Primary aldosteronism: Higher volume load, cardiac output and arterial stiffness than in essential hypertension.

BACKGROUND: The diagnostics of primary aldosteronism (PA) are usually carried out in patients taking antihypertensive medications. We compared haemodynamics between medicated PA, medicated essential hypertension (EH), never-medicated EH and normotensive controls (n = 130 in all groups). METHODS: The hypertensive groups were matched for age (53 years), sex (84 male/46 female) and body mass index (BMI) (30 kg m-2 ); normotensive controls had similar sex distribution (age 48 years, BMI 27 kg m-2 ). Haemodynamics were recorded using whole-body impedance cardiography and radial pulse wave analysis, and the results were adjusted as appropriate. Radial blood pressure recordings were calibrated by brachial blood pressure measurements from the contralateral arm. RESULTS: Radial and aortic systolic and diastolic blood pressure was similar in PA and never-medicated EH, and higher than in medicated EH and normotensive controls (P ≤ 0.001 for all comparisons). Extracellular water balance was ~ 4% higher in PA than in all other groups (P < 0.05 for all), whilst cardiac output was ~ 8% higher in PA than in medicated EH (P = 0.012). Systemic vascular resistance and augmentation index were similarly increased in PA and both EH groups when compared with controls. Pulse wave velocity was higher in PA and never-medicated EH than in medicated EH and normotensive controls (P ≤ 0.033 for all comparisons). CONCLUSIONS: Medicated PA patients presented with corresponding systemic vascular resistance and wave reflection, but higher extracellular water volume, cardiac output and arterial stiffness than medicated EH patients. Whether the systematic evaluation of these features would benefit the clinical diagnostics of PA remains to be studied in future.

Supragastric belch may be related to globus symptom - a prospective clinical study.

BACKGROUND: The etiology of globus is poorly understood. It is controversial, whether gastroesophageal reflux disease (GERD) has a role in globus. To investigate the possible esophageal background of this symptom, we performed transnasal esophagoscopy (TNE), high-resolution manometry (HRM), and 24-h multichannel intraluminal impedance (MII) and pH monitoring on globus patients. METHODS: Thirty consecutive patients were referred to Helsinki University Hospital, Department of Otorhinolaryngology - Head and Neck Surgery for treatment of globus; 24 consecutive patients with difficult reflux symptoms from the Department of Surgery served as controls. We compared the results of the patient groups in endoscopies, HRM, and 24-h MII-pH monitoring. KEY RESULTS: In MII monitoring, globus patients had supragastric belch (6/20, 30% vs 1/24, 4%; p = 0.038) more often than controls. Total reflux time was higher in controls (p = 0.004), and they had more acid reflux events (p = 0.002) in MII, but between groups, the number of non-acid reflux events was similar. In pH monitoring, DeMeester score and total pH <4 time were higher in controls (P < 0.001). In HRM, the upper esophageal sphincter (UES) mean basal and residual pressures did not differ. CONCLUSIONS & INFERENCES: Supragastric belch was more common in globus patients, suggesting the possible role of this condition in globus sensation. However, globus patients in this series had no acid or non-acid GERD or elevated UES pressure.

Somatosensory and auditory processing in opioid-exposed newborns with neonatal abstinence syndrome: a magnetoencephalographic approach.

OBJECTIVE: Opioid exposure during pregnancy is a potential risk factor for the developing central nervous system of the fetus. We studied evoked responses in buprenorphine-exposed newborns who displayed neonatal abstinence syndrome (NAS) to elucidate the possible alterations in functioning of the somatosensory and auditory systems. METHODS: We compared somatosensory (SEFs) and auditory evoked magnetic fields (AEFs), recorded with magnetoencephalography (MEG), of 11 prenatally buprenorphine-exposed newborns with those of 12 healthy newborns. Peak latencies, source strength and location of SEFs or AEFs were recorded. RESULTS: AEFs were present in all buprenorphine-exposed newborns without significant differences from those of healthy newborns. In contrast, though no group level differences in SEFs existed, at individual level the response deviated from the typical neonatal morphology in four buprenorphine-exposed newborns. CONCLUSIONS: Although buprenorphine exposure during pregnancy does not seem to cause constant deficiencies in somatosensory or auditory processing, in some newborns the typical development of somatosensory networks may be - at least transiently - disrupted.

Magnetoencephalography in neonatology.

Magnetoencephalography (MEG) is a noninvasive method to study brain activity. In the previous decade the advantages of MEG -- good temporal resolution combined with good spatial resolution allowing separation of activated brain areas -- have been successfully used in gaining new information about the neonatal brain functioning. In this review, we discuss the findings from studies of spontaneous magnetoencephalogram and evoked responses to somatosensory, auditory, and visual stimulation. Our group has shown that stimulation of the upper limb in neonates evokes a response sequence reflecting activation of both primary (S(I)) and secondary somatosensory (S(II)) cortices. Like in mature brains, the earliest cortical response to median nerve stimulation reflects the arrival of afferent information to S(I). However, source modeling of the subsequent activation from S(I)suggests immature cortical functioning in neonates. Another feature typical for neonates is that the S(II)response is prominent in quiet sleep, unlike in adults in whom it diminishes in sleep. Interestingly, in very prematurely-born infants, we found alterations of the somatosensory responses at both group and individual levels. MEG provides a novel way to look at brain activity in neonates and can be used to increase knowledge of the development of brain processing and its disturbances.

Trigeminal somatosensory evoked magnetic fields to tactile stimulation.

OBJECTIVE: To characterise the activation of the contra- and ipsilateral primary somatosensory cortex (SI) after tactile stimulation of the face. METHODS: Trigeminal somatosensory evoked magnetic fields (TSEFs) were recorded after tactile stimulation of the lower lip, cheek, chin and forehead in 11 healthy subjects. The responses were determined visually from the waveforms and modelled with equivalent current dipoles (ECDs). RESULTS: Contralateral SI responses were evoked in all subjects after lip stimulation, and in 91% and 64% after right and left cheek, 73% and 82% after chin and 64% and 27% after forehead stimulation. The responses usually showed an early double-peak wave pattern, the underlying sources localising to the SI. In addition, altogether 37 ipsilateral SI responses were evoked in eight subjects. Fourteen of these responses were amenable to ECD modelling and localised to ipsilateral SI. CONCLUSIONS: Tactile stimulation of the lip area reliably activates the contralateral SI in normal subjects, but the success rate for other trigeminal areas is lower. Ipsilateral responses can be present after stimulation of any of the trigeminal branches in normal subjects. SIGNIFICANCE: Recording of TSEFs after tactile stimulation of particularly the lip area provides a non-invasive technique to study the function of the trigeminal nerve.

Hepatic subcapsular steatosis in diabetic CAPD patients treated with intraperitoneal insulin. Description of a typical pattern.

PURPOSE: To describe a specific imaging pattern of hepatic fatty change typical of diabetic patients on continuous ambulatory peritoneal dialysis (CAPD) treated with intraperitoneal (i.p.) insulin. MATERIAL AND METHODS: Liver ultrasound was applied in 16 CAPD patients with insulin-dependent diabetes mellitus. Presence of hepatic subcapsular steatosis and maximum thickness of the fatty layer were recorded. Liver MR examination was made of 1 patient found to have extensive subcapsular steatosis. RESULTS: Hepatic ultrasound revealed a typical pattern of subcapsular steatosis ("coating-of-fat") in 7/8 patients treated with i.p. insulin. None (0/8) of the diabetic CAPD patients treated with subcutaneous insulin had subcapsular steatosis. CONCLUSION: Hepatic subcapsular steatosis is specific to CAPD patients on i.p. insulin treatment. To our knowledge this is the first report to describe imaging findings in this particular form of hepatic fatty change.

Intraperitoneal insulin reduces plasma leptin concentration in diabetic patients on CAPD.

OBJECTIVE: To determine the effects of subcutaneous (SC) and intraperitoneal (IP) insulin on serum leptin concentration in type I diabetic patients with end-stage renal failure treated with continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Prospective, open, before-after study. SETTING: Tertiary-care university hospital. PARTICIPANTS: Twelve type I diabetic patients with stabilized CAPD, age 43.9 +/- 2.8 years, and duration of diabetes 30.4 +/- 3.5 years. INTERVENTION: After stabilized CAPD therapy, all patients were treated first with SC insulin for a median of 3 months, and thereafter with IP insulin for another 3 months. MAIN OUTCOME MEASURES: Plasma leptin, insulin sensitivity with euglycemic clamp, and glycemic and uremic status after both treatment periods. RESULTS: During SC insulin therapy, plasma leptin concentration was significantly higher than during IP insulin (19.8 +/- 5.9 ng/mL and 12.8 +/- 6.2 ng/mL, respectively; p < 0.001). Leptin concentration was higher in CAPD patients and was related to body mass index in both genders. No correlation was detected between plasma leptin and fasting insulin, glycemic control, glucose disposal rate, or serum lipids. CONCLUSION: Plasma leptin concentration is lower during IP insulin therapy compared to SC insulin. Insulin has probably a direct effect on both peritoneal leptin clearance and adipose tissue leptin production. The significance of leptin in regulating appetite and anorexia in uremia remains unclear.

High peritoneal permeability predisposes to hepatic steatosis in diabetic continuous ambulatory peritoneal dialysis patients receiving intraperitoneal insulin.

OBJECTIVE: To evaluate hepatic fat accumulation in diabetic patients taking intraperitoneal or subcutaneous insulin treatment during continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Cross-sectional study. SETTING: Tertiary-care university hospital. PATIENTS: We studied 16 patients with diabetic end-stage renal disease currently treated with CAPD. Median age was 42 years (range: 34-70 years), duration of diabetes was 27.5 years (range: 17-39 years), and duration of CAPD was 16.5 months (range: 2-59 months). OUTCOME MEASURES: Ultrasound measures of liver steatotic area and thickness, peritoneal equilibration test (PET), weekly Kt/V urea, protein catabolic rate (PCR), hemoglobin A1c (HbA1c), lipoproteins, alanine aminotransferase, alkaline phosphatase, insulin dose, and dialysate glucose load. RESULTS: Focal hepatic fat accumulation was found. The location of steatosis was subcapsular; a negligible amount was periportal. Hepatic subcapsular steatosis was present in 7 of 8 patients taking insulin intraperitoneally and in 0 of 8 patients taking insulin subcutaneously. The maximal thickness of subcapsular steatosis correlated directly with peritoneal transport rate (2-hour dialysate-to-plasma creatinine ratio in PET, r = 0.80, p < 0.05) and inversely with PCR (r = -0.82, p < 0.05). The area of the lesions correlated directly with body weight (r = 0.80, p < 0.05) and inversely with weekly Kt/V urea (r = -0.90, p < 0.01). CONCLUSIONS: Intraperitoneal insulin, together with glucose-based peritoneal dialysate, induces hepatic subcapsular steatosis. The amount of hepatic subcapsular steatosis increases when peritoneal transfer rate and body weight are high.

The effect of insulin delivery route on lipoproteins in type I diabetic patients on CAPD.

OBJECTIVE: To evaluate the influence of subcutaneous and intraperitoneal (i.p.) insulin on plasma lipoproteins in type I diabetic (IDDM) patients with end-stage renal failure (ESRD) treated with continuous ambulatory peritoneal dialysis (CAPD). DESIGN: A before-after trial. SETTING: University hospital outpatient care. PARTICIPANTS: Eleven IDDM patients with stabilized peritoneal dialysis, age 42.9 +/- 2.9 (SEM) years and duration of diabetes 31.4 +/- 3.4 years. INTERVENTION: Two treatment periods during stabilized CAPD. All patients were first treated with subcutaneous and then with i.p. insulin. The studies were performed after a median time of 3 months on each treatment. MAIN OUTCOME MEASURES: Plasma lipids; apoproteins (Apo) A-I, A-II, and B; high-density lipoprotein (HDL) subfractions; glycemic status; and uremic status. RESULTS: After changing from subcutaneous insulin to i.p. insulin, plasma HDL cholesterol decreased (from 1.29 +/- 0.13 mmol/L to 0.96 +/- 0.06 mmol/L, p < 0.05), and the low density to high density lipoprotein (LDL/HDL) cholesterol ratio increased (p < 0.05). The HDL cholesterol decreased in both HDL2 and HDL3 fractions, but significantly so only in HDL3 (p < 0.01). ApoA-I (p < 0.05) decreased while the ApoB/ApoA-I ratio (p < 0.01) and the ApoA-I/HDL-cholesterol ratio (p < 0.01) increased during i.p. insulin therapy. Intraperitoneal insulin resulted in significantly better glycemic control than subcutaneous insulin (p < 0.01). CONCLUSIONS: In diabetic patients on CAPD therapy, i.p. insulin, although inducing better glycemic control than subcutaneous insulin, was associated with lowered plasma HDL cholesterol and ApoA-I levels. The atherogenic potential is probably less than expected as the relative particle size of HDL remained unchanged.

The influence of peritoneal dialysis and the use of subcutaneous and intraperitoneal insulin on glucose metabolism and serum lipids in type 1 diabetic patients.

BACKGROUND: Intraperitoneally administered insulin is regarded as the most physiological replacement therapy, leading to lower peripheral insulin concentrations and equal or better glycaemic control than subcutaneous insulin. This two-part study was undertaken to evaluate the effect of CAPD, as well as the use of subcutaneous vs. intraperitoneal insulin on insulin sensitivity, glycaemic control and serum lipids in type 1 diabetes. METHODS: Eleven patients with type 1 diabetes mellitus and chronic renal failure participated the studies. Glycated haemoglobin (HbA1c), euglycaemic hyperin-sulinaemic clamp, serum lipids, and patient well-being were measured. During CAPD all patients were first treated with subcutaneous insulin and then with intraperitoneal insulin. The metabolic studies were repeated after both treatment periods for at least 3 months. Metabolic studies were performed on six of the patients also before initiation of CAPD. RESULTS: HbA1c rose after the initiation of CAPD from 8.85 +/- 0.54% to 9.58 +/- 0.66%, NS) and improved after changing from subcutaneous to intraperitoneally administered insulin (from 9.49 +/- 0.43% to 8.13 +/- 0.39%, P < 0.01). Insulin dose increased by 15% after initiation of CAPD and 128% after switching from subcutaneous to intraperitoneal insulin. Glucose disposal rate enhanced by 39% (P = 0.05) and 14% respectively (P < 0.01). Initiation of CAPD had no significant effects on serum lipids but intraperitoneally administered insulin reduced HDL cholesterol and increased LDL/HDL ratio significantly. CONCLUSIONS: Intraperitoneal insulin therapy offers better glycaemic control and insulin sensitivity than subcutaneous insulin. Deterioration of HbA1c after initiation of CAPD while patients remained on subcutaneous insulin may be partly due to absorbed energy from the dialysate. Intraperitoneal insulin therapy seems to have detrimental effects on serum lipids. The clinical significance in modifying the risk of atherosclerosis remains unclear.

Subcutaneous and intraperitoneal insulin therapy in diabetic patients on CAPD.

We evaluated in a cross-over manner the consequences of subcutaneously and intraperitoneally given insulin on glucose control, insulin sensitivity, and serum lipids in 8 type I diabetic patients on continuous ambulatory peritoneal dialysis (CAPD). The patients were treated with both subcutaneous and intraperitoneal insulin for at least three months. After each period, metabolic studies were performed. Despite significantly improved glycemic control (Hb A1c 10.00 +/- 0.38% after subcutaneous and 8.40 +/- 0.36% after intraperitoneal insulin, p = 0.01), serum lipids showed unfavorable changes. High-density lipoprotein (HDL)-cholesterol was significantly lower (1.28 +/- 0.18 mmol/L vs 0.88 +/- 0.06 mmol/L, p = 0.03) and low-density lipoprotein (LDL)/HDL-cholesterol ratio was higher (p = 0.025) during intraperitoneal insulin. Total cholesterol, LDL-cholesterol, and triglycerides were higher during intraperitoneal insulin administration. Severe hypoglycemic episodes were more common during subcutaneous than intraperitoneal insulin. It is concluded that, although intraperitoneal insulin administration offers significantly better glycemic control and insulin sensitivity than subcutaneous insulin, the effect of serum lipids is more disadvantageous possibly via a direct effect of insulin on the liver.