Pasireotide effects on biochemical control and glycometabolic profile in acromegaly patients switched from combination therapies or unconventional dosages of somatostatin analogs.

PURPOSE: To evaluate the impact of pasireotide (PAS) therapy on hormonal and glycometabolic outcome in patients with acromegaly previously treated with combination medical therapies or unconventional dosages of first-generation somatostatin receptor ligands (fg-SRLs). METHODS: Retrospective study carried out in two referral centers for pituitary diseases. Twenty-one acromegalic patients were switched to PAS (12 had biochemical control, 9 were uncontrolled). Data were collected after 3- and 6-months PAS treatment, and at the last available visit (median 35 months). RESULTS: After switching to PAS therapy, a significant reduction in IGF-1 values was observed [median 39%; 0.79 xULN (IQR 0.5-1.01) vs 1.29 xULN (IQR 1.06-1.83); p = 0.009]. IGF-1 reduction was statistically significant in the 9 patients previously uncontrolled (61%, p = 0.016), and in the 12 controlled subjects (33%, p = 0.037). At last follow-up, the number of patients reaching an acceptable biochemical control (IGF-1 < 1.3 xULN) raised from 57 to 90% (p = 0.032). Mean HbA1c levels increased from 5.7% (5.5-5.9) to 6.0% (5.9-7) (p = 0.002), and the percentage of diabetic patients raised from 14% (3/21) to 67% (14/21) (p = 0.004). At the last evaluation HbA1c was ≥ 7.0% in 5 patients (24%). Antidiabetic drugs were initiated in 9 new patients, and in 7 out of 9 metformin alone was effective. Younger age and male sex were predictors for the maintenance of glucose homeostasis. CONCLUSION: PAS monotherapy can be effective in acromegalic patients previously treated with combination medical therapies or unconventional dosages of fg-SRLs. Glucose imbalance can be managed in the vast majority of cases by use of lifestyle interventions and metformin.

Increased levels of dioxin-like substances in adipose tissue in patients with deep infiltrating endometriosis.

STUDY QUESTION: Are the levels of biologically active and the most toxic dioxin-like substances in adipose tissue of patients with deep infiltrating endometriosis (DIE) higher than in a control group without endometriosis? SUMMARY ANSWER: DIE patients have higher levels of dioxins and polychlorinated biphenyls (PCBs) in adipose tissue compared with controls without endometriosis. WHAT IS KNOWN ALREADY: Some studies have investigated the levels of dioxin-like substances, in serum samples, in patients with endometriosis, with inconsistent results. STUDY DESIGN, SIZE, DURATION: Case-control study including two groups of patients. The study group (DIE group) consisted of 30 patients undergoing laparoscopic surgery because of DIE. In all patients, an extensive preoperative work-up was performed including clinical exploration, magnetic resonance imaging (MRI) and transvaginal sonography. All patients with DIE underwent a confirmatory histological study for DIE after surgery. The non-endometriosis control group (control group), included the next consecutive patient undergoing laparoscopic surgery in our center due to adnexal benign gynecological disease (ovarian or tubal procedures other than endometriosis) after each DIE patient, and who did not present any type of endometriosis. PARTICIPANTS/MATERIALS, SETTING, METHODS: During the surgical procedure 1-2 g of adipose tissue from the omentum were obtained. Dioxin-like substances were analyzed in adipose tissue in DIE patients and controls without endometriosis. MAIN RESULTS AND THE ROLE OF CHANCE: The total toxic equivalence and concentrations of both dioxins and PCBs were significantly higher in patients with DIE in comparison with the control group (P < 0.05), mainly due to the significantly higher values of the two most toxic dioxins (2,3,7,8-tetrachlorodibenzo-p-dioxin [2,3,7,8-TCDD] and 1,2,3,7,8-pentachlorodibenzo-p-dioxin [1,2,3,7,8-PeCDD]) (P < 0.01 for each compound). The levels of furan 2,3,4,7,8-PeCDF were statistically higher in the DIE group compared with controls. Only four congeners of PCBs had toxic equivalence values and concentrations that were statistically higher in patients with DIE, but these included the most toxic and carcinogenic PCB-126 (PCB-114 P < 0.05; PCB-156 P < 0.05; PCB-189 P = 0.04; PCB-126 P < 0.01). LIMITATIONS, REASONS FOR CAUTION: Since few patients were recruited, the study is only exploratory. Our results need to be confirmed in larger and more heterogeneous population studies since environmental and even genetic factors involved in determining dioxins and PCBs widely vary in different countries. Furthermore, the strict eligibility criteria used may preclude generalization of the results to other populations and the surgery-based sampling frame may induce a selection bias. Finally, adipose tissue was obtained only from the omentum, and not from other adipose tissue of the body. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest a potential role of dioxin-like substances in the pathogenesis of DIE. Further studies are warranted to confirm our findings. STUDY FUNDING/COMPETING INTERESTS: None. TRIAL REGISTRATION NUMBER: Not applicable.

Protective effect of alpha-lipoic acid on cypermethrin-induced oxidative stress in Wistar rats.

Cypermethrin (CY), a class II pyrethroid pesticide, is globally used to control insects in the household and in agriculture. Despite beneficial roles, its uncontrolled and repetitive application leads to unintended effects in non-target organisms. In light of the relevant anti-oxidant properties of alpha-lipoic acid (ALA), in the work described herein we tested the effect of a commercially available ALA formulation on cypermethrin CY)-induced oxidative stress in Wistar rats. The rats were orally administered with 53.14 mg/kg of ALA and 35.71 mg/kg of CY for 60 days. The treatment with CY did not induce changes in either locomotor activities or in body weight. Differences were observed on superoxide dismutase (SOD), catalase (CAT) and lipid peroxidation that were re-established by ALA treatment at similar levels of the placebo group. Furthermore, ALA formulation increased glutathione (GSH) level and glutathione peroxidase (GPx) activity. Because of the widespread use of CY, higher amounts of pesticide residues are present in food, and a diet supplementation with ALA could be an active free radical scavenger protecting against diseases associated with oxidative stress.

Current use of high-resolution mass spectrometry in the environmental sciences.

During the last two decades, mass spectrometry (MS) has been increasingly used in the environmental sciences with the objective of investigating the presence of organic pollutants. MS has been widely coupled with chromatographic techniques, both gas chromatography (GC) and liquid chromatography (LC), because of their complementary nature when facing a broad range of organic pollutants of different polarity and volatility. A clear trend has been observed, from the very popular GC-MS with a single quadrupole mass analyser, to tandem mass spectrometry (MS-MS) and, more recently, high-resolution mass spectrometry (HRMS). For years GC has been coupled to HR magnetic sector instruments, mostly for dioxin analysis, although in the last ten years there has been growing interest in HRMS with time-of-flight (TOF) and Orbitrap mass analyzers, especially in LC-MS analysis. The increasing interest in the use of HRMS in the environmental sciences is because of its suitability for both targeted and untargeted analysis, owing to its sensitivity in full-scan acquisition mode and high mass accuracy. With the same instrument one can perform a variety of tasks: pre- and post-target analysis, retrospective analysis, discovery of metabolite and transformation products, and non-target analysis. All these functions are relevant to the environmental sciences, in which the analyst encounters thousands of different organic contaminants. Thus, wide-scope screening of environmental samples is one of the main applications of HRMS. This paper is a critical review of current use of HRMS in the environmental sciences. Needless to say, it is not the intention of the authors to summarise all contributions of HRMS in this field, as in classic descriptive reviews, but to give an overview of the main characteristics of HRMS, its strong potential in environmental mass spectrometry and the trends observed over the last few years. Most of the literature has been acquired since 2005, coinciding with the growth and popularity of HRMS in this field, with a few exceptions that deserve to be mentioned because of their relevance.

Effects of Rhodiola rosea L. extract on behavioural and physiological alterations induced by chronic mild stress in female rats.

Rhodiola rosea L. is one of the most popular adaptogen and an antistress plant in European and Asiatic traditional medicine. Our previous studies have confirmed the adaptogenic and antistress properties of a single administration of R. rosea L. extract in rats exposed to acute stress. There is increasing evidence that prolonged exposure to stressful life events and depression are both related to significant behavioural, endocrinological and neurobiological changes in human and animal subjects. The aim of this study was to determine whether chronic treatment with a hydroalcoholic R. rosea extract (RHO) standardized in 3% rosavin and 1% salidroside can prevent alterations induced in female rats following 6 weeks of a chronic mild stress (CMS) procedure. This was analysed through the behavioural and physiological parameters of consumption of 1% sucrose solution, locomotor and exploratory activities, body weight gain and oestrous cycle length. After the first 3 weeks of stress, RHO was administered daily by gavage at doses of 10, 15 and 20 mg/kg for the remaining 3 weeks. In addition, the antidepressant drug fluoxetine (10 mg/kg os), which has been shown to reverse CMS-induced disruptions, was used as the reference treatment. Rats subjected to the CMS procedure demonstrated decreased sucrose intake, reduced moving behaviour, minimized weight gain and dysregulation of their oestrous cycle. Treatment with RHO completely reverted all of these changes. The effects of RHO were comparable to those of fluoxetine. Interestingly, neither RHO nor fluoxetine influence the behavioural and physiological parameters tested in non-stressed animals. These findings strongly showed that chronic administration of RHO results in potent inhibition of the behavioural and physiological changes induced by chronic exposure to mild stressors.

Stereoisomeric sugar-derived indolizines as versatile building blocks: synthesis of enantiopure di- and tetrahydroxyindolizidines.

The synthesis of the sugar-derived (1S,2R,8aR)-1,2-di-O-isopropylidene-1,2,3,5,6,8a-hexahydro-5-oxoindolizine (8) and by analogy of the corresponding stereoisomers ent-8 and ent-7, an epimer at C2 of ent-8, has been accomplished in a straightforward manner. The carbon-carbon double bond and the carbonyl functionalities on the six-membered ring make these nitrogen-containing heterocycles useful building blocks for the efficient preparation of a variety of enantiopure polyhydroxylated indolizidines of interest for their glycosidase inhibitory activity. We report here the synthesis of 2,8a-diepilentiginosine 12 from 8 and the preparation of stereoisomeric 1,2,7,8-tetrahydroxyindolizidines 9-11 performed by OsO4-catalyzed double bond syn dihydroxylation of 7 and 8, followed by deoxygenation of the amide group.

Systemic hypoxia increases leukocyte emigration and vascular permeability in conscious rats.

We recently observed that acute systemic hypoxia produces rapid increases in leukocyte adherence in the mesenteric microcirculation of the anesthetized rat Wood JG, Johnson JS, Mattioli LF, and Gonzalez NC. J Appl Physiol 87: 1734-1740, 1999; Wood JG, Mattioli LF, and Gonzalez NC. J Appl Physiol 87: 873-881, 1999. Hypoxia-induced leukocyte adherence is associated with an increase in reactive oxygen species (ROS) generation and is attenuated by antioxidants or interventions that increase tissue levels of nitric oxide (NO). These results suggest that the acute effects of hypoxia on leukocyte-endothelial interactions are caused by a change in the ROS-NO balance. The present experiments were designed to extend our observations of the initial microcirculatory response to hypoxia; specifically, we wanted to determine whether the response to systemic hypoxia involves increased microvascular permeability and leukocyte emigration and whether ROS generation and decreased NO levels contribute to these responses. At this time, there is conflicting evidence, from in vitro studies, regarding the effect of hypoxia on these indexes of vascular function. Our studies were carried out in the physiological setting of the conscious animal, in which a prolonged hypoxic exposure is possible without the adverse effects that may develop under anesthesia. The central observation of these studies is that conscious animals exposed for 4 h to environmental hypoxia show increased microvascular permeability and emigration of leukocytes into the extravascular space of the mesenteric circulation. Furthermore, these events are dependent on increased ROS generation and, possibly, a subsequent decrease in tissue NO levels during systemic hypoxia. Our results show that systemic hypoxia profoundly affects vascular endothelial function through changes in the ROS-NO balance in the conscious animal.

Systemic hypoxia promotes leukocyte-endothelial adherence via reactive oxidant generation.

We recently demonstrated that systemic hypoxia during reduced inspired PO(2) produces a rapid increase in leukocyte adherence to rat mesenteric venules. Evidence suggests that the mechanism of this response involves decreased nitric oxide (NO) levels. One possible pathway for NO depletion could involve increased reactive oxygen species (ROS) generation resulting in inactivation of NO. The overall goal of the present study was to examine the role of ROS in promoting leukocyte-endothelial adherence during systemic hypoxia. Experiments were designed to 1) evaluate changes in ROS generation in the mesenteric microcirculation during systemic hypoxia, 2) determine how the ROS signal changes when PO(2) levels return to normal after a period of systemic hypoxia, 3) assess the effect of antioxidants on ROS generation during hypoxia, and 4) utilize antioxidants to examine the functional relationship between ROS generation and leukocyte adherence during hypoxia. The major findings from this study are that systemic hypoxia increases ROS generation within the mesenteric microcirculation and that antioxidants prevent the increase in leukocyte-endothelial adhesive interactions observed in hypoxia.

Hypoxia causes leukocyte adherence to mesenteric venules in nonacclimatized, but not in acclimatized, rats.

Although the effects of ischemia-reperfusion have received considerable attention, few studies have directly evaluated the microcirculatory response to systemic hypoxia. The overall objective of this study was to assess the effect of environmental hypoxia on adhesive interactions of circulating leukocytes with rat mesenteric venules by using intravital microscopy. Experiments were designed to 1) characterize the adhesive interactions of circulating leukocytes to venules during acute hypoxia produced by a reduction in inspired PO(2), 2) evaluate the role of nitric oxide in these adhesive interactions, 3) determine whether the effect of hypoxia on leukocyte adhesive interactions differs between acclimatized and nonacclimatized rats, and 4) assess whether compensatory changes in nitric oxide formation contribute to this difference. The results showed that acute hypoxia promotes leukocyte-endothelial adherence in mesenteric venules of nonacclimatized rats. The mechanism of this response is consistent with depletion of nitric oxide within the microcirculation. In contrast, no leukocyte-endothelial adherence occurred during hypoxia in rats acclimatized to hypobaric hypoxia. The results are consistent with increased nitric oxide formation due to expression of inducible nitric oxide synthase during the acclimatization period. Further studies are needed to establish the cause of nitric oxide depletion during acute hypoxia as well as to define the compensatory responses that attenuate hypoxia-induced leukocyte-endothelial adherence in the microvasculature of acclimatized rats.

Evaluation of remote stethoscopy for pediatric telecardiology.

OBJECTIVE: To investigate the interobserver reliability and diagnostic validity of a commercial electronic stethoscope for pediatric telecardiology. MATERIALS AND METHODS: Pairs of blinded pediatric cardiologists made independent diagnoses, recommendations concerning follow-up echocardiography, and specific judgments regarding heart sounds, murmurs, and congenital heart disease using an electronic (ES) or an acoustic (AS) stethoscope on 78 pediatric cardiology outpatients and at a distance of 450 km (280 miles) with 38 telemedicine cardiology outpatients. The kappa statistic (K) indexed the instruments' interexaminer reliabilities. The validity of ES was measured by K for ES versus AS and by the percentage of cases where the findings for ES and AS differed sufficiently to suggest an important ES screening error. RESULTS: For heart disease, AS, ES, and tele-ES reliabilities were satisfactory (K = 0.80, 0.67, and 0.80, respectively), as were AS agreement with hands-on ES (K = 0.65) and with tele-ES (K = 0.64). The AS and ES reliabilities and ES/AS agreement were also satisfactory for systolic regurgitant and diastolic pulmonic murmurs (K = 0.63-0.78) but were unsatisfactory for evaluable heart sounds and other murmurs (K = 0.16-0.60). The ES yielded clinically important disagreements with AS in 5.4% of the clinic cases and 10.5% of the telemedicine cases (P = 0.67). In determining the need for additional work-up (echocardiography) or follow-up appointments, hands-on ES and tele-ES had a combined accuracy of 92%, with a sensitivity of 88% and a specificity of 97%. CONCLUSIONS: Hands-on ES provided reliable and valid screening for congenital heart disease. Tele-ES was highly reliable but had reduced diagnostic validity. Examiner blinding, bandwidth limitations, and artificial restrictions on the remote assistant may have contributed to this reduced performance. As these factors are easily correctable, we regard the ES as a highly promising tool for pediatric telecardiology.

The acute effects of oral ethanol on the hypothalamic-pituitary-adrenal axis in normal human subjects.

OBJECTIVE: To evaluate the acute effects of oral ethanol on the hypothalamic-pituitary-adrenal axis in normal human subjects and, in particular, to examine the effect of background alcohol intake and gastrointestinal side-effects on this response. DESIGN: Plasma ethanol, cortisol, ACTH, corticotrophin-releasing hormone (CRH) and AVP were measured half-hourly for 4 hours following 1.1 ml/kg of 95% ethanol or placebo in a cross-over study. At least one week elapsed between each procedure. SUBJECTS: Twelve healthy non-alcoholic volunteers with a wide range of background alcohol intakes. MEASUREMENTS: Peptide hormones were measured by radioimmunoassay, cortisol by ELISA and blood ethanol by headspace gas chromatography. Results are expressed as mean +/- SEM. RESULTS: Blood ethanol levels peaked at one hour post ethanol ingestion. Three subjects developed significant gastrointestinal (GI) side-effects, with two vomiting and one experiencing moderate to severe nausea. There was no difference between peak blood ethanol levels in the groups with and without GI side-effects (34.5 +/- 2.4 mmol/l vs 34.3 +/- 1.7 mmol/l respectively). ACTH and cortisol rose in those subjects who experienced GI side-effects (P < 0.0001 for each). The remaining subjects had a tendency for ACTH and cortisol to be higher on the placebo day. The group with GI side-effects following ethanol administration had a significant rise in AVP (P < 0.02) that was synchronous with ACTH and cortisol. No consistent alcohol related changes were seen in peripheral CRH levels, although there was a significant increase over time on both active and placebo days (P < 0.0001). In the group with no GI side-effects, AVP did not significantly fall in the first half hour following ethanol, while a significant fall did occur following placebo (P < 0.05). Plasma renin activity was, however, increased by ethanol (P < 0.05). The background alcohol intake of the group with GI side-effects was significantly lower than the group without (18 +/- 7 vs 235 +/- 51 g/week, P < 0.05), but no hormonal response was seen in two subjects with a relatively low alcohol intake (< 100 g/week) who did not experience GI side-effects. CONCLUSION: Intoxicating levels of ethanol per se do not result in activation of the hypothalamic-pituitary-adrenal axis in humans. However, gastrointestinal side-effects induced by the ethanol do result in such activation, which appears to be mediated by AVP as the dominant ACTH secretagogue. One of the factors which influences the blood ethanol level at which GI side-effects occur appears to be background alcohol intake.

Balloon pulmonary valvuloplasty for isolated pulmonary valvular stenosis.

Fifteen balloon pulmonary valvuloplasties (BPVs) were performed on 13 infants and children with isolated pulmonary valvular stenosis (PVS). There were no complications. Two patients required repeat BPV, one for failure, the other for restenosis. At the time of the 13 latest BPVs, age ranged from three days to 13.1 years (mean 5.7 +/- SD 4.8 years). Average Doppler pulmonary valve pressure gradient preceding BVP was 75 +/- 22 mm Hg. At follow-up it was 25 +/- 9 mm Hg (p < .0001). Follow-up interval was 0.61 to 4.70 years (2.29 +/- 1.18). Restenosis occurred in 1/13 (8%) of the patients. The remaining 12/13 (92%) showed highly satisfactory sustained gradient reductions. Doppler gradients preceding BPV by as much as 4 months correlated highly with catheter gradients at time of BPV, confirming that Doppler echocardiography is a highly accurate indication of PVS severity. Catheterization for PVS should therefore not be used for diagnostic purposes alone. BPV can be performed safely, economically and effectively and is recommended as the treatment of choice for infants and children with moderate to severe isolated PVS. For very young patients, follow-up Doppler surveillance should be done semi-annually; for all others, annually.

Cerebrovascular stenoses with cerebral infarction in a child with Williams syndrome.

We report on a patient with Williams syndrome who suffered a cerebrovascular accident. Clinical evaluation demonstrated the presence of carotid and cerebral arterial stenoses. We believe these lesions led to acute cerebrovascular ischemia and a non-hemorrhagic cerebral infarction. It is possible the stenoses were exacerbated by a vasculitis. The stenoses were identified by both invasive and noninvasive imaging studies. These studies may have a role in the evaluation of persons with Williams syndrome.

The plasma interleukin-6 and stress hormone responses to acute pyelonephritis.

The relationships between the "stress hormones" corticotrophin (ACTH), vasopressin (AVP), corticotrophin releasing hormone (CRH) and cortisol, and the cytokines, interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor were studied during an acute infection. Ten patients (7 female, 3 male, age range 16-56 years) with acute pyelonephritis and normal renal function were studied during the first 72 hours following hospital admission. Peptide hormones were measured by radioimmunoassay, cortisol and cytokines by ELISA. Reference ranges for all hormones were from samples donated by 40 or more volunteers from the electoral roll. The reference data for IL-6 was obtained from 20 normal donor sera. The mean plasma IL-6, AVP and CRH concentrations on admission to hospital were significantly raised above the mean 08:00h values of the normal volunteers (p < 0.001 for AVP and CRH, p < 0.01 for IL-6), but mean plasma ACTH and cortisol were not. Mean plasma IL-6 and AVP were raised more than two standard deviations above the mean of the reference range for 72 hours, although IL-6 tended to fall after 24 hours. No change in plasma IL-1 and tumour necrosis factor was observed in three patients. The correlation between plasma IL-6 and cortisol concentrations at all sampling times and in all subjects was highly significant (p < 0.001). Significant correlations between plasma IL-6 and AVP (p < 0.005), and IL-6 and ACTH (p < 0.05) were also observed. No correlation between IL-6 and CRH could be demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma corticotrophin releasing hormone, vasopressin, ACTH and cortisol responses to acute myocardial infarction.

OBJECTIVES: We assessed the magnitude and duration of the response of hypothalamic-pituitary-adrenal hormones to the stress of myocardial infarction, in the presence and absence of angiotensin converting enzyme inhibitors. In particular, we wished to analyse the interrelationships between peripheral plasma levels of corticotrophin releasing hormone (CRH), vasopressin (AVP) and adrenocorticotrophin (ACTH), and also between ACTH and cortisol, during a prolonged medical stress. DESIGN: All hormones were measured within 6 hours of the onset of an acute myocardial infarction. Patients were randomly allocated to three different study groups according to a double blind procedure. PATIENTS: Group 1 (10 patients) received placebo treatment, Group 2 (13 patients) received a maintenance dose of captopril 25 mg three times daily, Group 3 (11 patients) received enalapril 5 mg three times daily. MEASUREMENTS: Peptide hormones were measured by radioimmunoassay, and cortisol by ELISA. Reference ranges for all hormones were obtained from 40 or more volunteers from the electoral roll. RESULTS: At the start of the study, mean +/- SEM plasma AVP (27.9 +/- 4.6 pmol/l) was significantly (P < 0.001) raised above the mean for the reference range (1.82 +/- 0.09 pmol/l), and 12 patients had values > 50 pmol/l. Mean plasma cortisol (960 +/- 89.6 nmol/l) was also raised above the reference range mean (554 +/- 28 nmol/l, P < 0.001), as was mean plasma CRH (4.97 +/- 0.5 pmol/l, reference mean 1.52 +/- 0.09 pmol/l, P < 0.001). By contrast, mean ACTH (3.88 +/- 0.66 pmol/l) was significantly less than the reference mean (10.7 +/- 0.7 pmol/l, P < 0.001). During the 72-hour observation period there was a highly significant fall (P < 0.001) in plasma CRH, AVP and cortisol. By contrast, plasma ACTH rose, and the change with time of ACTH was significantly different from the fall in plasma CRH, AVP or cortisol (P < 0.001 for each comparison). No significant differences in plasma CRH, AVP, ACTH or cortisol responses to placebo, captopril or enalapril were observed. CONCLUSIONS: Within 6 hours of a myocardial infarction, mean plasma CRH, AVP and cortisol values were very significantly raised above mean control values, while ACTH was very significantly reduced. During the 3 days following an acute myocardial infarction, plasma CRH, AVP and cortisol fell substantially, and this pattern was not influenced by angiotensin converting enzyme inhibitors. By contrast, plasma ACTH showed a significant increase with time. This suggests that the usual relationships between CRH, AVP and ACTH, and between ACTH and cortisol are disturbed in patients admitted to hospital with myocardial infarction. Maximum levels of AVP observed in 12 patients exceeded 50 pmol/l, which may be sufficiently high to interfere with tissue perfusion. It is postulated that V1 AVP receptor antagonists may have a therapeutic application in limiting infarct size.

Pediatric cardiology: auscultation from 280 miles away.

New long-distance audio/video and data communications links among health-care facilities promise to reduce rural patients' travel time and waiting time for subspecialty consultations. To offer a satisfactory alternative to face-to-face examination, the long-distance system must meet the subspecialty's minimum criteria. For pediatric cardiology in particular, the system has to permit satisfactory cardiac auscultation. A preliminary test of remote auscultation that uses an electronic stethoscope involved two pediatric cardiologists, one listening hands-on with an acoustic stethoscope, the other listening independently at long distance with the electronic instrument. Taking the acoustic findings as the reference standard, the electronic stethoscope did not miss the one case of heart disease, correctly recommended echocardiogram follow-up in the two cases requiring it, and agreed on 80% of the murmurs' qualitative specifics. The patients' parents also indicated that the system was highly acceptable. We are following up these results with a full-scale study of the effectiveness and parental acceptance of remote auscultation.

Neonatal aortic thrombosis complicating umbilical artery catheterization: successful treatment with retroperitoneal aortic thrombectomy.

A newborn infant with a history of umbilical artery catheterization had renal vascular hypertension and congestive heart failure. An abdominal ultrasound examination revealed aortic thrombosis extending from the celiac axis to the aortic bifurcation. Retroperitoneal aortic thrombectomy was performed without difficulty. The infant's hypertension and cardiac failure resolved. The retroperitoneal approach allowed excellent exposure of the aorta and avoided the postoperative gastrointestinal morbidity associated with a transperitoneal approach.

Early detection of vascular dysfunction in type I diabetes.

Blood flow and transcutaneous oxygen tension was measured by venous occlusion plethysmography and a transcutaneous oxygen electrode before and after 5 min of arterial occlusion in the forearm of young adult subjects with type I (insulin-dependent) diabetes without overt evidence of angiopathy. In control subjects (n = 21), the forearm blood flow increased by greater than or equal to 2.8-fold at 30 s after ischemia. Diabetic subjects with glycosylated hemoglobin (GHb) less than or equal to 9.5% (n = 15) exhibited a blood flow response that was not statistically different from normal control subjects. Diabetic subjects with GHb greater than or equal to 12.5% (n = 23) did not exhibit an increase in the postischemic blood flow. When blood flow patterns for the first 14 diabetic subjects were examined regardless of GHb value, four patterns of response were noted: 1) normal pattern (n = 3), 2) normal postischemic rise in blood flow with a prolonged elevation (n = 3), 3) no postischemic rise (n = 4), and 4) variable baseline blood flow with a decrease in blood flow postischemia (n = 4). This approach indicated that a comparison of means obscured potentially meaningful abnormal patterns. Abnormalities in the response of the transcutaneous oxygen tension to ischemia were observed in both groups of diabetic patients, but the difference between diabetic patients in good and poor control was less obvious. We have defined an abnormal response of blood flow and transcutaneous oxygen tension to ischemia that may correlate to glycemic control and have identified several patterns of blood flow after ischemia that may be important in defining the etiology and natural history of diabetic angiopathy.