The myosuppressin structure-activity relationship for cardiac contractility and its receptor interactions support the presence of a ligand-directed signaling pathway in heart.

The structural conservation and activity of the myosuppressin cardioinhibitory peptide across species suggests it plays an important role in physiology, yet much remains unknown regarding its signaling. We previously reported Drosophila melanogaster myosuppressin (dromyosuppressin, DMS; TDVDHVFLRF-NH2) decreases cardiac contractility through a G protein-coupled receptor, DMS-R2. Our study showed the DMS N-terminus amino acids influence its structure-activity relationship (SAR), yet how they act is not established. We predicted myosuppressin N-terminal amino acids played a role in signaling. Here, we tested our hypothesis in the beetle, Zophobas atratus, using a semi-isolated heart bioassay to explore SAR in a different Order and focus on cardiac signaling. We generated a series of myosuppressin truncated analogs by removing the N-terminal residue and measuring the activity of each structure on cardiac contractility. While DVDHVFLRF-NH2 decreased cardiac contractility, we found VDHVFLRF-NH2, DHVFLRF-NH2, and HVFLRF-NH2 increased activity. In contrast, VFLRF- NH2 decreased activity and FLRF-NH2 was inactive. Next, we analyzed molecular docking data and found the active truncated analogs interacted with the 3-6 lock in DMS-R2, the myosuppressin cardiac receptor, disrupting the salt bridge between H114 and E369, and K289 and Q372. Further, the docking results showed the inhibitory effect on contractility may be associated with contact to Y78, while the analogs that increased contractility lacked this interaction. The data from our study demonstrated N-terminal amino acids played a role in myosuppressin activity and signaling suggesting the cardiac receptor can be targeted by biased agonists. Our myosuppressin cardiac contractility data and predicted receptor interactions describe the presence of functional selectivity in a ligand-directed signaling pathway in heart.

The use of endocuff for the facilitation of endoscopic mucosal resection in defiant colonic polyps. A case series.

BACKGROUND: Endocuff has been suggested as a safe and useful device facilitating complex endoscopic mucosal resection (EMR) in the sigmoid colon; however, the existing data are sparse. In this case series, we report our experience with endocuff in facilitating EMR in defiant polyps throughout the colon. CASE SERIES: In colonoscopies where sufficient stability and, thus, reliable visualization of the lesion was not possible (defiant polyp), the endoscope was removed, and subsequently, an ENDOCUFF VISIONTM was mounted on its tip. Thereafter, the colonic area of interest underwent endoscopic re-examination. The study prospectively included fifteen patients with 16 sessile/flat polyps. Fifteen of the 16 EMRs were considered successful. CONCLUSIONS: This case series indicates the use of endocuff as an auxiliary device for facilitating EMR in defiant colonic polyps. HIPPOKRATIA 2021, 25 (3):134-137.

Pre-operative versus post-operative gait variability in patients with acute anterior cruciate ligament deficiency.

Change in gait variability at least 6 months after surgical reconstruction of the anterior cruciate ligament (ACL) was assessed in 20 male patients with acute ACL deficiency and compared with pre-operative data and that from 20 healthy male controls. Gait was measured using a triaxial accelerometer and data were analysed by the Gait Evaluation Differential Entropy Method (GEDEM) to determine gait variability. Pain was assessed with a visual analogue scale and functional ability with the Oswestry Disability Index and the International Knee Documentation Committee score. Mean gait variability was significantly lower after than before surgery, with values for the anterior-posterior axis being in the normal range of controls after 6 months, whereas in the mediolateral axis mean gait variability remained significantly higher, indicating that some rotational instability remained in the time-frame of the study. Pain and functional ability scores improved after surgery compared with before surgery. The combination of accelerometry and GEDEM may be a useful orthopaedic tool for the post-operative evaluation of patients who have undergone ACL reconstruction.

Influence of acute anterior cruciate ligament deficiency in gait variability.

The objective of this study was to compare the gait variability of patients with isolated anterior cruciate ligament (ACL) deficiency (experimental group) with that of healthy individuals (control group). The hypothesis was that the gait variability of the experimental group would be higher than the control group. The experimental group consisted of 20 men with an ACL tear and the control group consisted of 20 healthy men without any neurological and/or musculoskeletal pathology or injury. The gait acceleration signal was analysed using the Gait Evaluation Differential Entropy Method (GEDEM). The GEDEM index of the experimental group in the medio-lateral axis was significantly higher than that of the control subjects. A receiver operating characteristic (ROC) analysis was used to assess the diagnostic value of the method and to determine a cut-off entropy value. The GEDEM cut-off value had a 95.6% probability of separating isolated ACL patients from healthy subjects.

Chromogranin a levels in diagnosis, treatment and follow-up of 42 patients with non-functioning pancreatic endocrine tumours.

BACKGROUND/AIMS: Non-functioning pancreatic endocrine tumours (NFPET) constitute the largest component (35-50%) of pancreatic endocrine tumours. They are characterized by the absence of symptoms of hormone hypersecretion and frequently have clinical manifestations similar to the more common exocrine pancreatic adenocarcinoma. The present studyaims toevaluate the clinical features, diagnostic approach and, in particular, the significance of serum chromogranin A levels (CgA) in the management and outcome of 42 patients with NFPET (from a series of 121 patients with pancreatic endocrine tumours). METHODS: Twenty-five males and 17 females were included, and the mean age at diagnosis was 52.3 years (range: 26-68 years). The diagnosis for each patient was established by histopathological examination and immunohistochemistry. After the histopathological confirmation of diagnosis and during the follow-up period, patients were evaluated clinically and radiologically (including OctreoScan), whilst fasting gut hormones (including CgA) were also estimated. At diagnosis, all patients were checked for the presence of multiple endocrine neoplasia type I syndrome. The follow-up was complete and ranged from 12 to 86 months (mean: 49 months). RESULTS: Dyspepsia (66.5%) and weight loss (47.6%) were the most common symptoms at diagnosis, while in 21.4% of patients tumour lesions were revealed incidentally. Plasma CgA levels were significantly or moderately elevated in all patients with liver metastases at diagnosis (64.3%). The levels also reflected tumour progression or response to treatment during the follow-up period. OctreoScan showed avid uptake in 77.8% of patients with hepatic metastases. Moreover, in 2 patients OctreoScan revealed unexpected metastatic mesenteric deposits, which had not been found by the other studies. However, it was negative in 6 patients with liver metastases, in whom tumours were proved to be poorly differentiated (high-grade). CONCLUSIONS: (1) NFPET may present with clinical manifestations similar to those of an exocrine pancreatic tumour; (2) plasma CgA levels reflect tumour load, and also seem to correlate with tumour progression or response to treatment; (3) surgeryin patients with localized disease at presentation can be curative, while it can also reduce tumour burden in patients with metastases; (4) long-acting somatostatin analogues provide good quality of life and temporary disease stabilization in patients with low-grade tumours; (5) systemic chemotherapy or chemoembolization seem to be beneficial in high-grade and progressive tumours.

Abdominal rectus muscle sheath abscess after spontaneous vaginal delivery. A case report.

Postpartum infections cause severe morbidity of the mother. Abdominal wound infection and abscess formation are common complications after cesarean delivery. We report a case with abscess formation inside the abdominal rectus muscle sheath after normal, spontaneous vaginal delivery. A 32-year-old woman, para 2, had a normal vaginal delivery at term. The second postpartum day she complained of lower abdominal pain and was unable to stand up or walk. The fourth day, cellulitis of the skin of the lower abdomen developed and was treated with broad-spectrum intravenous antibiotics. The seventh day the patient developed septic fever and an abdominal rectus muscle sheath abscess was diagnosed. The abscess was treated with incisions and evacuation and the patient was discharged the 12th postoperative day. The abscess in this case, as hematoma formation was not preceded, was referred to ascending contamination via the lymphatic vessels.

Fetal small bowel obstruction: report of two cases.

Fetal small bowel obstruction is usually diagnosed by sonography in the late second or early third trimester. We report two such cases of different etiology: a case of meconium ileus due to cystic fibrosis and a case of intestinal atresia. The only sonographic finding that allowed differentiation between them was the echogenic bowel in the case of cystic fibrosis.

Congestive heart failure and VVI pacing mode: dynamic behavior of the dispersion of ventricular repolarization.

Dynamic Behavior of the Dispersion of Ventricular Repolarization. The aim of this study was to evaluate the circadian variation in the spatial dispersion of ventricular repolarization in continuously paced patients with congestive heart failure (CHF). Fourteen patients (10 males, 4 females, aged 65 +/- 8 years) with CHF due to dilated cardiomyopathy (DCM) and an echocardiographic ejection fraction of 28% +/- 3% were studied. All patients underwent AV junctional RF ablation and permanent pacemaker implantation for drug refractory chronic atrial fibrillation (AF). Patients were evaluated at 1 month postimplant with a three-channel 24-hour Holter monitor, using the three plane Frank orthogonal leads (X, Y, and Z), in VVI pacing mode at 70 beats/min. For each hour, the mean value of spike-T interval dispersion of the first five beats was measured. The control group consisted of 20 patients without structural heart disease, but with AF and complete AV block, continuously paced in VVI mode at 70 beats/min. The dispersion of the spike-T interval had a circadian behavior in the study population, with higher values at night and lower during the daytime. During the daytime, the mean value of spike-T interval dispersion was 39 +/- 5 ms and during the nighttime it was 45 +/- 7 ms (P = 0.003). Such a difference between day and night was not found in the control group (38 +/- 6 ms and 40 +/- 8 ms, respectively, P = NS). In the daytime period the mean value of spike-T interval dispersion of our study population was comparable to that of the control group (P = NS), while during the nighttime it was significantly higher (P = 0.0004). In conclusion, by evaluating the dispersion of ventricular repolarization in two dimensions, space and time, a circadian variation was found in paced patients with CHF due to DCM. The increased QT dispersion in these patients during the nighttime period was attributed to different effects of vagal activity in normal and abnormal myocardial areas.

Talar impingement by the anteroinferior tibiofibular ligament. A cause of chronic pain in the ankle after inversion sprain.

Seven patients who had pain in the anterior aspect of the ankle were found to have a thickened distal fascicle of the anteroinferior tibiofibular ligament. Each patient had a history of an inversion sprain of the ankle followed by chronic pain in the anterior aspect of the ankle. The thickened distal fascicle was resected without loss of stability of the ankle. Five patients needed débridement of an area of abraded hyaline cartilage on the anterolateral aspect of the talus. Six patients were followed for a mean of thirty-nine months (range, twenty-four to fifty-nine months). Four of them had no pain in the ankle or limitation in activities, and two reported marked improvement, with only occasional pain in the ankle related to overuse. A separate distal fascicle of the anteroinferior tibiofibular ligament is present in most human ankles and can be a cause of talar impingement, abrasion of the articular cartilage, and pain in the anterior aspect of the ankle. Resection of this ligament usually will alleviate the pain caused by the impingement.

Computed tomography of hamstring muscle strains.

Acute hamstring muscle strains occurring in ten college athletes were evaluated using computed tomography to identify the location and characteristics of these common injuries. Acute muscle strains appeared as areas of hypodensity within the muscle 1-2 d following injury. This suggests that inflammation and edema are the major component of injury, not bleeding as commonly assumed. Injuries were seen most commonly in the proximal and lateral portions of the hamstring muscle group, particularly in the biceps femoris.

Effect of nifedipine on the sick sinus syndrome.

The effect of nifedipine (N) on sinus node (SN) function was studied in 15 patients (9 males, 6 females) sixty-two to seventy-six (mean 68.1 +/- 11) years old, with sick sinus syndrome (SSS). SSS was characterized electrophysiologically by a prolonged corrected sinus node recovery time (CSNRT greater than 535 msec) and/or prolonged sinoatrial conduction time (SACT greater than 125 msec), assessed by applying premature atrial stimulation. Ten mg N was given sublingually, and CSNRT and SACT were again evaluated sixty minutes after N administration, and again ten minutes after 1.5 mg atropine (A) was given IV. Heart rate increased significantly after N (p less than 0.005), systolic blood pressure (SBP) diminished significantly (p less than 0.005), and CSNRT and SACT shortened significantly (p less than 0.005, p less than 0.005) and became normal in 7 and 5 patients respectively. After A administration, a further significant increase of heart rate (p less than 0.005) and decrease of CSNRT (p less than 0.005) and SACT (p less than 0.005) were observed. CSNRT and SACT became normal in 8 and 7 patients respectively. SBP remained stable.

The effect of muscle architecture on the biomechanical failure properties of skeletal muscle under passive extension.

This study investigates the biomechanical failure properties of five architecturally different skeletal muscles and examines the role muscle structure plays in the passive extension characteristics of musculotendinous units. The muscles used in this study fall into four morphologic categories: fusiform, unipennate, bipennate, and multipennate. Each muscle was pulled to failure at three different rates of strain (1, 10, and 100 cm/min). Specimens of fusiform, unipennate, and bipennate muscles were pulled from their proximal as well as distal attachments. The relationship of elongation to failure of the entire musculotendinous unit to resting muscle fiber length was examined to determine the effect of angle of pennation and fiber length on the failure properties. Our results demonstrate that all four muscle types tested show injury and rupture at the musculotendinous junction whether pulled from proximal or distal attachment, regardless of muscle structure and rate of strain. There was a statistically significant difference (P less than 0.005) in the degree of elongation to failure relative to resting muscle fiber length, with a tendency to greater elongation relative to fiber length for muscles with more pennate structure (tibialis anterior, 72.7% +/- 1.0%; extensor digitorum longus, 113.1% +/- 3.5%; rectus femoris, 225.5% +/- 3.7% elongation in percent resting fiber length).

Arrhythmogenic right ventricular dysplasia: case report presentation and review of the literature.

A man complaining of palpitations was found to have ventricular tachycardia (VT) with LBBB configuration. From the investigations which followed, he was diagnosed as having arrhythmogenic right ventricular dysplasia (ARVD). The patient has been treated with amiodarone and propafenon for 7 months without VT recurrence. ARVD and Uhl's anomaly, which is its most extreme form, may be familial and represent an important cause of sudden death among young people: Prophylactic antiarrhythmic therapy and sometimes surgical treatment are required in case of refractory VT.

Biomechanical and histological evaluation of muscle after controlled strain injury.

This study correlates force generation and healing in muscle after controlled strain injury. Right tibialis anterior (TA) muscles from 30 rabbits were strained to approximately 80% of failure while the left TA muscles served as control. Both injured and control muscles were then tested for ability to generate force. Seven animals were sacrificed immediately after testing and the muscles were examined grossly and histologically. Remaining animals were retested at 24 hours (N = 7), 48 hours (N = 8), and 7 days (N = 8). Contractile ability following injury was 70.5% of control immediately, 51.1% at 24 hours, 74.5% at 48 hours, and 92.5% at 7 days. Immediate histology showed limited distal fiber rupture and hemorrhage. By 24 hours, histology showed fiber necrosis, infiltration of inflammatory cells, edema, and hemorrhage. At 48 hours there was complete fiber breakdown and intense inflammatory cell proliferation. At 7 days inflammation was reduced and collagen fibrosis more advanced. Our findings demonstrate that injured muscle begins functional recovery by 48 hours despite inflammation and active healing. This suggests that decreasing muscle function seen clinically between 24 and 48 hours following strain injury may result from pain due to inflammation. Scarring and fibrosis seen at 7 days may explain the frequent recurrence of injury to strained muscles.

Anterior cruciate ligament allograft transplantation. Long-term function, histology, revascularization, and operative technique.

In recent years much effort has been devoted to finding a satisfactory replacement for the injured ACL. None of the reconstruction techniques used in the past can be considered ideal because of their inability to duplicate the complex geometry, structure, and function of the ligament. Current advances in allograft transplantation and cryopreservation have led us to design and implement an experimental model for testing the feasibility of cryopreserved ACL allotransplantation. Groups of dogs were used to evaluate the effect of cryopreservation on ligament strength and to compare the relative performance of both autograft and allograft ACL transplants up to 18 months after implantation. The ligaments were examined mechanically, histologically, and microangiographically. The cryopreservation process and duration of storage had no effect on the biomechanical or structural properties of the ligament. The mechanical integrity of the allografts was similar to that of the autografts, with both achieving nearly 90% of control ligament strength by 36 weeks. Revascularization approached normal by 24 weeks in both autograft and allograft. No evidence of structural degradation or immunological reaction was seen. Based on these results, we believe that a cryopreserved ACL allograft can provide the ideal material for ACL reconstruction. We have outlined a surgical technique for harvesting and implanting this graft clinically.

Functional disturbance of the inferior radio-ulnar joint due to hypoplasia of the lower end of the ulna.

Variations in the difference between the ulnar and radial length are described as the ulnar variance. The frequency of these variants are studied in a Greek population. It was found that the commonest is the neutral variant (51.7%) and less common the minus variant (33.6%). Five cases of an extreme bilateral minus variant is also reported. These cases were accompanied, except the hypoplasia of the ulna, by increased obliquity of the radial lower epiphysis. Functional disturbance from this abnormality was found to be minimal.