibitors act preferentially on microalbuminuria due to diabetic nephropathy. The objective is to demonstrate the efficacy of a thiazide-like diuretic, indapamide sustained release (SR), at reducing microalbuminuria in hypertensive type 2 diabetic patients in comparison with an ACE inhibitor, enalapril. The study is an international multicentre, 12-month, randomized, double-blind, controlled, two parallel group study of type 2 diabetic patients with hypertension (140 mmHg < or = systolic blood pressure <180 mmHg and diastolic blood pressure <110 mmHg) and microalbuminuria. Intervention is after a 4-week placebo period, patients with microalbuminuria > or = 20 and < or = 200 microg/min are randomized to indapamide SR 1.5 mg or to enalapril 10 mg once a day for a one-year treatment period. An additional label treatment by amlodipine 5-10 mg (1st step) and atenolol 50-100 mg (2nd step) a day is permitted after 6 weeks of treatment based upon blood pressure response. The main outcome measures are microalbuminuria expressed as urinary albumin to creatinine ratio, albumin fractional clearance, and albumin excretion rate evaluated on overnight urine collections. Secondary criteria are supine and standing systolic, diastolic and mean blood pressure; and biological and clinical safety. This study will complete the knowledge of the efficacy of indapamide SR in hypertension and target organ damage and will provide valuable information on the management of type 2 diabetic hypertensives with microalbuminuria.

Background: Hyperuricemia can be the consequence of an increased urate production, a decreased renal excretion, or both. An increased prevalence of hyperuricemia has been described in essential hypertensive patients partly due to a decreased renal urinary urate excretion (UUE). Hyperuricemia has been shown to be associated with an increased risk of cardiovascular disease in hypertensive patients in some but not in all epidemiological studies in which this relationship has been investigated., Objective: To assess the influence of low UUE in the association between serum urate, renal function and hypertension severity., Patients and Methods: This cross-sectional study was carried out in a sample of 677 male hypertensive patients, aged 35-60 years, with essential arterial hypertension consecutively attended in a hospital hypertension unit. The presence of hypertension-related organ damage at diagnosis was classified according to classical WHO criteria as grade 1, 2 or 3. Urate underexcretion was defined as 24-h urinary urate below the product serum urate x 100., Results: Mean serum urate levels were 6.4 +/- 1.6 mg/dl in the total sample. Hyperuricemia (serum urate >7 mg/dl) was present in 28.5% of patients and only 17.0% had underexcretory hyperuricemia. This subgroup of patients exhibited the higher rate of hypertension-related target organ damage (TOD). A multivariate analysis, showed that underexcretory hyperuricemia but not hyperuricemia remained an independent predictor of TOD (odds ratio 2.5. 95% CI 1.6-3.89). Serum urate correlated positively with serum creatinine in hyperuricemic patients (r = 0.50, p < 0.001), but not in patients with underexcretory hyperuricemia (r = 0.21, p = 0.18)., Conclusions: Underexcretory hyperuricemia is strongly related to hypertensive organ damage and this relationship does not seem to be mediated by a decreased renal function. This aspect could underline the predictive value of hyperuricemia independently of serum creatinine. UUE could improve the clinical predictive value of hyperuricemia as a cardiovascular risk factor.

Increased serum urate concentration is commonly seen in clinical practice. It does not represent a specific disease, nor is it an indication for therapy. Hyperuricemia can be the consequence of increased uric acid production and/or decreased renal capacity to excrete uric acid. In essential hypertension, it has been described in up to one third of patients and is directly related to an increase in renal vascular resistance and inversely correlated with renal plasma flow. In other words, abnormal renal hemodynamics, commonly seen in the initial stages of the disease, account for the increased serum urate concentration. This can be maintained if a decrease in glomerular filtration rate takes place. The increase in uric acid has been shown to be a potent predictor of the development of cardiovascular events and death. In addition, uric acid, particularly when elevated, could represent an independent risk factor. On the other hand, an altered renal function predicts in an independent manner a higher cardiovascular risk. For this reason, the predictive capacity of uric acid could be partly dependent on the fact that hyperuricemia runs in parallel with a deranged renal function.

Objective: To compare the efficacy and tolerability of angiotensin II (Ang II) antagonist losartan and the beta-blocker atenolol in the treatment of patients with isolated systolic hypertension (ISH) after 16 weeks of treatment., Methods: A double-blind, randomized, multi-country study was carried out in 273 patients with ISH. Patients with a sitting systolic blood pressure (SiSBP) of 160-205 mmHg, and a sitting diastolic blood pressure (SiDBP) < 90 mmHg at screening and at placebo baseline were subjected to a 4-week placebo period and then randomly grouped to receive 50 mg losartan or 50 mg atenolol once daily for 16 weeks. At 8 and 12 weeks, patients not controlled (SiDBP > or = 160 mmHg) were given additional treatment of 12.5 mg hydrochlorothiazide (HCTZ) once daily., Results: Similar significant reductions in SiSBPs (mean +/- SD) were obtained with 50 mg losartan and 50 mg atenolol, from 173.7 +/- 10.3 and 173.5 +/- 10.7 mmHg at baseline to 149.0 +/- 15.5 and 148.2 +/- 15.3 mmHg after 16 weeks of losartan or atenolol treatment respectively. Sixty-seven percent of the losartan-treated and 64% of the atenolol-treated patients remained on monotherapy throughout the study. Only 1.5% of the losartan-treated patients withdrew because of a clinical adverse event (CAE) compared with 7.2% in the atenolol-treatment group (P= 0.035). Drug-related CAEs were observed significantly more frequently with atenolol than with losartan treatment (20.3 versus 10.4%; P = 0.029)., Conclusion: It is concluded that 50 mg losartan and 50 mg atenolol produced comparable reductions in SiSBP in patients with ISH but losartan was better tolerated. This is the first demonstration of the therapeutic value of selective Ang II receptor blockade with losartan in the treatment of ISH.

A double-blind, randomised, parallel group, multicentre, multinational study compared the effects of 12 months' treatment with lisinopril (10-20 mg once daily) or nifedipine retard tablets (20-40 mg twice daily) in 239 males (aged 18-75 years) and 96 post-menopausal females (aged 40-75 years). They all had a history of clinically stable type II diabetes > 3 months, microalbuminuria and early diabetic nephropathy (a urinary albumin excretion (UAE) rate ranging from 20 to 300 micrograms/min) and a sitting diastolic blood pressure (DBP) 90-100 mm Hg (Korotkoff phase V) inclusive at both entry and after 3-4 weeks' placebo treatment. The aim of treatment was to achieve a reduction in sitting DBP to < 90 mm Hg 24-30 h after the last dose of lisinopril or 12-18 hours after the last dose of nifedipine and to evaluate the effect of these treatments on UAE over 12 months. The effect of the two treatments on ambulatory blood pressure (BP) was also evaluated in a subset of patients. Management of diabetes with oral hypoglycaemic drugs, diet and insulin alone or in combination was permitted. Median UAE fell on lisinopril from 65.5 (range 20-297) micrograms/min at baseline to 39.0 (2-510) micrograms/min after 12 months. On nifedipine median UAE fell from 63.0 (range 20-289) micrograms/min at baseline to 58.0 (9-1192) micrograms/min after 12 months. The estimated median difference between the effects of the two treatments was 20 micrograms/min (P = 0.0006). Over 12 months both treatments produced similar falls in sitting BP from 163 +/- 17/99 +/- 6 mm Hg (mean +/- s.d.) to 147 +/- 18/88 +/- 10 mm Hg for lisinopril and from 161 +/- 18/97 +/- 5 mm Hg to 150 +/- 18/88 +/- 9 mm Hg for nifedipine. Ambulatory BP was assessed in a subset of patients and using areas under the BP-time curve (AUC) a comparison of the effects of the two treatments showed no between-treatment differences. Creatinine clearance, glycaemic control (HbA1c) and lipid profiles did not change significantly during either treatment. Frequency of withdrawals and adverse events were similar for both treatments. We conclude that lisinopril has a significantly more beneficial effect on UAE than nifedipine despite similar effects on both BP and glycaemic control in type II diabetic patients with hypertension.

Pulmonary function was studied in 22 patients with systemic lupus erythematosus without pulmonary clinical symptoms. The most striking features were: a) a restrictive functional pattern with hyperinflation, characterized by a decreased vital capacity and increased residual volume; b) alteration of the elastic properties of the lung, with increased pulmonary elastance; c) impairment of the alveolar-capillary gas transfer capacity, with very significant changes of the CO diffusion and arterio-alveolar gradients for O2 and CO2. No marked differences were found in functional disturbance among patients in the active or inactive phase of the disease.

We reviewed 2110 bone marrow aspirations from the same number of patients to establish the incidence and associations of peripheral and bone marrow basophilia. Of these, 125 cases of marrow basophilia (5.9% incidence) and 63 cases of peripheral basophilia (3.0% incidence) were identified. There were 33 patients with simultaneous marrow and peripheral basophilia, which was only significantly associated with chronic myelogenous leukemia (24 cases). Isolated peripheral basophilia was rarely seen (30 patients, 1.4% incidence) and it did not reflect any significant pathologic association. Marrow basophilia was significantly present in chronic myeloproliferative disorders, idiopathic myelodysplasia, certain erythrocyte disorders, such as iron deficiency anemia, and aplastic anemia. The incidence of marrow basophilia in patients with lymphoma, acute leukemia, or solid carcinoma was not significantly different from what it would be as a chance occurrence. Our findings suggest that marrow basophilia is a specific, but not sensitive, marker of myeloproliferative and dysmyelopoietic syndromes.

Pyrazinamide and probenecid tests were used to study the renal mechanisms for urate excretion in 10 normal subjects in the state of low serum uric acid levels (below 3.5 mg/dl), normal serum urate concentrations (between 3.6 and 6.4 mg/dl) and high serum uric acid levels (above 6.5 mg/dl). Presecretory reabsorption of urate was above 99% in all three conditions of uricemia, indicating that filtered urate is nearly completely reabsorbed in the proximal tubule regardless of serum uric acid concentrations. Urate secretion was significantly higher and postsecretory reabsorption was significantly lower when serum uric acid was raised than when serum urate levels were normal or low. The findings indicate that both urate secretion and postsecretory reabsorption play a role in urate homeostasis in states of hyperuricemia.