Relative safety of 4 weeks of blood flow-restricted resistance exercise in young, healthy adults.

This study evaluated the effect of 4 weeks of low-load resistance exercise with blood flow restriction (BFRE) on increasing strength in comparison with high-load resistance exercise (HLE), and assessed changes in blood, vascular and neural function. Healthy adults performed leg extension BFRE or HLE 3 days/week at 30% and 80% of strength, respectively. During BFRE, a cuff on the upper leg was inflated to 30% above systolic blood pressure. Strength, pulse-wave velocity (PWV), ankle-brachial index (ABI), prothrombin time (PT) and nerve conduction (NC) were measured before and after training. Markers of coagulation (fibrinogen and D-dimer), fibrinolysis [tissue plasminogen activator (tPA)] and inflammation [high sensitivity C-reactive protein (hsCRP)] were measured in response to the first and last exercise bouts. Strength increased 8% with BFRE and 13% with HLE (P<0.01). No changes in PWV, ABI, PT or NC were observed following training for either group (P>0.05). tPA antigen increased 30-40% immediately following acute bouts of BFRE and HLE (P=0.01). No changes were observed in fibrinogen, D-dimer or hsCRP (P>0.05). These findings indicate that both protocols increase the strength without altering nerve or vascular function, and that a single bout of both protocols increases fibrinolytic activity without altering selected markers of coagulation or inflammation in healthy individuals.

Understanding the Clinical Implications of Resident Involvement in Uncommon Operations.

OBJECTIVE: The objective of this study was to examine uncommon operations in greater detail given that the outcomes of uncommon operations are largely understudied. This study examines the incidence of postoperative events and the role of the resident following uncommon operations. DESIGN: We identified uncommon general surgical operations using the ACS National Surgical Quality Improvement Program Participant Use file (2008-2011). Death or serious morbidity (DSM) within 30 days of the operation was the primary outcome of interest. Failure to rescue (FTR) and prolonged operative time (PRopt) were evaluated as secondary outcome measures. PRopt was defined as ≥90 percentile of operative time for each procedure type. Independent multivariate logistic regression models were generated to examine the impact of these descriptors on the outcomes of interest. SETTING/PARTICIPANTS: The dataset utilized was the United States National Surgical Quality Improvement Program Participant Use File which leverages data points from over 700 hospitals that range from primary to quaternary care centers. Resident participation was defined as resident involved (RI) or no resident involved (NRI), and stratified by postgraduate year (PGY): 1-3, 4-5, and 6+. RESULTS: Resident participant data was available for 21,453 (84.5%) uncommon operations with NRI in 25.4% (5447). With regard to resident participation, PGY1-3 were found in 12.6% (2699), PGY4-5 in 50.4% (10,817), and PGY6+ in 11.6% (2490). The overall observed DSM rate was 28.6% and the observed FTR rate was 5.8%. Overall, there was no difference in DSM by RI status (NRI: 1528; 28.1% vs RI: 4602; 28.8%; p = 0.324); however, PGY level was associated with DSM (PGY1-3: 774, 28.7%, PGY4-5: 3210, 29.7%, PGY6+: 618, 24.8%; p < 0.001). Any RI was associated with a lower rate of FTR (5.1%) when compared to NRI (8.3%, p < 0.001) with decreasing FTR events by increasing PGY (PGY1-3: 6.4%, PGY4-5: 5.2%, PGY6+: 3.3%; p < 0.001). After adjustment for patient risk factors, any RI remained associated with a lower likelihood of FTR than NRI (odds ratio: 0.65, 95% confidence interval: 0.49-0.87) while only the PGY4-5 and PGY6+ groups were associated with lower likelihood of FTR in comparison to NRI. RI was associated with PRopt in univariate and multivariable analyses. CONCLUSIONS: Uncommon operations were associated with substantial DSM. The involvement of PGY4-5 residents was associated with the greatest likelihood of DSM. With increasing PGY of the involved resident, cases with PGY > 5 demonstrated a lower likelihood of risk-adjusted FTR. The explanation for these findings is not clear; however, the involvement of more senior residents in the technical aspects of uncommon operations may lead to improved results.

Histidine decarboxylase expression in human melanoma.

Histamine has been implicated as one of the mediators involved in regulation of proliferation in both normal and neoplastic tissues. Histidine decarboxylase, the only enzyme that catalyzes the formation of histamine from L-histidine, is an essential regulator of histamine levels. In this study, we investigated the gene and protein expression of histidine decarboxylase in melanoma. Reverse transcriptase polymerase chain reaction and in situ hybridization studies of WM-35, WM-983/B, HT-168, and M1 human melanoma cell lines both resulted in positive signals for histidine decarboxylase messenger RNA. A polyclonal chicken antibody was developed against human histidine decarboxylase and protein expression was confirmed by western blot analysis of the cell lysates, revealing a predominant immunoreactive band at approximately 54 kDa corresponding to monomeric histidine decarboxylase. Protein expression of histidine decarboxylase was also shown by flow cytometric analysis and strong punctate cytoplasmic staining of melanoma cell lines. Moreover, both primary and metastatic human melanoma tissues were brightly stained for histidine decarboxylase. When compared with the very weak or no reactions on cultivated human melanocytes both western blot and immunohistochemical studies showed much stronger histidine decarboxylase expression in melanoma cells. These findings suggest that expression of histidine decarboxylase is elevated in human melanoma.

Structure-activity relationships in the 8-amino-6,7,8,9-tetrahydro-3H-benz[e]indole ring system. 1. Effects of substituents in the aromatic system on serotonin and dopamine receptor subtypes.

A series of 1-, 3-, and 4-substituted analogs to the potent 5-HT1A against 8-(dipropylamino)-6,7,8,9-tetrahydro-3H-benz[e]indole-1-carbaldehyde (5) were prepared and tested in vitro at 5-HT1A, 5-HT1D alpha, 5-HT1D beta, D2, and D3 receptors and in vivo for agonist activity in the 5-HTP and DOPA accumulation assays in reserpine-pretreated rats. Some of the compounds were resolved. The substituents used in the 1-position were chosen from a principal component analysis (PCA) plot constructed from both tabulated variables and variables calculated by semiempirical methods (PM3) and molecular mechanics software (MMX). Among the analogs prepared, some, e.g., compound 21, were equipotent to compound 5 with respect to 5-HT1A effects. All compounds were more or less selective for the 5-HT1A receptor, but many of the compounds displayed higher affinities for 5-HT1D alpha than for 5-HT1D beta receptors.

Structure-activity relationships in the 8-amino-6,7,8,9-tetrahydro-3H-benz[e]indole ring system. 2. Effects of 8-amino nitrogen substitution on serotonin receptor binding and pharmacology.

A series of analogs of the potent and selective 5-HT1A agonist 8-(di-n-propylamino)-6,7,8,9-tetrahydro-3H-benz[e]indole-1-carbaldehyde (2b) (OSU191) was prepared in which the dipropylamino group was modified to bear a variety of substituents. These compounds were evaluated for both in vitro and in vivo effects, including the establishment of a receptor binding profile for these analogs at the 5-HT1A, dopamine D-2, dopamine D-3, 5-HT1D alpha, and 5-HT1D beta sites. Several of the analogs were evaluated for their biochemical effects in reserpinized rats, specifically with regard to in vivo changes in brain levels of 5-HTP and DOPA. Nearly all of the compounds prepared for this study were exceedingly potent at the 5-HT1A receptor, although most also displayed significant affinity for the dopamine D-2 receptor. A strong preference for the 5-HT1D alpha over the 5-HT1D beta receptor was also apparent. An analog bearing a butylglutarimide side chain, S-7k, was extremely selective for the 5-HT1A receptor. Although this compound possessed a Ki of 0.6 nM, it elicited only modest changes in 5-HTP brain levels. However, this compound did not appear as an antagonist when tested in a cyclic-AMP-based intrinsic activity assay.

Differential pharmacology between the guinea-pig and the gorilla 5-HT1D receptor as probed with isochromans (5-HT1D-selective ligands).

1. Both the 5-HT1D and 5-HT1B receptors are implicated in migraine pathophysiology. Recently isochromans have been discovered to bind primate 5-HT1D receptors with much higher affinity than 5-HT1B receptors. In the guinea-pig, a primary animal model for anti-migraine drug testing, however, isochromans bound the 5-HT1D receptor with lower affinity than the gorilla receptor. 2. This species-specific pharmacology was investigated, using site-directed mutagenesis on cloned guinea-pig receptors heterologously expressed in human embryonic kidney 293 cells. Mutations of threonine 100 and arginine 102 at the extracellular side of transmembrane II of the guinea-pig 5-HT1D receptor to the corresponding primate residues, isoleucine and histidine, respectively, enhanced its affinity for isochromans to that of the gorilla receptor, with little effects on its affinities for serotonin, sumatriptan and metergoline. Free energy change from the R102H mutation was about twice as much as that from the T100I mutation. 3. For G protein-coupling, serotonin marginally enhanced GTPgamma35S binding in membranes expressing the guinea-pig 5-HT1D receptor and its mutants, but robustly in membranes expressing the gorilla receptor. Sumatriptan enhanced GTPgamma35S binding in the latter nearly as much as serotonin, and several isochromans by 30-60% of serotonin. 4. We discovered key differences in the function and binding properties of guinea-pig and gorilla 5-HT1D receptors, and identified contributions of I100 and H102 of primate 5-HT1D receptors to isochroman binding. Among common experimental animals, only the rabbit shares I100 and H102 with primates, and could be useful for studying isochroman actions in vivo.

Surgical correction of severe mitral prolapse without mitral insufficiency but with pronounced cardiac arrhythmias.

Despite what was considered adequate pharmacological treatment, the condition of six patients with severe mitral valve prolapse but with trivial or no mitral regurgitation deteriorated. These patients had marked weakness, chest pain, dyspnea, and arrhythmias. Because these patients found their condition to be intolerable, the prolapsed mitral valve was repaired. Electrocardiography, treadmill stress testing, and left ventirculography performed following operation showed complete repair of the valve and significant improvement over the preoperative findings in all six patients. Repair of the floppy mitral valve did not eradicate all abnormalities; however, it did significantly improve the chest pain, weakness, dyspnea, and arrhythmias in all six patients. Five patients no longer require any medication. The prolapsed mitral valve contributed significantly to the symptoms and arrhythmias, but it could not have been the sole cause for these patients' signs and symptoms. With complete correction of the prolapse in all six patients, few of the signs and symptoms of the disease persisted. Repair of severe mitral valve prolapse without mitral regurgitation is recommended only for those patients who continue to be severely symptomatic from chest pain, dyspnea, or ventricular arrhythmias after an extensive trial of adequate medical therapy.

Inositol--clinical applications for exogenous use.

Recent advances in nutritional and biochemical research have documented inositol as an important dietary and cellular constituent. The processes involved in inositol metabolism and its derivatives in the tissues of mammals have been characterized in vivo as well as at the enzymatic level. Biochemical functions defined for phosphatidylinositol in biological membranes include the regulation of cellular responses to external stimuli and/or nerve transmission as well as the mediation of enzyme activity through interactions with various specific proteins. Altered production of inositol has been documented in patients with diabetes mellitus, chronic renal failure, galactosemia, and multiple sclerosis. Inositol has been reported to be effective in treating central nervous system disorders such as depression, Alzheimer's disease, panic disorder, and obsessive-compulsive disorder. It has documented benefit for use in pediatric respiratory depression syndrome. In addition, recent studies have evaluated its usefulness as an analgesic. Inositol has been studied extensively as potential treatment to alleviate some negative effects associated with lithium therapy. The use of inositol in pregnant women remains controversial. Although its benefit in preventing neural tube defects in embryonic mice is documented, the risk of inducing uterine contractions limits its usefulness in pregnancy.

Sparse decompositions for exploratory pattern analysis.

We define and verify the utility of a pattern analysis procedure called sparse decomposition. This technique involves sequentially ``peeling'' sparse subsets of patterns from a pattern set, where sparse subsets are sets of patterns which possess a certain degree of regularity or compactness as measured by a compactness measure c. If this is repeated until all patterns are deleted, then the sequence of decomposition ``layers'' derived by this procedure provides a wealth of information from which inferences about the original pattern set may be made. A statistic P is derived from this information and is shown to be powerful in detecting clustering tendency for data in reasonably compact sampling windows. The test is applied to both synthetic and real data.

A survey of causes of bovine abortion occurring in the San Joaquin Valley, California.

The causes of abortion in cattle in the San Joaquin Valley of California were surveyed from submissions to the California Veterinary Diagnostic Laboratory at Tulare. Four hundred sixty-eight abortion cases were examined. Most submissions (89%) were from large drylot dairies, milking an average of 814 cows. Abortion evaluations included necropsy, histopathology, bacteriology, virology, and other immunologic and serologic tests. A specific cause was identified in 29.5% of the abortions. Bacterial infections, most of which were sporadic, accounted for 16% of all abortions. Viral causes and protozoal infections were diagnosed in 5.6% and 3.2% of the abortions, respectively. Fetuses with protozoal infection had histologic lesions of focal nonsuppurative necrotizing encephalitis, and protozoa were detected. Similar histologic lesions were seen in 80 additional fetuses (17.1%), and although an etiologic agent was not identified for these cases, a protozoal infection was suspected.

Maxillary sinus cysts in two cattle.

Two adult Holstein cattle were found to have unilateral maxillary sinus cysts. One had dyspnea and partial airway obstruction; the other had a swelling over the sinus. Both had a nonfetid, mucoid nasal discharge. Deviation of the nasal septum away from the cyst, soft-tissue opacity involving the left maxillary sinus, and a gas-capped fluid line on lateral projection were identified radiographically. The cyst fluid did not have an odor, was relatively acellular, and was of a mucoid (animal 1) or gelatinous (animal 2) nature. In 1 animal, the cyst wall and fluid were removed through a dorsolateral bone flap. The owner reported that the animal improved rapidly and remained clinically normal 27 months after surgery. In the second animal, the cyst was drained and the cyst lining was curetted through a trephine hole in the sinus. The animal improved, but was euthanatized 4 days after surgery because of concurrent problems (displaced abomasum, poor milk production) and financial constraints of the owner. The cyst walls were composed of granulation tissue and were line with stratified squamous epithelium.

Neospora-like protozoan infection as a major cause of abortion in California dairy cattle.

Ninety-five aborted bovine fetuses received from California dairies over a 4.5-year period had histologic lesions of focal encephalitis. Protozoa that reacted with Neospora caninum antiserum were detected in the brain of 88 of these fetuses and in the heart of 1 fetus. Sarcocystis spp schizonts were seen in the vascular endothelium of 1 fetus. It was concluded that a Neospora-like cyst-forming coccidian may be a major cause of abortion in California dairy cattle.