Outcomes following a shortage of high dependency unit beds for surgical patients.

In an environment of resource rationing there are numerous patients who are unable to be admitted to a high-dependency unit (HDU) postoperatively despite the belief that this is the optimal discharge destination for them from the recovery room. It is unknown if this is associated with an increase in adverse outcomes. We performed an observational study, over a two-month period, comparing outcomes between patients who were admitted to HDU postoperatively and patients who, although an HDU bed was preferred, were discharged from the recovery room to the general ward due to an unavailability of HDU beds. Our primary outcome variable was hospital length-of-stay. We found an almost twofold increase in hospital length-of-stay in the group of patients admitted to the HDU. ASA IV patients were more likely to be admitted to HDU. However, the increased length-of-stay in the HDU group persisted even after stratifying patients according to ASA status. There was no difference between groups in all other baseline demographic variables, including POSSUM score, which is used as a predictor of postoperative morbidity and mortality. We believe that the most likely explanation for our findings is that the baseline risk between groups is, in fact, subtly different. This is not detected by preoperative scoring systems. However, clinical judgement in the recovery room appears to select a group of patients for HDU admission who subsequently have a slower postoperative recovery, despite no measurable increase in complication rate. That there was no increase in adverse events in the group of patients unable to be admitted to HDU due to a lack of bed availability suggests that current clinical judgement in a resource-rationed environment is functioning adequately, but the study was not powered to detect such a difference.

Outcome of surgery for chronic Achilles tendinopathy. A critical review.

Achilles tendinopathy is often treated surgically after failure of nonoperative management, but results are not uniformly excellent. We critically assessed the methods of 26 studies that reported surgical outcomes of patients with this condition. Using 10 previously published criteria, and blinded to study outcomes, we derived a "methodology score" (0 to 100) for each study. This score was highly reproducible (r = 0.99, P < 0.01). Scores were generally low concerning the type of study, subject selection process, and outcome measures, which indicates methods deficiency in the way the study was designed, performed, and analyzed. We found a negative correlation between reported success rate and overall methods scores (r = -0.53, P < 0.01), and a positive correlation between year of publication and overall methods score (r = 0.70, P < 0.01). Study methods may influence reported surgical outcome, and we suggest guidelines for improving study design in this area of clinical research. We acknowledge that study methods have improved over the course of the past 20 years.

Asymptomatic hypoechoic regions on patellar tendon ultrasound: A 4-year clinical and ultrasound followup of 46 tendons.

Patellar tendon ultrasound appearance is commonly used in clinical practice to diagnose patellar tendinopathy and guide management. Using a longitudinal study design we examined whether or not the presence of a hypoechoic ultrasonographic lesion in an asymptomatic patellar tendon conferred a risk for developing jumper's knee compared with a tendon that was ultrasonographically normal. Ultrasonographic, symptomatic and anthropometric assessment was completed at baseline and followup. Magnetic resonance imaging was performed on four tendons that resolved ultrasonographically in the study period. Forty-six patellar tendons were followed over 47+/-11.8 months. Eighteen tendons were hypoechoic at baseline and 28 were ultrasonographically normal. Five tendons resolved ultrasonographically in the study period. Magnetic resonance imaging in four of these tendons was normal. Seven normal patellar tendons at baseline developed a hypoechoic area but only two became symptomatic. Analysis of ultrasonography at baseline and clinical outcome with Fisher's exact test shows there is no association between baseline ultrasound changes and symptoms at followup. In this study there is no statistically significant relationship between ultrasonographic patellar tendon abnormalities and clinical outcome in elite male athletes. Management of jumper's knee should not be solely based on ultrasonographic appearance; clinical assessment remains the cornerstone of appropriate management.

Elastic stability of DNA configurations. II. Supercoiled plasmids with self-contact.

Configurations of protein-free DNA miniplasmids are calculated with the effects of impenetrability and self-contact forces taken into account by using exact solutions of Kirchhoff's equations of equilibrium for elastic rods of circular cross section. Bifurcation diagrams are presented as graphs of excess link, DeltaL, versus writhe, W, and the stability criteria derived in paper I of this series are employed in a search for regions of such diagrams that correspond to configurations that are stable, in the sense that they give local minima to elastic energy. Primary bifurcation branches that originate at circular configurations are composed of configurations with D(m) symmetry (m=2,3,...). Among the results obtained are the following. (i) There are configurations with C2 symmetry forming secondary bifurcation branches which emerge from the primary branch with m=3, and bifurcation of such secondary branches gives rise to tertiary branches of configurations without symmetry. (ii) Whether or not self-contact occurs, a noncircular configuration in the primary branch with m=2, called branch alpha, is stable when for it the derivative dDeltaL/dW, computed along that branch, is strictly positive. (iii) For configurations not in alpha, the condition dDeltaL/dW>0 is not sufficient for stability; in fact, each nonplanar contact-free configuration that is in a branch other than alpha is unstable. A rule relating the number of points of self-contact and the occurrence of intervals of such contact to the magnitude of DeltaL, which in paper I was found to hold for segments of DNA subject to strong anchoring end conditions, is here observed to hold for computed configurations of protein-free miniplasmids.

Elastic stability of DNA configurations. I. General theory.

Results are presented in the theory of the elastic rod model for DNA, among which are criteria enabling one to determine whether a calculated equilibrium configuration of a DNA segment is stable in the sense that it gives a local minimum to the sum of the segment's elastic energy and the potential of forces acting on it. The derived stability criteria are applicable to plasmids and to linear segments subject to strong anchoring end conditions. Their utility is illustrated with an example from the theory of configurations of the extranucleosomal loop of a DNA miniplasmid in a mononucleosome, with emphasis placed on the influence that nicking and ligation on one hand, and changes in the ratio of elastic coefficients on the other, have on the stability of equilibrium configurations. In that example, the configurations studied are calculated using an extension of the method of explicit solutions to cases in which the elastic rod modeling a DNA segment is considered impenetrable, and hence excluded volume effects and forces arising from self-contact are taken into account.

Open and arthroscopic patellar tenotomy for chronic patellar tendinopathy. A retrospective outcome study. Victorian Institute of Sport Tendon Study Group.

Chronic patellar tendinopathy often requires surgical treatment. We compared the outcomes in 25 subjects (29 tendons) who had had open patellar tenotomy and 23 subjects (25 tendons) who had had arthroscopic patellar tenotomy at a mean follow-up of 3.8 and 4.3 years, respectively. At follow-up, outcomes in the open and arthroscopic groups were as follows: 1) symptomatic benefit was seen in 81% of open and 96% of arthroscopic tenotomy patients, 2) sporting success was seen in 54% of open and 46% of arthroscopic tenotomy patients, 3) median time to return to preinjury level of activity was 10 months for open and 6 months for arthroscopic tenotomy patients, and 4) median Victorian Institute of Sport Assessment score at follow-up was 88 for open and 77 for arthroscopic tenotomy patients. There were no significant differences between groups for all outcomes. The appearance of the tendon on sonography remained abnormal in over 70% of subjects at follow-up, and sonographic appearance did not correlate with clinical outcome. Thus, arthroscopic patellar tenotomy was as successful as the traditional open procedure. Both procedures provided virtually all subjects with symptomatic benefit, but only about half the subjects who underwent either open or arthroscopic patellar tenotomy were competing at their former sporting level at follow-up.

Studies of surgical outcome after patellar tendinopathy: clinical significance of methodological deficiencies and guidelines for future studies. Victorian Institute of Sport Tendon Study Group.

Patellar tendinopathy is often treated surgically after failure of conservative treatment but clinical experience suggests that results are not uniformly excellent. The aim of this review was to (i) identify the different surgical techniques that have been reported and compare their success rates, and (ii) critically assess the methodology of studies that have reported surgical outcomes. Twenty-three papers and two abstracts were included in the review. Surgical procedures were categorized and outcomes summarized. Using ten criteria, an overall methodology score was derived for each paper. Criteria for which scores were generally low (indicating methodological deficiency) concerned the type of study, subject selection process and outcome measures. We found a negative correlation between papers' reported success rates and overall methodology scores (r= -0.57, P<0.01). There was a positive correlation between year of publication and overall methodology score (r=0.68, P<0.001). We conclude that study methodology may influence reported surgical outcome. We suggest practical guidelines for improving study design in this area of clinical research, as improved study design would provide clinicians with a more rigorous evidence-base for treating patients who have recalcitrant patellar tendinopathy.

Correlation of ultrasound and magnetic resonance imaging with clinical outcome after patellar tenotomy: prospective and retrospective studies. Victorian Institute of Sport Tendon Study Group.

OBJECTIVE: To report the appearances of ultrasound (US) and magnetic resonance imaging (MRI) before and after surgery for chronic patellar tendinopathy and to correlate postoperative appearances with clinical outcome. DESIGN: A 12-month prospective longitudinal study and a retrospective study, each part using different patients. Prospective study included clinical assessment, ultrasound, and MRI all performed before and 12 months after surgery. Retrospective study included ultrasound and clinical assessment only (i.e., no MRI) 24 to 67 months after surgery. SETTING: Institutional athlete study group in Australia (Victorian Institute of Sport Tendon Study Group). PATIENTS: In the prospective study, 13 patients (all male; 15 tendons) who underwent patellar tenotomy; in the retrospective study, 17 different patients (18 tendons) who had undergone identical surgery. MAIN OUTCOME MEASURES: Ultrasound and MRI appearances and clinical assessment at baseline and 12 months after surgery (prospective study). Ultrasound appearance and clinical assessment 24 to 67 months after surgery (retrospective study). Dimensions of abnormal regions on imaging were measured. Clinical assessment included categorical rating and numerical Victorian Institute of Sport Assessment (VISA) score. RESULTS: In the prospective study, preoperative ultrasound and MRI appearances confirmed the clinical diagnosis of patellar tendinopathy. Postoperative ultrasound and MRI also revealed abnormalities consistent with patellar tendinopathy. Despite this, 11 of 15 (73%) tendons were rated clinically as either good or excellent. Imaging modalities were unable to distinguish tendons rated as good or excellent from those rated poor at 12 months. In the retrospective study, ultrasound images revealed abnormalities despite full clinical recovery. There was no correlation between dimension of ultrasound abnormality and either VISA score or time since surgery. CONCLUSION: After open patellar tenotomy, MRI and ultrasound findings remain abnormal despite clinical recovery. Thus, clinicians ought to base postoperative management of patients undergoing patellar tenotomy on clinical grounds rather than imaging findings. At present, there appears to be no role for routine postoperative imaging of patients recovering slowly after patellar tenotomy. However, this is not to suggest that imaging cannot play a role in special circumstances.

The elastic rod model for DNA and its application to the tertiary structure of DNA minicircles in mononucleosomes.

Explicit solutions to the equations of equilibrium in the theory of the elastic rod model for DNA are employed to develop a procedure for finding the configuration that minimizes the elastic energy of a minicircle in a mononucleosome with specified values of the minicircle size N in base pairs, the extent w of wrapping of DNA about the histone core particle, the helical repeat h(0)b of the bound DNA, and the linking number Lk of the minicircle. The procedure permits a determination of the set Y(N, w, h(0)b) of integral values of Lk for which the minimum energy configuration does not involve self-contact, and graphs of writhe versus w are presented for such values of Lk. For the range of N of interest here, 330 < N < 370, the set Y(N, w, h(0)b) is of primary importance: when Lk is not in Y(N, w, h(0)b), the configurations compatible with Lk have elastic energies high enough to preclude the occurrence of an observable concentration of topoisomer Lk in an equilibrium distribution of topoisomers. Equilibrium distributions of Lk, calculated by setting differences in the free energy of the extranucleosomal loop equal to differences in equilibrium elastic energy, are found to be very close to Gaussian when computed under the assumption that w is fixed, but far from Gaussian when it is assumed that w fluctuates between two values. The theoretical results given suggest a method by which one may calculate DNA-histone binding energies from measured equilibrium distributions of Lk.

Immunohistochemical localization of GAP-43 in rat and human sympathetic nervous system--effects of aging and diabetes.

The neuronal 43 kDa growth associated peptide (GAP-43) is expressed in conditions of embryonic growth, axonal regeneration, and, to a limited degree, within the central nervous system as an indicator of synaptic plasticity. Although much is known about the expression of GAP-43 in cultured sympathetic neurons, information concerning the existence, immunolocalization and response of GAP-43 to experimental injury is not available for intact sympathetic ganglia in vivo. In this study we have characterized the in situ distribution and identity of GAP-43 in adult rat and human prevertebral and paravertebral sympathetic ganglia using immunohistochemical and biochemical methods. Antisera to GAP-43 intensely labeled intraganglionic presynaptic axons and synapses terminating on neurons of normal adult rat and human sympathetic ganglia in situ. There was minimal GAP-43 immunoreactivity of principal sympathetic neuron perikarya, proximal dendrites and initial axonal segments. The immunohistologic appearance of GAP-43 was unchanged in the ganglia of aged and diabetic rats and elderly humans, conditions in which presynaptic terminal axons and synapses show evidence of chronic degeneration, regeneration and neuroaxonal dystrophy, an unusual ultrastructural alteration which may represent disordered synaptic plasticity. Radioimmunoassay of ganglionic GAP-43 is comparable in young adult, aged and diabetic rat prevertebral or paravertebral sympathetic ganglia. Double immunolocalization of NPY (which labeled markedly swollen dystrophic axons) and GAP-43 in human sympathetic ganglia using a sequential immunogold-silver/fluorescence technique demonstrated that typical dystrophic axons contain little GAP-43.

Effects of sorbinil, dietary myo-inositol supplementation, and insulin on resolution of neuroaxonal dystrophy in mesenteric nerves of streptozocin-induced diabetic rats.

Previous studies indicate that experimental diabetic autonomic neuropathy can be largely prevented by initiating therapy at the onset of diabetes. More clinically relevant, however, is the ability of therapy to reverse established neuropathy produced by long-standing diabetes. We have examined the effect of selected therapies on established neuroaxonal dystrophy (NAD) in ileal mesenteric nerves, a rat model of diabetic autonomic neuropathy. Groups of 3-mo-old rats were made diabetic with streptozocin (STZ-D) and allowed to survive untreated for 5 mo, at which time they were begun on sorbinil, dietary myo-inositol, and daily insulin therapies or left untreated for an additional 2 or 4 mo. Ultrastructural evidence of NAD was demonstrated in ileal mesenteric nerves of rats with untreated 5-mo STZ-D and increased with the duration of diabetes. No lesions were demonstrated in control rats of any age. myo-Inositol or sorbinil administration failed to alter the severity of diabetes as measured by its metabolic indices. Institution of sorbinil or insulin treatment at 5 mo of diabetes prevented the increase in, but did not normalize, NAD at 7 or 9 mo. Dietary myo-inositol failed to significantly reverse established NAD or prevent its initial development. Morphometric examination of ileal mesenteric nerves demonstrated a decrease in the number of axons comprising each diabetic Schwann cell unit, suggestive of chronic cycles of axonal degeneration and regeneration. This parameter, clearly abnormal by 5 mo of diabetes, was not normalized by 2 or 4 mo of insulin, sorbinil, or myo-inositol treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential effect of chronic vitamin E deficiency on the development of neuroaxonal dystrophy in rat gracile/cuneate nuclei and prevertebral sympathetic ganglia.

Chronic vitamin E deficiency results in the premature and exaggerated development of neuroaxonal dystrophy (NAD) in primary sensory axon terminals in rat medullary gracile/cuneate nuclei, sites in which NAD develops normally with age. In the current study we determined if chronic Vitamin E deprivation had a similar effect on the development of NAD in the celiac/superior mesenteric sympathetic ganglia (C/SMG), another site with age-dependent NAD. The frequency of NAD failed to increase in the SMG of the same vitamin-E deficient animals in which a marked increase in severity of NAD was found in the gracile nucleus. These findings indicate that different populations of neurons are selectively involved in vitamin E deficiency and that the distribution of axonopathy in the E-deficient C/SMG does not duplicate the pattern of experimental diabetes and aging.

CNS injection of CCK in rats: effects on real and sham feeding and gastric emptying.

Cholecystokinin (CCK) released from the intestine during feeding may have a physiological role in satiety. There is also evidence that activation of central CCK-containing pathways is involved in the control of feeding behavior. This study was carried out to determine whether CCK-8 administered into the lateral cerebral ventricles (lv) of rats suppresses both sham feeding (SF) and real feeding (RF). Rats with lv guides and gastric cannulas ate a liquid diet with cannulas open (SF) or closed (RF) after lv (0, 0.05, 0.5 micrograms) or intraperitoneal (ip) (0, 4 micrograms/kg) injection of CCK-8. Both RF and SF were significantly decreased by ip CCK-8. RF was also decreased in a dose-related manner after lv CCK-8, but SF was not affected by lv CCK-8. Decreased feeding after ip CCK-8 may be due in part to its suppression of gastric emptying rate (GER). To determine whether central nervous system (CNS) CCK might also be involved in the control of gastric function, GER was measured after lv (0, 0.05, 0.5 micrograms) or ip (0, 4 micrograms/kg) injection of CCK-8. GER was significantly decreased after ip CCK-8, but lv CCK-8 had no effect on GER. Although both CNS and peripheral CCK peptide systems may be involved in satiety, CNS CCK appears to depend on concurrent peripheral nutrient-related stimuli in eliciting satiety.

Central nervous system injection of dynorphin-(1-13) overrides gastric satiety factors in sheep.

Signals from the gastrointestinal (GI) tract, arising during ingestion and digestion of food, are important in the termination of feeding. This study was carried out to determine whether the satiety triggered by specific GI stimuli in sheep could be reversed by central nervous system (CNS) administration of dynorphin, a putative endogenous kappa-opiate receptor ligand, which has been shown to be a potent feed-intake stimulant in many species. Rumen distension and increased intraruminal concentration of propionic acid (an energy substrate produced during fermentation in the rumen) both significantly decreased feed intake in fasted sheep. When either of these stimuli were combined with continuous 60-min lateral cerebroventricular injection of [D-Ala2]dynorphin A-(1-13) (0.32 nmol/min), feed intake returned to control levels. Increasing feed intake in food-producing animals is an important way of improving production efficiency. The findings of these experiments illustrate how manipulation of a CNS opioid system can modify the effects of feed intake-limiting factors generated by ingestion of a meal, thereby promoting greater feed intake.

Cholecystokinin concentration in specific brain areas of rats fed during the light or dark phase of the circadian cycle.

Measurement of peptide concentration in specific areas can be used as an initial investigative method for identifying brain sites in which the peptides may be acting. In this study cholecystokinin (CCK) concentration in specific hypothalamic and hindbrain areas of male Sprague-Dawley rats was measured in order to determine whether changes occurred as a result of feeding activity during different portions of the circadian cycle. Three groups of 40 rats each were studied: Group 1 were fasted 16 hr during the dark phase then sacrificed immediately or after a 20 min light phase meal. Group 2 were fasted 16 hr during the light phase then sacrificed immediately after lights out or after a 20 min dark-onset meal. Group 3 were fed ad lib and sacrificed immediately after light out or after a 20 min dark-onset meal. CCK was extracted from dissected areas and concentration was measured by RIA. There was no difference in CCK concentration of any of the 9 brain areas in rats fasted during the dark phase and fed during the light phase. In rats fasted during the light phase CCK concentration of the paraventricular nucleus (PVN) was greater in those that subsequently ate a meal at dark-onset than in those that did not eat (p less than 0.05). In ad lib fed rats CCK concentration was less in the anterior hypothalamus (AH) and greater in the supraoptic nucleus (SON) in rats that ate a dark-onset meal than in rats that did not (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Theory of the dependence of population levels on environmental history for semelparous species with short reproductive seasons.

A population that is strongly self-regulating through density-dependent effects is expected to be such that, if many generations have elapsed since its establishment, its present size should not be sensitive to its initial size but should instead be determined by the history of the variables that describe the influence of the environment on fecundity, mortality, and dispersal. Here we discuss the dependence of abundance on environmental history for a semelparous population in which reproduction is synchronous. It is assumed that at each instant t: (i) the rate of loss of members of age a by mortality and dispersal is given by a function rho of t, a, and the present number x = x(a,t) of such members; and (ii) the number x(0,t) of members born in the population is given by a function F of t and the number of x(a(f),t) at a specified age a(f) of fecundity. It is further assumed that the functions rho and F have the forms rho(x,a,t) = pi(1)(a,t)x + pi(2)(a,t)x(2) and F(x(a(f),t),t) = nu(t)x(a(f),t). For such a population, a change in the environment is significant only if it results in a change in nu(t) pi(1)(a,t), or pi(2)(a,t), and, hence, the history of the environment up to time t is described by giving nu(tau), pi(1)(a,tau), and pi(2)(a,tau) for each tau

Theory of the response of the limulus retina to periodic excitation.

Analytical and numerical solutions are given for several problems which arise from a mathematical description of inhibitory interactions in the Limulus retina. The theory developed here takes into account the delay in lateral inhibition and the gradual decay of lateral and self-inhibition. Emphasis is laid on the calculation of responses to excitation fields which are periodic in time and either spatially uniform or of traveling wave type. The analytical solutions given are intended to help experimenters determine the range in which certain linearized equations and reduced measures of excitation are useful for the design and interpretation of experiments. Certain of the numerical solutions obtained describe intrinsically non-linear effects, such as "periodic bursting" under constant excitation.