Thirty minutes of handgrip exercise potentiates flow-mediated dilatation in response to sustained and transient shear stress stimuli to a similar extent.

NEW FINDINGS: What is the central question of this study? This study sought to determine whether enhancement of brachial artery flow-mediated dilatation (FMD) after acute exposure to a sustained elevation in shear stress is greater when the shear stress stimulus for FMD is also sustained. What is the main finding and its importance? Brachial artery FMD in response to a sustained (handgrip exercise) and transient (reactive hyperaemia) shear stress stimulus was enhanced to a similar extent 10 min after a 30 min handgrip exercise intervention. This suggests that prior exposure to a sustained elevation in shear stress results in a similar acute augmentation of the ability of the endothelium to transduce sustained and transient shear stress stimuli. ABSTRACT: Brief (30 min) exposure of the brachial artery (BA) to a sustained elevation in shear stress has been shown to potentiate subsequent BA flow-mediated dilatation (FMD) in response to a transient shear stress stimulus [reactive hyperaemia (RH) FMD]. It is unknown whether matching the sustained shear stress exposure to a subsequent sustained shear stress stimulus for FMD [via handgrip exercise (SS-FMD)] might enhance the potentiation of FMD. The purpose of the study, therefore, was to assess the impact of a 30 min handgrip exercise intervention-induced elevation in shear stress on subsequent BA SS-FMD versus RH-FMD. Nineteen healthy men (22 ± 3 years) preformed a 30 min rhythmic handgrip exercise intervention on two experimental days. BA-FMD was assessed using either an RH or a 6 min sustained shear stress stimulus created via handgrip exercise (order of visits counterbalanced) at three time points: pre-intervention and 10 and 60 min post-intervention. The FMD was assessed using duplex ultrasound. Shear stress was estimated as shear rate (SR = BA blood velocity/BA diameter). Data are mean ± SD. Both SS and RH-FMD increased from pre-intervention to 10 min post-intervention [SS-FMD (6 min average), from 0.11 ± 0.05 to 0.16 ± 0.08 mm; P = 0.008; Cohen's d = 0.66; and RH-FMD, from 0.25 ± 0.1 to 0.32 ± 0.11 mm; P = 0.013; Cohen's d = 0.68]. The magnitude of enhancement in RH and SS-FMD did not differ (change in RH versus SS-FMD pre- versus 10 min post-intervention, P = 0.344). These findings suggest that exposure to elevated shear stress via 30 min of handgrip exercise potentiates subsequent FMD in response to sustained and transient elevations in shear stress to a similar extent.

Medical student assessments-frequency of radiological images used: a national study.

OBJECTIVES: Assessments are a key part of life for medical students at University. We know there is variation in these assessments across Universities. The aims of this study were to expatiate summative assessments in Scottish Medical Schools and to examine how frequently radiological images feature in them. METHODS: All Scottish medical schools were invited to participate in the study. Data on objective structured clinical examinations (OSCEs; 5 years) and written assessments (3 years) were retrospectively collected for each university and results were collated. Each University was randomly assigned a letter from A to E and anonymised for data presentation. RESULTS: 10,534 multiple choice questions (MCQ) and 1083 OSCE stations were included in this study. There was wide variation in the number, type and timing of assessments across Scottish medical schools. There were highly significant differences in the number of OSCE stations and the number of MCQs set over the study period (p < 0.0001). Radiological images were used on average 0.6 times (range 0-1.1) in each OSCE examination and 2.4 times (range 0.1-3.7) for written assessments. CONCLUSION: In this detailed study, we demonstrated significant differences in medical student assessments across Scottish Universities. Given the importance of Radiology in modern medicine, the frequency and differences in which radiological images were used in assessments across Universities should be addressed. ADVANCES IN KNOWLEDGE: This is the first national longitudinal study to quantify the role of radiological images in summative Medical Student Assessments. Great variability exists in the extent and how (clinical versus written assessments) radiological images are used to assess Scottish medical students. Radiological images are used infrequently in clinical assessments, but are present in every written assessment. These findings could help inform medical schools and academic radiologists as they prepare medical students for the imminent unified medical licensing examination, where Clinical Imaging is a subject with one of the highest number of associated conditions examinable.

Idiopathic scoliosis and pineal lesions in Australian children.

PURPOSE: To determine whether treatment of pineal lesions in children is associated with development of idiopathic scoliosis. METHODS: 38 boys and 10 girls with pineal lesions were identified. Their mean age at presentation was 10 years. The pineal pathology varied from cysts and epidermoid to teratoma, germinoma, pineocytoma, and glioblastoma. Treatment ranged from biopsy/extirpation to radiotherapy. RESULTS: 12 patients died. No scoliosis was found in any females or any of the deceased. Two boys had scoliosis: one had a 12-degree right upper thoracic curve with 32-degree kyphosis and the other had a 60-degree right thoracolumbar idiopathic curve, requiring a 2-stage arthrodesis. CONCLUSION: Pineal ablation is not related to the development of idiopathic scoliosis in humans.

The novel long PDE4A10 cyclic AMP phosphodiesterase shows a pattern of expression within brain that is distinct from the long PDE4A5 and short PDE4A1 isoforms.

In situ hybridisation methods were used to map the distribution of the novel long PDE4A10 isoform in the brain. PDE4A10 distribution was compared to that of the long PDE4A5 isoform and the short PDE4A1 isoform using probes specific for unique sequences within each of these isoforms. Coronal sections of the brain, taken at the level of the olfactory bulb, prefrontal cortex, striatum, thalamus, hippocampus and cerebellum, were analysed. Strongest expression of PDE4A isoforms was found in the olfactory bulb granular layer with high signals also in the piriform cortex, the dentate gyrus and the CA1 and CA2 pyramidal cells. For the two long forms, level general staining was noted throughout the striatum, thalamus and hippocampus but no signal was evident in the cerebellum. The long PDE4A10 and PDE4A5 isoforms localised to essentially the same regions throughout the brain, although PDE4A10 was uniquely expressed in the major island of Calleja. A signal for the short PDE4A1 isoform was found in regions in which the two long isoforms were both expressed, with the exception of the medial nucleus of the amygdala where weak signals for PDE4A5 and PDE4A10 were detected but PDE4A1 was absent. Uniquely, strong signals for PDE4A1 were detected in the glomerular layer of the olfactory bulb, the CA3 pyramidal cell region and the cerebellum; areas where signals for the two long forms were not evident. PDE4A transcripts for both PDE4A5 and PDE4A10 were not apparent in the brain stem and those for PDE4A1 were low. PDE4A isoforms are present in several key areas of the brain and therefore present valid targets for therapeutic interventions. Whilst the two long PDE4A isoforms show a remarkably similar distribution, in at least three regions there is clear segregation between their pattern of expression and that of the PDE4A1 short form. This identifies differential regulation of the expression of PDE4A long and short isoforms. We suggest that specific PDE4A isoforms may have distinct functional roles in the brain, indicating that PDE4A isoform-selective inhibitors may have specific therapeutic and pharmacologic properties.

Use of an activation-specific probe to show that Rap1A and Rap1B display different sensitivities to activation by forskolin in rat1 cells.

Rap1A and Rap1B are small GTPases of the Ras superfamily whose activation can be measured using a probe that interacts specifically with the GTP-bound forms of Rap1A and Rap1B. Using this procedure we demonstrate that the cyclic AMP-elevating agent forskolin activates both Rap1A and Rap1B in Rat1 cells. Whilst the protein kinase A inhibitor H89 ablated the ability of forskolin to cause cAMP response element binding protein (CREB) phosphorylation in Rat1 cells, it did not affect the ability of forskolin to activate either Rap1A and Rap1B. Forskolin differentially activated Rap1A and Rap1B isoforms in a time- and dose-dependent manner. The cAMP-specific type 4 family phosphodiesterase inhibitor rolipram potentiated the rate of activation of both Rap1A and Rap1B by forskolin challenge of Rat1 cells. Challenge of Rat1 cells with rolipram alone was able to elicit the phosphorylation of CREB but not activation of either Rap1A or Rap1B.

Localization and treatment of familial malignant nonfunctional paraganglioma with iodine-131 MIBG: report of two cases.

Two cases of familial, malignant, nonfunctional paraganglioma are reported. Uptake of iodine-131 metaiodobenzylguanidine ([131I]MIBG) by the tumors and metastases was demonstrated. In the first case, with multicentric and locally invasive disease, [131I]MIBG correctly localized a right carotid body paraganglioma which had been missed arteriographically. In the second case, with widespread, symptomatic metastatic disease, a therapeutic dose of [131I]MIBG produced palliation of bone pain after the failure of radio- and chemotherapy. Uptake of [131I]MIBG by paragangliomas does not correlate with catecholamine secretory activity. Iodine-131 MIBG should be considered as a therapeutic option in unresectable, malignant paragangliomas which take up this radiopharmaceutical.

Sub-family selective actions in the ability of Erk2 MAP kinase to phosphorylate and regulate the activity of PDE4 cyclic AMP-specific phosphodiesterases.

Expressed in intact cells and in vitro, PDE4B and PDE4C isoenzymes of cyclic nucleotide phosphodiesterase (PDE), in common with PDE4D isoenzymes, are shown to provide substrates for C-terminal catalytic unit phosphorylation by the extracellular signal-regulated kinase Erk2 (p42(MAPK)). In contrast, PDE4A isoenzymes do not provide substrates for C-terminal catalytic unit phosphorylation by Erk2. Mutant PDE4 enzymes were generated to show that Erk2 phosphorylation occurs at a single, cognate serine residue located within the C-terminal portion of the PDE4 catalytic unit. PDE4 long-form isoenzymes were markedly inhibited by Erk2 phosphorylation. The short-form PDE4B2 isoenzyme was activated by Erk2 phosphorylation. These functional changes in PDE activity were mimicked by mutation of the target serine for Erk2 phosphorylation to the negatively charged amino acid, aspartic acid. Epidermal growth factor (EGF) challenge caused diametrically opposed changes in cyclic AMP levels in COS1 cells transfected to express the long PDE4B1 isoenzyme compared to cells expressing the short PDE4B2 isoenzyme. We suggest that PDE4 enzymes may provide a pivotal point for integrating cyclic AMP and Erk signal transduction in cells with 4 genes encoding enzymes that are either insensitive to Erk2 action or may either be activated or inhibited. This indicates that PDE4 isoenzymes have distinct functional roles, giving credence to the notion that distinct therapeutic benefits may accrue using either PDE4 subfamily or isoenzyme-selective inhibitors.

Spinal fractures and dislocations in children and adolescents.

During the years 1962 through 1978 a total of 42 children under the age of 15 years with fractures or dislocations of the spine were admitted to the Royal Brisbane Hospital Complex. Sixty-three percent of these children were males. The predominate causes of injury were fall/jump (40%), road traffic accidents (29%), and water-related injuries (19%). Half the injuries occurred to the cervical spine, while injuries at more than one level occurred in 35% of patients. Cord injuries occurred in 14% of patients, while skeletal and head injuries occurred in over half of the spinal injuries associated with road trauma. The response of the immature spine following trauma differs from that of the adult, especially in respect to a growth potential, ultimate vertebral stability, and neurologic function.

Inappropriate secretion of antidiuretic hormone in postoperative scoliosis patients: the role of fluid management.

STUDY DESIGN: The present study examined the hypothesis that hypotonic saline therapy before surgery was a major factor in the development of the syndrome of inappropriate antidiuretic hormone secretion. OBJECTIVES: The influence of fluid therapy and its relationship to the syndrome of inappropriate antidiuretic hormone secretion was studied by measuring patient electrolyte and osmolar responses at given times after surgery. SUMMARY OF BACKGROUND DATA: Mild renal dysfunction and increased plasma antidiuretic hormone occurs after surgery. Occurrence of the syndrome of inappropriate secretion of antidiuretic hormone after spine surgery is rare. The development of the syndrome of inappropriate secretion hormone after surgery may be related to hypotonic fluid replacement during and after surgery. METHODS: Twelve patients undergoing surgery for correction of idiopathic scoliosis were assigned randomly to two groups. The control group (five patients) was given isotonic saline, and the trial group (seven patients) was given hypotonic saline. RESULTS: The trial group developed syndrome of inappropriate antidiuretic hormone secretion with a significant decrease in serum sodium and osmolarity. The control group did not develop syndrome of inappropriate antidiuretic hormone secretion. CONCLUSIONS: Hypotonic saline therapy predisposes to the development of syndrome of inappropriate antidiuretic hormone secretion, whereas isotonic saline protects patients from syndrome of inappropriate antidiuretic hormone secretion when undergoing surgery for scoliosis.

Reduction of severe spondylolisthesis. A preliminary report.

This report describes the development of a technique for reduction and fusion of spondylolisthesis that includes posterior mobilization with alartransverse fusion, halo-femoral traction with the patient in some extension, and finally, anterior interbody fusion of the lumbosacral joint. The report emphasizes the technique, which has been employed in the care of 8 patients thus far.

Factors influencing wound healing after surgery for metastatic disease of the spine.

STUDY DESIGN: The study group consisted of 53 patients who underwent 75 operations for spine metastases. Patient and tumor demographic factors, preoperative nutritional status, and perioperative adjunctive therapy were retrospectively reviewed. OBJECTIVE: To determine the risk factors for wound breakdown and infection in patients undergoing surgery for spinal metastases. SUMMARY OF BACKGROUND DATA: Spinal fusion using spine implants may be associated with an infection rate of 5% or more. Surgery for spine metastases is associated with an infection rate of more than 10%. Factors other than the type of surgery performed may account for the greater infection rate. METHODS: Data were obtained by reviewing patient records. Age, sex, and neurologic status of the patient; tumor type and site; and surgical details were noted. Adjunctive treatment with corticosteroids and radiotherapy was recorded. Nutritional status was evaluated by determining serum protein and serum albumin concentrations and by total lymphocyte count. RESULTS: Wound breakdown and infection occurred in 15 of 75 wounds. No patient or tumor demographic factors other than intraoperative blood loss (P < 0.1) were statistically associated with infection. The correlation between preoperative protein deficiency (P < 0.01) or perioperative corticosteroid administration (P < 0.10) and wound infection was significant. There was no statistical correlation between lymphocyte count or perioperative radiotherapy and wound infection. CONCLUSIONS: The results indicate that preoperative protein depletion and perioperative administration of corticosteroids are risk factors for wound infection in patients undergoing surgery for spine metastases. Perioperative correction of nutritional depletion and cessation of steroid therapy may reduce wound complications.

Scoliosis in symptomatic spondylolisthesis.

The association between spondylolisthesis and scoliosis was studied in 84 patients who presented during a 30-year period with symptomatic spondylolisthesis. The incidence of scoliosis was 42 per cent, the majority of cases being lumbar or thoracolumbar curves of less than 15 degrees. The incidence was highest in the group of patients with spondylolisthesis at L4--5 where all except one had scoliosis. Scoliosis was present in 47 per cent of patients with dysplastic spondylolisthesis at the lumbosacral junction; in this group, the incidence of scoliosis was greater where the displacement exceeded 25 per cent. The lowest incidence (25 per cent) was found in the group with isthmic spondylolisthesis at the lumbosacral junction. There appeared to be no relationship between excessive lumbar lordosis or tightness of the hamstrings and scoliosis.

Cypermethrin pour-on for control of the sheep body louse (Damalinia ovis).

The sheep body louse Damalinia ovis is a potentially serious problem affecting the value of the fleece and possibly causing reduced weight gains. Control has been based on the dipping or showering of sheep using insecticidal oil in water emulsions. The results using a pour-on formulation of the synthetic pyrethroid cypermethrin to control louse infestation are reported. Application rates of 5 mg/kg or more gave 99 to 100 per cent control.

Assessment of pregnancy in sheep by analysis of plasma progesterone using an amplified enzyme immunoassay technique.

An amplified enzyme immunoassay kit for progesterone analysis was used to diagnose pregnancy in a flock of 130 mule ewes. An accuracy of 100 per cent was obtained after the analysis of progesterone in plasma samples taken 15 to 16 days after mating. In mule ewes a plasma progesterone level greater than 5.9 nmol/litre was indicative of pregnancy. In the validation of the technique, duplicate ewe plasma samples and progesterone standards were compared with a radio immunoassay technique; the regression coefficient between the two techniques was r = 0.82.

Copper heptonate for the treatment of hypocupraemia in sheep.

Trials were carried out to compare the efficacy of copper heptonate with other available therapeutic products. On nine farms with a copper deficiency problem, over 2000 ewes were treated in mid-pregnancy. All the treatments increased whole blood copper levels and plasma caeruloplasmin (ferroxidase) activity in ewes, and protected their lambs from swayback. The lambs from ewes treated with copper heptonate and copper oxide needles had significantly higher blood copper levels than lambs from untreated control ewes. Treatment with copper heptonate was shown to have a therapeutic index of at least 5 in Swaledale ewes of normal copper status. In two groups of Welsh mountain sheep from different backgrounds, both with normal blood copper levels before treatment, the therapeutic indices were 3 to 5.

Trials with a long acting parenteral selenium preparation in ruminants: sheep.

Barium selenate was developed as a long-acting subcutaneous injection for selenium treatment. The results from trials using this product show that it is a safe preparation for treating and preventing selenium deficiency in sheep. It produces a satisfactory selenium status which will be maintained for at least six months and, when injected into pregnant ewes, results in the transfer of selenium from the ewe to its progeny.

Palliative care nurses' perceptions of good and bad deaths and care expectations: a qualitative analysis.

Individuals who are involved with the death of a person with a terminal illness will often classify the death as either 'good' or 'bad'. Families and healthcare practitioners assess many factors when determining their 'success' or 'failure' in assisting someone in the terminal phase. Palliative care nurses are particularly vulnerable to self-assessments about care of the dying, because death is a daily occurrence. Feelings of failure, unmet expectations and feeling of regret about not being able to prevent a traumatic death may be a source of stress for palliative care nurse and may affect their abilities to function effectively. This article reports the findings of a study involving interviews with 20 palliative care nurses to determine their perceptions of a good and bad death. The study also examined the expectations they hold of themselves and that they believe others hold of them in helping patients to attain a good death. Clinical implications are discussed based on these findings.

The surgical management of degenerative lumbar scoliosis. Posterior instrumentation alone versus two stage surgery.

Twenty-one patients who underwent surgery for degenerative scoliosis were retrospectively reviewed. Eleven patients underwent staged anterior and posterior surgery. Ten patients had a single posterior procedure. Posterior instrumentation to the sacrum was done in all cases. Average length of follow-up was 3.8 years (range: 2 to 7 years). All patients were assessed by the Oswestry Disability Questionnaire and Low-Back Outcome Score. Additional questions included analogue scales for pain and quality of life, and self-rating of the outcome of treatment. Nine patients that had two stage surgery and 4 patients that had single posterior surgery considered their outcome to be good or excellent (p = 0.13). This correlated with better functional tolerance, specifically sleep, lifting, sitting, and social life. Although pain intensity was the same for both groups, only the staged group reported significant reduction in analgesic intake. Significant correction in scoliosis and the lumbosacral fractional curve was noted only following staged surgery. A solid spinal fusion determined a satisfactory outcome irrespective of the method of treatment. Staged anterior and posterior surgery for degenerative lumbar scoliosis resulted in a better fusion rate, greater correction of deformity, and more improvement in function than did posterior surgery alone.

Outcomes following treatment of metastatic spine tumors.

Fifty seven consecutive patients with metastatic spine tumors were assessed for their suitability for operative treatment or radiotherapy and/or chemotherapy using a modified version of the Nihon University scoring system. Using this scoring system 29 patients underwent surgery and 28 received radiotherapy/chemotherapy. The outcomes were assessed to determine if a modified scoring had any effect on patient survival. No statistical difference was found between the two groups, though a trend was noted--the group receiving surgery had a mean survival of 30 weeks compared to a mean survival of 16 weeks found in the non-surgical group.