No longer a historical ailment: two cases of childhood scurvy with recommendations for bone health providers.

PURPOSE: Scurvy, due to vitamin C deficiency, is commonly referenced as a "forgotten" or "historical" disease. A growing number of case reports challenge this notion. Bone health providers are often consulted early in the presentation of scurvy to evaluate musculoskeletal complaints resulting from impaired collagen production and disrupted endochondral bone formation. In this report, we describe two cases of childhood scurvy. Our objective is to summarize the key features of scurvy for bone health providers, with the goal of raising awareness and facilitating diagnosis in future cases. CASE DESCRIPTIONS: Case one occurred in a 12-year-old non-verbal, non-ambulatory female on a ketogenic diet for refractory epilepsy. Clinical findings included hemarthrosis, transfusion dependent anemia, elevated inflammatory markers, and epiphysiolysis. Magnetic resonance imaging (MRI) revealed multi-focal bone marrow signal abnormalities and physeal irregularities. Case two occurred in a typically developing 5-year-old male presenting with limp and knee pain. Symptoms progressed despite casting and immobilization. Mild anemia, elevated inflammatory markers, and multi-focal marrow and physeal MRI abnormalities were identified. Subsequent dietary history revealed total absence of fruit or vegetable consumption. The diagnosis of scurvy was confirmed in both cases by undetectable plasma vitamin C concentrations. Treatment with vitamin C led to rapid clinical improvement. CONCLUSION: Scurvy can no longer be considered a historical diagnosis and should not be forgotten when evaluating children with musculoskeletal ailments. Early recognition of the signs, symptoms, and imaging findings of scurvy can reduce the clinical burden of this disease with the timely initiation of vitamin C therapy.

A systematic review of animal models for Staphylococcus aureus osteomyelitis.

Staphylococcus aureus (S. aureus) osteomyelitis is a significant complication for orthopaedic patients undergoing surgery, particularly with fracture fixation and arthroplasty. Given the difficulty in studying S. aureus infections in human subjects, animal models serve an integral role in exploring the pathogenesis of osteomyelitis, and aid in determining the efficacy of prophylactic and therapeutic treatments. Animal models should mimic the clinical scenarios seen in patients as closely as possible to permit the experimental results to be translated to the corresponding clinical care. To help understand existing animal models of S. aureus, we conducted a systematic search of PubMed and Ovid MEDLINE to identify in vivo animal experiments that have investigated the management of S. aureus osteomyelitis in the context of fractures and metallic implants. In this review, experimental studies are categorised by animal species and are further classified by the setting of the infection. Study methods are summarised and the relevant advantages and disadvantages of each species and model are discussed. While no ideal animal model exists, the understanding of a model's strengths and limitations should assist clinicians and researchers to appropriately select an animal model to translate the conclusions to the clinical setting.

Inpatient consultations to an orthopaedic service: the hidden workload.

BACKGROUND: While the quality and efficiency of out-patient orthopaedic referrals are well documented in the literature, there is little on the standard and appropriateness of inpatient orthopaedic consultations. AIM: To prospectively audit the pattern of inpatient consultations to an orthopaedic service. METHODS: Data were prospectively collected on all inpatients referred to the orthopaedic service over a 4-month period. RESULTS: Sixty-eight consultations were received in the study period. The average age was 68 years (range 20-86 years). Seventy-two percent of consultations were from medical services, 25% from other surgical specialties and the remainder (3%) from the psychiatric department. Eight (12%) patients required surgical intervention. Twenty patients (29%) had previously been seen in the outpatient department. CONCLUSIONS: Inpatient orthopaedic consultations generate a significant workload and the majority of such patients could be seen as outpatients. Clear and explicit guidelines on appropriate referral pathways, as well as enhanced education in the management of musculoskeletal disorders and available services may optimise delivery of patient care in the inpatient setting.

Isolated proximal tibiofibular joint dislocation in an elite rugby union player.

The case is presented of a professional international rugby union player who sustained an isolated proximal tibiofibular dislocation in a training ground injury. Diagnosis was made based on clinical details, plain radiography and magnetic resonance imaging. An initial attempt at closed reduction failed. Open reduction and internal fixation were subsequently carried out. Following early rehabilitation, the patient made a successful try-scoring return to international rugby union.

Traumatic asphyxia complicated by unwitnessed cardiac arrest.

We report a case of traumatic asphyxia complicated by unwitnessed cardiac arrest in which the patient has made a good, functional recovery. Traumatic asphyxia is an uncommon clinical syndrome usually occurring after chest compression. Associated physical findings include subconjunctival hemorrhage and purple-blue neck and face discoloration. These facial changes can mimic those seen with massive closed head injury; however, cerebral injury after traumatic asphyxia usually occurs due to cerebral hypoxia. When such features are observed, the diagnosis of traumatic asphyxia should be considered. Prompt treatment with attention to the reestablishment of oxygenation and perfusion may result in good outcomes.

Low lumbar burst fractures: comparison between conservative and surgical treatments.

Twenty-two low lumbar burst fractures (L3-L5) were treated, with an average follow up of 56.2 and 39.0 months in the conservative and surgically treated groups, respectively. Twenty patients were available for review; seven were treated conservatively and 13 were stabilized surgically. All patients were evaluated clinically for work status, activity level, residual pain, and subsequent development of neurologic symptoms. Roentgenograms were reviewed for severity of initial fracture, canal compromise, and maintenance of initial correction. In general, neurologically intact patients in both groups returned to similar postinjury employment levels. Persistent back pain was found to be more disabling in the surgically treated group, in which a fusion incorporating four or five lumbar segments was performed. There was no evidence of significant loss of initial reduction, and no patients experienced late neurological compromise in the surgical group. An average follow-up kyphosis of 9.2 degrees and 31% loss of vertebral height were observed in the conservative group, while a follow-up lordosis of 1 degree and 19% loss of vertebral height were observed in the surgical group. Conservative treatment of low lumbar burst fracture is a viable option in neurologically intact patients, but loss of lordosis and vertebral height may persist. Biomechanical and anatomic characteristics of the low lumbar spine differ from the thoracolumbar region and may account for the inherent stability of these injuries. If surgery is chosen, a long fusion with distraction instrumentation should be avoided in the low lumbar spine. A short rigid fixation with pedicular instrumentation may be of greater benefit.

Age-based rationing of health care: a descriptive study of professional attitudes.

A national search for actual attitudes toward age-based rationing of health care among professionals in positions to support or change medical policies revealed that support for, or opposition to, medical limits for the elderly depended less upon affiliation, demographic factors, and political-economic ideology than did the sub-issues related to the rapid expansion of medical technology and spiraling health care costs in an unprepared society. The consensus was that American health care standards should continue to protect Granny Doe as well as Baby Doe.

Epithelial influence on the tracheal nonadrenergic inhibitory response.

1. The role of epithelium in the non-adrenergic non-cholinergic (NANC) inhibitory response to electrical nerve stimulation as well as to the putative neurotransmitter, vasoactive intestinal polypeptide (VIP), was evaluated in guinea-pigs anaesthetized with chloralose-urethane. 2. The tracheal pouch, an in vivo method to demonstrate the NANC inhibitory response, was used in all experiments. The relaxation response was measured as a pressure drop (cm of H2O) in the pouch. The animals were given atropine (5 mg kg-1) and propranolol (1 mg kg-1) intraperitoneally to block adrenergic and cholinergic responses in the pouch. Cervical vagi were isolated and cut craneally. The distal ends were positioned on bipolar electrodes for subsequent stimulation with 5V pulses of 2 ms duration at 15 Hz for a total of 90 s. 3. The reproducibility of NANC responses to two consecutive nerve stimulations at 20 min apart was determined in group 1. 4. In group 2 pouch relaxations to electrical nerve stimulations were determined before and after complete epithelial denudation (determined by histological and pharmacological methods) of the pouch. 5. To determine the influence of relaxant prostaglandins synthesized by the epithelial cells, the effect of indomethacin (given either intravenously or into the pouch) on the pouch relaxation due to NANC stimulation was studied in groups 3 and 4 respectively. 6. In group 5, in order to distinguish between the effects of epithelium removal and prostaglandins, the animals were pretreated with indomethacin (i.v.) 30 min before the experiment. The pouch relaxation to nerve stimulation was then determined before and after the removal of epithelium. 7. The reproducibility of the pouch relaxations to consecutive single doses of VIP 10(-9) M at 20 min apart was determined in group 6. 8. In group 7, the pouch relaxation to a single dose of VIP was determined before and after intravenous indomethacin administration, but with the pouch epithelium left intact. 9. The effect of epithelium removal on VIP-induced pouch relaxation was determined in group 8. VIP-induced response was determined before and after the epithelium removal. 10. The study showed that both epithelium removal and indomethacin administration independently had significant effects on the decrease of the pouch relaxation (NANC inhibitory response). However, epithelium removal significantly diminished pouch relaxation despite indomethacin pretreatment suggesting a second, non-arachidonic dependent, mechanism (possibly via a relaxing factor) whereby epithelium maintains airway homeostasis.(ABSTRACT TRUNCATED AT 400 WORDS)

Evidence for vasoactive intestinal peptide as a mediator of non-adrenergic non-cholinergic neurotransmission in the trachea.

1. The tracheal pouch, a surgical preparation designed to demonstrate non-adrenergic non-cholinergic inhibition, was prepared in chloralose/urethane-anaesthetized and positively ventilated guinea-pigs. The animals were given atropine and propranolol intraperitoneally to block cholinergic and adrenergic divisions of the autonomic innervation. The cervical vagi and sympathetic trunks were isolated bilaterally and cut cranially. 2. The relaxation responses of the pouch to graded concentrations of VIP (10(-11) M to 10(-6) M) were determined. Two consecutive dose-response curves at 20 min apart were determined in the control group. The VIP dose-response curves in the control group were reproducible and failed to show statistical significance upon paired Student's t-test. 3. [Ac-Tyr1,D-Phe2]-GRF(1-29)-amide, a VIP antagonist hereby referred to as antagonist-1 was tested for its ability to inhibit the VIP-induced pouch relaxation. Separate groups of animals were used for each concentration (10(-8) M, 10(-6) M or 10(-5) M) of the antagonist. VIP dose-response curves were determined before and after the pouch was incubated with the antagonist for 10 min. The second curve was determined after rinsing the pouch gently with saline and allowing 5 min for the pouch to stabilize. Statistical analysis showed that only 10(-5) M of the antagonist significantly blocked the VIP-induced tracheal pouch relaxation. 4. [4-C1-D-Phe6,Leu17]-VIP, another VIP antagonist hereby referred to as antagonist-2 was tested similarly for its ability to block the VIP-induced pouch relaxation. The significant blockade of the VIP-induced pouch relaxation was obtained with this antagonist at a concentration of 10(-6) M.(ABSTRACT TRUNCATED AT 250 WORDS)

Compartment syndrome as a presentation of non-Hodgkin's lymphoma.

An 80-year-old woman sustained an injury to her left leg and presented having a compartment syndrome. Biopsy at the time of fasciotomy revealed lymphoma infiltrating the muscles of the left leg. We conclude that tumors may present as compartment syndrome and should be included with the differential diagnosis.

Comparison of arrhythmogenic doses of epinephrine in heartworm-infected and noninfected dogs.

The arrhythmogenic dose of epinephrine (ADE) was determined in heartworm-infected and noninfected (control) dogs during thiamylal-induced and halothane-maintained anesthesia to assess the myocardial sensitization. The ADE in heartworm-infected dogs (2.42 +/- 0.26 micrograms/kg of body weight) was significantly lower than that for the controls (3.36 +/- 0.29 micrograms/kg). After 2 weeks, ADE was determined again in these dogs after atropine treatment. Atropine treatment lowered the ADE to 1.76 +/- 0.33 micrograms/kg and 1.77 +/- 0.19 micrograms/kg in heartworm-positive and -negative dogs, respectively. After 2 weeks more, the ADE was determined after administration of prazosin, an alpha 1-antagonist. Only 2 of 6 controls and 3 of 6 heartworm-positive dogs had arrhythmias after a threefold increase of ADE. The mean ADE in the dogs that responded to treatment were 7.4 micrograms/kg and 7.2 micrograms/kg for heartworm-positive and -negative dogs, respectively. The finding of this study indicated that ADE in heartworm-infected dogs were lower than those in the control dogs, which makes the heartworm-infected dogs more vulnerable to arrhythmia during anesthesia. Atropine did not protect the dogs of either group. However, prazosin protected the dogs of both groups by significantly increasing the threshold of the ADE. On the basis of our findings, to reduce the risk of arrhythmia, we suggest that routine screening of dogs for heartworm infection be done before anesthetics are used.

Effects of beta-adrenergic blockade on ventilation and gas exchange during incremental exercise.

Controversy exists concerning the effects of acute beta-adrenergic blockade on ventilation during exercise. Hence, the purpose of this study was to determine the effects of acute beta blockade on ventilation and gas exchange during incremental exercise. Nine male subjects underwent incremental exercise on a cycle ergometer (30 W.min-1) to exhaustion, with one trial being performed 60 min after the subject ingested propranolol hydrochloride (Inderal 1 mg.kg-1 BW) while the second test served as control. The treatment order was counterbalanced to preclude any ordering effect on the results, and 1 week separated the tests. Ventilation and gas exchange were monitored by open circuit techniques. No difference (p greater than 0.05) existed in VE, % Hb sat, VCO2, ventilatory threshold, and VE/VCO2 between treatments at the same exercise stage. VO2max was lowered from 3.82 to 3.26 l.min-1 (p less than 0.05) and HRmax was reduced from 190 to 150 bpm (p less than 0.05) as a result of beta blockade. These data suggested that acute beta blockade had no effect on exercise ventilation, but decreased HRmax at comparable work rates. In addition, VO2max and exercise time to exhaustion were hindered, probably due to beta blockade limitation of HRmax, and, thus, oxygen transport.

Cross-desensitization of VIP- and NANC-mediated inhibition of the guinea-pig tracheal pouch.

1. Chloralose/urethane anaesthetized guinea-pigs were used for preparation of the tracheal pouch, which demonstrates the NANC innervation. Isolated vagi cut cranially were positioned on bipolar electrodes for subsequent stimulation. The animals were given atropine and propranolol intraperitoneally before the experimental procedure to assure that responses would be from non-adrenergic, non-cholinergic components. 2. ATP and VIP, two putative neurotransmitters for non-adrenergic, non-cholinergic (NANC) inhibitory innervation caused relaxation responses of the pouch. Both VIP and ATP (10(-9) M) caused auto-desensitization after four repeated administrations into the pouch. 3. If NANC nerve stimulation causes relaxation of tracheal smooth muscle by release of one of these agents onto a specific receptor, repeated exposure to that agent by nerve stimulation or exogenous application could cause diminished responsiveness from cross-desensitization, yet maintained responsiveness to an agent acting at other receptors. 4. Relaxation responses to vagal stimulation were determined before and after the pouch was incubated for a 10-min period with either ATP or VIP (10(-6) M). ATP incubation did not produce significant (P less than 0.05) change in the degree of relaxation in response to nerve stimulation. In contrast, VIP incubation did cause diminished relaxation of the pouch in response to subsequent nerve stimulation. 5. The ability of the agents at 10(-9) M and 10(-6) M to cause relaxation of the pouch was next examined before and after repeated NANC nerve stimulation. Relaxation of the pouch to ATP was not significantly affected by intervening repeated nerve stimulations. However, relaxation in response to VIP was significantly inhibited by repeated nerve stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of beta-adrenergic blockade on ventilation and gas exchange during the rest to work transition.

The purpose of these experiments was to determine the effects of acute beta-blockade on the kinetics of oxygen uptake (VO2), expired carbon dioxide (VCO2), and expired ventilation (VE) in the transition from rest to submaximal exercise. Six male subjects exercised for 6 min on a cycle ergometer (60 W) initiated as a square wave from rest on two occasions. The beta-blockade experiment began 60 min after the subject ingested propranolol hydrochloride (1 mg.kg-1 BW) while the second experiment served as control with the treatment order counterbalanced. Ventilation and gas exchange were monitored by open circuit techniques and the data were modeled with a single-component exponential function using a time delay. No differences existed (p greater than 0.05) in the steady state VO2, VCO2, or VE nor the kinetics of VCO2 and VE between treatments. However, the rate of adaptation of VO2 toward steady state was significantly slowed (p less than 0.05) with beta-blockade. These data suggest that acute beta blockade results in diminished VO2 kinetics in the transition from rest to steady-state exercise. We hypothesize that the mechanism to explain this finding is a slowed time course of cardiac output adjustment at the beginning of exercise.

Brain-stem auditory evoked potentials in the alligator. Effects of temperature and hypoxia.

Brain-stem auditory evoked potentials (BAEPs) were recorded from young alligators (Alligator mississippiensis), and the effects of hypothermia, hyperthermia and hypoxia on the wave forms were determined. The wave form shape was similar to the human BAEP, although extra waves were routinely seen. The responses were highly repeatable and varied in a predictable manner as a function of stimulus frequency, polarity, intensity, and body temperature. Rarefaction clicks produced longer wave form latencies than condensation clicks. BAEPs were present over the entire temperature range studied (0-36 degrees C). In contrast, mammalian BAEPs disappear over the temperature range of 20-27 degrees C, and seizures occur at 20-21 degrees C. At temperatures below 20 degrees C, the alligator BAEP peak amplitudes decreased with decreased temperature, but latencies only decreased slightly. At temperatures above 20 degrees C the peak amplitudes increased, and the latencies decreased with temperature. Peak I was largely unaffected by temperature change, while peaks IIIa and V increased 0.015 and 0.018 msec/degree C, respectively, at temperatures above 24 degrees C. Transient brain hypoxia, achieved by inverting the alligator, produced a progressive decrease in BAEP waves to an isoelectric amplitude without greatly altered latencies. The reverse sequence of changes was seen during recovery. Postural effects on blood flow were documented in two alligators with implanted flow probes. Carotid artery blood flow decreased 43% with body inversion, in both anesthetized and unanesthetized alligators, but no sequelae from the hypoxia could be detected. Metabolic differences between mammals and the alligator may account for the alligator's resistance to hypothermia, hyperthermia and hypoxia.

Smooth muscle inhibition by an extract of Sesbania drummondii.

The acute effects of an extract of Sesbania drummondii were assessed in vitro on the smooth muscle contractility of intestine and lung parenchyma in the chicken and aortic arch in the rat. Dose-response contraction curves for histamine, carbachol, and norepinephrine were obtained in the ileal, parenchymal, and aortic strips, respectively. After washing was completed, the strips returned to baseline tensions and then were incubated for 10 minutes with an ethyl acetate extraction fraction of S drummondii (molecular weight less than 500). Dose-response curves to the same agonists were repeated at the end of the incubation period. Contractile responsiveness of chicken ileum was little affected by acute incubation of the tissue with the extract. Comparison with the great inhibition of in vitro ileal contractility seen previously in chickens with chronic toxicosis indicated that intestinal inhibition was not due to acute effects of sesbania, but required time for a toxic metabolite to be formed or for damage to occur from affected vasculature. Contractile responsiveness of chicken lung parenchyma to histamine (10(-5) M and 10(-4) M) was significantly decreased, as was rat aortic responsiveness to norepinephrine (10(-7) M to 10(-4) M). Responses in parenchyma were not as greatly inhibited as those in tissue from animals with chronic toxicosis. Greatest inhibition of contractility was seen in the vascular strips, indicating that vascular inhibition has a role in pathologic changes. To test the vasculature inhibition effect in vivo, anesthetized, catheterized rats were given 100-microliter aliquots of dilutions of the extract, IV.(ABSTRACT TRUNCATED AT 250 WORDS)

Autonomic interplay in VIP-induced tracheal smooth muscle relaxation.

VIP-induced inhibitory responses of the guinea-pig tracheal pouch, an in vivo preparation designed to demonstrate non-noradrenergic non-cholinergic innervation, where determined in chloraloseurethane anaesthetized animals under control conditions, or pretreated with atropine, propranolol, both atropine and propranolol or atropine-propranolol with indomethacin. Of the five groups, the control group showed a significantly greater cumulative dose-response relaxation to VIP than did the treatment groups. Among the treatment groups, the propranolol pretreated animals showed significantly greater relaxation than the remaining treatments. The group that received atropine alone and the combination of atropine and propranolol showed the least relaxation to VIP. The relaxations in these two groups did not differ significantly. The significantly greater relaxation of the pouch to VIP in the propranolol treated group suggested that the non-noradrenergic inhibitory mechanism for VIP is dependent upon the existing smooth muscle tone of the pouch. Pretreatment of the guinea-pigs with indomethacin did not cause a significant change in the relaxation of the pouch due to VIP suggesting that VIP caused airway smooth muscle relaxation by a mechanism other than that of the release of bronchodilator prostaglandins.

Effects of ATP and VIP on guinea pig airways.

The bronchodilator effects of vasoactive intestinal peptide (VIP) and adenosine triphosphate (ATP), putative neurotransmitters of nonadrenergic, noncholinergic innervation, were compared with those of isoproterenol (ISP) in guinea pig airways by in vivo and in vitro techniques. In both studies, the test agents produced dose-dependent relaxations. The response of airway smooth muscle to ISP was significantly greater than the responses to the test agents. In the in vivo studies, the test agents produced statistically equieffective responses. However, in the in vitro studies, VIP produced complete relaxation of the precontracted tissues to the baseline, whereas ATP could not, suggesting VIP as a more effective relaxant than ATP.

In vitro responses of bronchial spirals and parenchymal strips from healthy and heartworm-infected dogs.

Bronchial spirals and pulmonary parenchymal strips from control (noninfected) and Dirofilaria immitis-infected dogs were tested for isometric contractile response to histamine and carbamylcholine. Responses of bronchial spirals from control dogs and from D immitis-positive groups did not differ in responses to histamine or carbamylcholine. Parenchymal strips from D immitis-positive dogs showed greater response to histamine than did those from controls; responses to carbamylcholine did not differ.