Search

Objective: To report the rate of thrombolysis for treating acute stroke in South Australia from October 2007 to September 2009. We hypothesised that the rate of thrombolytic therapy would be related to distance from an acute stroke unit.Design, Setting and Patients: An observational, population-based, retrospective review of case notes and imaging, using multiple case-ascertainment methods. Patients administered a thrombolytic agent by any method for suspected ischaemic stroke in urban, rural, public and private hospitals in SA (covering a population of 1.5 million people) were included.Main Outcome Measures: Absolute and relative contraindications for thrombolysis administration in each case, according to the 2007 National Stroke Foundation guidelines; incidence of haemorrhage; and population thrombolysis rates according to distance from an acute stroke unit.Results: A total of 158 cases of thrombolytic therapy for suspected acute ischaemic stroke were identified in 157 patients. Fifteen patients (10%) had symptomatic intracranial haemorrhage, of whom eight (5%) died within 3 months. Seven patients had symptomatic extracranial haemorrhage. Five patients (3%) received thrombolysis despite absolute contraindications. Patients living closer to stroke units were more likely to receive thrombolysis.Conclusions: Rates of symptomatic haemorrhage after thrombolysis were similar to those in voluntary registries. A large proportion of South Australians are currently missing out on acute stroke therapy as a result of poor access to acute stroke units in both urban and rural settings. It is estimated that fewer than 2% of ischaemic stroke patients are administered thrombolysis in SA. [ABSTRACT FROM AUTHOR]

Objective: To define the uniqueness of chest CT infiltrative features associated with COVID-19 image characteristics as potential diagnostic biomarkers., Methods: We retrospectively collected chest CT exams including n = 498 on 151 unique patients RT-PCR positive for COVID-19 and n = 497 unique patients with community-acquired pneumonia (CAP). Both COVID-19 and CAP image sets were partitioned into three groups for training, validation, and testing respectively. In an attempt to discriminate COVID-19 from CAP, we developed several classifiers based on three-dimensional (3D) convolutional neural networks (CNNs). We also asked two experienced radiologists to visually interpret the testing set and discriminate COVID-19 from CAP. The classification performance of the computer algorithms and the radiologists was assessed using the receiver operating characteristic (ROC) analysis, and the nonparametric approaches with multiplicity adjustments when necessary., Results: One of the considered models showed non-trivial, but moderate diagnostic ability overall (AUC of 0.70 with 99% CI 0.56-0.85). This model allowed for the identification of 8-50% of CAP patients with only 2% of COVID-19 patients., Conclusions: Professional or automated interpretation of CT exams has a moderately low ability to distinguish between COVID-19 and CAP cases. However, the automated image analysis is promising for targeted decision-making due to being able to accurately identify a sizable subsect of non-COVID-19 cases., Key Points: • Both human experts and artificial intelligent models were used to classify the CT scans. • ROC analysis and the nonparametric approaches were used to analyze the performance of the radiologists and computer algorithms. • Unique image features or patterns may not exist for reliably distinguishing all COVID-19 from CAP; however, there may be imaging markers that can identify a sizable subset of non-COVID-19 cases.

Armour® Thyroid (Forest Pharmaceuticals, LLC; affiliate of Allergan, Dublin, Ireland) is a natural porcine derivative thyroid supplement that is frequently used without physician monitoring by health enthusiasts as a weight loss supplement. Although there are no publications associating Armour Thyroid and major coronary events, significant drug interactions may exist. A 32-year-old male with a history of hypothyroidism, cystic acne, and solitary congenital kidney presented to the emergency room after experiencing crushing substernal chest pain radiating to his left shoulder, accompanied by diaphoresis and shortness of breath. The patient denied any tobacco use or family history of heart disease. He was self-administering 120 mg of Armour Thyroid daily.   On examination, the patient was well-developed with cystic acne and a flushed appearance. His vital signs on admission were a blood pressure of 171/106 mmHg, heart rate of 88 beats per minute (bpm), and respiratory rate of 16 breaths/min. The electrocardiogram revealed marked ST-segment elevation in the anterior chest leads. Laboratory studies revealed elevated troponins. Urine drug screen was negative. The patient underwent an emergent coronary angiogram, which confirmed an occluded left anterior descending artery. He was treated successfully by thrombectomy and stenting of his left anterior descending artery. Evaluation for other causes of thrombosis was negative: glycosylated hemoglobin (HbA1C) 5.5%, low-density lipoprotein (LDL) 127 mg/dL, high-density lipoprotein (HDL) 33 mg/dL, hypercoagulable evaluation negative, and hemoglobin (Hgb) 17.1 gm/dL. Luteinizing hormone (LH) and follicle stimulating hormone (FSH) were < 0.20 miu/mL. Thyroid profile results were thyroid-stimulating hormone (TSH) 0.20 miu/mL (low), T3 free 4.08 pg/mL (high), and T4 total 1.2 mcg/dL (low), which were consistent with exogenous thyroid hormone administration. Focused questioning triggered by his cystic acne led to the discovery that the patient was self-administering exogenous testosterone replacement therapy. The patient declined to share specifics with the healthcare team. This was confirmed by a high testosterone level of 1,311 ng/dL. Hyperthyroidism increases the risk of cardiovascular events two to three times through the propagation of a hypercoagulable, hypofibrinolytic state possibly via an increase in clotting factors, a decrease in fibrinolytic enzymes, and an increased inhibition of the protein C pathway. The effect of androgens on cardiovascular mortality is uncertain. Androgens stimulate the hemostatic system, increase adverse lipid profile, and erythropoiesis. The combined therapy likely resulted in a synergistic potentiation of hypercoagulable, hypofibrinolytic effects of both agents. Given the absence of other cardiovascular risk factors, the cause of the myocardial infarction in our patient was likely due to drug interaction between Armour Thyroid and exogenous testosterone therapy. Due to the potential drug interaction between both natural and prescribed thyroid hormone and testosterone supplements, patients should be discouraged from self-administration of thyroid or anabolic steroids. Due to the lack of standardization in the T3 content, the use of Armour Thyroid should be avoided., Competing Interests: The authors have declared that no competing interests exist.

Background: Studies show increased rates of mortality for admissions on the weekend (WE) versus the weekday (WD). However, scepticism exists of this so-called 'weekend effect' on patient outcome. It remains poorly investigated, particularly the timing of the day of surgery and post-operative outcomes. A UK study found higher odds of death when operated on Friday and the WE, versus WD. This relationship was investigated by interrogating the Australian and New Zealand Audit of Surgical Mortality database., Methods: A standardized tool is used to collect data after every surgical death. Data in this retrospective cohort study from participating private and public hospitals in Australia on elective and emergency operations were extracted and included 7718 patients who had a surgical procedure within 30 days of admission and who subsequently died. A proxy measure of early surgical mortality, namely odds of dying within the first 48 h following surgery, was used to compare surgical mortality across days of the week., Results: Unadjusted and adjusted odds of early surgical mortality were higher on the WE compared to WD, unadjusted and adjusted OR 1.30 (P < 0.001) and 1.19 (P = 0.026), respectively. When separated by day of week, there was a trend for higher surgical mortality on Friday, Saturday and Sunday versus all other days, although this did not reach statistical significance. ASA grade and specialty of surgery were important predictors of outcome., Conclusion: There appears to be an association between day of surgery and surgical outcome. The exact cause and contributing factors requires further investigation., (© 2015 Royal Australasian College of Surgeons.)

Background: The Australian and New Zealand Audit of Surgical Mortality (ANZASM) is a nationwide confidential peer review of deaths associated with surgical care. This study assesses the concordance between treating surgeons and peer reviewers in reporting clinical events and delays in management., Methods: This is a retrospective cross-sectional analysis of deaths in 2009 and 2010. Cases that went through the process of submission of details by the surgeon in a structured surgical case form (SCF), first-line assessment (FLA) and a more detailed second-line assessment (SLA) were included. Significant clinical events reported for these patients were categorized and analysed for concordance., Results: Of the 11,303 notifications of death to the ANZASM, 6507 (57.6%) were audited and 685 (10.5%) required the entire review process. Nationally, the most significant events were post-operative complications, poor preoperative assessment and delay to surgery or diagnosis. The SCF submissions reported 338 events, as compared with 1009 and 985 events reported through FLA and SLA, respectively (P = 0.01). Treating surgeons and assessors attributed 29-30% of events to factors outside the surgeon's control. Surgeons felt that delay to surgery or diagnosis was a significant event in 6.6% of cases, in contrast to 20% by assessors (P = 0.01). Preoperative management could be improved in 19% of cases according to surgeons, compared with 45 and 36% according to the assessors (P < 0.001)., Conclusion: There is significant discordance between treating surgeons and assessors. This suggests the need for in-depth analysis and possible refinement of the audit process., (© 2014 Royal Australasian College of Surgeons.)

Sediment monitoring, tracing and modelling are widely used to identify suspended sediment sources. Although each method has inherent limitations and uncertainties, their integration provides opportunities to form collective knowledge and encourages robust management strategies. This paper presents a Weight-of-Evidence approach to integrate multiple Lines-of-Evidence for identifying suspended sediment sources. Three sources of evidence were used: i) stream flow and suspended sediment monitoring at river gauges; ii) geochemical sediment tracing at river junctions; and iii) catchment-scale suspended sediment modelling of hillslope, gully, streambank and unsealed road erosion. We applied this approach on two data-poor catchments in Australia. Some reaches were consistently identified as major sources of sediment from all Lines-of-Evidence. However, inconsistencies between the types of evidence in other areas highlighted the high uncertainty in identifying suspended sediment sources in these areas and the need for further investigation. The integration framework maximised the use of scarce information, enabled explicit consideration of uncertainties for catchment management and identified where future monitoring and research should be targeted., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: In bimodal electric tissue ablation (BETA), the cathode of the DC circuit is attached to the radiofrequency (RF) electrode to increase the surrounding tissue hydration. This will delay tissue desiccation and allowing the ablation process to continue for a longer period of time before "roll-off" occurs, resulting in larger ablations compared with standard radiofrequency ablation (RFA). Previous research showed that attaching the anode to the skin using electrosurgical grounding pads would reduce the efficacy of BETA because of the high electrical resistivity of the skin. This study investigated the ablation size produced when the anode was attached to the peritoneum (BETA-peritoneum) and the liver (BETA-liver) respectively., Materials and Methods: The anode of the DC circuit in BETA was attached to the peritoneum and the liver in a pig model using ECG dots. In BETA, 9 V of DC was provided for 10 min, after which the radiofrequency generator were switched on and both electrical circuits allowed to run concurrently until "roll-off." The size of ablations produced was compared to when the anode attached to the skin (BETA-skin) and standard RFA, respectively. The sites of anode placement were examined for local tissue injury., Results: The transverse diameters in BETA-peritoneum and BETA-liver were significantly larger compared with BETA-skin and standard RFA, respectively (P < 0.001). The axial diameter in the BETA-peritoneum and BETA-liver groups were also larger compared with the BETA-skin and RFA groups, although the differences did not reach statistical significance (P = 0.09). Hematoxylin and eosin (H and E) examination of the peritoneum and the liver where the anode was attached showed coagulation necrosis involving the superficial epithelium and the liver capsule, respectively., Conclusions: BETA can be used to treat larger liver tumors more effectively and may reduce the tumor recurrence rates compared with standard RFA. The efficacy of BETA depends on ensuring good electrical conductivity between the cathode and the anode of the DC circuit. Research so far has shown that BETA works best when the anode is placed deep to the skin as the stratum corneum consisted of a layer of a-nucleated cells, which have high electrical resistivity. The liver could be the ideal location to place the anode as it has excellent electrical conductivity, therefore ensuring maximum tissue hydration around the cathode to produce the largest ablations possible., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Bimodal electric tissue ablation (BETA) is a new technique that uses the direct current in electrolysis to improve the efficacy of radio frequency (RF) ablation. It was hypothesized that attaching the cathode of the electrolytic circuit to the RF electrode will increase the tissue hydration, therefore delaying tissue desiccation during ablation. Consequently, the ablation process can continue for a longer period of time and produce larger ablations. This hypothesis was tested by reversing the polarity of the electrolytic circuit, which theoretically would cause tissue desiccation and therefore produce smaller ablations. This new setup is called reversed polarity bimodal electric ablation (RP-BEA)., Materials and Methods: Three types of ablations standard radiofrequency ablation (RFA), BETA, and RP-BEA) were tested in a pig liver model. In BETA and RP-BEA, 9 V of direct current were provided for 10 min, after which the rf generator were switched on and both electrical circuits allowed to run concurrently. In all three setups, ablations were continued until "roll-off." The size of ablation was measured and compared with each other., Results: The duration of ablation was significantly shorted in RP-BEA compared with standard RFA and BETA (48 s verus 148 s and 84 s, respectively, P = 0.004). The sizes of ablations in RP-BEA were also significantly smaller compared with standard RFA and BETA-skin., Conclusion: RP-BEA caused tissue desiccation resulting in a shorter duration of ablation and smaller ablations. Therefore, the theory that BETA increases ablation size due to the effects of increased tissue hydration around the rf electrode is correct., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Bimodal electric tissue ablation (BETA) incorporates the process of electrolysis into radiofrequency ablation (RFA) to increase the size of tissue ablation. This study investigated whether BETA could increase the efficacy of the Cool-Tip RF system (Covidien, Boulder, CO, USA) to produce larger ablations. It also investigated whether applying electrolysis only during the pretreatment phase (called electrochemical treatment (ECT)/RFA group) is as effective as BETA (where electrolysis was used during both the pretreatment and RFA phases)., Methods: A Cool-Tip RF system (Covidien) was used to test three types of ablations (RFA, BETA, and ECT/RFA) in a pig liver model. In BETA, 9 V of direct current was provided for 10 min, after which the RF generator was started and both electrical circuits were allowed to run concurrently. In ECT/RFA, however, the direct current circuit was switched off after 10 min of pretreatment and only RFA was performed as described above. Ablation sizes were measured in three dimensions., Results: The size of ablations (transverse diameter A and B) produced by BETA and ECT/RFA was significantly larger compared with standard RFA (P < 0/001). BETA also created larger ablations compared with ECT/RFA (P < 0.001)., Conclusion: BETA could improve the efficacy of the Cool-Tip RF system (Covidien) to achieve larger ablations. The increased tissue hydration improved delivery of electrical energy to the tissues and delayed the process of desiccation, thus allowing the ablation process to continue for longer periods of time to produce larger ablations. BETA could be used to treat larger liver tumours more effectively than standard RFA., (© 2012 The Authors. ANZ Journal of Surgery © 2012 Royal Australasian College of Surgeons.)

Objectives: To determine the practice patterns of members of Society of Gynecologic Oncologists (SGO) in different clinical situations involving the intra-operative detection of nodal metastasis in early stage cervical cancer., Methods: A study questionnaire was mailed to the current members of SGO (n=874). Data were collected using an internet survey database. Frequency distributions were determined, and non parametric tests were performed., Results: Thirty percent SGO members responded (n=274). Only 38.6% routinely performed an intra-operative frozen section evaluation of the lymph nodes. Of these; most (79%) did not abort the radical hysterectomy (RH) for an isolated microscopically positive pelvic lymph node. The likelihood of aborting RH for microscopic nodal involvement increased however with number of positive pelvic lymph nodes (21% with 1, 40% with 2-3, and 61% with >3 positive pelvic lymph nodes), involvement of para-aortic lymph nodes (61%), or bilaterally positive lymph nodes (54%). Similarly, a large number did not complete the RH due to gross involvement of pelvic (45%) or para-aortic lymph node/s (69%). Most (90%) completed the lymphadenectomy before aborting RH. When completing RH, the majority tailored its extent to perform a less radical resection. Variables significantly associated with the likelihood of completing RH in different clinical situations included: location of current practice (West), practice type (private), years in practice (>15 years), and number of cases seen per year (>10/month)., Conclusion: Practice patterns of SGO members are considerably diverse, which is reflective of the conflicting evidence available in the literature. Well designed studies are required to determine the best overall approach., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objectives: The Marsh classification is a semiquantitative method for the diagnosis and monitoring of changes in duodenal biopsies in celiac disease. We have explored the possibility that quantitative changes in villous area and crypt length (morphometry) may provide better information on changes in duodenal morphology, particularly after the introduction of a gluten-free diet., Methods: We measured villous height, apical and basal villous widths, and crypt length in 57 adults with celiac disease and 83 control subjects. Villous area was calculated as a trapezoid approximation. Serial changes in villous area and crypt length were determined at regular intervals for up to 4 years after the introduction of a gluten-free diet. Morphometric changes were also correlated with Marsh grade, self-reported adherence to a gluten-free diet, and changes in celiac serology., Results: The gluten-free diet resulted in a progressive increase in villous area and a progressive decrease in crypt length. Morphometric improvement reached a plateau after 6-12 months with mean villous area attaining a value approximately half that of control subjects. Morphometric data were more sensitive than Marsh grade. Improvement in morphometric indices was significantly associated with the disappearance of anti-endomysial IgA antibody but not with dietary compliance., Conclusions: Morphometry is a sensitive way to document changes in duodenal biopsies in celiac disease. In adults treated with a gluten-free diet, it is uncommon for villous area to return to values observed in control subjects, but morphometric improvement is associated with the disappearance of anti-endomysial IgA antibody.

Background: In older people, undernutrition is associated with increased hospitalization rates and mortality. Because weight loss in older people often reflects a disproportionate reduction of skeletal muscle, anabolic treatments may be beneficial., Objective: Our aim was to evaluate the hypothesis that testosterone treatment and a nutritional supplement have additive benefits., Design: Oral testosterone undecanoate (40 mg daily for women, 80 mg twice daily for men) and an oral nutritional supplement (475 kcal/d) were administered, alone or combined, for 1 y to 49 community-dwelling, undernourished people [Mini Nutritional Assessment score <24 and low body weight (body mass index, in kg/m(2): <22) or recent weight loss (>7.5% over 3 mo)] aged >65 y (mean age: 77 y; 26 women and 23 men). Hospital admissions and other variables were assessed., Results: In subjects receiving combined testosterone and nutritional supplements (n = 11), there were no hospital admissions, whereas there were 9 admissions (2 elective) in 13 subjects in the no-treatment group, 4 in the testosterone-treated group (n = 12), and 5 in the supplement-treated group (n = 13); P = 0.06 with no-treatment compared with combined treatment. When compared with the no-treatment group, the combined-treatment group had significantly fewer subjects admitted to hospital (0 compared with 5, P = 0.03), fewer days in hospital (0 compared with 74, P = 0.041), and a longer time to hospital admission (P = 0.017)., Conclusions: In undernourished older people, combined treatment with testosterone and nutritional supplementation reduced the number of people hospitalized and the duration of hospital admissions, which are important endpoints in this group. Larger, confirmatory studies are now needed. This trial was registered before commencement at clinical trials.gov as NCT00117000.

Unlabelled: Ischemia-reperfusion injury (IRI) to the lower extremities causes both local damage and serious dysfunction to remote organs, including lungs and kidneys. However, effective therapies are not available. This study aims to determine if simvastatin reduced the severity of remote damage following IRI., Methods: Rats were given simvastatin before hind limb IRI. Lung and kidney tissues were assessed for neutrophil infiltration using myeloperoxidase assays and basement membrane damage by quantitative immunohistochemical measurement of collagen IV. The effect of nitric oxide synthase (NOS) inhibition on remote damage after IRI and simvastatin was assessed using the NOS inhibitor, L-NIO., Results: Simvastatin (2 mg/kg) protected kidneys against IRI-induced neutrophil infiltration. Simvastatin also inhibited the IRI-induced activation of MMP-9 in the lungs. However, paradoxically, simvastatin exacerbated IRI-induced neutrophil infiltration into the lungs. IRI induced collagen IV degradation in the lungs but not in the kidneys. The degree of collagen breakdown in the lungs was significantly ameliorated by 2 mg/kg simvastatin. NOS inhibition markedly protected both the lungs and the kidneys against IRI-induced neutrophil infiltration but did not alter collagen IV degradation. Administration of simvastatin to L-Nio-treated animals enhanced the degree of protection against IRI-induced neutrophil infiltration in the kidneys but not in the lungs., Conclusions: Simvastatin protects against remote IRI-induced damage in the lungs and kidneys, suggesting statins may reduce the severity of IRI during major vascular surgery.

Background: Neutrophil infiltration is a major determinant of ischemia-reperfusion injury (IRI). Statins improve endothelial function by elevating nitric oxide synthase activity and inhibiting adhesion molecule expression and may, therefore, inhibit IRI-induced neutrophil extravasation. Although statins are protective against myocardial IRI and stroke, a role for statins in ameliorating skeletal muscle IRI has not yet been confirmed. This study, therefore, addressed the hypothesis that simvastatin would attenuate the severity of tissue damage during skeletal muscle IRI., Methods: Rats were administered simvastatin for 6 d before 4 h hind limb ischemia and 24 h reperfusion. Neutrophil infiltration was assessed using myeloperoxidase (MPO) assays and tissue damage by quantitative immunohistochemical analysis of collagen IV. The effect of reducing nitric oxide levels on the severity of IRI was assessed by administering the NOS inhibitor, N-Imino-L-ornithine (L-NIO), before ischemia., Results: Simvastatin significantly inhibited IRI-induced MPO activity but not collagen degradation in postischemic skeletal muscle. Inhibition of nitric oxide synthase by L-NIO markedly inhibited neutrophil infiltration and protected against IRI-induced collagen degradation. When both simvastatin and L-NIO were administered before IRI, the IRI-induced elevation in MPO activity was completely inhibited. However, paradoxically, simvastatin counteracted the protective effect of L-NIO against IRI-induced collagen IV degradation., Conclusions: The inhibition by simvastatin of IRI-induced neutrophil infiltration in skeletal muscle suggests that statins may be a useful therapy to attenuate the severity of IRI but their precise mechanisms of action remains to be determined. Nitric oxide also plays a cytotoxic, rather than protective, role in mediating IRI in this model.

Background: This study aimed to report the computer-enhanced robotic surgery experience of the authors' gynecologic oncology division., Methods: From January 2001 to August 2006, 41 patients underwent laparoscopic surgery by our gynecologic oncology service using a computer-enhanced surgical robot. This report describes a retrospective review of these patients., Results: The patients ranged in age from 27 to 77 years (mean, 44.2 years), in weight from 44 to 131 kg (mean, 72.1 kg), in operative time from 1 h and 50 min to 9 h (mean, 5 h and 2 min), and in estimated blood loss from 50 to 1,500 ml (mean, 253 ml). Of the 20 patients with gynecologic malignancies, 14 had cervical cancer. A total of 21 patients had benign indications for surgery. Complications included shoulder palsy, robot failure, colotomy, bradycardia, and intraabdominal bleeding requiring minilaparotomy and ligation of a bleeding pedicle., Conclusion: This case series is one of the first to report the use of a computer-enhanced surgical robot in gynecologic oncology. This approach proved to be feasible and well tolerated in this series of patients and deserves further study for clarification of its indications, benefits, and safety.

Objectives/hypothesis: The main objective was to demonstrate that human papillomavirus (HPV) type 11 is an aggressive virus that plays a significant role in the development of laryngeal cancer in patients with a history of recurrent respiratory papillomatosis (RRP). We have done so by preliminary investigation into the molecular mechanism underlying the malignant transformation of RRP to invasive squamous cell carcinoma., Study Design: An experimental, nonrandomized, retrospective study using tissue specimens from nine patients with a history of RRP that progressed to laryngeal or bronchogenic cancer was performed., Methods: DNA and RNA were extracted from 20 formalin-fixed, paraffin-embedded specimens from six patients with a history of early onset RRP and laryngeal cancer and from three patients with early onset RRP and bronchogenic cancer. Polymerase chain reaction (PCR) was performed on DNA to determine the HPV type in each specimen. Reverse-transcriptase PCR specific for virus transcripts was performed on RNA to determine whether the viral genome was integrated into the host genome., Results: HPV-11 but not HPV-6, 16, or 18 was found in all of the laryngeal and bronchogenic cancers in patients with a history of early onset RRP in this study. RNA, sufficiently intact for examination, was obtained from seven patients. Analysis of HPV 11 transcripts revealed integration of the viral genome in three of seven patients., Conclusions: HPV type 6 and 11 are considered "low-risk" viruses and are not associated with genital cancers, as are HPV types 16 and 18. However, our data suggests that HPV type 11 is an aggressive virus in laryngeal papilloma that should be monitored in patients with RRP.

Controversy exists as to whether acute administration of growth hormone has insulin-like effects. In conscious dogs, acute effects on plasma flows, plasma glucose, hepatic glucose output, free fatty acids, ketone bodies, insulin, and glucagon were determined following intravenous injection of 1 mg of growth hormone extracted from the canine pituitary gland. The following results were obtained: (1) Plasma flows in the portal vein, hepatic artery and hepatic vein were significantly increased 20 min after growth hormone administration. (2) By 40 min after growth hormone, the glucose concentration in these three vessels was significantly increased. (3) Hepatic glucose output was significantly increased 60 min after growth hormone administration. (4) Free fatty acids levels were significantly but transiently increased at 20 min, while ketone body concentrations were elevated at 120-180 min. (5) The insulin levels in the three vessels demonstrated a biphasic response. In the portal vein, they were significantly higher 20 min after growth hormone and again at 150-180 min. Glucagon concentrations were increased in all three vessels by 20 min and remained elevated for the remainder of the experiment. These results do not support an acute insulin-like action of growth hormone in normal dogs.

The present study was undertaken to investigate the efficacy of a new, highly purified (purity greater than 91%), ethyl esterification product from natural eicosapentaenoic acid (EPA-E, C20:5 omega 3) in patients with type II diabetes mellitus (NIDDM). Hemodynamic changes were assessed at the level of the dorsalis pedis artery using an ultrasonic color Doppler duplex system before and after oral administration of EPA-E at a dose of 1800 mg/day for 48 weeks. The cross-sectional area of the dorsalis pedis artery increased significantly from 2.5 +/- 0.2 to 3.9 +/- 0.4 mm2 (48 weeks, mean +/- SE, p < 0.05). Moreover, EPA-E improved the clinical symptom (coldness, numbness) as well as the vibration perception threshold sense of the lower extremities [from 32.1 +/- 8.5 to 16.1 +/- 4.8 (48 weeks) microns]. A significant decrease of serum triglycerides was also noted by EPA-E administration. Furthermore, significant decrease of the excretion of albumin in urine [from 24.4 +/- 3.3 to 13.9 +/- 1.8 (48 weeks) mg/g.Cr, p < 0.05]. The results of this study suggest that EPA-E has significant beneficial effects on diabetic neuropathy and serum lipids as well as other diabetic complications such as nephropathy and macroangiopathy.

Although a growing body of evidence supports that alkali therapy in diabetic ketoacidosis (DKA) might be counterproductive, our knowledge about the consequences of this treatment on ketone metabolism is limited. Consequently, we performed clinical and animal studies to further examine this topic. The clinical studies assessed seven patients with DKA treated with continuous insulin infusion at a low dosage. Three of them also received sodium bicarbonate (NaHCO3), whereas the remaining four acted as controls. The group receiving NaHCO3 showed a 6-h delay in the improvement of ketosis as compared with controls. In addition, there was an increase in acetoacetate (AcAc) levels during alkali administration, followed by an increase in 3-hydroxybutyrate (3-OHB) level after its completion. Significant differences were not found between groups in the response of plasma glucose to the overall therapy. The animal study examined the effects of a NaHCO3-rich perfusate on the hepatic production of ketones with the in situ rat-liver preparation. Alkali loading resulted in an immediate increase in the AcAc level followed by increases in both the 3-OHB level and the 3-OHB/AcAc ratio after its completion. Hepatic ketogenesis increased even further, to about twice the basal level, after termination of the NaHCO3 loading. This investigation confirms that alkali administration augments ketone production and unravels an effect of bicarbonate infusion that promotes a selective build up of AcAc in body fluids. The data support that alkali therapy in DKA has nonsaltuary effects in the metabolism and plasma levels of ketones.

This study examined the effect of growth hormone (GH) on hepatic glucose metabolism and on the fractional extraction of insulin and glucagon after oral glucose administration. GH treatment [canine GH (0.75 mg/day for 7 days)] significantly increased basal portal vein and hepatic artery flow (P < 0.01 compared with pre-GH treatment). After GH treatment and after oral glucose, glucose levels significantly exceeded those before GH at 100 and 120 min in arterial and portal vein plasma and 120 min in the hepatic vein. The net hepatic uptake of glucose was similar before and after GH treatment. The increment of net nonhepatic splanchnic insulin balance above basal was 131 +/- 31 mU.kg-1.3 h-1 before and 272 +/- 46 mU.kg-1.3 h-1 after GH treatment (P < 0.05). An increase in fractional hepatic extraction of insulin occurred before GH treatment and was significantly greater at 60 min. In summary, despite the increased insulin content after GH administration, there was no change in hepatic uptake of glucose, indicating that the liver was also the site of insulin resistance.

Bovine crystalline insulin, mixed with an absorption enhancer, was loaded by hand into gelatin capsules, which were then coated with an azopolymer designed to deliver the insulin in the upper colon. In 34 experiments with 14 pancreatectomized mongrel dogs of both sexes, the coated capsules were administered orally after a pre-dose period of 1 h. The dogs had cannulae in the portal vein, hepatic vein and femoral artery and Doppler flow probes on the portal vein and hepatic artery. Insulin and food were withdrawn the day before an experiment. Responses measured were plasma glucose, plasma insulin, hepatic glucose production rate, hepatic plasma flow rate and plasma glucagon-like immunoactivity (GLI). Control experiments, with capsules without insulin, produced small changes from 'pre-dose' values. Insulin-containing capsules, without the azopolymer coating, resulted in some early changes consistent with upper gastrointestinal absorption. Single oral doses (66 to 400 nmol/kg) of insulin in completely coated capsules produced peaks of portal plasma insulin and transient decreases in plasma glucose, hepatic glucose production, hepatic plasma flow and plasma GLI. The changes usually began 1.5-2 h after administration of a single dose, and lasted for up to 3 h, but were not significantly related to the dose of insulin. Multiple oral doses of insulin, given at 1.5-h intervals, resulted in multiple peaks of plasma insulin, a continuing dose-dependent fall in plasma glucose to near-euglycaemia with the highest dose, and profound decreases in hepatic glucose production and plasma GLI. These data demonstrate that insulin absorbed from the gastrointestinal tract causes changes in glucose metabolism in the diabetic dog that are consistent with the action of insulin primarily on the liver and that repeated oral doses are necessary to correct the hyperglycaemia.

The role of thyroid hormones in a short loop feedback in the thyroid is controversial. This process was studied in dog thyroid slices stimulated by TSH, carbachol and phorbol esters. Incubation of thyroid slices with T3 and T4 for 1 hour inhibited the subsequent stimulation of glucose oxidation induced by carbachol and phorbol esters but not by TSH. T3 also inhibited the stimulation of 32P incorporation into phospholipids stimulated by these two agonists. Glucose oxidation stimulated by TSH, carbachol and 12-0-tetradecanoyl-phorbol-13-acetate (TPA) was inhibited by rT3 and the inhibition was not reversed by methimazole, which did abolish the inhibition induced by iodide, MIT and DIT. TSH stimulation of cAMP was not blocked by T3 or T4 but was by rT3 and MIT- and DIT. The mechanism of such inhibition appears to be complex, possibly involving formation of iodide from rT3, MIT and DIT but also dependent on the intact iodothyronine. Moreover, our data suggest that T3 and T4 exert their inhibition on the thyroid through the phospholipids cascade and this mechanism is probably independent on the release of iodide from these iodocompounds.

The time course of changes in hepatic lipid metabolism (non-esterified fatty acids (NEFA), ketone body) after ingestion of glucose was assessed in normal dogs. Glucose ingestion suppressed significantly (p less than 0.01) the amount of NEFA reaching the liver (12.4 +/- 1.0 to a nadir of 2.9 +/- 0.6 mumol/kg/min at 80 min) and increased significantly (p less than 0.05) net hepatic balance (-1.8 +/- 0.6 to 0.5 +/- 0.4 mumol/kg/min at 120 min). After glucose ingestion, the amount of total ketone body presented to the liver decreased significantly (p less than 0.05) to a nadir of 1.1 +/- 0.4 mumol/kg/min at 60 min and gradually increased after 120 min. These changes reflect the increased insulin secretion induced by glucose ingestion. The hyperinsulinemia would inhibit peripheral lipolysis and stimulate esterification of fatty acids. It would reduce ketone body concentration both by a direct effect on hepatic production as well as the consequence of diminished NEFA levels. In summary, the present study clearly demonstrated the time course changes in NEFA and ketone body level after oral glucose ingestion.

Oral glucose administration increases insulin secretion to a greater extent than peripheral glucose infusion (incretin effect). It also augments protal vein blood flow, hepatic uptake of glucose, and fractional hepatic extraction of insulin. The mechanisms for these various effects are not known but could involve both neurogenic stimuli and gut hormones. The present studies examined the effect of a non-nutrient drink, 1 g/kg body wt oral mannitol, on these parameters during an intravenous glucose infusion in conscious dogs. The dogs had chronically implanted Doppler flow probes on the portal vein and hepatic artery and catheters in the portal vein, hepatic vein, and femoral artery. After a 30-min control period, an infusion of atropine, propranolol, phentolamine, or propranolol and phentolamine was begun. Thirty minutes later, glucose (13 mg.kg-1.min-1) was then infused into a peripheral vein for 120 min with continuation of the atropine and adrenergic blockade. Water or mannitol (10% solution) was administered orally 50 min after the initiation of the glucose infusion. Mannitol, but not water, significantly enhanced the insulin response to intravenous glucose, as indicated by higher insulin concentrations in the portal vein as well as more rapid reduction of the plasma glucose. This incretin effect was significantly attenuated by infusion of propranolol but not by atropine or phentolamine. Mannitol did not increase portal vein blood flow or have any effect on the hepatic uptake of glucose or the fractional hepatic extraction of insulin. Thus absorption of nutrient is not necessary for the incretin effect but is for the increased portal vein blood flow and increased fractional extraction of insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

The present studies were undertaken to quantitate the relative contributions of the indirect and direct pathways for hepatic glycogen repletion and to determine the role of splanchnic tissues in provision of C precursors used for the indirect pathway. For this purpose, we administered oral glucose (1.4 g/kg) enriched with [1-14C]glucose to 18-h fasted dogs and measured net hepatic and net gastrointestinal glucose, lactate, and alanine balance, hepatic and gastrointestinal fractional extraction [( 3H]lactate), release and uptake of lactate, as well as the total amount of hepatic glycogen formed from the oral glucose and the 14C labeling pattern of the glycogen-glucose C. Although net hepatic glucose uptake (8.7 +/- 0.6 g, 27% of the oral load) exceeded the amount of glycogen formed from the oral glucose (6.3 +/- 1.1 g), analysis of radioactivity in C-1 of the glycogen glucose indicated that nearly 50% of the glycogen was formed by the indirect pathway. Net hepatic uptake of lactate (1.4 +/- 0.1 g) and alanine (1.5 +/- 0.1 g) could account for greater than 90% of glycogen formed by the indirect pathway if all of the lactate and alanine taken up by the liver had been incorporated into glycogen. Release of lactate and alanine by splanchnic tissues approximated the amount of lactate and alanine taken up by the liver. However, in addition to taking up lactate, the liver also produced nearly as much lactate as the gastrointestinal tract (1.8 +/- 0.2 vs. 2.0 +/- 0.3 g, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Amiodarone, an iodine-containing antiarrhythmic drug, has been reported to interfere with thyroid function and thyroid hormone metabolism. We studied the effects of amiodarone on basal and agonist [thyroid-stimulating hormone (TSH), phorbol ester, or carbachol]-stimulated glucose oxidation, 32PO4 incorporation into phospholipids, and adenosine 3',5'-cyclic monophosphate (cAMP) concentration in dog thyroid slices. Slices were preincubated with amiodarone at 37 degrees C for 1 h before the addition of agonist and the appropriate radioisotope. cAMP stimulation was measured after 20 min, glucose oxidation for 45 min, and 32PO4 incorporation into phospholipids for 2 h. Amiodarone (0.5 mM) had no effect on basal 14CO2 formation or 32PO4 incorporation into phospholipids but significantly inhibited TSH, phorbol ester, and carbachol stimulation of these parameters. It also inhibited cAMP stimulation by TSH. Inhibition of TSH-stimulated [14C]glucose oxidation was also obtained with another iodide-containing compound, iopanoic acid (0.5 mM), but not with iothalamate (up to 10 mM). Inhibition by amiodarone was still present, but to a lesser extent, when it was added at the same time as the agonist. Inhibition of stimulated [14C]glucose oxidation persisted even after the slices were incubated without amiodarone for 6 h. Inhibition by amiodarone, in contrast to that by inorganic iodide, was not prevented by 1 mM methimazole added at the same time as amiodarone. These results indicate that the inhibitory effects of amiodarone on thyroid function are not due to dissociation of iodide from the molecule.

Thyrotropin (TSH) and carbachol stimulated in a dose-dependent manner the accumulation of 3H-glycerophosphoinositol (GPI), 3H-inositol monophosphate (IP1), 3H-inositol bisphosphate (IP2) and 3H-inositol trisphosphate (IP3) in primary cultures of dog thyroid cells prelabeled with myo-[2-3H]inositol. TSH, 250 mU/mL, stimulated 3H-IP3 level after a 10-minute incubation while 10 mU/mL TSH increased it during a 60-minute incubation. The effect of carbachol was more rapid and greater than that of TSH. Carbachol, 100 mumol/L, elevated 3H-IP3 after a 2-minute incubation and 3H-IP3 formation was increased by as little as 1 mumol/L carbachol. TSH stimulation was observed only if the cells were deprived of TSH for 5 days before being labeled with 3H-inositol. Prolongation of the labeling period or addition of TSH, (Bu)2cAMP or carbachol during the labeling increased 3H-inositol incorporation into polyphoinositides (PIPs). When the cells were labeled without any other addition, control and TSH-stimulated 3H-IP3 levels increased in parallel with 3H-PIP levels. However, TSH or carbachol-stimulated 3H-IP3 levels did not increase in proportion to 3H-PIPs level when the cells were labeled with TSH or (Bu)2cAMP. Thus, the ratio of 3H-IP3/3H-PIPs (both control and TSH or carbachol-stimulated) decreased in the cells labeled with TSH or (Bu)2cAMP, which might reflect TSH stimulation of 3H-inositol incorporation into PIPs pool(s) that do not participate in hormone-induced hydrolysis of PIPs.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypoglycemia can be defined as the occurrence of a wide variety of symptoms in association with a plasma glucose concentration of 50 mg per dl or less. It may be asymptomatic, and the relief of the symptoms by administration of glucose is not sufficient to establish a diagnosis. Although the symptoms may be quite variable, they can be classified as adrenergic or neuroglycopenic. Hypothermia, hyperthermia, or localizing neurologic findings may be seen as a consequence of hypoglycemia. Severe, repeated episodes of hypoglycemia can cause a distal neuropathy that is primarily motor but can also have a sensory component. Hypoglycemia can be classified as fasting, reactive, surreptitious, or artifactual. Some causes of hypoglycemia are unique to infants and children. Underlying diseases such as liver disease, endocrine disease, or renal disease can be diagnosed by the characteristic physical findings and laboratory tests. Other causes of hypoglycemia can be identified by a variety of diagnostic tests involving measurement of glucose, insulin, C-peptide, and other related compounds.