Characterization of the inflammatory cells in ascending thoracic aortic aneurysms in patients with Marfan syndrome, familial thoracic aortic aneurysms, and sporadic aneurysms.

OBJECTIVE: This study sought to characterize the inflammatory infiltrate in ascending thoracic aortic aneurysm in patients with Marfan syndrome, familial thoracic aortic aneurysm, or nonfamilial thoracic aortic aneurysm. BACKGROUND: Thoracic aortic aneurysms are associated with a pathologic lesion termed "medial degeneration," which is described as a noninflammatory lesion. Thoracic aortic aneurysms are a complication of Marfan syndrome and can be inherited in an autosomal dominant manner of familial thoracic aortic aneurysm. METHODS: Full aortic segments were collected from patients undergoing elective repair with Marfan syndrome (n = 5), familial thoracic aortic aneurysm (n = 6), and thoracic aortic aneurysms (n = 9), along with control aortas (n = 5). Immunohistochemistry staining was performed using antibodies directed against markers of lymphocytes and macrophages. Real-time polymerase chain reaction analysis was performed to quantify the expression level of the T-cell receptor beta-chain variable region gene. RESULTS: Immunohistochemistry of thoracic aortic aneurysm aortas demonstrated that the media and adventitia from Marfan syndrome, familial thoracic aortic aneurysm, and sporadic cases had increased numbers of T lymphocytes and macrophages when compared with control aortas. The number of T cells and macrophages in the aortic media of the aneurysm correlated inversely with the patient's age at the time of prophylactic surgical repair of the aorta. T-cell receptor profiling indicated a similar clonal nature of the T cells in the aortic wall in a majority of aneurysms, whether the patient had Marfan syndrome, familial thoracic aortic aneurysm, or sporadic disease. CONCLUSION: These results indicate that the infiltration of inflammatory cells contributes to the pathogenesis of thoracic aortic aneurysms. Superantigen-driven stimulation of T lymphocytes in the aortic tissues of patients with thoracic aortic aneurysms may contribute to the initial immune response.

Development of micro-electrospray mass spectrometry for ultra high sensitivity and application in the study of drugs of abuse on endogenous \lbrack Met\rbrack $\sp5$-enkephalin release

A micro-electrospray interface was developed specifically for the neurobiological applications described in this dissertation. Incorporation of a unique nano-flow liquid chromatography micro-electrospray "needle" into the micro-electrospray interface (micro-ES/MS) increased the sensitivity of the mass spectrometric assay by $\sim$1000 fold and thus permitted the first analysis of specific neuroactive compounds in brain extracellular fluid collected by in vivo microdialysis (Md).^ Initial in vivo data presented deals with the pharmacodynamics of a novel GABA$\sb{\rm B}$ antagonist and the availability of the compound in its parent (unmetabolized) form to the brain of the anesthetized rat. Next, the first structurally specific endogenous release of (Met) $\sp5$-enkephalin was demonstrated in unanesthetized freely-moving animals (release of $\sim$6.5 fmole of (Met) $\sp5$-enkephalin into the dialysate by direct neuronal depolarization). The Md/micro-ES/MS system was used to test the acute effects of drugs of abuse on the endogenous release of (Met) $\sp5$-enkephalin from the globus pallidus/ventral pallidum brain region in rats. Four drugs known to be abused by man (morphine, cocaine, methamphetamine and diazepam) were tested. Morphine and cocaine both elicited a two-fold or more increase in the release of (Met) $\sp5$-enkephalin over vehicle controls. Diazepam elicited a small decrease in (Met) $\sp5$-enkephalin levels and methamphetamine showed no significant effect on (Met) $\sp5$-enkephalin. These results imply that (Met) $\sp5$-enkephalin may be involved in the reward pathway of certain drugs of abuse. ^

Neuromuscular disuse and atrophy: {\it In vivo\/} magnetic resonance studies of intramuscular lipid metabolism and fluid shift changes

We postulated that neuromuscular disuse results in deleteriously affected tissue-vascular fluid exchange processes and subsequently damages the important oxidative bioenergetic process of intramuscular lipid metabolism. The in-depth research reported in the literature is somewhat limited by the ex vivo nature and sporadic time-course characterization of disuse atrophy and recovery. Thus, an in vivo controlled, localized animal model of disuse atrophy was developed in one of the hindlimbs of laboratory rabbits (employing surgically implanted tetrodotoxin (TTX)-filled mini-osmotic pump-sciatic nerve superfusion system) and tested repeatedly with magnetic resonance (MR) throughout the 2-week period of temporarily induced disuse and during the recovery period (following explantation of the TTX-filled pump) for a period of 3 weeks. Controls consisted of saline/"sham"-implanted rabbit hindlimbs. The validity of this model was established with repeated electrophysiologic nerve conduction testing using a clinically appropriate protocol and percutaneously inserted small needle stimulating and recording electrodes. Evoked responses recorded from proximal (P) and distal (D) sites to the sciatic nerve cuff in the TTX-implanted group revealed significantly decreased (p $<$ 0.001) proximal-to-distal (P/D) amplitude ratios (as much as 50-70% below Baseline/pre-implanted and sham-implanted group values) and significantly increased (p $<$ 0.01) differential latency (PL-DL) values (as much as 1.5 times the pre- and sham-implanted groups). By Day 21 of recovery, observed P/D and PL-DL levels matched Baseline/sham-implemented levels. MRI-determined cross-sectional area (CSA) values of Baseline/pre-implanted, sham- or TTX-implanted, and recovering/explanted and the corresponding contralateral hindlimb tibialis anterior (TA) muscles normalized to tibial bone (TB) CSA (in TA/TB ratios) revealed that there was a significant decline (indicative of atrophic response) from pre- and sham-implanted controls by as much as 20% (p $<$ 0.01) at Day 7 and 50-55% (p $<$ 0.001) at Day 13 of TTX-implantation. In the non-implanted contralaterals, a significant increase (indicative of hypertrophic response) by as much as 10% (p $<$ 0.025) at Day 7 and 27% (p $<$ 0.001) at Day 13 + TTX was found. The induced atrophic/hypertrophic TA muscles were observed to be fully recovered by Day 21 post-explantation as evidenced by image TA/TB ratios. End-point biopsy results from a small group of rabbits revealed comprehensive atrophy of both Type I and Type II fibers, although the heterogeneity of the response supports the use of image-guided, volume-localized proton magnetic resonance spectroscopy (MRS) to noninvasively assess tissue-level metabolic changes. MRS-determined results of a 0.25cc volume of tissue within implanted limb TA muscles under resting/pre-ischemic, ischemic-stressed, and post-ischemic conditions at timepoints during and following disuse atrophy/recovery revealed significantly increased intramuscular spectral lipid levels, as much as 2-3 times (p $<$ 0.01) the Baseline/pre-implanted values at Day 7 and 6-7 times (p $<$ 0.001) at Day 13 + TTX, which approached normal levels (compared to pre- and sham-implanted groups) by Day 21 of post-explanation recovery. (Abstract shortened by UMI.) ^

Introduction of two novel devices for investigating the influence of non-mechanical components such as therapeutic qi in acupuncture

OBJECTIVE: Acupuncture is a complex intervention consisting of specific and non-specific components. Acupuncture studies more frequently focus on collecting data from the patients’ perspective and response, but the acupuncturist’s role remains relatively unclear. In order to investigate potential non-mechanical active factors originating from the acupuncturist and transmitted to the patient during treatment, two novel devices for basic research in acupuncture were designed. The Acuplicator allows the researcher to insert needles without touching the needles themselves, while the Veliusator locks the needle in its place so that no mechanical movement can be transferred. METHODS: The Acuplicator was used to insert needles at Neiguan (PC6) on the right forearm of 23 volunteers. The insertion depth was measured using a depth gauge. The transfer of mechanical movements from the handle to the tip was detected with a precision length gauge with a motoric-tactile sensor. RESULTS: The mean insertion depth was (12.3 ± 1.5) mm (range 9.5 to 15.0 mm). Even with intense manipulation of the needle handle, no movements within ± 1 μm could be detected at the tip when the needle was locked. CONCLUSION: With these two devices it will be possible to investigate the influence of non-mechanical components such as therapeutic qi in acupuncture.

Relationship between onset-to-door time and door-to-thrombolysis time: a pooled analysis of 10 dedicated stroke centers

BACKGROUND AND PURPOSE Inverse relationship between onset-to-door time (ODT) and door-to-needle time (DNT) in stroke thrombolysis was reported from various registries. We analyzed this relationship and other determinants of DNT in dedicated stroke centers. METHODS Prospectively collected data of consecutive ischemic stroke patients from 10 centers who received IV thrombolysis within 4.5 hours from symptom onset were merged (n=7106). DNT was analyzed as a function of demographic and prehospital variables using regression analyses, and change over time was considered. RESULTS In 6348 eligible patients with known treatment delays, median DNT was 42 minutes and kept decreasing steeply every year (P<0.001). Median DNT of 55 minutes was observed in patients with ODT ≤30 minutes, whereas it declined for patients presenting within the last 30 minutes of the 3-hour time window (median, 33 minutes) and of the 4.5-hour time window (20 minutes). For ODT within the first 30 minutes of the extended time window (181-210 minutes), DNT increased to 42 minutes. DNT was stable for ODT for 30 to 150 minutes (40-45 minutes). We found a weak inverse overall correlation between ODT and DNT (R(2)=-0.12; P<0.001), but it was strong in patients treated between 3 and 4.5 hours (R(2)=-0.75; P<0.001). ODT was independently inversely associated with DNT (P<0.001) in regression analysis. Octogenarians and women tended to have longer DNT. CONCLUSIONS DNT was decreasing steeply over the last years in dedicated stroke centers; however, significant oscillations of in-hospital treatment delays occurred at both ends of the time window. This suggests that further improvements can be achieved, particularly in the elderly.

Voluntary ingestion of antiparasitic drugs emulsified in honey represents an alternative to gavage in mice

The oral route is the most frequently used method of drug intake in humans. Oral administration of drugs to laboratory animals such as mice typically is achieved through gavage, in which a feeding needle is introduced into the esophagus and the drug is delivered directly into the stomach. This method requires technical skill, is stressful for animals, and introduces risk of injury, pain and morbidity. Here we investigated another method of drug administration. The benzimidazole derivative albendazole was emulsified in commercially available honey and administered to mice by voluntary feeding or gavage. Mice that received albendazole by either gavage or honey ingestion had virtually identical levels of serum albendazole sulfoxide, indicating that uptake and metabolism of albendazole was similar for both administration techniques. In addition, dosing mice with the albendazole-honey mixture for 8 wk had antiparasitic activity comparable to earlier studies using gavage for drug administration. Compared with gavage, voluntary ingestion of a drug in honey is more rapid, less stressful to the animal, and less technically demanding for the administrator. Because of its low cost and ready availability, honey presents a viable vehicle for drug delivery.

Validation of a magnetic resonance imaging guided stereotactic access to the ovine brainstem.

BackgroundAnatomical differences between humans and domestic mammals preclude the use of reported stereotactic approaches to the brainstem in animals. In animals, brainstem biopsies are required both for histopathological diagnosis of neurological disorders and for research purposes. Sheep are used as a translational model for various types of brain disease and therefore a species-specific approach needs to be developed. The aim of the present study was to establish a minimally invasive, accurate and reproducible stereotactic approach to the brainstem of sheep, using the magnetic resonance imaging guided BrainsightTM frameless stereotactic system.ResultsA transoccipital transcerebellar approach with an entry point in the occipital bone above the vermis between the transverse sinus and the external occipital protuberance was chosen. This approach provided access to the target site in all heads. The overall mean needle placement error was 1.85¿±¿1.22 mm.ConclusionsThe developed transoccipital transcerebellar route is short, provides accurate access to the ovine caudal cranial fossa and is a promising approach to be assessed further in live animals.

Treatment of lower extremity telangiectasias in women by foam sclerotherapy vs. Nd:YAG laser: a prospective, comparative, randomized, open-label trial.

BACKGROUND Telangiectasias of the lower extremities are very common. There are no blinded, randomized, controlled clinical trials comparing laser modalities with the gold standard sclerotherapy, while the few available studies encompass small patients cohorts. OBJECTIVE This prospective, randomized, open-label trial compares the efficacy of sclerotherapy with polidocanol vs. long-pulsed neodymium-doped yttrium aluminium garnet (Nd:YAG) laser in the treatment of leg telangiectasias. PATIENTS AND METHODS Fifty-six female patients with primary leg telangiectasias and reticular veins (C1A or S Ep AS 1 PN ) were included in the study. One leg was randomly assigned to get treatment with the multiple synchronized long-pulsed Nd:YAG laser, while the other received foam sclerotherapy with polidocanol 0.5%. The patients were treated in two sessions at intervals of 6 weeks. The patients were evaluated by the handling physician after 6 weeks and 6 months. Two investigators assessed blindly at the end of the study the photographs for clearing of the vessels using a six-point scale from 1 (no change) to 6 (100% cleared). Patients reported about pain sensation and outcome satisfaction. RESULTS According to the handling dermatologist, at the last follow-up, there was an improvement of 30-40% with a median of 3 (IQR 2) and a good improvement of 50-70% with a median of 4 (IQR 2) after laser treatment and sclerotherapy respectively. In contrast, according to the blinded investigators, there was a median of 5 (IQR 1) with a very good improvement of >70% after both therapies. Improvement was achieved more quickly by sclerotherapy, although at the last follow-up visit there was no difference in clearance between the two groups as assessed by the blinded experts (P-value 0.84). The degree of patient's satisfaction was very good and similar with both therapeutic approaches. There was a significant difference (P-value 0.003) regarding pain perception between the types of therapy. Laser was felt more painful than sclerotherapy. CONCLUSION Telangiectasias of the lower extremities can be successfully treated with either synchronized long-pulsed Nd:YAG laser or sclerotherapy. The 1064-nm long-pulsed Nd:YAG laser is associated with more pain and is suitable especially in case of needle phobia, allergy to sclerosants and in presence of small veins with telangiectatic matting, while sclerotherapy can also treat the feeder veins.

Acupuncture for post anaesthetic recovery and postoperative pain: study protocol for a randomised controlled trial.

BACKGROUND We report on the design and implementation of a study protocol entitled Acupuncture randomised trial for post anaesthetic recovery and postoperative pain - a pilot study (ACUARP) designed to investigate the effectiveness of acupuncture therapy performed in the perioperative period on post anaesthetic recovery and postoperative pain. METHODS/DESIGN The study is designed as a randomised controlled pilot trial with three arms and partial double blinding. We will compare (a) press needle acupuncture, (b) no treatment and (c) press plaster acupressure in a standardised anaesthetic setting. Seventy-five patients scheduled for laparoscopic surgery to the uterus or ovaries will be allocated randomly to one of the three trial arms. The total observation period will begin one day before surgery and end on the second postoperative day. Twelve press needles and press plasters are to be administered preoperatively at seven acupuncture points. The primary outcome measure will be time from extubation to 'ready for discharge' from the post anaesthesia care unit (in minutes). The 'ready for discharge' end point will be assessed using three different scores: the Aldrete score, the Post Anaesthetic Discharge Scoring System and an In-House score. Secondary outcome measures will comprise pre-, intra- and postoperative variables (which are anxiety, pain, nausea and vomiting, concomitant medication). DISCUSSION The results of this study will provide information on whether acupuncture may improve patient post anaesthetic recovery. Comparing acupuncture with acupressure will provide insight into potential therapeutic differences between invasive and non-invasive acupuncture techniques. TRIAL REGISTRATION NCT01816386 (First received: 28 October 2012).

Peritonitis, abscessation and haemorrhage: Complications of transcutaneous caecal decompression

Transcutaneous needle decompression of the caecum through the right flank is a valuable, routine procedure performed to resolve cases of large intestinal tympany. Nevertheless, it can be the cause of potentially life-threatening complications as highlighted by the 3 cases presented in this case report. Abscess formation, septic peritonitis and haemorrhage following needle decompression are described.

Multiple myeloma-associated amyloidoma of the sacrum: case report and review of the literature.

Study Design Case report. Objectives With only two previously reported cases, localized amyloidosis of the sacrum is extremely rare. Here we report a 64-year-old woman with a large osteolytic lesion accompanied by weakness and paresthesia of the right leg and difficulties in bladder control. Methods Fine needle biopsy and standard staging procedures revealed a primary solitary amyloidoma that was treated with intralesional resection, lumbopelvic stabilization, and consolidation radiotherapy. Results Clinical follow-up revealed the diagnosis of multiple myeloma 9 months after initial treatment. At 12 months, no local recurrence has occurred, the neurologic symptoms have resolved, and the systemic disease is in remission. Conclusions Intralesional resection with adjuvant radiotherapy of the amyloidoma achieved good local tumor control with limited morbidity.

Electrodiagnostic evaluation in feline hypertrophic muscular dystrophy

Standard needle electromyography (EMG) of 56 muscles and nerve conduction velocities (NCV) of the ulnar and common peroneal nerves were investigated in each of six cats affected with hypertrophic feline muscular dystrophy, 10 related heterozygote carriers and 10 normal cats. The EMG findings were considered normal in carrier and control cats, and consisted of 33% normal readings, 22% myotonic discharges, 18% fibrillation potentials, 11% prolonged insertional potentials, 10% complex repetitive discharges and 6% positive sharp waves in affected cats. Muscles of the proximal limbs were most frequently affected. No differences in NCV were found between the three cat groups. It was concluded that dystrophin-deficient dystrophic cats have widespread and frequent EMG changes, predominantly myotonic discharges and fibrillation potentials, which are most pronounced in the proximal appendicular muscles.

Magnetic resonance imaging features of an extranodal T-cell rich B-cell lymphoma in the pharyngeal mucosa in a horse

An 11-year-old Warmblood gelding was presented for inspiratory stridor and dysphagia. Based on history and clinical examination, a solitary mass localised in the oropharynx was suspected. Due to its inaccessibility and defensive behaviour of the horse, it was difficult to visualise this mass either by upper airway endoscopy or by oral examination and the conventional imaging methods (radiology and ultrasound) provided only limited information. Fine needle aspiration cytology was suggestive of lymphoma, but the exact localisation and the extent of tissue infiltration of the tumour could only be defined by magnetic resonance imaging (MRI). MRI has proved to be a very useful diagnostic tool in equine lameness investigation and, as this case illustrates, it has considerable diagnostic potential for soft tissue examination of the equine head.

Hepatic fungal infection in a young beagle with unrecognised hereditary cobalamin deficiency (Imerslund-Gräsbeck syndrome)

A 12-month-old beagle presented for anorexia, pyrexia and vomiting. The dog had been treated intermittently with antibiotics and corticosteroids for inappetence and lethargy since five months of age. Previous laboratory abnormalities included macrocytosis and neutropenia. At presentation, the dog was lethargic, febrile and thin. Laboratory examination findings included anaemia, a left shift, thrombocytopenia, hypoglycaemia and hyperbilirubinaemia. Multiple, small, hypoechoic, round hepatic lesions were observed on abdominal ultrasound. Cytological examination of hepatic fine needle aspirates revealed a fungal infection and associated pyogranulomatous inflammation. The dog's general condition deteriorated despite supportive measures and treatment with fluconazole, and owners opted for euthanasia before hypocobalaminaemia was identified. Subsequent genomic analysis revealed a CUBN:c.786delC mutation in a homozygous state, confirming hereditary cobalamin malabsorption (Imerslund-Gräsbeck syndrome). Similar to human infants, dogs with Imerslund-Gräsbeck syndrome may rarely be presented for infectious diseases, distracting focus from the underlying primary disorder.

Percutaneous management of left atrial appendage perforation during device closure.

A 76-year-old male patient was admitted for percutaneous left atrial appendage (LAA) closure because of chronic atrial fibrillation and a history of gastrointestinal bleeding under oral anticoagulation. The procedure was complicated by perforation of the LAA with the lobe of the closure device being placed in the pericardial space. Keeping access to the pericardial space with the delivery sheath, the LAA closure device was replaced by an atrial septal defect closure device to seal the perforation. Then the initial LAA closure device was reimplanted in a correct position. Needle pericardiocentesis was required but the subsequent course was uneventful.