Hypoglycaemia requiring medical assistance in patients with diabetes: a prospective multicentre survey in tertiary hospitals.

AIM: Hypoglycaemia is considered a factor contributing to morbidity and mortality in patients with diabetes. The aim of the present study was to examine the frequency, clinical characteristics, predisposing factors and outcomes of iatrogenic hypoglycaemia requiring medical assistance. METHODS: Eight hospitals participated in this prospective survey of documented iatrogenic hypoglycaemia at their emergency departments. Cases with type 2 diabetes (T2D) were compared with a control group, consisting of patients visiting the outpatients' diabetes clinics of the same hospitals during the same time period. RESULTS: Median survey duration was 16.5 months, and 295 episodes of iatrogenic hypoglycaemia were recorded. Frequency varied across centres from 0.25 to 0.78 cases per 100 presenting patients. Most cases (90.8%) were observed in patients with T2D (mean age: 76.7±10.1 years), while 8.1% of events were recorded in patients with type 1 diabetes (mean age: 42.7±18.3 years). Total in-hospital mortality was 3.4%, and all involved patients with T2D. In T2D patients, advanced age (OR: 1.3 [1.20-1.45] for 5-year increase), use of sulphonylureas (OR: 4.0 [2.5-6.36]), use of insulin (OR: 2.35 [1.42-3.95]), lower estimated GFR (OR: 1.15 [1.07-1.23] at 10mL/min) and number of comorbidities (OR: 1.74 [1.34-2.27]) were each independently associated with hypoglycaemia requiring medical assistance. CONCLUSION: Hypoglycaemia requiring medical assistance in patients with diabetes is a moderately common condition seen in emergency departments and has a mortality rate of 3.4%. The majority of cases involve elderly individuals with T2D who are suffering from serious comorbidities and treated with insulin and/or sulphonylureas.

Unifying model of carpal mechanics based on computationally derived isometric constraints and rules-based motion - the stable central column theory.

This study was part of a larger project to develop a (kinetic) theory of carpal motion based on computationally derived isometric constraints. Three-dimensional models were created from computed tomography scans of the wrists of ten normal subjects and carpal spatial relationships at physiological motion extremes were assessed. Specific points on the surface of the various carpal bones and the radius that remained isometric through range of movement were identified. Analysis of the isometric constraints and intercarpal motion suggests that the carpus functions as a stable central column (lunate-capitate-hamate-trapezoid-trapezium) with a supporting lateral column (scaphoid), which behaves as a 'two gear four bar linkage'. The triquetrum functions as an ulnar translation restraint, as well as controlling lunate flexion. The 'trapezoid'-shaped trapezoid places the trapezium anterior to the transverse plane of the radius and ulna, and thus rotates the principal axis of the central column to correspond to that used in the 'dart thrower's motion'. This study presents a forward kinematic analysis of the carpus that provides the basis for the development of a unifying kinetic theory of wrist motion based on isometric constraints and rules-based motion.

Study comparing sutures and nonpenetrating titanium clips for arteriotomy closure after embolectomy.

BACKGROUND: The vascular closure staple (VCS) clip applier system is an alternative to suture for closing arteriotomies and performing vascular anastomoses. This study was designed to evaluate the possible advantages of its use in closing arteriotomies after embolectomy. METHODS: In this study, 26 patients with upper or lower extremity embolism underwent embolectomy, and the arteriotomy was closed using either VCS clips (group A) or sutures (group B). RESULTS: The time required for arteriotomy closure with clips (11.2 +/- 2.7s) was considerably shorter than the time required with sutures (241.2 +/- 48.7s; p < 0.0001), resulting also in shorter clamp times (380.8 +/- 127.3s vs 612.7 +/- 112.6 s; p < 0.0001). No hemodynamically significant stenoses or pseudoaneurysms were detected at the arteriotomy sites in any of the patients up to 1 year after embolectomy. CONCLUSIONS: The VCS clip applier system, a quick and easy method for closing arteriotomies, is as safe as sutures in terms of narrowing of the artery and formation of pseudoaneurysm.

Recurrent peripheral arterial embolism from pulmonary cancer. Case report and review of the literature.

Peripheral arterial embolism arising from a malignant tumour is an infrequent manifestation of neoplastic disease and also a rare cause of acute arterial occlusion. A case of recurrent arterial embolism of the lower extremities due to a primary lung cancer is reported and the literature on this topic is reviewed.

Therapeutic efficacy of flavonoids in oedema following reperfusion on acutely ischaemic legs.

BACKGROUND: The aim of this study was to investigate the effect of a purified, micronised, flavonoid fraction (Daflon) in lower limb oedema developed after delayed embolectomy and successful reperfusion of acutely ischaemic legs. METHODS: Our series consisted of 19 patients with prolonged, acute ischaemia of the lower extremity caused by arterial embolism, who had undergone successful embolectomy. Patients were randomised into two groups; ten patients (group I) treated with flavonoids, were compared to nine given a placebo. Ankle and calf circumferences, venous capacitance and venous emptying time were measured preoperatively [T1], on the 2nd [T2], 5th [T3], 8th [T4] and 30th [T5] postoperative days. RESULTS: An increase of ankle and calf circumference up to 9% and 13.5% respectively, as compared with preoperative values was demonstrated. There was a reduction in oedema formation in patients with the Daflon group, which reached statistical significance only in the ankles (p=0.0276). Calf differences were statistically significant on the second and fifth postoperative days (p<0.05). Venous haemodynamics were considerably improved by Daflon (p<0.001). CONCLUSIONS: Daflon 500 mg had an inhibitory effect on moderate oedema developed after revascularisation of an ischaemic limb.

Galanin inhibits continuous and phasic firing in rat hypothalamic magnocellular neurosecretory cells.

The effects of galanin (GAL) on magnocellular neurosecretory cells (MNCs) were examined during microelectrode recordings from supraoptic neurons in superfused hypothalamic explants. Application of the full-length peptide (GAL1-29) or of the N-terminal fragment GAL1-16 produced reversible membrane hyperpolarization with an IC50 near 10 nM. These effects were associated with an increase of membrane conductance, with a reversal potential near -70 mV, and were not blocked by tetrodotoxin, indicating that the receptors mediating these effects are located postsynaptically. Hyperpolarizing responses were also observed in response to the GAL-like chimeric ligands M35 and M40, suggesting that these behave as partial agonists at galanin receptors. The reversal potential of the GAL-mediated effect was unaffected by reducing extracellular chloride or by intracellular chloride injection, indicating that the effects of galanin are not mediated by modulation of chloride conductances. In contrast, reducing the external concentration of potassium ions from 3 to 1 mM shifted the reversal potential of the responses to -85 mV, suggesting the involvement of a potassium conductance. When tested on spontaneously active MNCs, the hyperpolarizing effects of galanin were associated with a suppression of firing in both continuously active and phasically active neurons. Inhibition of phasic bursts was mediated both through the inhibitory effects of the hyperpolarization and through a GAL-mediated inhibition of the depolarizing afterpotential that is responsible for the production of individual bursts. These results suggest that galanin may be a potent endogenous modulator of firing pattern in hypothalamic neuroendocrine cells.

Total knee arthroplasty in patellectomized patients.

Thirty-two total knee arthroplasties (TKAs) in patellectomized patients were evaluated with recent clinical and radiographic examinations. Eighteen patients had a primary TKA with a mean follow-up period of 49 months, and 14 patients had a revision TKA with a mean follow-up period of 36 months. A control group of 13 TKA patients with intact patellae were randomly generated but matched for age, sex, follow-up data, diagnosis, and prosthesis. Posterior cruciate ligament-retaining types of prostheses were used in the primary knees, while the revision knees underwent arthroplasties with the more constrained, posterior cruciate ligament-substituting prostheses. All knees were evaluated based on the Knee Society's clinical and radiographic scoring system. In addition, 18 patients (9 primary, 9 revision) underwent isokinetic dynamometer testing for quantitation of peak quadriceps and hamstring torque. The knee score, indicative of pain relief, averaged 82.5 in the primary group (16 good/excellent, 1 fair, 1 poor), 86.5 in the revision group (12 good/excellent, 1 fair, 1 poor), and 93.9 in the control group (13/13 excellent). The function score averaged 59.7 in the primary group (6 good/excellent, 6 fair, 6 poor), 60.0 in the revision group (5 good/excellent, 2 fair, 7 poor), and 80.9 in the control group (12 good/excellent, 1 fair). The lower function scores predominantly reflected the patients' difficulty in independently climbing or descending stairs. This was also reflected in their higher flexion to extension peak torque ratios. There was one failure in the primary group requiring a revision and one failure in the revision group requiring a knee fusion. There was no radiographic evidence of impending failure in any of the remaining knees. No clinical or radiographic differences were found between the patients with osteoarthritis or rheumatoid arthritis. Although the knee and function scores were lower in the patellectomized patients, the overall results were generally satisfactory without a high incidence of failures. Satisfactory results were obtained in the primary TKAs using the minimally constrained prostheses when the posterior cruciate ligament was intact. Revision TKAs, in which the posterior cruciate ligament was absent, also demonstrated satisfactory results with the more constrained, posterior cruciate ligament-substituting prostheses.

The NMDA receptor contributes to anoxic aglycemic induced irreversible inhibition of synaptic transmission.

Percent recovery of CA1 field EPSP amplitude following various anoxic aglycemic (AA) periods was examined in rat hippocampal slices superfused with MK-801 (0.1 microM, 1 microM, 10 microM) or Mg(2+)-free artificial cerebrospinal fluid. Slices treated with 0.1 microM MK-801 showed greater percent recuperation of EPSP amplitude following 3 min 30 s of AA (36 +/- 12% vs 6 +/- 4% in controls). Higher concentrations of MK-801 resulted in a greater recovery of EPSP amplitudes in more than one time period of AA, with 10 microM MK-801 providing protection in up to 4 min 30 s AA. Percent recuperation of EPSP amplitude was smaller in Mg(2+)-free slices following 2 min (34 +/- 15% vs 81 +/- 11% in controls) and 2 min 30 (25 +/- 14% vs 77 +/- 10% in controls) of AA. These results suggest that the activation of the N-methyl-D-aspartate (NMDA) receptor channel may contribute to irreversible AA induced synaptic failure in CA1.

Cycloheximide Reduces the Effects of Anoxic Insult In Vivo and In Vitro.

In vivo and in vitro techniques were utilized to examine the influence of a protein synthesis blocker, cycloheximide (CHX), on the damaging effects of anoxia in the rat. CHX administered 1 h before transient (30 min) forebrain ischaemia increased the survival of animals, decreased body weight loss and reduced the occurrence of delayed degeneration in the CA1 pyramidal region. The same dose of CHX injected 1 h after ischaemia induced status epilepticus, a decrease in survival rate, and did not reduce weight loss or CA1 damage in any of the surviving rats. Electrophysiological techniques were then used to determine the effects of various periods of anoxia and aglycaemia (AA) on CA1 field excitatory postsynaptic potentials (EPSPs) in hippocampal slices incubated in the presence or absence of CHX. In CHX-treated slices, recuperation of EPSP amplitude (45 +/- 16%) was significantly greater than in control slices (9 +/- 9%) following an AA episode of 3 min 45 s. No difference was seen in the percent recuperation of EPSPs in the control and CHX-treated slices after shorter or longer episodes of AA. From these studies, it appears that CHX protects against the damaging effect of ischaemia in vivo or AA in vitro.

Electrophysiological evidence of baroreceptor input to area postrema.

Subpopulations of rat area postrema (AP) and nucleus tractus solitarius (NTS) neurons exist that are responsive to changes in blood pressure. The hypothesis that these effects may be mediated by afferent baroreceptor input was examined. Orthodromic responses of AP and NTS neurons to aortic depressor nerve (ADN) stimulation were observed. Sixty-three percent of AP neurons were affected by ADN stimulation, with most exhibiting short-duration excitatory responses (latency, 27 +/- 1 ms; duration, 11 +/- 1 ms). Fifty-five percent of NTS neurons were influenced by ADN stimulation, although effects in this region were more heterogeneous (24% of neurons excited, 31% inhibited). Thus, in the rat, apparently both AP and NTS neurons receive afferent barosensory information.

Effects of parabrachial stimulation on angiotensin and blood pressure sensitive area postrema neurons.

Subpopulations of neurons in the area postrema (AP) and commissural nucleus tractus solitarius (NTS) have been identified according to their responses to systemic angiotensin-II (ANG-II) and increases in blood pressure (BP). In order to further define the functional connections of these subpopulations of cells, electrophysiological single unit recording studies have been done to determine the orthodromic effects of parabrachial nucleus (PBN) stimulation on these functionally defined cell groups. Orthodromic effects were seen in a similar proportion of ANG-II sensitive neurons in the AP (31.5%) and NTS (31%). PBN stimulation influenced a similar percentage of BP sensitive neurons in the AP (35%), although a larger proportion of this group of NTS cells was affected (55.5%). Twenty-five percent of ANG-II/BP sensitive neurons in the AP were orthodromically influenced, and 71.5% of this group of NTS neurons were affected by PBN stimulation. Small proportions of the neurons in the unaffected subpopulation of AP (10%) and NTS (27%) were also orthodromically affected by PBN stimulation. The remaining neurons in each group were not affected. This study suggests that there is no apparent preferential distribution of excitatory or inhibitory PBN efferents to any of the identified subpopulations of AP and NTS neurons.

The blink reflex in patients with idiopathic torsion dystonia.

The blink reflex and its recovery cycle were examined in 57 patients with idiopathic dystonia affecting different parts of the body. The group comprised 9 patients with generalized and 15 with segmental forms, 19 with torticollis, and 14 with focal arm dystonia. None had blepharospasm. The duration and amplitude of the R2 component of the blink reflex showed only minor changes. However, its recovery cycle to paired supraorbital nerve stimuli was abnormal in all groups of patients, except those with focal arm dystonia. These findings may be interpreted as showing abnormal control of the interneuronal networks mediating the blink reflex in patients with dystonia affecting sites other than the facial muscles. The fact that the principal changes were seen in patients with torticollis, and generalized or segmental dystonia, suggests that the extent of dystonia (rather than the severity) and, therefore, the close proximity to the cranial muscles was important in determining the extent of the abnormal interneuron function.

Electrophysiological characterization of reciprocal connections between the parabrachial nucleus and the area postrema in the rat.

Neuroanatomical studies have demonstrated reciprocal connections between the parabrachial nucleus (PBN) and both the area postrema (AP) and the nucleus tractus solitarius (NTS). To functionally characterize these projections, antidromic identification of AP and NTS neurons projecting to the PBN was attempted. Orthodromic influences on these cells, resulting from PBN stimulation, were also examined. Four percent of AP neurons tested (n = 74) were antidromically identified as projecting to the PBN [latency (L) = 26 +/- 4 msec, threshold current (T) = 79 +/- 11 microA]. Parabrachial stimulation orthodromically influenced 24% of AP cells. Equal numbers of these neurons (12%) were excited [L = 25 +/- 9 msec, duration (D) = 29 +/- 14 msec] and inhibited (L = 28 +/- 8 msec, D = 107 +/- 40 msec). Of 46 NTS neurons tested, 11% were antidromically identified as projecting to the PBN (L = 12 +/- 4 msec, T = 61 +/- 18 microA), while orthodromic influences were seen in 41% of these neurons. Initial responses of 30% of the cells were excitatory (L = 34 +/- 14 msec, D = 63 +/- 24 msec), PBN stimulation inhibited the remaining 11% of NTS neurons (L = 30 +/- 10 msec, D = 108 +/- 32 msec). These findings suggest that a functional heterogeneity exists in the PBN efferents to the AP and NTS. However, the small proportion of antidromically identified AP and NTS efferents to the PBN disagrees with neuroanatomical studies suggesting a denser projection.

Circumventricular structures: CNS sensors of circulating peptides and autonomic control centres.

Previous studies have suggested the subfornical organ (SFO) to be the CNS site at which circulating angiotensin (ANG) acts to influence a variety of regulatory control mechanisms. We have utilised electrophysiological techniques: 1. to examine the neural connections through which the SFO exerts such control over hypothalamic regulatory control centres; 2. to investigate the responsiveness of neurons in a second circumventricular organ, the area postrema (AP), to circulating peptides. In accordance with previous endocrine studies we have demonstrated excitatory influences of SFO efferents on hypothalamic neurosecretory neurons putatively identified as vasopressin, oxytocin, CRH, and LHRH secreting. In addition systemic ANG increased the activity of the former three groups of these neurons, an effect which was abolished by destruction of the SFO. Single unit recordings from AP neurons have demonstrated subpopulations of cells in this regions to be sensitive to either circulating ANG or changes in blood pressure.

Electrophysiological evidence that systemic angiotensin influences rat area postrema neurons.

Extracellular single-unit recordings from neurons in the area postrema (AP) and the nucleus tractus solitarius (NTS) in anesthetized male rats demonstrated that most cells in these regions have spontaneous activities of 5 Hz or less. Systemic angiotensin (ANG II) (50-500 ng) enhanced the activity of 55% of AP cells tested (n = 76), whereas 53% of tested NTS neurons (n = 62) were inhibited by ANG II. To determine whether these neurons were influenced specifically by circulating ANG II or by the accompanying increase in mean arterial blood pressure (BP), the effects of adrenergic agonists given intravenously on ANG II influenced neurons were also examined. Subsequently two cell types were characterized: cells responding to iv ANG II but not to the adrenergic agonist ("ANG II sensitive") and cells responding in a similar way to both agents ("BP sensitive"). Most ANG II-responsive neurons in the AP (53.5%) and the NTS (65%) were determined to be BP sensitive. These data demonstrate that ANG II influences the activity of AP neurons. In addition, there exists a second population of AP neurons apparently responsive to perturbations of the cardiovascular system. These studies further emphasize the potential roles of the AP in the regulation of body fluid balance.

Bovine 'neurophysin II' stimulates growth hormone release in the estradiol-primed male rat.

Basal plasma concentrations of growth hormone (GH) were monitored in both normal and estradiol-primed male rats by the collection of sequential blood samples from freely moving rats, via chronic intraatrial cannulae. Blood was sampled every 2 min for a period of 80 min and plasma GH levels determined by radioimmunoassay. The normal male rats displayed a pulsatile release of GH, while the estradiol-primed male rats exhibited a relatively steady level of plasma GH concentration. The rats exposed to high levels of estradiol (1.59 +/- 0.42 nmol/l plasma) also had a higher mean value of basal GH concentration. An injection of 100 micrograms/kg of bovine neurophysin II did not alter GH release in the normal male rats. However, it did significantly elevate GH levels in the estradiol-primed animals to a mean peak level approximately six times the mean basal level. The administration of 100 micrograms/kg of bovine neurophysin I to estradiol-primed male rats did not produce any change in plasma GH levels and thus eliminates the possibility of the nonspecific stimulation of neurophysin II on GH release.

Current status of the rat prolactin releasing factor.

The release of prolactin is governed by both inhibiting and releasing factors. Basal plasma concentration of prolactin is controlled mainly through inhibition by a prolactin release-inhibiting factor (PIF), while acute stimulation of prolactin release is believed to be caused by a prolactin-releasing factor (PRF). It is the general consensus that PIF is dopamine. The PRF plays an important role in stimulation of prolactin release, and there are promising putative PRFs.

Amenorrhea following the use of oral contraceptives.

Clinical aspects and the incidence of the various underlying etiologic factors were studied in 86 patients with post-oral contraceptive amenorrhea. Patients were divided into two groups according to the presence or absence of detectable galactorrhea. Group I was composed of 55 amenorrheic patients without detectable galactorrhea and group II included 31 patients with amenorrhea associated with galactorrhea. Both groups were comparable for age, gravidity, duration of intake of oral contraceptives, and duration of amenorrhea. The incidence of previous oligomenorrhea and late menarche was high in both groups. The most striking difference between the two groups was in the incidence of pituitary prolactin-secreting tumor--32% among patients with galactorrhea and less than 2% among patients without galactorrhea. Identification of galactorrhea and accurate diagnosis of its causes are mandatory for successful management of postpill amenorrhea.

Pituitary responses to synthetic luteinizing hormone-releasing hormone in thirty-four cases of amenorrhea or oligomenorrhea associated with galactorrhea.

Pituitary responses to 100 mcg. of luteinizing hormone-releasing hormone (LH-RH) administered subcutaneously were studied in 34 cases of amenorrhea or anovulatory oligomenorrhea associated with galactorrhea. Twenty-six patients had pituitary prolactin-secreting tumors (group I); eight patients had a normal sella turcica and remission of the syndrome either spontaneously or after thyroid replacement therapy (group 2). Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) responses to LH-RH were variable in each group of patients, ranging from poor to exaggerated, and no statistically significant difference could be observed between the groups. A positive correlation was found between FSH pituitary responses and basal FSH levels (r=0.50; P less than 0.01). No positive correlation was observed between either LH responses and basal LH levels or the gonadotropin responses and plasma estradiol levels, serum prolactin concentrations, duration of amenorrhea, or size of the tumor.