Function of Natural Internal Mammary-to-Coronary Artery Bypasses and Its Effect on Myocardial Ischemia.

BACKGROUND The function of naturally existing internal mammary (IMA)-to-coronary artery bypasses and their quantitative effect on myocardial ischemia are unknown. METHODS AND RESULTS The primary end point of this study was collateral flow index (CFI) obtained during two 1-minute coronary artery balloon occlusions, the first with and the second without simultaneous distal IMA occlusion. The secondary study end point was the quantitatively determined intracoronary ECG ST-segment elevation. CFI is the ratio of simultaneously recorded mean coronary occlusive pressure divided by mean aortic pressure both subtracted by mean central venous pressure. A total of 180 pairs of CFI measurements were performed among 120 patients. With and without IMA occlusion, CFI was 0.110±0.074 and 0.096±0.072, respectively (P<0.0001). The difference of CFI obtained in the presence minus CFI obtained in the absence of IMA occlusion was highest and most consistently positive during left IMA with left anterior descending artery occlusion and during right IMA with right coronary artery occlusion (ipsilateral occlusions): 0.033±0.044 and 0.025±0.027, respectively. This CFI difference was absent during right IMA with left anterior descending artery occlusion and during left IMA with right coronary artery occlusion (contralateral occlusions): -0.007±0.034 and 0.001±0.023, respectively (P=0.0002 versus ipsilateral occlusions). The respective CFI differences during either IMA with left circumflex artery occlusion were inconsistently positive. Intracoronary ECG ST-segment elevations were significantly reduced during ipsilateral IMA occlusions but not during contralateral or left circumflex artery occlusions. CONCLUSION There is a functional, ischemia-reducing extracardiac coronary artery supply via ipsilateral but not via contralateral natural IMA bypasses. CLINICAL TRIAL REGISTRATION URL http://www.clinicaltrials.gov. Unique identifier: NCTO1676207.

Rapamycin impairs endothelial cell function in human internal thoracic arteries.

BACKGROUND Definitive fate of the coronary endothelium after implantation of a drug-eluting stent remains unclear, but evidence has accumulated that treatment with rapamycin-eluting stents impairs endothelial function in human coronary arteries. The aim of our study was to demonstrate this phenomenon on functional, morphological and biochemical level in human internal thoracic arteries (ITA) serving as coronary artery model. METHODS After exposure to rapamycin for 20 h, functional activity of ITA rings was investigated using the organ bath technique. Morphological analysis was performed by scanning electron microscopy and evaluated by two independent observers in blinded fashion. For measurement of endothelial nitric oxide synthase (eNOS) release, mammalian target of rapamycin (mTOR) and protein kinase B (PKB) (Akt) activation, Western blotting on human mammary epithelial cells-1 and on ITA homogenates was performed. RESULTS Comparison of the acetylcholine-induced relaxation revealed a significant concentration-dependent decrease to 66 ± 7 % and 36 ± 7 % (mean ± SEM) after 20-h incubation with 1 and 10 μM rapamycin. Electron microscopic evaluation of the endothelial layer showed no differences between controls and samples exposed to 10 μM rapamycin. Western blots after 20-h incubation with rapamycin (10 nM-1 μM) revealed a significant and concentration-dependent reduction of p (Ser 1177)-eNOS (down to 38 ± 8 %) in human mammary epithelial cells (Hmec)-1. Furthermore, 1 μM rapamycin significantly reduced activation of p (Ser2481)-mTOR (58 ± 11 %), p (Ser2481)-mTOR (23 ± 4 %) and p (Ser473)-Akt (38 ± 6 %) in ITA homogenates leaving Akt protein levels unchanged. CONCLUSIONS The present data suggests that 20-h exposure of ITA rings to rapamycin reduces endothelium-mediated relaxation through down-regulation of Akt-phosphorylation via the mTOR signalling axis within the ITA tissue without injuring the endothelial cell layer.

Perceived functional ability assessed with the spinal function sort: is it valid for European rehabilitation settings in patients with non-specific non-acute low back pain?

The aim of this study involving 170 patients suffering from non-specific low back pain was to test the validity of the spinal function sort (SFS) in a European rehabilitation setting. The SFS, a picture-based questionnaire, assesses perceived functional ability of work tasks involving the spine. All measurements were taken by a blinded research assistant; work status was assessed with questionnaires. Our study demonstrated a high internal consistency shown by a Cronbach's alpha of 0.98, reasonable evidence for unidimensionality, spearman correlations of >0.6 with work activities, and discriminating power for work status at 3 and 12 months by ROC curve analysis (area under curve = 0.760 (95% CI 0.689-0.822), respectively, 0.801 (95% CI 0.731-0.859). The standardised response mean within the two treatment groups was 0.18 and -0.31. As a result, we conclude that the perceived functional ability for work tasks can be validly assessed with the SFS in a European rehabilitation setting in patients with non-specific low back pain, and is predictive for future work status.

The Peri-Implant Sulcus Compared with Internal Implant and Suprastructure Components: A Microbiological Analysis

Purpose: A recent in vivo study has shown considerable contamination of internal implant and suprastructure components with great biodiversity, indicating bacterial leakage along the implant-abutment interface, abutment-prosthesis interface, and restorative margins. The goal of the present study was to compare microbiologically the peri-implant sulcus to these internal components on implants with no clinical signs of peri-implantitis and in function for many years. Checkerboard DNA-DNA hybridization was used to identify and quantify 40 species. Material and Methods: Fifty-eight turned titanium Brånemark implants in eight systemically healthy patients (seven women, one man) under regular supportive care were examined. All implants had been placed in the maxilla and loaded with a screw-retained full-arch bridge for an average of 9.6 years. Gingival fluid samples were collected from the deepest sulcus per implant for microbiological analysis. As all fixed restorations were removed, the cotton pellet enclosed in the intra-coronal compartment and the abutment screw were retrieved and microbiologically evaluated. Results: The pellet enclosed in the suprastructure was very similar to the peri-implant sulcus in terms of bacterial detection frequencies and levels for practically all the species included in the panel. Yet, there was virtually no microbial link between these compartments. When comparing the abutment screw to the peri-implant sulcus, the majority of the species were less frequently found, and in lower numbers at the former. However, a relevant link in counts for a lot of bacteria was described between these compartments. Even though all implants in the present study showed no clinical signs of peri-implantitis, the high prevalence of numerous species associated with pathology was striking. Conclusions: Intra-coronal compartments of screw-retained fixed restorations were heavily contaminated. The restorative margin may have been the principal pathway for bacterial leakage. Contamination of abutment screws most likely occurred from the peri-implant sulcus via the implant-abutment interface and abutment-prosthesis interface.

7-year follow-up after open reduction and internal screw fixation in Bennett fractures

Bennett fractures are unstable, and, with inadequate treatment, lead to osteoarthritis, weakness and loss of function of the first carpometacarpal joint. This study focuses on long-term functional and radiological outcomes after open reduction and internal fixation.

Complex genital system of a haplogyne spider (Arachnida, Araneae, Tetrablemmidae) indicates internal fertilization and full female control over transferred sperm

The female genital organs of the tetrablemmid Indicoblemma lannaianum are astonishingly complex. The copulatory orifice lies anterior to the opening of the uterus externus and leads into a narrow insertion duct that ends in a genital cavity. The genital cavity continues laterally in paired tube-like copulatory ducts, which lead into paired, large, sac-like receptacula. Each receptaculum has a sclerotized pore plate with associated gland cells. Paired small fertilization ducts originate in the receptacula and take their curved course inside the copulatory ducts. The fertilization ducts end in slit-like openings in the sclerotized posterior walls of the copulatory ducts. Huge masses of secretions forming large balls are detectable in the female receptacula. An important function of these secretory balls seems to be the encapsulation of spermatozoa in discrete packages in order to avoid the mixing of sperm from different males. In this way, sperm competition may be completely prevented or at least severely limited. Females seem to have full control over transferred sperm and be able to express preference for spermatozoa of certain males. The lumen of the sperm containing secretory balls is connected with the fertilization duct. Activated spermatozoa are only found in the uterus internus of females, which is an indication of internal fertilization. The sperm cells in the uterus internus are characterized by an extensive cytoplasm and an elongated, cone-shaped nucleus. The male genital system of I. lannaianum consists of thick testes and thin convoluted vasa deferentia that open into the wide ductus ejaculatorius. The voluminous globular palpal bulb is filled with seminal fluid consisting of a globular secretion in which only a few spermatozoa are embedded. The spermatozoa are encapsulated by a sheath produced in the genital system. The secretions in females may at least partly consist of male secretions that could be involved in the building of the secretory balls or play a role in sperm activation. The male secretions could also afford nutriments to the spermatozoa.

Limited open reduction and internal fixation of displaced intra-articular fractures of the calcaneum

The extended lateral L-shaped approach for the treatment of displaced intra-articular fractures of the calcaneum may be complicated by wound infection, haematoma, dehiscence and injury to the sural nerve. In an effort to reduce the risk of problems with wound healing a technique was developed that combined open reduction and fixation of the joint fragments and of the anterior process with percutaneous reduction and screw fixation of the tuberosity. A group of 24 patients with unilateral isolated closed Sanders type II and III fractures was treated using this technique and compared to a similar group of 26 patients managed by the extended approach and lateral plating. The operation was significantly shorter (p < 0.001) in the first group, but more minor secondary procedures and removal of heel screws were necessary. There were no wound complications in this group, whereas four minor complications occurred in the second group. The accuracy and maintenance of reduction, and ultimate function were equivalent.

Prognostic clinical and radiological parameters for immediate facial nerve function following vestibular schwannoma surgery

OBJECTIVE: The paper aims to define the parameters available before surgery which could predict immediate facial nerve function after excision of a vestibular schwannoma (VS). METHODS: Ninety-nine patients with VS operated consecutively by a single surgeon using an identical surgical technique have been evaluated retrospectively. Data were collected regarding patients' sex, age at onset of symptoms and at surgery, initial symptoms, neurological status at presentation, early post-operative neurological status and complications. The main radiological parameters included in the study were tumour extension pattern, diameters, shape, and volume, as well as extent of bony changes of the internal auditory canal. RESULTS: As the tumour stage and volume increase, facial nerve function is worse after surgery (p < 0.001 and p < 0.05, respectively). Concomitantly, larger extra-meatal tumour diameters in three dimensions (sagittal, coronal and axial) led to worse function (p < 0.01). Anterior and/or caudal tumour extension (p = 0.001 and p = 0.004, respectively) had more significant correlation than posterior and/or cranial extension (p = 0.022 and p = 0.353, respectively). Polycyclic VS had the worst prognosis, followed by the tumours with oval shape. The extent of intra-meatal tumour growth does not correlate with immediate facial nerve outcome. The different angles, lengths and diameters of the internal auditory channel showed no significant correlation with facial nerve outcome. Patients with headache as an initial symptom and those with gait instability and/or pre-operative poor facial nerve function had significantly worse immediate facial nerve outcome. CONCLUSION: Our data suggests that the analysis of the radiological and neurological patient data prior to surgery could give reliable clues regarding the immediate post-operative facial nerve function.

Frameless linac-based (Novalis TX) stereotactic treatment for vestibular schwannoma that extend distally into the iac (Internal Acoustic Canal): an analysis of the dose to the cochlea

Objectives: We compare the dose parameters between 3 different radiosurgery delivery techniques which may have an impact on cochlea function. Methods: Five patients with unilateral vestibular schwannoma (VS) were selected for this study. Planning procedure was carried out using the BrainLAB® iPlan planning system v. 4.5. For each patient three different planning techniques were used: dynamic arc (DA) with 5 arcs per plan, hybrid arc (HA) with 5 arcs per plan and IMRT with 8 fields per plan. For each technique, two plans were generated with different methods: with the first method (PTV coverage) it was the goal to fully cover the PTV with at least 12 Gy (normalization: 12 Gy covered 99% of the PTV) and with the second method (cochlea sparing) it was the goal to spare the cochlea (normalization: 12 Gy covers 50% of the PTV/V4Gy of cochlea lower than 1%). Plan evaluation was done considering target volume and coverage (conformity and homogeneity) and OAR constraints (mean (Dmean) and maximum dose (Dmax) to cochlea, Dmax to brainstem and cochlea). The total number of monitor units (MU) was analyzed. Results: The median tumor volume was 0.95 cm³ (range, 0.86-3 cm³). The median PTV was 1.44 cm³ (range, 1-3.5 cm³). The median distance between the tumor and the cochlea's modiulus was 2.7 mm (range, 1.8-6.3 mm). For the PTV coverage method, when we compared the cochlear dose in VS patients planned with DA, HA and IMRT, there were no significant differences in Dmax (p = 0.872) and in Dmean (p= 0.860). We found a significant correlation (p< 0.05) between the target volume and the cochlear Dmean for all plans with Pearson's coefficient correlation of 0.90, 0.92 and 0.94 for the DA, HA and IMRT techniques, respectively. For the cochlea sparing method, when we compared the cochlear dose in VS patients planned with DA, HA and IMRT, there were no significant differences in Dmax (p = 0.310) and in Dmean (p= 0.275). However, in this group the V4Gy of the ipsilateral cochlea represents less than 1%. When using the HA or IMRT technique, the homogeneity and conformity in the PTV, but also the number of MUs were increased in comparison to the DA technique. Conclusion: VS tumors that extend distally into the IAC had an equivalent sparing of cochlea with DA approach compared with the HA and IMRT techniques. Disclosure: No significant relationships.

Immunization against gonadotropin-releasing hormone in dairy cattle: Antibody titers, ovarian function, hormonal levels, and reversibility

Suppression of cyclic activity in cattle is often desired in alpine farming and for feedlot cattle not intended for breeding. A cattle-specific anti-GnRH vaccination (Bopriva, Zoetis Australia Ltd., West Ryde, Australia) is approved for use in heifers and bulls in New Zealand, Australia, Mexico, Brazil, Argentina, Turkey, and Peru. Eleven healthy, cyclic Swiss Fleckvieh cows were included in the study and vaccinated twice with Bopriva 4wk apart. Injection site, rectal body temperature, and heart and respiratory rates were recorded before and 3d following each vaccination. Blood samples were taken weekly for progesterone and estrogen analysis and to determine GnRH antibody titer. Ovaries were examined weekly, using ultrasound to count the number of follicles and identify the presence of a corpus luteum. Thirty weeks after the first vaccination, the cows were subjected to a controlled internal drug-releasing device-based Select-Synch treatment. The GnRH antibody titers increased after the second vaccination and peaked 2wk later. Estrogen levels were not influenced by vaccination, and progesterone level decreased in 7 of 11 cows up to 3wk after the second vaccination and remained low for 10 to 15wk following the second vaccination. The number of class I follicles (diameter ≤5mm) was not influenced by vaccination, whereas the number of class II follicles (diameter 6-9mm) decreased between 7 and 16wk after the first vaccination. Class III follicles (diameter >9mm) were totally absent during this period in most cows. The median period until recurrence of class III follicles was 78d from the day of the second vaccination (95% confidence interval: 60-92d). After vaccination, all cows showed swelling and pain at the injection site, and these reactions subsided within 2wk. Body temperature and heart and respiratory rates increased after the first and second vaccinations and returned to normal values within 2d of each vaccination. The cows in our study were not observed to display estrus behavior until 30wk after the first vaccination. Therefore, a Select-Synch protocol was initiated at that time. Ten cows became pregnant after the first insemination (the remaining cow was reinseminated once until confirmed pregnancy). Bopriva induced a reliable and reversible suppression of reproductive cyclicity for more than 2mo. The best practical predictor for the length of the anestrus period was the absence of class III follicles.

Osteotomy of the greater trochanter: effect on gluteus medius function

PURPOSE Advancement of the greater trochanter alters the function of the gluteus medius muscle. However, with the exception of clinical studies and biomechanical lever arm studies, no publications that analyze the consequences of advancement of the greater trochanter on the muscle function exist. The aim of the study was to analyze the mechanical changes of gluteus medius after osteotomy of the greater trochanter in a lab setting. METHODS An anatomical study of origin and insertion of the gluteus medius was carried out on four hips. Based on the dissections, a string model was developed dividing the muscle into five sectors. Changes in muscle fiber length were measured for every 10° of flexion, internal and external rotation and abduction with the trochanter in anatomic, proximalized and distalized positions. RESULTS Distalization of the trochanter leads to an imbalance of muscle action, moving the isometric sector of the muscle anteriorly with more muscle sectors being active during flexion and less during extension. Stretching of the muscle increases passive forces but decreases the force generation capacity of the muscle and at the same time increased muscle fiber excursion may require more energy consumption, which may explain earlier fatigue of the abductor musculature after distalization of the trochanter. For abduction, distalization of the muscle attachment leads to a change in contraction pattern from isometric to isotonic. Optimal balancing and excursion of the muscle is when the tip of the greater trochanter is at level with the hip rotation center. CONCLUSIONS In hips with high riding trochanter, the optimal position is at the level of the center of hip rotation. Excessive distalization should be avoided. As the conclusions and considerations are based on a lab setting, transfer to clinical practice may not necessarily apply.

Relative femoral neck lengthening improves pain and hip function in proximal femoral deformities with a high-riding trochanter

BACKGROUND Complex proximal femoral deformities, including an elevated greater trochanter, short femoral neck, and aspherical head-neck junction, often result in pain and impaired hip function resulting from intra-/extraarticular impingement. Relative femoral neck lengthening may address these deformities, but mid-term results of this approach have not been widely reported. QUESTIONS/PURPOSES Do patients who have undergone relative femoral neck lengthening show (1) less hip pain and greater function; (2) improved radiographic parameters; (3) significant complications requiring subsequent surgery; and (4) progression of osteoarthrosis (OA) or conversion to total hip arthroplasty (THA) at mid-term followup? METHODS We retrospectively reviewed 40 patients (41 hips) with isolated relative femoral neck lengthening between 1998 and 2006 with sequelae of Legg-Calvé-Perthes disease (38 hips [93%]), slipped capital femoral epiphysis (two hips [5%]), and postseptic arthritis (one hip [2%]). During this time, the general indications for this procedure included a high-riding greater trochanter with a short femoral neck with abductor weakness and symptomatic intra-/extraarticular impingement. Mean patient followup was 8 years (range, 5-13 years), and complete followup was available in 38 patients (39 hips [95%]). We evaluated pain and function with the impingement test, limp, abductor force, Merle d'Aubigné-Postel score, and range of motion. Radiographic parameters included trochanteric height, alpha angle, and progression of OA. Subsequent surgeries, complications, and conversion to THA were summarized. RESULTS The proportion of positive anterior impingement tests decreased from 93% (38 of 41 hips) preoperatively to 49% (17 of 35 hips) at latest followup (p = 0.002); the proportion of limp decreased from 76% (31 of 41 hips) to 9% (three of 35 hips; p < 0.001); the proportion of normal abductor strength increased from 17% (seven of 41 hips) to 91% (32 of 35 hips; p < 0.001); mean Merle d'Aubigné-Postel score increased from 14 ± 1.7 (range, 9-17) to 17 ± 1.5 (range, 13-18; p < 0.001); mean internal rotation increased to 25° ± 15° (range, 0°-60°; p = 0.045), external rotation to 32° ± 14° (range, 5°-70°; p = 0.013), and abduction to 37° ± 13° (range, 10°-50°; p = 0.004). Eighty percent of hips (33 of 41 hips) showed normal trochanteric height; alpha angle improved to 42° ± 10° (range, 27°-90°). Two hips (5%) had subsequent surgeries as a result of lack of containment; four of 41 hips (10%) had complications resulting in reoperation. Fourteen of 35 hips (40%) showed progression of OA; four of 40 hips (10%) converted to THA. CONCLUSIONS Relative femoral neck lengthening in hips with combined intra- and extraarticular impingement results in reduced pain, improved function, and improved radiographic parameters of the proximal femur. Although lack of long-term complications is gratifying, progression of OA was not prevented and remains an area for future research.

Temporary Internal Fixation for Ligamentous and Osseous Lisfranc Injuries: Outcome and Technical Tip

BACKGROUND Open rather than closed reduction and internal fixation as well as primary definitive arthrodesis are well accepted for ligamentous and osseous Lisfranc injuries. For ligamentous injuries, a better outcome after primary definitive partial arthrodesis has been published. METHODS Of 135 Lisfranc injuries that were treated from 1998 to 2012 with open reduction, temporary internal fixation by screws and plates, and restricted weight bearing in a lower leg cast for 3 months followed by an arch support for another 4 to 6 weeks, 29 ligamentous Lisfranc injuries were available for follow-up. They were compared with 29 osseous Lisfranc injuries matched in age and gender. RESULTS Between the groups, there were no significant differences in average age (39.9 vs 38 years) or in average follow-up time (8.3 vs 9.1 years). Also, no significant differences were seen in the AOFAS midfoot score (84 vs 85.3 points), the FFI pain scale (9.9 vs 14.9 points), SF 36 physical component (56.2 vs 53.9 points), SF 36 mental component (57 vs 56.4 points), or VAS for pain (1.6 vs 1.5 points). The FFI function scale was significantly lower in the ligamentous group (11.6 vs 19.5 points). Radiographically, loss of reduction was recorded 3 times in the ligamentous injuries and 4 times in the osseous injuries. Arthritis was mild/moderate/severe in 5/3/0 ligamentous injuries and in 7/2/1 osseous injuries, requiring 1 definitive secondary Lisfranc arthrodesis in each group. CONCLUSION With longer and conservative postoperative management, open reduction and temporary internal fixation in ligamentous and osseous Lisfranc injuries led to equal medium-term outcome. Inferior outcome in ligamentous injuries was not found. LEVEL OF EVIDENCE Level III, retrospective comparative cohort study.

Thyroid function within the normal range and risk of coronary heart disease: an individual participant data analysis of 14 cohorts

IMPORTANCE Some experts suggest that serum thyrotropin levels in the upper part of the current reference range should be considered abnormal, an approach that would reclassify many individuals as having mild hypothyroidism. Health hazards associated with such thyrotropin levels are poorly documented, but conflicting evidence suggests that thyrotropin levels in the upper part of the reference range may be associated with an increased risk of coronary heart disease (CHD). OBJECTIVE To assess the association between differences in thyroid function within the reference range and CHD risk. DESIGN, SETTING, AND PARTICIPANTS Individual participant data analysis of 14 cohorts with baseline examinations between July 1972 and April 2002 and with median follow-up ranging from 3.3 to 20.0 years. Participants included 55,412 individuals with serum thyrotropin levels of 0.45 to 4.49 mIU/L and no previously known thyroid or cardiovascular disease at baseline. EXPOSURES Thyroid function as expressed by serum thyrotropin levels at baseline. MAIN OUTCOMES AND MEASURES Hazard ratios (HRs) of CHD mortality and CHD events according to thyrotropin levels after adjustment for age, sex, and smoking status. RESULTS Among 55,412 individuals, 1813 people (3.3%) died of CHD during 643,183 person-years of follow-up. In 10 cohorts with information on both nonfatal and fatal CHD events, 4666 of 48,875 individuals (9.5%) experienced a first-time CHD event during 533,408 person-years of follow-up. For each 1-mIU/L higher thyrotropin level, the HR was 0.97 (95% CI, 0.90-1.04) for CHD mortality and 1.00 (95% CI, 0.97-1.03) for a first-time CHD event. Similarly, in analyses by categories of thyrotropin, the HRs of CHD mortality (0.94 [95% CI, 0.74-1.20]) and CHD events (0.97 [95% CI, 0.83-1.13]) were similar among participants with the highest (3.50-4.49 mIU/L) compared with the lowest (0.45-1.49 mIU/L) thyrotropin levels. Subgroup analyses by sex and age group yielded similar results. CONCLUSIONS AND RELEVANCE Thyrotropin levels within the reference range are not associated with risk of CHD events or CHD mortality. This finding suggests that differences in thyroid function within the population reference range do not influence the risk of CHD. Increased CHD risk does not appear to be a reason for lowering the upper thyrotropin reference limit.