Angiotensin-converting enzyme inhibitor (ACE-I)- and angiotensin receptor blocker (ARB)-related angioedema: A neglected issue in daily practice in Greece

Several reports on angioedema (AE) related to the use of angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARB) have been published recently. This study reports on the experience gained at the Ear, Nose, and Throat (ENT) Clinic of the University Hospital of Heraklion, Crete. A retrospective chart review of the patients admitted to this clinic, in a 42-month period (1999–2003), and discharged with a diagnosis ENT code for AE was performed (14 eligible patients). A complementary telephone survey was conducted during January 2005. Ten patients responded to our invitation. Of those patients, five were under ACE-I and one was under ARB treatment during the AE episode. The mean length of time between the onset of symptoms and presentation to the hospital was 4.5 hours (range 0.5–12 hours). The mean duration between the initiation of antihypertensive treatment and AE episode was 26.2 months (range 1–60 months). Patients reported that no information was provided about the possible adverse effects of these drugs. Although AE introduced by ACE-I and ARBs is an uncommon side effect, this case series conveys a key message to primary care physicians.     

高通量血液透析和低通量血液透析不同模式对老年维持性血液透析患者血压的影响

目的 观察高通量血液透析(HFHD)与低通量血液透析(LFHD)的不同模式运用到老年患者维持性血液透析(MHD)中对其血压的影响。方法 选择2015年2月—2017年10月本院治疗的MHD老年患者74例,先为其施LFHD 3个月,再为其辅以3个月的HFHD,3次/周,4 h/次,对比不同透析模式对患者血压的影响。结果 实施HFHD后患者的平均动脉压(MAP)有所降低,在第3 h与第4 h透析后,血压把控优于LFHD(P<0.05)。结论 对于MHD老年患者来说,实施HFHD是优良的透析方法。     

A Multicenter,Open-Label,Observational Study of Testosterone Gel (1%) in the Treatment of Adolescent Boys With Klinefelter Syndrome or Anorchia

PurposeTo assess the safety and clinical outcomes of 6-month treatment with testosterone gel 1% therapy in adolescent boys with primary hypogonadism resulting from Klinefelter syndrome (KS) or anorchia.MethodsThis was a subgroup analysis of a multicenter, open-label study of adolescent boys (N = 86) with delayed puberty who received .5–5.0 g testosterone gel 1% daily for ≤6 months. Adolescent boys 12–17 years of age with KS (n = 21) or anorchia (n = 8), bone age ≥10.5 years, and baseline growth data ≥6 months were included in this analysis. Serum hormone levels (total/free testosterone, luteinizing hormone, dihydrotestosterone, follicle-stimulating hormone, and estradiol) were measured using validated assays. Safety was assessed through adverse events (AEs).ResultsAt baseline, patients with KS were taller, weighed more, and had higher total testosterone levels (mean 174 vs. 19 ng/dL) than patients with anorchia. At 6 months, total and free testosterone and dihydrotestosterone levels increased 1.8- to 2.3-fold in the KS group and eight- to 10-fold in anorchia patients. Estradiol levels increased 1.9-fold in the anorchia group and 1.4-fold in the KS group after treatment. No clinically significant changes were noted for luteinizing hormone, follicle-stimulating hormone, and sex hormone–binding globulin concentrations in either group. Cough was the most common AE (eight of 29), followed by acne and headache (both four of 29). One anorchia and two KS patients discontinued prematurely.ConclusionsOnce-daily testosterone gel application increased serum testosterone levels into the pubertal range and maintained pubertal testosterone levels during 6-month treatment. In this study, testosterone gel 1% raised testosterone levels and was associated with cough as the most common AE.     

Clinical inquiries. Which combination drug therapies are most effective for hypertension?

Insufficient evidence exists to determine which specific combinations most effectively decrease cardiovascular morbidity and mortality, although combinations of hypertension medications at lower doses generally reduce cardiovascular outcomes (stroke, coronary heart disease) more than monotherapy (strength of recommendation [SOR]: A, large meta-analyses).The combination of benazepril and amlodipine reduces the composite endpoint of cardiovascular events and deaths more than benazepril plus hydrochlorothiazide with similar rates of adverse effects (SOR: A, randomized controlled trial [RCT]).Combining an angiotensin converting enzyme inhibitor (ACE-I) with a thiazide, ?-blocker, or calcium channel blocker produces side effects similar to monotherapy, as does combining an angiotensin receptor blocker (ARB) with a thiazide or calcium channel blocker (SOR: A, meta-analyses). However, an ACE-I combined with an ARB increases the risk of renal complications and death more than monotherapy (SOR: A, RCT)..     

Long term thyroid function after (131)I treatment for toxic adenoma

Radioactive iodine is a widely used treatment for hyperthyroidism caused by solitary autonomously functioning thyroid nodule (toxic adenoma). The aim of this retrospective analysis is to report the long term effects of this therapy on the thyroid function of patients with toxic adenoma treated in our department. Between 1968 and 1996, 160 patients received a single dose of (131)I (range 25-40 mCi) for hyperthyroidism caused by toxic adenoma. In 126 of these (110 females, 26 males), follow-up was feasible either in our Endocrine Outpatient Clinic or through correspondence. The mean observation period was 5.3 years (range 1-21 years, median 4.0). Post treatment evaluation revealed that: a) 57 patients became euthyroid and remained free of disease up to the last visit (mean observation period 5.76+/-0.52 years, range 1-21 years, median 5 years), b) 69 patients developed hypothyroidism, all within 1 to 12 months (5.9+/-0.49 months), c) persistence or recurrence of the disease (ie. thyrotoxicosis) was not observed, d) the (131)I dose, or the (131)I pretreatment TSH levels were not different between patients who developed hypothyroidism and those who became and remained euthyroid. CONCLUSION: 131I administration in the above-mentioned dose to patients with toxic adenoma: a) was a safe and very effective therapy, and b) led to hypothyroidism which developed within the first year after (131)I administration in 55% of the patients.     

Evaluation of diet and growth in children with and without atopic eczema: follow-up study from birth to 4 years

Current research into dietary factors contributing to the development of allergic diseases is directed towards new active approaches instead of passive elimination diets. The present study aimed to investigate the explanatory role of the diet in a probiotic intervention study on the appearance of atopic eczema (AE) in childhood and the safety of perinatal supplementation with probiotics (Lactobacillus rhamnosus strain GG; ATCC 53 103). A prospective follow-up study from birth to 48 months of children (n 159) with a family history of allergic disease was carried out. Outcome measures included growth, dietary intake assessed with 4 d food diaries and their association with AE by logistic regression models. Increased intakes of retinol, Ca and Zn, with perinatal administration of probiotics, reduced the risk of AE, whilst an increase in intake of ascorbic acid increased the likelihood of AE. Perinatal administration of probiotics was safe, as it did not influence the height (mean difference 0.04 (95 % CI -0.33, 0.40) sd scores, P=0.852) or the weight-for-height (mean difference -3.35 (95 % CI -7.07, 0.37)%, P=0.077) of the children at 48 months with and without perinatal administration of probiotics. Up to 48 months, AE did not affect height (mean difference -0.05 (95 % CI -0.42, 0.33) sd scores, P=0.815), but mean weight-for-height in children with AE was -5.1 % (95 % CI -8.9, -1.2 %) lower compared with children without (P=0.010). The joint effects of nutrients and probiotics need to be considered in active prevention and management schemes for allergic diseases.     

Efficacy of epigallocatechin-3-gallate and Amla (Emblica officinalis) extract for the treatment of diabetic-uremic patients

Uremic patients with diabetes suffer from high levels of oxidative stress due to regular hemodialysis therapy (neutrophil activation induced by hemo-incompatibility between the hemodialyser and blood) and complications associated with diabetes. Several plasma biomarkers were screened in 13 uremic diabetic patients after receiving the mixture of (-)-epigallocatechin gallate (EGCG), a major component of green tea extract, and Amla extract (AE), from Emblica officinalis, the Indian gooseberry, for 3 months. We found that oral administration of a 1:1 mixture of EGCG and AE for 3 months significantly improved antioxidant defense as well as diabetic and atherogenic indices in uremic patients with diabetes. Furthermore, no significant changes in hepatic function, renal function, or inflammatory responses were observed. These results suggest that a 1:1 combination of EGCG and AE is a safe and effective treatment for uremic patients with diabetes.     

Malaria: treatment efficacy of halofantrine (WR 171,669) in initial field trials in Thailand

Halofantrine (WR 171,669) hydrochloride was administered orally to 82 patients infected with Plasmodium falciparum malaria on the Thai—Kampuchean border between June 1982 and December 1983 in a randomized double-blind treatment trial which compared the efficacy of halofantrine with that of mefloquine. Halofantrine was curative with oral treatment on a single day in 65% of patients (13/20) who received 1000 mg followed 6 hours later by an additional 500 mg, and in 88% of patients (53/60) who received 500 mg every 6 hours for 3 doses. Mefloquine was curative in 88% of patients (22/25) given a single oral dose of 1000 mg and in 97% of patients (38/39) given a single oral dose of 1500 mg. The difference in cure rates between the 3-dose halofantrine regimen and either of the mefloquine regimens was not significant. The mean parasite clearance time for all regimens ranged from 75 to 84 hours. The mean fever clearance time for all four treatment groups was in the range 50-60 hours, with no significant differences between groups. Post-dosing side-effects in patients treated with halofantrine consisted of nausea, vomiting, abdominal pain and diarrhoea and were not significantly different from those treated with mefloquine. Halofantrine therefore appeared to be of comparable efficacy to mefloquine in the treatment of multidrug-resistant P. falciparum malaria.     

Controlled trial of a Y-set dialysis delivery system to prevent peritonitis in patients receiving continuous ambulatory peritoneal dialysis.

Peritonitis rates were compared in patients receiving continuous ambulatory peritoneal dialysis (CAPD) via either a Y-set dialysate delivery system or a standard system. Forty patients in each arm of the trial were matched for age (range 20-67 years, mean 49 years), and remained in the study for similar periods (range 3-36 months, mean 14.1 months). The observation time was 564 patient-months for each arm of the trial. There were 22 episodes of peritonitis in nine out of 40 patients using the Y-set and 57 episodes in 21 out of 40 patients using the standard system (P = 0.005 Wilcoxon signed rank test for episodes, P = 0.02 McNemar's chi 2 test for patients). Peritonitis rates were one episode per 25 patient-months in the Y-set group, and one episode per 9.7 patient-months in the standard group. In the Y-set group there were significantly fewer episodes caused by coagulase-negative staphylococci and Acinetobacter spp. There was no difference in the rate of episodes caused by Staphylococcus aureus, streptococci, enterococci, corynebacteria, enterobacteria or pseudomonads. There was no difference in the incidence of catheter exit wound infections. The Y-set dialysis delivery system is effective in reducing peritonitis rates in CAPD patients caused by organisms derived from the commensal skin flora, principally coagulase-negative staphylococci, but does not reduce peritonitis caused by other organisms.     

Neurological complications of vaccination with outer surface protein A (OspA)

A wide range of neurological complications have been reported via the medical literature and the VAERS system after vaccination with recombinant outer surface protein A (OspA) of Borrelia. To explore this issue, 24 patients reporting neurological adverse events (AE) after vaccination with Lymerix, out of a group of 94 patients reporting adverse events after Lymerix vaccination, were examined for causation. Five reports of cerebral ischemia, two transient Ischemic attacks, five demyelinating events, two optic neuritis, two reports of transverse myelitis, and one non-specific demyelinating condition are evaluated in this paper. Caution is raised on not actively looking for neurologic AE, and for not considering causation when the incidence rate is too low to raise a calculable difference to natural occurence.     

An epidemiological study of rotavirus diarrhoea in a cohort of Nigerian infants: II. Incidence of diarrhoea in the first two years of life

In a community-based prospective study of diarrhoeal diseases carried out in Ibadan, 131 infants were selected at birth. The maximum possible length of follow-up ranged from 16 to 24 months. Weekly surveillance for diarrhoea was carried out at home by Primary Health Care workers. Each child was also required to attend a monthly clinic. Of the 131 babies, 95 (73%) completed at least one year of follow-up. All of these had at least one episode of diarrhoea within the first year of life. The incidence rate of diarrhoea in the first year of life was 3.2 cases/child/year. The mean duration of diarrhoea days in the first year of life was 16 per child per year (range 3-34 days). The peak incidence of diarrhoea and the greatest number of diarrhoea days were in the age interval 6-9 months. The mean duration of diarrhoea was five days per episode. Faecal samples for 280 diarrhoea episodes during the first year of life were examined for rotavirus using the ELISA technique: 22 (7.7%) were found to be positive. The mean duration of rotavirus diarrhoea episodes was eight days.     

Rifampicin and sodium fusidate reduces the frequency of methicillin-resistant Staphylococcus aureus (MRSA) isolation in adults with cystic fibrosis and chronic MRSA infection

Nosocomial transmission of methicillin-resistant Staphylococcus aureus (MRSA) to patients with cystic fibrosis (CF) frequently results in chronic respiratory tract carriage. This is an increasing problem, adds to the burden of glycopeptide antibiotic use in hospitals, and represents a relative contraindication to lung transplantation. The aim of this study was to determine whether it is possible to eradicate MRSA with prolonged oral combination antibiotics, and whether this treatment is associated with improved clinical status. Adult CF patients (six male, one female) with chronic MRSA infection were treated for six months with rifampicin and sodium fusidate. Outcome data were examined for six months before treatment, on treatment and after treatment. The patients had a mean age of 29.3 (standard deviation=6.3) years and FEV(1) of 36.1% (standard deviation=12.7) predicted. The mean duration of MRSA isolation was 31 months. MRSA isolates identified in these patients was of the same lineage as the known endemic strain at the hospital when assessed by pulsed-field gel electrophoresis. Five of the seven had no evidence of MRSA during and for at least six months after rifampicin and sodium fusidate. The proportion of sputum samples positive for MRSA was lower during the six months of treatment (0.13) and after treatment (0.19) compared with before treatment (0.85) (P<0.0001). There was a reduction in the number of days of intravenous antibiotics per six months with 20.3+/-17.6 on treatment compared with 50.7 before treatment and 33.0 after treatment (P=0.02). There was no change in lung function. Gastrointestinal side effects occurred in three, but led to therapy cessation in only one patient. Despite the use of antibiotics with anti-staphylococcal activity for treatment of respiratory exacerbation, MRSA infection persists. MRSA can be eradicated from the sputum of patients with CF and chronic MRSA carriage by using rifampicin and sodium fusidate for six months. This finding was associated with a significant reduction in the duration of intravenous antibiotic treatment during therapy.     

Modifications in cyclosporine (CsA) microemulsion blood concentrations by olestra.

OBJECTIVE: Determine whether olestra alters the absorption of cyclosporine microemulsion in pediatric renal transplant recipients. DESIGN: Prospective, open-label, crossover pharmacokinetic study. SETTING: General clinical research center in a university medical setting providing tertiary care. PARTICIPANTS: Seven pediatric-adolescent renal transplant recipients, ages 9 to 18, 5 to 24 months post-transplant with mean serum creatinine of 0.9 mg/dL (range, 0.7-1.6 mg/dL). METHODOLOGY: Patients participated in 2 study periods: 1. Patients were given their usual dose of Neoral (Novartis Pharmaceuticals Corporation, East Hanover, NJ) without olestra, 2. patients were given their usual dose of Neoral combined with 0.35 g/kg (maximum of 16 g of olestra or approximately 2 ounces of Lays WOW [Frito Lay, Plano, TX] potato chips). The 2 study periods were separated by a minimum 7-day washout period. CsA blood concentrations were obtained at 1, 2, 3, 4, 6, 8, and 12 hours after drug administration. RESULTS: Each patient in the study had a consistent decrease in area under the curve (AUC) when given olestra along with their usual dose of Neoral, compared with giving Neoral alone (5,018 ng*hr/mL versus 4,086 ng*hr/mL; P <.001). There also was a decrease in maximum concentration (Cmax) when Neoral was given with olestra compared with giving Neoral alone (1,202 ng/mL versus 876 ng/mL; P =.015). There was no statistical difference in the mean elimination rate or the trough values for both regimens (half-life 4.767 hours versus 4.771 hours and trough levels of 143 ng/mL versus 124 ng/mL). CONCLUSION: Olestra decreases total CsA exposure in pediatric renal transplant recipients. The noted decrease in AUC was not adequately predicted by CsA trough values which could lead to rejection episodes in the clinical setting.     

Outcome variables in the evaluation of alcoholics' treatment: lessons from the Italian Assessment of Alcoholism Treatment (ASSALT) Project

The observational evaluation of alcoholics' treatments requires a combined analysis of alcoholic behaviour during treatment and of adherence to therapeutic programmes. The application of survival analysis techniques in this setting has been explored in this study. Two hundred and seventy alcoholics admitted to 15 Italian treatment units in a 1-year period were followed-up for 2 years, recording date and length of every recurrence episode and of definitive or transitory interruption of the planned treatment. An extensive use of several survival analysis techniques was made. The length of time between the start of the treatment and the first episode of relapse did not give a reliable measure of frequency of failures. Conversely, the length of time between the start of treatment and withdrawal appeared to be unbiased. The cumulative proportions of treatment-compliant patients (and the corresponding 95% confidence intervals) were 71% (66-76%), 63% (57-69%) and 53% (47-60%) after 6 months, 1 year and 2 years respectively from the start of treatment. Cumulative abstinence duration before withdrawal was significantly and positively associated with the risk of first, of definitive, and of every episode of treatment interruption. This first application of survival analysis techniques to the combined study of alcoholic behaviour and of adherence to treatment can improve our knowledge of treatment evaluation. Our results suggest that compliance to treatment is an objective and versatile outcome measure. Long-term follow-up studies aimed to elucidate the determinants of withdrawal should be performed.     

后腹腔镜肾蒂阻断下保留肾单位肾肿瘤手术(附6例报告)

目的 探讨后腹腔镜肾蒂阻断下保留肾单位治疗肾肿瘤的方法及手术技巧. 方法收治肾脏外生性实体肿瘤6例患者,其中.肾细胞癌2例,肿瘤直径分别为2.5 cm和2.2 cm;肾错构瘤4例,肿瘤直径为2.5～3.5 cm.经后腹腔镜径路在自制的肾蒂阻断装置中阻断肾蒂,做保留肾单位的肾肿瘤手术,术中距肿瘤0.5～1.0cm处行肾脏部分切除术,创面缝合止血.结果 6例手术均成功,手术时间120～210min,中位数150min.术中出血150～200ml,中位数170ml.肾蒂血流阻断时间18～33 min,中位数22 min.2例肾细胞癌术后切缘阴性.术后随访6～12个月,未见肿瘤残留及复发.结论 后腹腔镜肾脏部分切除术中应用自制的肾蒂阻断装置,具有良好的止血效果、手术创伤小、视野清晰、操作方便、能最大限度地保留患肾等优点,术后恢复良好.     

Secondary prevention of upper gastrointestinal bleeding associated with maintenance acid-suppressing treatment in patients with peptic ulcer bleed

We studied the recurrence of upper gastrointestinal bleeding (UGIB) in a cohort of patients who had an episode of peptic ulcer bleed, and we investigated the effect of maintenance treatment with cimetidine, omeprazole, and ranitidine. We identified 952 patients with a hospitalization for an episode of peptic ulcer bleed by searching the General Practice Research Database in the United Kingdom. The mean follow-up time was 33 months. Less than 10% of the cohort presented with a new episode of UGIB. We calculated incidence rates of recurrent UGIB and estimated the relative risk (RR) of UGIB associated with use of the various acid-suppressing drugs. The greatest protection for recurrent UGIB associated with maintenance acid-suppressing treatment was seen with omeprazole (relative risk 0.2; 95% CI, 0.02-1.0). The corresponding estimates with cimetidine and ranitidine were 0.9 (0.3-2.3) and 0.9 (0.5-1.8). Among nonsteroidal anti-inflammatory drug users, concomitant use of omeprazole afforded protection against a new bleed (RR 0.0; 0.0-1.0), and there was a suggestion of a protective effect with misoprostol, 0.4 (0.01-3.2). The degree of lowered risk of recurrent UGIB in patients on omeprazole maintenance therapy compared with cimetidine or ranitidine therapy is comparable with the protection provided through profound reduction of gastric acidity achieved with proton-pump inhibitors.