[A male with ossification of the lungs]. / Een man met botvorming in de longen.

A 71-year old man, known with unclassified pulmonary fibrosis for years, shows dendriform pulmonary ossification (DPO) on a chest CT-scan after spontaneous pneumothorax. DPO is a rare finding with a mostly benign, slowly progressive course. Pneumothorax is an uncommon but clinically important complication of DPO with high chance of recurrence.

Synergistic effect of low K and D vitamin status on arterial stiffness in a general population.

Both vitamins K and D are nutrients with pleiotropic functions in human tissues. The metabolic role of these vitamins overlaps considerably in calcium homeostasis. We analyzed their potential synergetic effect on arterial stiffness. In a cross-sectional study, we analyzed aortic pulse wave velocity (aPWV) in 1023 subjects from the Czech post-MONICA study. Desphospho-uncarboxylated matrix γ-carboxyglutamate protein (dp-ucMGP), a biomarker of vitamin K status, was measured by sandwich ELISA and 25-hydroxyvitamin D3 (25-OH-D3) by a commercial immunochemical assay. In a subsample of 431 subjects without chronic disease or pharmacotherapy, we detected rs2228570 polymorphism for the vitamin D receptor. After adjustment for confounders, aPWV was independently associated with both factors: dp-ucMGP [ß-coefficient(S.E.M.)=13.91(4.87); P=.004] and 25-OH-D3 [0.624(0.28); P=.027]. In a further analysis, we divided subjects according to dp-ucMGP and 25-OH-D3 quartiles, resulting in 16 subgroups. The highest aPWV had subjects in the top quartile of dp-ucMGP plus bottom quartile of 25-OH-D3 (i.e., in those with insufficient status of both vitamin K and vitamin D), while the lowest aPVW had subjects in the bottom quartile of dp-ucMGP plus top quartile of 25-OH-D3 [9.8 (SD2.6) versus 6.6 (SD1.6) m/s; P<.0001]. When we compared these extreme groups of vitamin K and D status, the adjusted odds ratio for aPWV≥9.3 m/s was 6.83 (95% CI:1.95-20.9). The aPWV was also significantly higher among subjects bearing the GG genotype of rs2228570, but only in those with a concomitantly poor vitamin K status. In conclusion, we confirmed substantial interaction of insufficient K and D vitamin status in terms of increased aortic stiffness.

Short-term Cold Acclimation Recruits Brown Adipose Tissue in Obese Humans.

Recruitment of brown adipose tissue (BAT) has emerged as a potential tool to combat obesity and associated metabolic complications. Short-term cold acclimation has been shown not only to enhance the presence and activity of BAT in lean humans but also to improve the metabolic profile of skeletal muscle to benefit glucose uptake in patients with type 2 diabetes. Here we examined whether short-term cold acclimation also induced such adaptations in 10 metabolically healthy obese male subjects. A 10-day cold acclimation period resulted in increased cold-induced glucose uptake in BAT, as assessed by [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography. BAT activity was negatively related to age, with a similar trend for body fat percentage. In addition, cold-induced glucose uptake in BAT was positively related to glucose uptake in visceral white adipose tissue, although glucose uptake in visceral and subcutaneous white adipose tissue depots was unchanged upon cold acclimation. Cold-induced skeletal muscle glucose uptake tended to increase upon cold acclimation, which was paralleled by increased basal GLUT4 localization in the sarcolemma, as assessed through muscle biopsies. Proximal skin temperature was increased and subjective responses to cold were slightly improved at the end of the acclimation period. These metabolic adaptations to prolonged exposure to mild cold may lead to improved glucose metabolism or prevent the development of obesity-associated insulin resistance and hyperglycemia.

Facile One-step Micropatterning Using Photodegradable Methacrylated Gelatin Hydrogels for Improved Cardiomyocyte Organization and Alignment.

Hydrogels are often employed as temporary platforms for cell proliferation and tissue organization in vitro. Researchers have incorporated photodegradable moieties into synthetic polymeric hydrogels as a means of achieving spatiotemporal control over material properties. In this study protein-based photodegradable hydrogels composed of methacrylated gelatin (GelMA) and a crosslinker containing o-nitrobenzyl ester groups have been developed. The hydrogels are able to degrade rapidly and specifically in response to UV light and can be photopatterned to a variety of shapes and dimensions in a one-step process. Micropatterned photodegradable hydrogels are shown to improve cell distribution, alignment and beating regularity of cultured neonatal rat cardiomyocytes. Overall this work introduces a new class of photodegradable hydrogel based on natural and biofunctional polymers as cell culture substrates for improving cellular organization and function.

Sympathetic nerve-derived ATP regulates renal medullary vasa recta diameter via pericyte cells: a role for regulating medullary blood flow?

Pericyte cells are now known to be a novel locus of blood flow control, being able to regulate capillary diameter via their unique morphology and expression of contractile proteins. We have previously shown that exogenous ATP causes constriction of vasa recta via renal pericytes, acting at a variety of membrane bound P2 receptors on descending vasa recta (DVR), and therefore may be able to regulate medullary blood flow (MBF). Regulation of MBF is essential for appropriate urine concentration and providing essential oxygen and nutrients to this region of high, and variable, metabolic demand. Various sources of endogenous ATP have been proposed, including from epithelial, endothelial, and red blood cells in response to stimuli such as mechanical stimulation, local acidosis, hypoxia, and exposure to various hormones. Extensive sympathetic innervation of the nephron has previously been shown, however the innervation reported has focused around the proximal and distal tubules, and ascending loop of Henle. We hypothesize that sympathetic nerves are an additional source of ATP acting at renal pericytes and therefore regulate MBF. Using a rat live kidney slice model in combination with video imaging and confocal microscopy techniques we firstly show sympathetic nerves in close proximity to vasa recta pericytes in both the outer and inner medulla. Secondly, we demonstrate pharmacological stimulation of sympathetic nerves in situ (by tyramine) evokes pericyte-mediated vasoconstriction of vasa recta capillaries; inhibited by the application of the P2 receptor antagonist suramin. Lastly, tyramine-evoked vasoconstriction of vasa recta by pericytes is significantly less than ATP-evoked vasoconstriction. Sympathetic innervation may provide an additional level of functional regulation in the renal medulla that is highly localized. It now needs to be determined under which physiological/pathophysiological circumstances that sympathetic innervation of renal pericytes is important.

The gastrin gene promoter is regulated by p73 isoforms in tumor cells.

p73, a new p53 family member, is a transcription factor that is increasingly recognized in cancer research as an important player in tumorigenesis as well as in chemotherapeutic drug sensitivity. Despite the substantial structural and functional similarities to p53, accumulating evidence suggests that p53 and p73 may differently regulate their transcriptional targets. In this study, we have investigated the role of p73 in regulation of the gastrin gene promoter. Gastrin is a peptide hormone and an important factor in determining the progression of a number of human malignancies. Our results show that p73 can bind to the gastrin promoter. This leads to transcriptional upregulation of gastrin mRNA. We also found that the levels of gastrin and p73 transcripts correlate in primary gastric tumors. Taken together, our results demonstrate a novel mechanism for regulation of gastrin gene transcription and support a concept that p53 and p73 may have different biological roles in tumors.

Intrathecal diamorphine for analgesia after caesarean section. A dose finding study and assessment of side-effects.

Eighty women undergoing elective Caesarean section under spinal anaesthesia using hyperbaric bupivacaine 0.5% were randomly allocated to receive, in addition, intrathecal diamorphine 0.125, 0.25 or 0.375 mg or saline. Postoperative morphine requirements, measured using a patient-controlled analgesia system, were reduced in a dose-dependent manner by diamorphine. Pain scores were significantly lower at 2 and 6 h following the two larger doses of diamorphine. Less supplemental analgesia was required intra-operatively if intrathecal diamorphine had been given. The incidences of vomiting and pruritus were also dose-related. No respiratory rates of less than 14 breath.min-1 were recorded and the incidence of oxygen saturation readings less than 95% and 90% did not differ between groups. There were no adverse neonatal effects. Intrathecal diamorphine in the present study was found to be safe in doses of up to 0.375 mg following Caesarean section. However, minor side-effects were frequently observed.

A comparison of the effect of intrathecal and extradural fentanyl on gastric emptying in laboring women.

UNLABELLED: We studied gastric emptying, using acetaminophen absorption, in 105 women in labor divided into three equal groups of 35 each, after intrathecal (i.t.) (25 micrograms, Group S) or extradural (50 micrograms, Group E) fentanyl in combination with bupivacaine and compared with a control group (Group C) receiving extradural bupivacaine only. The time to maximal acetaminophen concentration (tCamax), maximal acetaminophen concentration (Camax), and areas under the acetaminophen concentration-time curve at 90 and 120 min (AUC90 and AUC120, respectively) were determined. Median (range) tCamax values were 120 (15-180), 82.5 (15-180), and 90 (15-180) min in Groups S, E, and C, respectively (P < 0.05). Mean +/- SD Camax was 13.4 +/- 8.82, 17.9 +/- 8.06, and 15.0 +/- 6.22 micrograms/mL in Groups S, E, and C, respectively (P < 0.05). Mean +/- SD AUC90 and AUC120 were also significantly smaller in Group S than in the other two groups (430 +/- 616, 736 +/- 504, and 672 +/- 453; and 649 +/- 592, 1063 +/- 627, and 1053 +/- 616 micrograms.mL-1.min-1 in Groups S, E, and C, respectively). We conclude that the administration of fentanyl 25 micrograms i.t. delays gastric emptying in labor compared with both extradural fentanyl 50 micrograms with bupivacaine and extradural bupivacaine alone. IMPLICATIONS: We examined emptying of the stomach in women in labor after administration of analgesics by the spinal or the epidural route. We observed that the analgesic, fentanyl, administered by the spinal route, although relieving pain rapidly, may delay emptying of the stomach. In theory, delayed gastric emptying may increase the chance of vomiting and aspiration of gastric contents.

Low dose epidural bupivacaine/fentanyl infusion does not mask uterine rupture.

A patient is described in whom the symptoms and signs of uterine rupture were not masked by combined spinal epidural analgesia with an epidural infusion of 0.1% bupivacaine and 1.5 microg ml(-l) fentanyl. Early recognition of the dehiscence of a previous caesarean section scar resulted in an excellent neonatal and maternal outcome.

Respiratory effects of spinal anaesthesia for caesarean section.

We report the changes observed in a number of pulmonary function tests performed on 36 patients undergoing Caesarean section under spinal anaesthesia. The tests comprised peak expiratory flow, forced expiratory volume in one second, forced vital capacity, forced expiratory volume in one second to forced vital capacity ratio and the maximal mid-expiratory flow. Significant changes occurred that are consistent with a restrictive ventilatory defect. These changes persisted for four hours after the induction of spinal anaesthesia. Administration of 35% oxygen by facemask failed to change significantly fetal umbilical vein pH or partial pressure of oxygen.

Use of a modified non-rebreathing mask during upper intestinal endoscopy.

BACKGROUND AND STUDY AIMS: Recently, attention has been drawn to the significant occurrence of respiratory and other complications during upper intestinal endoscopy. This prospective study was designed to compare the incidence and severity of oxygen desaturation when two different methods of oxygen delivery were used during elective oesophagogastroduodenoscopy. PATIENTS AND METHODS: After local medical ethics committee approval and written informed consent, one hundred patients undergoing elective oesophagogastroduodenoscopy were randomly allocated to receive supplemental oxygen at either four litres per minute via nasal specular or ten litres per minute through a specially modified non-rebreathing mask. Oxygen saturations during endoscopy facilitated by midazolam sedation were recorded, and non-parametric tests were used to compare the oxygen saturations in the two groups. RESULTS: The mean oxygen saturations were significantly better during the procedure for American Society of Anesthesiology (ASA) grade 2 and 3 patients who received oxygen with the modified mask than for those who received oxygen via nasal specular (98.6% vs. 97.0%, P = 0.004 for ASA grade 2 and 98.4% vs. 95.5, P = 0.006 for ASA grade 3). CONCLUSIONS: For ASA grade 2 and 3 patients, the modified non-rebreathing mask significantly improves oxygen saturations during upper intestinal endoscopy. This technique should be more widely used for patients at moderate and high risk.

Relief of tension subcutaneous emphysema using a large bore subcutaneous drain.

We report a case of subcutaneous emphysema following multiple attempts to cannulate both subclavian veins for pacemaker insertion. Initial bilateral pneumothoraces were complicated by subcutaneous emphysema which became so severe that respiration and cardiac output became seriously impaired. The insertion of a single large bore subcutaneous drain produced a dramatic improvement. The aetiology, complications and management of tension subcutaneous emphysema are discussed.

Effect of nebulized lignocaine on airway irritation and haemodynamic changes during induction of anaesthesia with desflurane.

This study was designed to assess the effect of nebulized lignocaine or saline given before induction on the quality of induction of anaesthesia with desflurane in unpremedicated, young, adult males. Of the first six patients, five developed laryngospasm, breath-holding, coughing and increased secretions. In four patients oxygen saturation decreased to 92% or less. Significant tachycardia and hypertension occurred in four patients, and bradyarrhythmia after induction occurred in three patients. Hiccups and bronchospasm occurred in one patient. Because of the unacceptably high incidence of complications, the study was discontinued. The incidence and severity of complications were not decreased by administration of nebulized lignocaine and were higher than those reported by other workers. We conclude that in unpremedicated, young, adult males, induction of anaesthesia with desflurane and nitrous oxide in oxygen was associated with a high incidence of respiratory irritant effects, tachycardia, hypertension and post-induction bradyarrhythmia. We also found that lignocaine, as used in this study, did not appear to obtund the cardiovascular and respiratory complications during inhalation induction using desflurane.

A case of amniotic fluid embolism in a twin pregnancy in the second trimester.

We present a case of amniotic fluid embolism which is unusual in its presentation in the second trimester of a twin pregnancy, and which, after prompt and aggressive management, produced an equally unusual excellent maternal outcome.

Patients' perception of day case surgery.

A postal questionnaire was used to assess patient compliance with instructions, post-operative sequelae and general practitioner workload resulting from the day case unit of Daisy Hill Hospital, Newry. Compliance with instructions was good. There was little post-operative pain but there was a high incidence of other side effects. Few patients needed to see their general practitioner in the week following surgery.