Nutritional supplementation with l-arginine prevents pelvic radiation-induced changes in morphology, density, and regulating factors of blood vessels in the wall of rat bladder

Purpose

To determine whether l-arginine has protective effects against radiation-induced alterations in the morphology and regulatory factors of vesical blood vessels in rats.

Methods

Male rats aged 3–4 months were divided into groups of 10 animals each: (a) controls, consisting of non-treated animals; (b) radiated-only rats; and (c) radiated rats receiving l-arginine supplementation. Radiation was in one session of 10 Gy and was aimed at the pelvic-abdominal region. l-arginine was administered once a day (0.65 g/kg body weight), starting 7 days before radiation and continuing until killing on the 16th day after radiation. The density, relative area, and wall thickness of blood vessels were measured in the vesical lamina propria using histological methods, and the expression of vascular endothelial growth factor (VEGF) and fibroblast growth factors (FGF) in the bladder wall was assessed by RT-PCR.

Results

Compared with controls, radiation alone decreased the density and relative area of blood vessels by 32 % (p < 0.01) and 25 % (p < 0.05), respectively, and reduced the arterial wall thickness by 42 % (p < 0.004). VEGF and FGF mRNA levels after radiation were diminished by 67 % (p < 0.002) and 56 % (p < 0.04), respectively. The radiated animals supplemented with l-arginine were not significantly different from controls.

Conclusions

Pelvic radiation leads to significant vesical modifications, as in the morphology of blood vessels and in VEGF and FGF expression. All these changes, however, were prevented by l-arginine treatment. These results emphasize, therefore, the potential use of this amino acid as a radioprotective drug.     

Dramatic decrease of carnitine esters after interruption of exogenous carnitine supply in hemodialysis patients

L-carnitine supplementation is extensively used in patients on maintenance hemodialysis (HD) to improve dialysis-related clinical symptoms. In a series of studies, we investigated the dynamics of carnitine pool in carnitine-supplemented HD patients; here we report dramatic decrease with special changes of the ester profile due to interruption of the exogenous intake after the last HD session. Serum samples were collected from 18 L-carnitine-repleted end-stage renal disease (ESRD) patients before the L-carnitine supplementation, after completion of a carnitine supplementation period treatment (12 weeks, 1 g/IV/HD), right before the HD session, and 44 h after the dialysis. Levels of free carnitine (FC) and the individual esters were determined using electrospray MS/MS technique. Normally, L-carnitine supplementation causes significant elevation of all carnitine compounds to supraphysiological levels, which reaches a standard steady-state-like profile. In this study we found a dramatic decrease in the level of FC, and in short- and medium-chain acylcarnitines (ACs) 44 h after the last dialysis. At the end of this interdialytic period, FC levels increased to only 65% of the predialysis level, whereas the amounts of C2 and C3 esters recovered to only 50%. The level of C6 was 65% of the predialysis level, whereas the amount of C8 chain length ACs returned to 72% of the predialysis level. No significant change was seen in AC concentrations above C10 chain length. Omission of one single dosage of supplemental carnitine in long-term administration schemes results in dramatic decrease and reprofiling of carnitine esters even after the usual 44 h of interdialytic period.     

Is Nitric Oxide a Mediator of the Effects of Low-Intensity Electrical Stimulation on Bone in Ovariectomized Rats?

Low-intensity electrical stimulation (LIES) may counteract the effects of ovariectomy (OVX) on nitric oxide synthase (NOS) expression, osteocyte viability, bone structure, and microarchitecture in rats (Lirani-Galvão et al., Calcif Tissue Int 84:502–509, 2009). The aim of the present study was to investigate if these effects of LIES could be mediated by NO. We analyzed the effects of NO blockage (by l-NAME) in the response to LIES on osteocyte viability, bone structure, and microarchitecture in OVX rats. Sixty rats (200–220 g) were divided into six groups: sham, sham-l-NAME (6 mg/kg/day), OVX, OVX-l-NAME, OVX-LIES, and OVX-LIES-l-NAME. After 12 weeks, rats were killed and tibiae collected for histomorphometric analysis and immunohistochemical detection of endothelial NOS (eNOS), inducible NOS (iNOS), and osteocyte apoptosis (caspase-3 and TUNEL). In the presence of l-NAME, LIES did not counteract the OVX-induced effects on bone volume and trabecular number (as on OVX-LIES). l-NAME blocked the stimulatory effects of LIES on iNOS and eNOS expression of OVX rats. Both l-NAME and LIES decreased osteocyte apoptosis. Our results showed that in OVX rats l-NAME partially blocks the effects of LIES on bone structure, turnover, and expression of iNOS and eNOS, suggesting that NO may be a mediator of some positive effects of LIES on bone.     

d-mannose powder for prophylaxis of recurrent urinary tract infections in women: a randomized clinical trial

Purpose

To test whether d-mannose powder is effective for recurrent urinary tract infection (UTI) prevention.

Materials and methods

After initial antibiotic treatment of acute cystitis, 308 women with history of recurrent UTI and no other significant comorbidities were randomly allocated to three groups. The first group (n = 103) received prophylaxis with 2 g of d-mannose powder in 200 ml of water daily for 6 months, the second (n = 103) received 50 mg Nitrofurantoin daily, and the third (n = 102) did not receive prophylaxis.

Results

Overall 98 patients (31.8 %) had recurrent UTI: 15 (14.6) in the d-mannose group, 21 (20.4) in Nitrofurantoin group, and 62 (60.8) in no prophylaxis group, with the rate significantly higher in no prophylaxis group compared to active groups (P < 0.001). Patients in d-mannose group and Nitrofurantoin group had a significantly lower risk of recurrent UTI episode during prophylactic therapy compared to patients in no prophylaxis group (RR 0.239 and 0.335, P < 0.0001). In active groups, 17.9 % of patients reported side effects but they were mild and did not require stopping the prophylaxis. Patients in d-mannose group had a significantly lower risk of side effects compared to patients in Nitrofurantoin group (RR 0.276, P < 0.0001), but the clinical importance of this finding is low because Nitrofurantoin was well tolerated.

Conclusions

In our study, d-mannose powder had significantly reduced the risk of recurrent UTI which was no different than in Nitrofurantoin group. More studies will be needed to validate the results of this study, but initial findings show that d-mannose may be useful for UTI prevention.     

Antinociceptive effect of intracerebroventricular administration of d-serine on formalin-induced pain

Purpose

In a previous study using the tail-flick test, we found that intracerebroventricular administration of d-serine, an endogenous co-agonist at the glycine sites of N-methyl-d-aspartate (NMDA) receptors, elicited an antinociceptive effect on thermal nociception. The purpose of the present study was to evaluate the effect of intracerebroventricular administration of d-serine on nociception induced by tissue damage or inflammation using the formalin test.

Methods

Infusion of drugs into the third ventricle in rat was performed via indwelling cannulae. Drugs were infused at a volume of 10 μl over 2 min, and the infusion cannula was left in place for 2 min before removal. The formalin test was performed 10 min after drug administration.

Results

Intracerebroventricular administration of d-serine significantly and dose-dependently decreased the number of flinches in both the early and late phases in the formalin test. This antinociceptive effect was antagonized by intracerebroventricular administration of L-701,324, a selective antagonist at the glycine sites of NMDA receptors.

Conclusion

The present data suggest that activation of NMDA receptors via glycine sites at the supraspinal level induces an antinociceptive effect on both acute and tonic pain.     

Cardiopulmonary Exercise Testing for Preoperative Risk Assessment before Pancreaticoduodenectomy for Cancer

Objective

Pancreaticoduodenectomy is the standard of care for tumors confined to the head of pancreas and can be undertaken with low operative mortality. The procedure has a high morbidity, particularly in older patient populations with preexisting comorbidities. This study evaluated the role of cardiopulmonary exercise testing to predict postoperative morbidity and outcome in high-risk patients undergoing pancreaticoduodenectomy.

Methods

In a prospective cohort of consecutive patients undergoing pancreaticoduodenectomy, those aged over 65 years (or younger with comorbidity) were categorized as high risk and underwent preoperative assessment by cardiopulmonary exercise testing (CPET) according to a predefined protocol. Data were collected on functional status, postoperative complications, and survival.

Results

A total of 143 patients underwent preoperative assessment, 50 of whom were deemed to be at low risk for surgery per study protocol. Of 93 high-risk patients, 64 proceeded to surgery after preoperative CPET. Neither anaerobic threshold (AT) nor maximal oxygen consumption ( $ \dot{V} $ o ₂ MAX) predicted patient mortality or morbidity. However, ventilatory equivalent of carbon dioxide ( $ \dot{V} $ e/ $ \dot{V} $ co ₂) at AT was a predictive marker of postoperative mortality, with an area under the curve (AUC) of 0.84 (95 % confidence interval [CI] 0.63–1.00, p = 0.020); a threshold of 41 was 75 % sensitive and 95 % specific (positive predictive value 50 %, negative predictive value 98 %). Above this threshold, raised $ \dot{V} $ e/ $ \dot{V} $ co ₂ predicted poor long-term survival (hazard ratio 2.05, 95 % CI 1.09–3.86, p = 0.026).

Conclusions

CPET is a useful adjunctive test for predicting postoperative outcome in patients being assessed for pancreaticoduodenectomy. Raised CPET-derived $ \dot{V} $ e/ $ \dot{V} $ co ₂ predicts early postoperative death and poor long-term survival.     

Role of low-intensity laser therapy on naloxone-precipitated morphine withdrawal signs in mice: is nitric oxide a possible candidate mediator?

In the present study, the potential involvement of nitric oxide (NO) system in attenuating effects of low-intensity laser therapy (LILT) on naloxone-induced morphine withdrawal signs was evaluated. A hundred mice were rendered morphine-dependent using three escalating doses of morphine sulfate during three consecutive days. After the last dose on day 4, animals were given naloxone HCl (2 mg/kg s.c) to induce withdrawal signs. The effects of LILT (12.5 J/cm²) and l-NG-nitroarginine methyl ester (l-NAME) (10, 20, 50, and 100 mg/kg) and their coadministration on escape jump count and stool weight as typical withdrawal signs were assessed. LILT and l-NAME (20, 50, and 100 mg/kg) per se significantly decreased escape jump count and stool weight in morphine-dependent naloxone-treated mice (p?l-NAME (20, 50, and 100 mg/kg) also reduced escape jump and stool weight (p?l-NAME follow the same track of changes in escape jump and stool weight. Conceivably, it seems that LILT acts partly via NO system, but the exact path is still obscure and rather intricate. The precise mechanisms need to be clarified.     

The Effect of Bariatric Surgery on Intestinal Absorption and Transit Time

Background

Bariatric surgical procedures are classified by their presumed mechanisms of action: restrictive, malabsorptive or a combination of both. However, this dogma is questionable and remains unproven. We investigated post-operative changes in nutrient absorption and transit time following bariatric surgery.

Methods

Participants were recruited into four groups: obese controls (body mass index (BMI) >30 kg/m², n?=?7), adjustable gastric banding (n?=?6), Roux-en-Y gastric bypass (RYGB, n?=?7) and biliopancreatic diversion with duodenal switch (DS, n?=?5). Participants underwent sulphasalazine/sulphapyridine tests (oro-caecal transit time); fasting plasma citrulline (functional enterocyte mass); 3 days faecal collection for faecal elastase 1 (FE-1); calprotectin (FCp); faecal fatty acids (pancreatic exocrine function, gut inflammation and fat excretion, respectively); and 5 h d-xylose, l-rhamnose and lactulose test (intestinal absorption and permeability).

Results

Age and gender were not different but BMI differed between groups (p?=?0.001). No difference in oro-caecal transit time (p?=?0.935) or functional enterocyte mass (p?=?0.819) was detected. FCp was elevated post-RYGB vs obese (p?=?0.016) and FE-1 was reduced post-RYGB vs obese (p?=?0.002). Faecal fat concentrations were increased post-DS vs obese (p?=?0.038) and RYGB (p?=?0.024) and were also higher post-RYGB vs obese (p?=?0.033). Urinary excretion of d-xylose and l-rhamnose was not different between the groups; however, lactulose/rhamnose ratio was elevated post-DS vs other groups (all p?<?0.02), suggesting increased intestinal permeability.

Conclusions

Following RYGB, there are surprisingly few abnormalities or indications of severe malabsorption of fats or sugars. Small bowel adaptation after bariatric surgery may be key to understanding the mechanisms responsible for the beneficial metabolic effects of these operations.     

Increasedl-arginine transport in a nitric oxide-producing metastatic colon cancer cell line

Background: Little is known about amino acid transport in human neoplastic cells. We previously characterizedl-arginine transport in the primary human colon cancer cell line, SW480, and found it is principally mediated by the sodium-independent system y⁺. In this study, we characterizedl-arginine transport in the metastatic cell line, SW620, and compared it with that in the primary cell line, SW480. Methods: Transport of³H-l-arginine in cell monolayers was analyzed in the presence and absence of sodium. Kinetic studies were performed over a range ofl-arginine concentrations to determine transporter affinity (K_m) and maximal transport velocity (V_max). Transport was further characterized through blockade with known amino acids. In addition, the effect of cell age (i.e., time in culture) on arginine transport was examined at 2 and 9 days after seeding. Cellular proliferation was asssessed by using the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Results: l-Arginine uptake was primarily sodium independent in the SW620 cell line. Kinetic and amino acid-inhibition studies revealed a single high-affinity, sodium-independentl-arginine transporter (V_max=1286.3 ± 158.3 pmol/mg protein/30 s; K_m=46.8 ± 4.2 μM). Sodium-independent transport was blocked by system y⁺ substratesl-homoarginine,l-ornithine andl-lysine. Sodium-dependent uptake occurs through a single transporter with system B^O,+ characteristics (K_m=16.15 ± 2.1 μM; V_max=329.94 ± 29.7 pmol/mg protein/30 s). Arginine transport increased with time in culture with day 2 cells transport velocity =241.7 ± 33.6 pmol/mg protein/30s, whereas day 9 cells transport velocity =377 ± 15.4 pmol/mg protein/30 s (p<0.01). Cellular-proliferation studies revealed a doubling time of 3.2 days for SW620 and 5.4 days for SW480 (p<0.05). Conclusions: l-Arginine transport in these neoplastic cell lines occurs primarily through sodium-independent, high-affinity system y⁺. V_max was increased 180% in the metastatic variant (SW620), suggesting upregulation of the y⁺ transporter. The increased y⁺ activity may be a mechanism to provide continuous substrate for tumor growth.     

The value of the serum I-FABP level for diagnosing acute mesenteric ischemia

Purpose

This study examined the feasibility of using the serum intestinal fatty acid binding protein (I-FABP) level for the early diagnosis of acute mesenteric ischemia, and investigated whether it contributes to the clinical decision-making process.

Method

Thirty patients diagnosed with acute mesenteric ischemia, 27 patients with other types of acute abdomen who presented with acute abdomen symptoms but were not diagnosed with acute mesenteric ischemia, and 20 healthy people were included in the study. Mesenteric ischemia was confirmed by a pathological evaluation in patients who underwent intestinal resection due to detection of mesenteric ischemia during surgery.

Results

There was no significant difference in the leukocyte counts and d-dimer levels between subjects with mesenteric ischemia and acute abdomen due to other causes (p > 0.05). There was a significant difference in the serum I-FABP level between these groups (p < 0.001).

Conclusion

The I-FABP level is a more reliable parameter for diagnosing acute mesenteric ischemia compared to leukocytosis and d-dimer elevation.     

Mechanisms of Action of the Gasotransmitter Hydrogen Sulfide in Modulating Contractile Activity of Longitudinal Muscle of Rat Ileum

Aim

This study aims to determine mechanisms of action of the gasotransmitter hydrogen sulfide (H₂S) on contractile activity in longitudinal muscle of rat ileum.

Methods

Ileal longitudinal muscle strips were prepared to measure isometric contractions. Effects of sodium hydrosulfide (NaHS), a donor of H₂S, were evaluated on spontaneous contractile activity and after enhanced contractile activity with bethanechol. l-cysteine was evaluated as a potential endogenous donor of H₂S. We evaluated involvement of extrinsic nerves, enteric nervous system, visceral afferent nerves, nitric oxide, and K _ATP ⁺ channel and K _Ca ⁺ channel activity on the action of H₂S using non-adrenergic/non-cholinergic conditions, tetrodotoxin, capsaicin, l-N^G-nitro arginine (l-NNA), glibenclamide, and apamin, respectively, as well as electrical field stimulation.

Result

NaHS dose-dependently and reversibly inhibited spontaneous and bethanechol-stimulated contractile activity (p?<?0.05). l-cysteine had no inhibitory effect. Non-adrenergic/non-cholinergic conditions, tetrodotoxin, capsaicin, l-NNA, glibenclamide, or apamin had no major effect on total contractile activity by NaHS, although both tetrodotoxin and apamin decreased the frequency of bethanechol-enhanced contractile activity (p?<?0.05). We could not demonstrate H₂S release by electrical field stimulation but did show that inhibition of cystathionine ?? synthase, an endogenous source of H₂S, augmented the inhibitory effect of low-frequency electrical field stimulation.

Conclusion

H₂S inhibits contractile activity of ileal longitudinal muscle dose-dependently but not through pathways mediated by the extrinsic or enteric nervous system, visceral afferent nerves, nitric oxide, K _ATP ⁺ channels, or K _Ca ⁺ channels.     

CD147/basigin reflects renal dysfunction in patients with acute kidney injury

Background

Acute tubular necrosis (ATN) describes a form of intrinsic acute kidney injury (AKI) that results from persistent hypoperfusion and subsequent activation of the immune system. A glycosylated transmembrane protein, CD147/basigin, is involved in the pathogenesis of renal ischemia and fibrosis. The present study investigated whether CD147 can reflect pathological features and renal dysfunction in patients with AKI.

Methods

Plasma and spot urine samples were collected from 24 patients (12 controls and 12 with ATN) who underwent renal biopsy between 2008 and 2012. In another study, patients undergoing open surgery to treat abdominal aortic aneurysms (AAAs) were enrolled in 2004. We collected urine and plasma samples from seven patients with AKI and 33 patients without AKI, respectively. In these experiments, plasma and urinary CD147, and urinary l-fatty acid-binding protein (l-FABP) levels were measured, and the former expression in kidneys was examined by immunostaining.

Results

In biopsy tissues of ATN with severe histological features, CD147 induction was strikingly present in inflammatory cells such as macrophages and lymphocytes in the injured interstitium, but not in damaged tubules representing atrophy. Both plasma and urinary CD147 levels were strikingly increased in ATN patients; both values showed greater correlations with renal dysfunction compared to urinary l-FABP. In patients who had undergone open AAA surgery, urinary and plasma CD147 values in AKI patients were significantly higher than in non-AKI patients at post-operative day 1, similar to the profile of urinary l-FABP.

Conclusion

CD147 was prominent in its ability to detect AKI and may allow the start of preemptive medication.     

A comparison of four infrared tympanic thermometers with tympanic membrane temperatures measured by thermocouples

Purpose

To compare measurements made with four infrared tympanic thermometers (Genius®, Thermopit®, Quickthermo®, and Thermoscan®) with those recorded from thermocouples positioned in the contralateral ear.

Methods

Four tympanic thermometers were evaluated in 50 healthy volunteers (12 female and 38 male). Temperatures were measured, in random order, at the right tympanic membrane four times and the highest temperature was considered to be the true value measured by each thermometer. The control temperature was measured at the left tympanic membrane using Mon-a-Therm® thermocouples.

Results

The tympanic membrane temperature measured by Genius® correlated best with the Mon-a-therm® measurement (T _m ) (r = 0.74). The tympanic membrane temperatures measured by Thermopit®, Quickthermo®, and Thermoscan® correlated moderately with T _m (r = 0.56, 0.63, and 0.58, respectively). Mean differences between T _m and each temperature (T _g , T _tp , T _q , and T _ts ) were ?0.3, 0.73, 0.42, and ?0.3°C, respectively. Likewise standard deviations were 0.33, 0.37,0.35, and 0.35.

Conclusion

We conclude that all but the Thermopit® (T _tp ) are similarly useful for the management of patients during anaesthesia.     

Biodegradable microspherical implants containing teicoplanin for the treatment of methicillin-resistant Staphylococcus aureus osteomyelitis

Background

The aim of this study was to prepare poly(d,l-lactide-co-glycolide) (PLGA) microspherical implants containing teicoplanin (TCP) using a double emulsion solvent evaporation method and to evaluate its efficacy for the local treatment of chronic osteomyelitis.

Methods

The particle size and distribution, morphological characteristics, thermal behaviour, drug content, encapsulation efficiency and in vitro release assessments of the formulations were carried out. Sterile TCP–PLGA microspheres were implanted in the proximal tibia of rats with methicillin resistant Staphylococcus aureus (MRSA) osteomyelitis. After 3 weeks of treatment, bone samples were analysed with a microbiological assay and evaluated histopathologically.

Results

Microspheres between the size ranges of 2.01 and 3.91 μm were obtained. Production yield of all formulations was found to be higher than 82% and encapsulation efficiencies of 33.6–69.8% were obtained. DSC thermogram showed that the TCP was in an amorphous state in microspheres. In vitro drug release studies had indicated that the drug release rate of microspheres was decreased upon increasing the polymer:drug ratio. Based on the in vivo data, rats treated with implants and intramuscular injection showed 1.7 × 10³ ± 1.3 × 10³ and 5.8 × 10⁴ ± 5.3 × 10⁴ colony forming unit of MRSA in 1 g bone samples (CFU/g), respectively (P < 0.01).

Conclusions

The in vitro and in vivo studies had shown that the TCP–PLGA microspheres were effective for the treatment of chronic osteomyelitis in an animal experimental model. Hence, these microspheres may be potentially useful in the clinical setting with the need for further investigation for optimal dosing of TCP–PLGA microspheres.     

Accelerated Gastric Emptying but No Carbohydrate Malabsorption 1 Year After Gastric Bypass Surgery (GBP)

Background

Following gastric bypass surgery (GBP), there is a post-prandial rise of incretin and satiety gut peptides. The mechanisms of enhanced incretin release in response to nutrients after GBP is not elucidated and may be in relation to altered nutrient transit time and/or malabsorption.

Methods

Seven morbidly obese subjects (BMI?=?44.5?±?2.8?kg/m²) were studied before and 1?year after GBP with a d-xylose test. After ingestion of 25?g of d-xylose in 200?mL of non-carbonated water, blood samples were collected at frequent time intervals to determine gastric emptying (time to appearance of d-xylose) and carbohydrate absorption using standard criteria.

Results

One year after GBP, subjects lost 45.0?±?9.7?kg and had a BMI of 27.1?±?4.7?kg/m². Gastric emptying was more rapid after GBP. The mean time to appearance of d-xylose in serum decreased from 18.6?±?6.9?min prior to GBP to 7.9?±?2.7?min after GBP (p?=?0.006). There was no significant difference in absorption before (serum d-xylose concentrations?=?35.6?±?12.6?mg/dL at 60?min and 33.9?±?9.1?mg/dL at 180?min) or 1?year after GBP (serum d-xylose?=?31.5?±?18.1?mg/dL at 60?min and 27.2?±?11.9?mg/dL at 180?min).

Conclusions

These data confirm the acceleration of gastric emptying for liquid and the absence of carbohydrate malabsorption 1?year after GBP. Rapid gastric emptying may play a role in incretin response after GBP and the resulting improved glucose homeostasis.     

Changes in PCO2 with acute changes in cardiac index

Purpose

A direct relationship between cardiac index (CI) and end-tidal PCO₂ (PetCO₂) shortly after decreased CI was reported, but arterial PCO₂ was not measured. Our purpose was to supply the missing information on the immediate effects of alterations in CI on PaCO₂,PetCO₂ and thus on Pa-PetCO₂.

Methods

We measured CI, Pa andPetCO₂ and calculated the difference in 20 patients scheduled for elective heart surgery just before and immediately after the sternotomy. The measurements were made using standard methods: thermodilution for CI, infra-red and blood gas analysis forPet and PaCO₂ respectively. The results were analyzed by linear regression.

Results

Very significant, direct and immediate changes inPet and PaCO₂ with changes in CI were noted. The ratios were 3.8 and 4.2 mmHg L^?1 respectively. The calculated values of r were 0.75 (P < 0.001) forPetCO₂ and 0.64 (P < 0.005) for PaCO₂. The magnitude of individual change in PCO₂ varied considerably such that the alterations in Pa-PetCO₂ were also variable, without any correlation with the direction or magnitude of change in CI.

Conclusion

Our results explain the reported wide variations in Pa-PetCO₂ that accompany perturbations of cardiac output. Our observations pertain to the unsteady state only. The results suggest thatPetCO₂ can be used to estimate changes in CI with a reasonable degree of confidence.     

Degradation of poly-d-l-lactide (PDLLA) interference screws (Megafix®)

Introduction

Interference screw fixation is a standard procedure in anterior cruciate ligament (ACL) replacement. Aim of this study was to evaluate the degradation process of Poly-d-l-lactide (PDLLA) interference screws used for tibial ACL graft fixation.

Materials and methods

We evaluated magnetic resonance imaging (MRI) scans of 18 patients who underwent ACL revision surgery at different time points after anatomic ACL reconstruction. At primary surgery, a tibial hybrid fixation was performed with a degradable interference (IF) screw made of PDLLA (Megafix^®) and a button.

Results

MRI revealed three different phases of degradation of the PDLLA screw. 6–8 months after surgery the IF screw was clearly visible as a well-defined structure on MRI and CT scan. After 12–16 months, the screws appeared less defined with central ingrowths’ of connective tissue. In some cases only fragmented screw material was visible. At these time points, there was a slight edema surrounding the tunnel visible on MRI. After 22 months and later, the mean screw site densities were comparable with the surrounding bone density. There was no edema or signs of inflammation around the bone tunnels visible. Presence of cystic or osteolytic changes was not detected.

Conclusion

After 22 months, a PDLLA screw may not interfere with ACL revision surgery. Regarding the degradation process of PDLLA screws, we noted three different phases. Furthermore, the degradation process observed by MRI resembles to that described by animal studies. The PDLLA screws fully absorb and are partially replaced by bone. The degradation process in humans seems to be longer than that described in animals.     

Tracheomotor response to cardiopulmonary bypass: influence of lung deflation and cardiac distension

The pressure within the water-filled cuff of an endotracheal tube (Pte) was used as a measure of tracheal smooth muscle tone in ten patients undergoing cardiopulmonary bypass (CPB). Pulmonary artery pressure (Ppa) and left atrial pressure (Pla) were also monitored. Institution of CPB, with acute reduction of pulmonary blood flow and lung deflation, caused no significant change inPte. Crystalloid cardioplegic administration without left ventricular decompression (VENT) resulted in statistically significant increases ofPpa (from 1.33 ± 0.15 to 1.88 ± 0.2 kPa) (p < 0.05) and ofPla (from 1.2 ± 0.11 to 2.2 ± 0.31 kPa) (p<0.05). Coincident with these changes a statistically significant increase inPte (from 4.95 ± 0.21 to 5.24 ± 0.27kPa) (p < 0.05) was detected. This increase inPte was significantly greater than the small random variations noted inPte prior to cardioplegic infusion with constantPla andPpa. Thus, minimal tracheomotor constriction in response to car-dioplegia administration occurred. Larger increases inPte were noted during cardiac compression suggesting that the water-filled cuff could have detected larger increases if they had occurred. These transient changes do not reflect clinically detectable increases in airway resistance at the termination of CPB when lung ventilation is started. Neither of these two physiological stimuli, lung deflation or cardioplegia administration, cause clinically significant increases of large airway tone during CPB.     

Malignant hyperthermia involving the administration of desflurane

Purpose

This report describes an episode of malignant hyperthermia (MH) in a ten year old boy receiving desflurane anaesthesia.

Clinical features

Following induction of general endotracheal anaesthesia with thiopentone and succinylcholine, desflurane was administered for maintenance of anaesthesia. Ten minutes after commencing desflurane administration, heart rate andPetCO₂ increased to 165 bpm and 50 mmHg, respectively. Initially, the tachycardia was attributed to a sympathetic response secondary to desflurane. Desflurane was discontinued and isoflurane was started. Minute ventilation was increased to decreasePetCO₂-Over the next five minutes, temperature increased to 38.4°C as thePetCO₂ increased to above 60 mmHg. Venous and arterial blood gases were drawn which showed acidosis and hypercapnia. Temperature andPetCO₂ continued to increase, reaching peak values of 41°C and 77 mmHg, respectively. Efforts to cool the patient were made. A total of 220 mg dantrolene sodium was administered iv. Following dantrolene, the temperature increase and acidosis subsided. Heart rate andPetCO₂ decreased to 130 bpm and 36 mmHg, respectively. The surgical procedure was expeditiously performed. Postoperatively, in the Paediatric Intensive Care Unit, a dantrolene infusion of 20 mg · hr^?1 was administered for 12 hr. The trachea was extubated the following morning. Several days later, the patient underwent another surgical procedure without complications using MH-safe anaesthetics.

Conclusion

Onset of tachycardia in a patient receiving desflurane may initially be attributed to desflurane-induced sympathetic hyperactivity. This poses a clinical challenge in the diagnosis of MH during desflurane anaesthesia.     

Light-emitting diode therapy induces analgesia in a mouse model of postoperative pain through activation of peripheral opioid receptors and the l-arginine/nitric oxide pathway

Light-emitting diode therapy (LEDT) has been clinically used as an alternative to low-level laser therapy; nevertheless, the molecular basis for LEDT effects remains unclear. The objective of this study was to evaluate the analgesic effect of LEDT in the mouse plantar incision (PI) model of postoperative pain, as well as to investigate some of the possible mechanisms involved in this effect, i.e., peripheral and central opioid receptors; migration of opioid-containing leukocytes to PI site and the l-arginine/nitric oxide (NO) pathway. To that end, mice were subjected to PI and treated with LEDT (950 nm, 80 mW/cm², 1 through 13 J/cm²). Mechanical hypersensitivity was assessed as withdrawal frequency percentage to 10 presentations of a 0.4-g von Frey filament. In addition, the animals were pretreated with systemic (i.p.), intra-plantar (i.pl.), or intrathecal injection (i.t) of naloxone (a nonselective opioid receptor antagonist; 1 mg/kg, i.p.; 5 μg/right paw or 5 μg/site, respectively) or a systemic injection of fucoidin (100 μg/mouse, i.p., an inhibitor of leukocyte rolling through binding to l- and p-selectins). Our results demonstrate, for the first time, that LEDT induced a dose–response analgesic effect in the model of PI in mice. At the dose of 9 J/cm² LEDT presented the most significant results through (1) activation of peripheral opioid receptors which involve, at least partially, the recruitment of opioid-containing leukocytes to the PI site and; (2) activation of the l-arginine/NO pathway. These results extend previous literature data and suggest that LEDT might be useful in the treatment of postoperative pain.