The relationship between resting heart rate and new-onset microalbuminuria in people with type 2 diabetes: An 8-year follow-up study.

AIMS: Microalbuminuria is an indicator of adverse cardiovascular events and chronic kidney disease. Studies have described an elevated resting heart rate as a risk factor for microalbuminuria in people with cardiovascular disease, but none have clarified its role in microalbuminuria development in people with type 2 diabetes. Therefore, this study investigated the relationship between resting heart rate and new-onset microalbuminuria in type 2 diabetes. METHODS: A total of 788 people from a glycaemic control trial in Taiwan were enrolled. Microalbuminuria was defined as a fasting urine albumin-to-creatinine ratio ≥30 mg/g in two consecutive urine tests. Resting heart rate and other covariates were measured at baseline. The quartile of resting heart rates, categorized as <70, 70-74, 75-80 and >80 beats/min, was used for analysis. Cox proportional hazard models were used to evaluate the association between resting heart rate and risk of microalbuminuria. RESULTS: During the follow-up period, 244 people (31%) developed microalbuminuria. Those who developed microalbuminuria had a longer diabetes duration (median = 3.0 vs. 2.0 years, p < 0.001), higher rate of hypertension (77% vs. 66%, p = 0.003), higher rate of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker treatment (50% vs. 38%, p = 0.001) and higher baseline HbA1c level (70 vs. 64 mmol/mol, 8.6 vs. 8.0%, p < 0.001). After adjusting for demographics, metabolic profiles and inflammatory markers, developing microalbuminuria was significantly associated with baseline resting heart rate of 70-74, 75-80 and >80 beats/min (with hazard ratios [95% CI] of 2.05 [1.32, 3.18], 2.10 [1.32, 3.32] and 1.62 [1.01, 2.59], respectively) compared to resting heart rates <70 beats/min. An average increased risk of microalbuminuria for increment of 10 beats/min was about 24% among those with hypertension (with hazard ratios of 1.24 [1.05, 1.47] in the multivariable Cox model). CONCLUSIONS: This prospective cohort study showed that resting heart rate may be an associative risk factor for developing microalbuminuria in type 2 diabetes.

Cholesterol homeostasis associated with probiotic supplementation in vivo.

AIMS: To determine the mechanism underlying the serum cholesterol reduction effect by probiotics isolated from local fermented tapioca (Tapai). METHODS AND RESULTS: Lactic acid bacteria strains were isolated and examined for acid tolerance, bile salt resistance and hypocholesterolemic properties. Among the isolates, Lactobacillus plantarum TAR4 showed the highest cholesterol reduction ability (48·01%). The focus in the in vivo trial was to elucidate the cholesterol balance from findings pertaining to serum cholesterol reduction in rat model fed with high fat diet via oral administration. Rats fed with high-cholesterol diet supplemented with Lact. plantarum TAR4 showed significant reduction in serum total cholesterol (29·55%), serum triglyceride (45·31%) and liver triglyceride (23·44%) as compared to high-cholesterol diet (HCD) group. There was a significant increment in faecal triglyceride (45·83%) and faecal total bile acid (384·95%) as compared to HCD group. CONCLUSIONS: The findings showed that probiotic Lact. plantarum TAR4 supplementation reduced the absorption of bile acids for enterohepatic recycling and increased the catabolism of cholesterol to bile acids and not by suppressing the rate of cholesterol synthesis. SIGNIFICANCE AND IMPACT OF STUDY: Probiotic supplements could provide a new nonpharmacological alternative to reduce cardiovascular risk factors.

Counseling in fetal medicine: evidence-based answers to clinical questions on morbidly adherent placenta.

Although the incidence of morbidly adherent placenta (MAP) has risen progressively in the last two decades, there remains uncertainty about the diagnosis and management of this condition. The aim of this review is to provide up-to-date and evidence-based answers to common clinical questions regarding the diagnosis and management of MAP. Different risk factors have been associated with MAP; however, previous Cesarean section and placenta previa are the most frequently associated. Ultrasound is the primary method for diagnosing MAP and has a good overall diagnostic accuracy for its detection. When considering the different ultrasound signs of MAP, color Doppler seems to provide the best diagnostic performance. Magnetic resonance imaging has the same accuracy in diagnosing MAP as does ultrasound examination; its use should be considered when a resective procedure, such as hysterectomy, is planned as it can provide detailed information about the topography of placental invasion and predict difficulties that may arise in surgery. The optimal gestational age for delivery in pregnancies with MAP is yet to be established; planning surgery between 34 and 36 weeks of gestation provides the best balance between fetal maturity and the risk of unexpected episodes of heavy bleeding, which are more likely to occur with delivery after this timepoint, especially in severe cases of MAP. The optimal surgical approach to MAP depends on multiple factors, including availability of an experienced team, specific surgical skills and hospital resources. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Outcome of molar pregnancies in Malaysia: a tertiary centre experience.

Gestational trophoblastic disease (GTD) is a common problem among Asian ethnics. A total of 102 women with molar pregnancies between 1 January 2005 and 31 December 2010, were analysed. The aim of the study was to determine the outcome of all molar pregnancies in our institution. The local incidence of molar pregnancy was 2.6 per 1,000 deliveries. A total of 48 women (47.1%) had complete hydatidiform mole and another 54 (52.9%) had partial mole. The mean age of the women with molar pregnancies was 32.0 ± 7.9 years. The mean gestational age at initial diagnosis was 11 weeks ± 3 days. The majority (97 women, 95.1%) had symptoms of vaginal bleeding and 18 (17.6%) women had a uterus larger than dates. A total of 48 (47.1%) women had ultrasound scan findings of 'snow-storm' appearance. None of the women with uncomplicated molar pregnancy had evidence of relapse following one undetectable serum ß-hCG level. Four out of the 102 women (3.9%) developed persistent trophoblastic disease before attaining one undetectable serum ß-hCG level. All four women required single agent methotrexate and they remained in remission. The prognosis for uncomplicated molar pregnancy is good. Establishment of a National Trophoblastic Centre is recommended to maintain optimal outcome.

Pencil Beam Scanning Proton Therapy Case Selection for Paediatric Abdominal Neuroblastoma: Effects of Tumour Location and Bowel Gas.

AIMS: Pencil beam scanning (PBS) proton therapy is an increasingly used radiation modality for childhood malignancies due to its ability to minimise dose to surrounding organs. However, the dosimetry is extremely sensitive to anatomical and density changes. The aims of this study were to investigate if there is a dosimetric benefit or detriment with PBS for paediatric abdominal neuroblastoma, assess gastrointestinal air variability and its dosimetric consequences, plus identify if there are factors that could assist case selection for PBS referral. MATERIALS AND METHODS: Twenty neuroblastoma cases were double-planned with PBS and intensity-modulated arc therapy (IMAT). Cases were divided into unilateral, midline unilateral and midline bilateral locations in relation to the kidneys. Plans were recalculated after the gastrointestinal volume was simulated as air (Hounsfield Units -700) and water (Hounsfield Units 0), then compared with nominal plans (recalculated - nominal, ΔD). Forty-three weekly cone beam computed tomography scans were analysed to quantify gastrointestinal air variability during treatment. RESULTS: PBS reduced the mean dose to normal tissues at all tumour locations, particularly unilateral tumours. However, 15% had better dosimetry with IMAT, all of which were midline tumours. Increased gastrointestinal air caused significant compromises to PBS versus IMAT plans for midline tumours [median/maximum ΔD95% clinical target volume (CTV) -2.4%/-15.7% PBS versus 1.4%/0% IMAT, P = 0.003], whereas minimal impact was observed for unilateral tumours (ΔD95% CTV -0.5%/-1.9% PBS versus 0.5%/-0.5% IMAT, P = 0.008). D95% CTV was significantly decreased in PBS plans if planning target volume (PTV) ≥400 cm3 (median -4.1%, P = 0.001) or PTV extension ≥60% anterior to vertebral body (-2.1%, P = 0.002). A larger variation in gastrointestinal air was observed in patients treated under general anaesthesia (median 38.4%) versus awake (11.5%); P = 0.004. CONCLUSION: In this planning study, tumours at the unilateral location consistently showed improved dose reductions to normal tissue with minimal dose degradation from increased gastrointestinal air with PBS plans. Tumour location, PTV volume and anterior extension of PTV are useful characteristics in facilitating patient selection for PBS.

Pencil Beam Scanning Proton Therapy for Paediatric Neuroblastoma with Motion Mitigation Strategy for Moving Target Volumes.

AIMS: More efforts are required to minimise late radiation side-effects for paediatric patients. Pencil beam scanning proton beam therapy (PBS-PT) allows increased sparing of normal tissues while maintaining conformality, but is prone to dose degradation from interplay effects due to respiratory motion. We report our clinical experience of motion mitigation with volumetric rescanning (vRSC) and outcomes of children with neuroblastoma. MATERIALS AND METHODS: Nineteen patients with high-risk (n = 16) and intermediate-risk (n = 3) neuroblastoma received PBS-PT. The median age at PBS-PT was 3.5 years (range 1.2-8.6) and the median PBS-PT dose was 21 Gy (relative biological effectiveness). Most children (89%) were treated under general anaesthesia. Seven patients (37%) underwent four-dimensional computed tomography for motion assessment and were treated with vRSC for motion mitigation. RESULTS: The mean result of maximum organ motion was 2.7 mm (cranial-caudal), 1.2 mm (left-right), 1.0 mm (anterior-posterior). Four anaesthetised children (21%) showing <5 mm motion had four-dimensional dose calculations (4DDC) to guide the number of vRSC. The mean deterioration or improvement to the planning target volume covered by 95% of the prescribed dose compared with static three-dimensional plans were: 4DDC no vRSC, -0.6%; 2 vRSC, +0.3%; 4 vRSC, +0.3%; and 8 vRSC, +0.1%. With a median follow-up of 14.9 months (range 2.7-49.0) there were no local recurrences. The 2-year overall survival was 94% and distant progression-free survival was 76%. Acute grade 2-4 toxicity was 11%. During the limited follow-up time, no late toxicities were observed. CONCLUSIONS: The early outcomes of mainly high-risk patients with neuroblastoma treated with PBS-PT were excellent. With a subset of our cohort undergoing PBS-PT with vRSC we have shown that it is logistically feasible and safe. The clinical relevance of vRSC is debatable in anaesthetised children with small pre-PBS-PT motion of <5 mm.

Case of Chronic Otitis Media with Intracranial Complication and Contralateral Extracranial Presentation.

Intracranial complications of chronic otitis media have been on the decline with advent of antibiotics. Septic thrombosis of the sigmoid sinus is rarer compared to commoner complications such as otogenic brain abscesses and meningitis. This patient presented with recurrent infection after left mastoidectomy secondary to cholesteatoma and a contralateral internal jugular vein thrombosis with parapharyngeal abscess, which was drained. He recovered well postoperatively with antibiotics.

Dydrogesterone in threatened abortion: pregnancy outcome.

OBJECTIVE: To determine whether therapy with dydrogesterone in threatened abortion during the first trimester of pregnancy will improve pregnancy outcome. DESIGN: Prospective open study. SUBJECTS: Pregnant women presenting to the obstetric and gynaecology clinic admitting center with vaginal bleeding before 13 weeks gestation were evaluated for entry into the study. Women were excluded if they had a history of recurrent miscarriage. METHOD: Eligible subjects were randomized to receive either dydrogesterone 40 mg stat dose followed by 10 mg twice a day for one week or conservative therapy. RESULTS: One hundred and 54 women were recruited. There was no statistically significant differences between the two groups with regard to pre-treatment status. The continuing pregnancy success rate was significantly (p=0.037) higher in women treated with dydrogesterone (95.9%) compared with women who received conservative treatment (86.3%). The odds ratio of the success rate between dydrogesterone treatment and non-treatment was 3.773 (95% confidence interval: 1.009-14.108). CONCLUSION: Corpus luteal support with dydrogesterone has been shown to reduce the incidence of pregnancy loss in threatened abortion during the first trimester in women without a history of recurrent abortion.

Large-scale mitochondrial DNA deletions in skeletal muscle of patients with end-stage renal disease.

End-stage renal disease (ESRD) is associated with enhanced oxidative stress. This disease state provides a unique system for investigating the deleterious effect of exogenous sources of free radicals and reactive oxygen species (ROS) on mitochondrial DNA (mtDNA). To test the hypothesis that uremic milieu might cause more severe damage to mtDNA, we investigated the prevalence and abundance of mtDNA deletions in the skeletal muscles of ESRD patients. The results showed that the frequencies of occurrence of the 4977 bp and 7436 bp deletions of mtDNA in the muscle tissues of the older ESRD patients were higher than those of the younger patients. The frequency of occurrence of the 4977 bp-deleted mtDNA in the muscle was 33.3% for the patients in the age group of < 40 years, 66.6% in the 41-60-year-old group, 100% in the 61-80-year-old group, and 100% in patients >80 years of age, respectively. Only 22% of the normal aged controls carried the 4977 bp mtDNA deletion, whereas 77% (17/22) of the ESRD patients exhibited the mtDNA deletion. Using a semiquantitative PCR method, we determined the proportion of the 4977 bp-deleted mtDNA from the muscles that had been confirmed to harbor the deletion. We found that the proportions of the 4977 bp-deleted mtDNA in the muscle were significantly higher than those of the aged matched controls. Using long-range PCR techniques, a distinctive array of mtDNA deletions was demonstrated in the muscle of uremic patients. In summary, we found diverse and multiple mtDNA deletions in the skeletal muscles of ESRD patients. These deletions are more prevalent and abundant in ESRD patients than those found in normal populations. Accumulation of uremic toxins and impaired free radical scavenging systems may be responsible for the increased oxidative stress in ESRD patients. Such stress may result in oxidative damage and aging-associated mutation of the mitochondrial genome.

Outcomes of severe hyperkalemia in cardiopulmonary resuscitation with concomitant hemodialysis.

OBJECTIVE: To investigate the efficacy of hemodialysis during cardiopulmonary resuscitation as an effective adjunct to the treatment of severe hyperkalemia. DESIGN: A prospective study. SETTING: In hospital dialysis units and intensive care units. PATIENTS: Renal failure patients who developed hyperkalemia induced cardiac arrest and failed to recover from conventional cardiopulmonary resuscitation (CPR) were included. Three patients entered into this study: 2 patients with chronic renal failure maintained on regular hemodialysis and one with acute renal failure who suffered from severe hyperkalemia. INTERVENTIONS: All three patients developed asystolic cardiac arrest with unrecordable blood pressure due to severe hyperkalemia. Aggressive CPR together with intravenous epinephrine, sodium bicarbonate and calcium chloride were instituted. External cardiac massage with cardiac defibrillation was unable to restore spontaneous heart action. After lack or response to intensive resuscitation, hemodialysis was performed concomitant with CPR to eliminate the potassium load. MEASUREMENTS AND RESULTS: Sinus rhythm and blood pressure were restored in all 3 patients but one of them eventually succumbed to her underlying disease. CONCLUSION: Hemodialysis during CPR is probably an effective adjunct to the treatment of severe hyperkalemia in patients with severe hemodynamic compromise and asystolic cardiac arrest.

Does lead play a role in the development of renal insufficiency in some patients with essential hypertension?

The association of excessive lead burden and essential hypertension has been a subject of much dispute. In particular, the potential detrimental effect of low level environmental exposure on BP has caused considerable concern. We studied the urinary excretion of lead following the infusion of EDTA (1 g of calcium disodium edetate) in 12 healthy controls (group I), 10 subjects with essential hypertension alone (Group II) and in 36 subjects with chronic renal insufficiency. Those subjects with renal insufficiency were further divided into three groups: group III, 12 patients with a history of 7-19 years of essential hypertension who subsequently developed into renal failure; group IV, patients with chronic renal failure alone; and group V, patients with chronic renal failure due to causes other than hypertensive nephropathy and associated with secondary hypertension. In comparison with other groups, subjects with hypertensive nephropathy (group III) had significantly elevated lead body burden. In addition, we found that five of the 12 subjects with hypertensive nephropathy had histories of acute gouty attacks after the development of renal function impairment. In conclusion, our observation of a higher EDTA postinfusional urinary lead excretion among some patients with essential hypertension with renal function impairment indicates that lead may play a crucial role in a subgroup of patients with hypertensive nephropathy.

Metformin-induced lactic acidosis: report of a case.

Lactic acidosis associated with diabetic patients receiving metformin therapy is rare but may cause significant morbidity and mortality. In nearly all reported cases of metformin-associated lactic acidosis, contraindications to its use were noted, especially renal insufficiency. We describe a 59-year-old diabetic man treated with metformin for more than three years. During the third year of use, he experienced progressive renal function impairment, and during the final month of use, he became azotemic. He was maintained on continuous ambulatory peritoneal dialysis. Several days prior to admission, he suffered from epigastralgia, nausea and vomiting, followed by progressive dyspnea which was Kussmaul in nature. Profound hypotension developed and he sank progressively into a coma. Wide-anion gap metabolic acidosis without ketonemia was detected. His blood lactate level was elevated and metformin-induced lactic acidosis was substantiated. An elevated plasma metformin level of greater than 50 mg/mL was determined later by high-performance chromatography. Rigorous treatment including bicarbonate therapy, bicarbonate hemodialysis and vasoactive agents as well as supportive measures were provided. With a return of pH to normal, the hypotension resolved and his consciousness level slowly improved. Our patient survived this disastrous event, but some neurologic sequelae remained. In order to avoid this life-threatening metabolic disturbance, patients with any contraindications should not be prescribed metformin.

Renal oncocytoma in acquired renal cystic disease.

Renal oncocytoma is a rare benign tumor of the kidney that accounts for about 5% of renal tumors. Acquired renal cystic disease (ARCD) is commonly seen in dialyzed patients. However, the occurrence of renal oncocytoma in ARCD has rarely been reported. We report such a case in a 67-year-old man who had hypertension-associated end-stage renal disease and had received regular hemodialysis for 5 years. Radiologic diagnostic studies demonstrated a renal mass in the left atrophic cystic kidney that increased in size from 2 cm to 4 cm during 2 years of follow-up. Under the diagnosis of renal cell carcinoma, he received left radical nephrectomy. The pathologic examination revealed renal oncocytoma with a well-cirumscribed, homogenous, mahogany-brown tumor on a background of ARCD. Although patients with ARCD have a higher incidence of renal malignancies, renal oncocytoma may occur in these patients and may be managed conservatively.

Effect of age and sex on plasma total homocysteine in Taiwanese subjects.

Plasma total homocysteine (tHcy) is now established as a clinical risk factor for coronary artery disease, as well as for other arterial and venous occlusive diseases. Therefore, we measured the plasma tHcy concentrations in 385 healthy Chinese subjects in Taiwan and in 40 patients with occluded coronary artery disease or maintenance hemodialysis. The plasma tHcy levels in Taiwanese male and female volunteers were found to increase gradually with age (age group: 20-29, 30-39, 40-49, 50-59, and >60; mean +/- SD 8.22 +/- 2.00, 8.51 +/- 2.67, 8.87 +/- 2.22, 11.41 +/- 2.50 and 13.28 +/- 2.31 microM for male volunteers and 6.49 +/- 1.75, 7.15 +/- 1.20, 7.40 +/- 1.30, 9.57 +/- 3.01 and 10.95 +/- 2.11 microM for female volunteers). At the same age, male volunteers were shown to have higher tHcy levels than female volunteers. In addition, the mean concentrations of plasma tHcy in occluded coronary artery disease (13.62 +/- 5.43 microM) or in maintenance hemodialysis (21.28 +/- 4.32 microM) were statistically higher than in age-matched normal subjects (11.02 +/- 2.85 microM). This study emphasizes the significance of age and sex-associated difference in the plasma tHcy levels, and underlines the importance of the range for plasma homocysteine in normal Taiwanese subjects.

Posterior tibial tendon dysfunction: secondary MR signs.

We evaluated four potential secondary magnetic resonance imaging signs to aid in clinical diagnosis of posterior tibial tendon (PTT) tears. Seventy-one ankles (25 PTT tears and 46 controls) were evaluated for the following secondary signs: (1) PTT sheath fluid, (2) a distal tibial spur located just anterior to the PTT, (3) unroofing of the talus, and (4) "bone bruise"--like medullary lesions. Two musculoskeletal radiologists rated their confidence using a scale and were compared for level of agreement. The presence of PTT sheath fluid had modest specificity and fair to moderate sensitivity. Tibial spurring and unroofing of the talus had excellent specificity and fair sensitivity. Bone bruise-like lesions were commonly seen in cases and controls. Examination of divergence of opinion between the two radiologists revealed pitfalls in interpretation of PTT sheath fluid and bone bruise-like lesions, which were commonly the result of adjacent vessels and inhomogeneous fat saturation, respectively. We conclude that secondary signs of PTT tears with high specificities include unroofing of the talus, tibial spurring, and PTT sheath fluid.

A study on SARS awareness and health-seeking behaviour - findings from a sampled population attending National Healthcare Group Polyclinics.

INTRODUCTION: The study aimed to assess the effectiveness of massive SARS public education effort on SARS awareness and the conduct of those suspected of having SARS. MATERIALS AND METHODS: Five hundred and ninety-three respondents attending the National Healthcare Group Polyclinics (NHGP) participated in the survey from 9 to 13 June 2003. Associations between awareness of SARS symptoms and (i) first action to be taken and (ii) mode of transportation used, if the respondent was suspected of having SARS, were analysed using Chi-square or Fisher's exact tests. Logistic regression was performed to adjust for relevant covariates. RESULTS: The majority (92.7%) of the respondents were aware of SARS symptoms. Television (91.6%), newspaper (65.2%) and radio (30.4%) formed the top 3 sources of information on SARS. Slightly more than half (51.6%) of those who suspect themselves of having SARS would choose to visit their primary health care doctors, while 22.7% of the respondents would go to Tan Tock Seng Hospital (TTSH). If they suspected themselves to have SARS, most (84.9%) of the 578 respondents would react appropriately by taking the SARS ambulance or driving themselves to TTSH. However, 60 respondents would nonetheless take public transport to TTSH [by taxi 8.5%, mass rapid transit (MRT) or bus 1.9%]. In particular, the retired with lower educational levels were likely to be oblivious both to the symptoms of SARS and the possible consequences of travelling by inappropriate transport. CONCLUSION: Despite more than 2 months of intensive SARS public education in Singapore, there remain important gaps in knowledge and appropriate behaviour that have to be bridged.