Did implementation of three ligament tenodesis improve patient outcome after chronic scapholunate instability? A retrospective study.

INTRODUCTION: Scapholunate instability frequently leads to chronic pain or even severe osteoarthritis of the wrist. Most favored reconstruction techniques of chronic SL-ligament injuries are based on the usage of a tendon, although there is still a lack of consensus which technique is superior. MATERIALS AND METHODS: In a retrospective cohort analysis we compared 9 patients who underwent SL-ligament repair according to Van den Abbeele and 12 patients who underwent modified three ligament tenodesis according to Garcia-Elias, performed at a single institution. RESULTS: Follow-up of Van den Abbeele group was 36-120 months and 13-39 months in the Garcia Elias cohort. Although both techniques showed good functional outcome in most cases, modified three ligament tenodesis seemed to be advantageous regarding wrist range of motion (162°) compared to Van den Abbeele cohort (87°). Moreover, pain score showed significant differences between the two cohorts during follow up (VAS Van den Abbeele 4.2; VAS Garcia Elias 1.7). Interestingly, DASH-score (16.1 Van den Abbeele; 16.8 Garcia Elias) and modified mayo wrist score (72 Van den Abbeele; 69 Garcia-Elias) did not show any differences between the two patient cohorts. CONCLUSIONS: Via implementation of modified three ligament tenodesis as a standard of care for our patients we could improve the functional outcome after SL-ligament injuries and effectively decrease postoperative pain.

Label-free screening of single biomolecules through resistive pulse sensing technology for precision medicine applications.

Employing integrated nano- and microfluidic circuits for detecting and characterizing biological compounds through resistive pulse sensing technology is a vibrant area of research at the interface of biotechnology and nanotechnology. Resistive pulse sensing platforms can be customized to study virtually any particle of choice which can be threaded through a fluidic channel and enable label-free single-particle interrogation with the primary read-out signal being an electric current fingerprint. The ability to perform label-free molecular screening with single-molecule and even single binding site resolution makes resistive pulse sensing technology a powerful tool for analyzing the smallest units of biological systems and how they interact with each other on a molecular level. This task is at the core of experimental systems biology and in particular 'omics research which in combination with next-generation DNA-sequencing and next-generation drug discovery and design forms the foundation of a novel disruptive medical paradigm commonly referred to as personalized medicine or precision medicine. DNA-sequencing has approached the 1000-Dollar-Genome milestone allowing for decoding a complete human genome with unmatched speed and at low cost. Increased sequencing efficiency yields massive amounts of genomic data. Analyzing this data in combination with medical and biometric health data eventually enables understanding the pathways from individual genes to physiological functions. Access to this information triggers fundamental questions for doctors and patients alike: what are the chances of an outbreak for a specific disease? Can individual risks be managed and if so how? Which drugs are available and how should they be applied? Could a new drug be tailored to an individual's genetic predisposition fast and in an affordable way? In order to provide answers and real-life value to patients, the rapid evolvement of novel computing approaches for analyzing big data in systems genomics has to be accompanied by an equally strong effort to develop next-generation DNA-sequencing and next-generation drug screening and design platforms. In that context lab-on-a-chip devices utilizing nanopore- and nanochannel based resistive pulse-sensing technology for DNA-sequencing and protein screening applications occupy a key role. This paper describes the status quo of resistive pulse sensing technology for these two application areas with a special focus on current technology trends and challenges ahead.

Optimizing remote ischemic conditioning (RIC) of cutaneous microcirculation in humans: Number of cycles and duration of acute effects.

OBJECTIVE: Non-invasive Remote Ischemic Conditioning (RIC) offers an approach to reduce tissue damage in various organs/tissues. Besides attenuation of Ischemia-Reperfusion injury (I/R), beneficial effects on cutaneous microcirculation of free microsurgical flaps have been reported. Given the recency of this technique, there are considerable gaps in the current understanding of its mechanism of action. As a result, clinical transfer of RIC is prolongated in several fields. We aimed to optimize the RIC protocol by examination of different RIC-cycle numbers and its effect on changes of cutaneous microcirculation and duration. METHODS: 80 subjects were divided into groups (1, 3, 5, 7 RIC cycles). RIC was applied via an inflatable tourniquet. Cutaneous microcirculation was continuously assessed at the contralateral anterior lateral thigh utilizing a ©O2C-device continuously. RESULTS: RIC caused significant and sustained changes in microcirculation. Four hours after completion of RIC, a maximum increase of +80.8% (CI 1.395-2.221) in blood flow and +23.5% (CI 1.098-1.372) in tissue oxygen saturation was measured (three-cycle group). A higher number of applied cycles was accompanied with significant higher mean pain. CONCLUSION: Acute improvement of cutaneous microcirculation due to RIC lasted for at least 4 h after completion of the RIC-protocol. Dose-dependent effects of RIC are likely. With regard to the increase in pain, we recommend a RIC protocol of 3 cycles for future clinical application.

The effect of fenofibrate on HDL cholesterol and HDL particle concentration in postmenopausal women on tibolone therapy.

BACKGROUND: Low high-density lipoprotein (HDL) cholesterol and particle concentration are risk factors for coronary heart disease in women. Tibolone lowers HDL cholesterol and HDL particle concentration, an effect that could be reversed by the peroxisome proliferator-activator receptor-α agonist fenofibrate. OBJECTIVE: To assess the effects of fenofibrate on plasma HDL particles in postmenopausal women taking tibolone therapy. DESIGN AND PARTICIPANTS: Randomized crossover study conducted in a women's health clinic. Fourteen postmenopausal women taking tibolone 2.5 mg daily for menopausal symptoms were randomized to either fenofibrate 160 mg daily or no treatment for 8 weeks, followed by a 3-week wash-out for fenofibrate and then crossed over to alternate therapy for another 8 weeks. The main outcome measure was changes in plasma HDL cholesterol concentration, apoA-I and apoA-II, LpA-I and LpA-I-A-II. RESULTS: After 8 weeks of fenofibrate therapy, there was no change in HDL cholesterol, 1.13 ± 0.06 v 1.16 ± 0.06 mmol/l (P = 0.47) or apoA-I, 1.19 ± 0.05 v 1.20 ± 0.05 g/l (P = 0.23). LpA-I fell significantly 0.35 ± 0.03 v 0.29 ± 0.02 (P = 0.02) but there was a rise in apoA-II, 0.35 ± 0.01 v 0.39 ± 0.01 g/l (P = 0.01). There was a significant fall in total cholesterol, triglycerides, low-density lipoprotein cholesterol and apoB. CONCLUSION: In women taking tibolone, fenofibrate increases plasma apoA-II concentration and effects a redistribution of HDL subfractions but does not correct tibolone-induced changes in HDL cholesterol or HDL particle concentration. The mechanism and significance of this require further investigation.

Myostatin serum concentration as an indicator for deviated muscle metabolism in severe burn injuries.

INTRODUCTION: Patients experiencing thermal injuries with an extent of over 20% of total body surface area suffer from systemic catabolic disease. The thermal trauma-induced loss of muscle mass causes a higher incidence for comorbidities and subsequently a higher mortality. In this study, we aimed to investigate the role of myostatin in the interplay with follistatin during muscle cachexia. METHODS: Patients with burn injuries (>10% total body surface area) between the ages of 18 and 75 were prospectively included within the first 48 h after trauma to determine deviations of parameters connected to muscle catabolism. In the chronic state of burn injury (9-12 months after trauma), we re-evaluated myostatin and follistatin concentrations as well as muscle strength of the non-dominant forearm. RESULTS: We were able to show a time-dependent alteration (9-12 months after burn injury) of myostatin with an initial decrease (p < 0.001) and long-term increase (p < 0.001) after thermal injury in blood serum. For follistatin, a reciprocal correlation was observed (r = -0.707, p = 0.001). Accordingly, muscle strength of the non-dominant hand and forearm was significantly decreased 9-12 months after injury in post-burn patients compared with healthy patients with a significant correlation to myostatin levels (r = -0.899, p < 0.001). In addition, initial myostatin serum concentration was predictive for long-term muscle strength impairment. CONCLUSION: With regard to the muscle metabolism after thermal trauma, our data suggest an acute anabolic response, presumably to spare muscle mass, which is converted to catabolic conditions accompanied by muscle strength reduction in the chronic phase. Myostatin plays a crucial role in this orchestration and initial myostatin concentration may predict the long-term muscle strength.

[Regulation of bone metabolism by the Wnt signaling pathway]. / Regulation des Knochenstoffwechsels durch den Wnt-Signalweg.

The development and homeostasis of multicellular organisms depends on a complex cellular interaction between proliferation, migration, differentiation, adhesion, and cell death. Wnt signaling pathways coordinate these different cellular responses. Wnt signaling plays a role as a regulatory pathway in the osteogenic differentiation of mesenchymal stem cells. The Wnt signaling pathway is an attractive therapeutic target with the potential to directly modulate stem cells responsible for the regeneration of skeletal tissue. Recent studies indicate that Wnt ligands are capable of promoting bone growth, suggesting that Wnt factors could be used to stimulate bone healing in osteogenic disorders.

Localization of eosinophil-derived neurotoxin and eosinophil cationic protein in neutrophilic leukocytes.

Eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) are generally regarded as eosinophil-specific proteins. We tested whether EDN and ECP are present in mature neutrophils. By indirect immunofluorescence, both eosinophils and neutrophils stained with antibodies to EDN and ECP. Lysates of purified (<0.1% eosinophil contamination) neutrophils contained EDN, 112+/-4 ng/10(6) cells, and ECP, 163+/-2 ng/10(6) cells, whereas eosinophil major basic protein (MBP) was not detectable. Electron microscopic examination of immunogold-labeled buffy coat cells stained with EDN antibody showed that EDN is localized to neutrophil granules. Finally, EDN mRNA was detected in lysates of highly purified neutrophils (0.001% eosinophil contamination) by the reverse transcription-polymerase chain reaction. We conclude that proteins that are either identical to or immunologically cross-reactive with EDN and ECP are present in neutrophils and that EDN is synthesized and localized to neutrophil granules. Thus, caution must be exercised in interpreting the presence of EDN and ECP as specific markers of eosinophil-associated inflammation in human disease.

Pregnancy-associated major basic protein: deposition of protein and expression of mRNA at the maternal-fetal junction in early and late gestation.

Pregnancy-associated major basic protein (pMBP) has previously been isolated from human placenta and localized to the X cell. Here we used immunofluorescence staining and in situ hybridization to determine the distribution of pMBP and pMBP mRNA throughout the maternal-fetal junction in both early gestation tissues and at term. In early gestation tissues, pMBP was present only at the placental insertion site. Specifically, pMBP was present in (a) the decidua basalis (in the extracellular space, in interstitial pools and inside endometrial glands) and (b) intracellularly within extravillous interstitial trophoblasts in the decidua, in the myometrium and surrounding but not within luminal cells of spiral arteries. At term, the placental bed showed intense extracellular pMBP staining with little intracellular pMBP. In situ hybridization showed the presence of pMBP mRNA in both the early and late gestational tissues. pMBP mRNA was present in cells in the decidua, at the decidual-myometrial junction and in cell islands. Quantitative image analysis showed statistically significant hybridization signals with the pMBP antisense probe as compared to the control/sense probe. These results indicate that pMBP mRNA is expressed and pMBP is extensively deposited at the maternal-fetal junction in early pregnancy and at term.

Plasma levels of eosinophil granule major basic protein in pregnant cynomolgus monkeys.

The sera of all pregnant women contain increased amounts of a protein biochemically and immunologically similar to the eosinophil granule major basic protein (MBP). Immunofluorescence shows that the pregnancy-associated MBP is localized to placental trophoblastic cells. This information raises important questions about the function of pregnancy-associated MBP because of the potential biological functions attributed to its eosinophil counterpart (namely, its potent toxic and cytostimulatory activities). Previous studies demonstrated the presence of an immunologically cross-reactive protein in the placentae and plasma of pregnant non-human primates. Here, plasma MBP levels were measured throughout gestation in cynomolgus monkeys. In early pregnancy, only modest increases in MBP were found in contrast to the sharp rise observed in the first 20 weeks of human pregnancy. During the final one-third of gestation, striking increases in plasma MBP occurred in the monkeys. This parallels the late rise in MBP seen in humans in the third trimester. Thus, the cynomolgus monkey may serve as a model to clarify the role of the MBP in the biochemical events that culminate in parturition.

Analysis of pregnancy-associated major basic protein levels throughout gestation.

Previous studies have shown that MBP levels rise before labour and have suggested the use of pMBP levels as a predictor of labour. We hypothesize that pMBP levels show a common pattern in pregnant women including a late third trimester rise in pMBP which predicts the onset of labour. Serum pMBP levels were measured throughout gestation in 112 pregnant women. We then analysed the relationship of pMBP levels to the time of labour onset, and to other features of pregnancy. An exponential increase in pMBP levels was seen early in gestation from weeks 5 to 21 in all pregnant women. In total, 79 per cent of the women showed rises in pMBP of > or = 25 per cent above baseline during the third trimester. pMBP levels were shown to be associated with placental weight, multiple gestation, and parity. pMBP levels could not, however, be used to form a precise model for the prediction of labour. The role of pMBP in pregnancy remains unclear.

Placental site trophoblastic tumor: human placental lactogen and pregnancy-associated major basic protein as immunohistologic markers.

Placental site trophoblastic tumor (PSTT) consists of a neoplastic proliferation of intermediate or extravillous trophoblast (also known as X cells). Pregnancy-associated major basic protein (pMBP) is a marker for placental intermediate trophoblast. We compared the distribution of pMBP and human placental lactogen (hPL) in 24 PSTT and 3 exaggerated placental site (EPS) specimens using two distinct immunohistologic methods. Statistical analyses were used to compare staining intensities in metastatic and nonmetastatic lesions. By immunofluorescence, 77% of the PSTT specimens and 100% of the EPS specimens stained with antibodies to pMBP, and the pMBP was localized in intermediate trophoblast and surrounding extracellular areas. By immunohistochemistry, 78% of the PSTT specimens and 100% of the EPS specimens stained for pMBP with a pattern comparable with that of immunofluorescence. Likewise, by immunohistochemistry, hPL stained 96% of the PSTT specimens and 100% of the EPS specimens. Immunohistochemical staining intensities for pMBP and hPL correlated (r2 = +.24; P = .013), but hPL staining was mainly confined to intermediate trophoblast and was more intense. Anti-pMBP tended to stain metastatic PSTT weakly. Thus, pMBP is a useful marker for intermediate trophoblast tumors and could help distinguish these from other forms of trophoblastic disease.

Localization of eosinophil granule major basic protein in paracoccidioidomycosis lesions.

Paracoccidioidomycosis is a chronic granulomatous disease caused by the fungus Paracoccidioides brasiliensis. Although eosinophils have long been associated with the immune defense against helminths, the role of eosinophils in the immune response to fungal diseases is not as well studied. The eosinophil granule major basic protein is toxic to helminths and mammalian cells in vitro, and its release has been used as a marker of eosinophil localization and degranulation. To determine whether eosinophil infiltration and degranulation, as evidenced by the deposition of major basic protein, occur in lesions of P. brasiliensis, we used an immunofluorescence technique to localize the P. brasiliensis organisms and eosinophils and major basic protein. Initially, all tissues were stained with polyclonal antibody to major basic protein; subsequently, colocalization of major basic protein and P. brasiliensis by double staining with mouse and rabbit antibodies, respectively, was performed. Nine biopsy tissues from seven patients were analyzed. All nine biopsies showed infiltration of intact eosinophils using both the monoclonal and the polyclonal anti-major basic protein antibodies, along with the presence of P. brasiliensis. Furthermore, using the polyclonal anti-major basic protein antibody, nine of nine tissues showed extracellular major basic protein deposition (granular or diffuse fluorescence staining outside of intact eosinophils). The double staining procedure using the anti-major basic protein monoclonal antibody showed extracellular deposition in five of eight biopsies; in these five biopsies, approximately 60% of the areas containing P. brasiliensis had extracellular major basic protein deposited on the organisms. These observations support the hypothesis that the eosinophil, through toxic granule proteins such as major basic protein, participates in the pathophysiology of paracoccidioidomycosis.

Prevalence and significance of acanthosis nigricans in an adult obese population.

BACKGROUND AND DESIGN: Acanthosis nigricans develops commonly in obese individuals, yet its prevalence and significance in an unselected adult obese population has not been determined. To address these issues, 34 patients enrolled in the Adult Obesity Clinic at Parkland Memorial Hospital (Dallas, Tex) were chosen at random and examined. RESULTS: Acanthosis nigricans was observed in fully 74% of patients; its prevalence correlated positively with severity of obesity. Black obese patients demonstrated a greater propensity for manifesting the cutaneous disorder than did white obese individuals. Patients with acanthosis nigricans exhibited fasting plasma insulin levels that were markedly higher than those of nonacanthotic cohorts. CONCLUSIONS: Obesity is a significant risk factor for the development of acanthosis nigricans. Conversely, acanthosis nigricans is a reliable cutaneous marker of hyperinsulinemia in obese individuals.

Analyzing and adjusting for variables in a large-scale standardized-patient examination.

BACKGROUND: Structuring a clinical performance examination that uses standardized patients (SPs) for large groups of examinees often involves the use of two or more parallel forms of the examination with different SPs portraying the same case on the different forms. In addition, each form may be administered more than once on different days and/or in different locations. METHOD: To determine the effects of critical variables, such as day of examination, time of day (AM/PM), which of two simultaneous forms were taken, and sequencing effects, a univariate nested factorial analysis of variance was conducted for each of four annual SP examinations (1990-1993) at the University of Texas Southwestern Medical School. The examinations were given to approximately 200 second-year students per year at the end of their Introduction to Clinical Medicine course, and were graded on a pass/fail basis. RESULTS: Statistically significant differences were found for the following variables: (1) time of day (AM or PM) and day were significant but were inconsistent and of small magnitude; (2) sequencing for the first two stations was significant in each form of the examination and in all four years; and (3) form-within-case differences (i.e., differences between SPs) were significant between the two forms of the examination in each year of administration. To minimize the impacts of these variables, two mean equating formulas were applied to the scores. Few examinees' pass/fail status would have been affected by either adjustment. CONCLUSION: The parallel-forms examination format is minimally affected by the variables evaluated and is a fair pass/fail assessment of a student's performance. Mean equating is a valuable tool in minimizing the possibly unfair impact of variables on pass/fail decisions for homogeneous student populations.

The behavioral response to stress is altered in adult rats exposed prenatally to cocaine.

The behaviors displayed during and following acute stress exposure were investigated in rats prenatally exposed to cocaine. Offspring from Sprague-Dawley rat dams given SC injections of 40 mg/kg/3 cc cocaine HCl (C40) daily from gestational days 8-20, pair-fed dams injected daily with saline (PF), and untreated control dams (LC) were examined. Adult male rats 60 days old (P60) from the three prenatal groups were given either a 5-min forced swim test (FS), 10 min of intermittent foot shock exposure, or were not exposed to either acute stressor. Amount of immobility or inactivity during acute stress exposure was recorded. One day later, all animals were given a 5-min open field test. During both of the acute stressors, C40 offspring exhibited significantly less immobility than PF and LC control offspring. Whereas prior foot shock experience enhanced the amount of immobility shown by LC and PF offspring in the open field, similar immobility scores were observed between shocked and nonstressed C40 rats. In contrast, prior foot shock experience reduced locomotion in all prenatal treatment groups. These findings suggest that prenatal cocaine exposure results in altered behavioral reactivity in terms of the immediate and delayed response to stressful experiences.

Exact inversion of the exponential x-ray transform for rotating slant-hole (RSH) SPECT.

The RSH SPECT scanner provides parallel-beam attenuated projections for a fully 3D acquisition geometry. The geometry can be represented by circles on the unit sphere of projection directions, one circle for each position of the detector head. Unlike most other fully 3D geometries this one is particularly challenging because there are no 2D subsets in the data. When no attenuation is present, it is well known that an unmeasured projection can be synthesized if it lies inside one of the measured circles. The main result of this work is that under some assumptions on the attenuation distribution, attenuated projections within a circle can be synthesized from available attenuated projections. One consequence is that RSH SPECT projections can be rebinned into a conventional SPECT geometry for which analytic attenuation correction techniques are available.

Play behavior and stress responsivity in periadolescent offspring exposed prenatally to cocaine.

Play behavior and stress responsiveness were examined in offspring exposed gestationally to cocaine. The subjects were offspring of Sprague-Dawley rat dams given s.c. injections of 40 mg/kg/3 cc cocaine HC1 daily from gestational days 8-20 (C40), pair-fed dams injected daily with saline (PF), and untreated control dams (LC). Periadolescent (postnatal day (P) 30-36) male and female rats were assigned to either pretest Stress or No Stress conditions. Every other day Stress animals were exposed to a stressor (on P30--foot shock; P32--white noise; P34--forced swim; P36--foot shock), with each stressor being administered 4 h prior to a play session. Immobility during one of the stressors, foot shock, was used to assess stress responsiveness. Play sessions consisted of pairing each experimental animal with a same-sex, nonexperimentally manipulated conspecific for 7 min. The results indicated that periadolescent offspring exposed gestationally to cocaine differed from controls in their stress responsivity, as evidenced by a failure to show increased immobility during the final foot shock session. Also, while cocaine-exposed juveniles did not differ from controls in their own play behavior, these offspring elicited less play solicitation from conspecifics, as evidenced by an increased latency to be pounced, and decreased frequency and duration of being pounced. These findings parallel earlier evidence for altered stress responsiveness in adult cocaine-exposed rats and also suggest that prenatal exposure to cocaine results in altered social cues.

Internal medicine preceptorships: three successful programs.

Undergraduate medical education is evolving to include community physicians in the training of students in the outpatient setting. The task of designing and implementing such preceptorships can be hindered by financial, institutional, and logistic factors. Nonetheless, several institutions have successfully begun such preceptorships, even in the absence of major federal or philanthropic funding. In this article, three institutions offer suggestions for overcoming the factors hindering the development of a successful preceptorship.

Brachydactyly type B with its distinct facies and 'Cooks syndrome' are the same entity.

A sibling pair with brachydactyly type B born to a normal non-consanguineous couple are described and the severity of their condition discussed. It is proposed that a subgroup of individuals with brachydactyly type B principally involving the nails and distal phalanges, and also having distinct facies, might be identical to individuals having 'Cooks syndrome'.