Chronic inflammation decreases arcuate kisspeptin expression in male sheep.

Lipopolysaccharide (LPS) from Gram-negative bacteria induces an immune response and impairs reproduction through suppression of gonadotropin releasing hormone (GnRH), subsequently luteinizing hormone (LH) secretion. While there is evidence that acute inflammation inhibits kisspeptin, little is known about the impact of chronic inflammation on this key reproductive neuropeptide in livestock species. Thus, we sought to examine a central mechanism whereby LPS suppresses LH secretion in sheep. Twenty wethers were randomly assigned to one of five treatment groups: control (CON; n=4), single acute IV LPS dose (SAD; n=4), daily acute IV LPS dose (DAD; n=4), daily increasing IV LPS dose (DID; n=4), and chronic subcutaneous LPS dose (CSD; n=4). On Days 1 and 7, blood samples were collected every 12 minutes for 360 minutes using jugular venipuncture. Following blood collection on Day 7, all animals were euthanized, brain tissue was perfused with 4% paraformaldehyde, and hypothalamic blocks were removed and processed for immunohistochemistry. On Day 1, LH pulse frequency was significantly lower (p=0.02) in SAD (0.25 ± 0.1 pulses/hour), DAD (0.25 ± 0.1 pulses/hour), DID (0.35 ± 0.1 pulses/hour), and CSD (0.40 ± 0.1 pulses/hour) compared to CON (0.70 ±0.1 pulses/hour). On Day 7, only DID animals (0.35 ± 0.1 pulses/hour) had significantly lower (p=0.049) LH pulse frequency compared to controls (0.85 ± 0.1 pulse/hour). Furthermore, only DID animals (33.3 ± 10.9 cells/section/animal) had significantly fewer (p=0.001) kisspeptin-immunopositive cells compared to controls (82.6 ± 13.6 cells/section/animal). Taken together, we suggest that daily increasing doses of LPS is a powerful inhibitor of kisspeptin neurons in young male sheep and a physiologically relevant model to examine the impact of chronic inflammation on the reproductive axis in livestock.

Does gadolinium improve magnetic resonance arthrography of the hip beyond fluid distension alone?

AIM: To determine if there is a difference in the detection of labral tears and cartilage lesions using the T2-weighted sequences of magnetic resonance arthrography (MRA) only, which simulate MRA with saline alone, compared with the full examination including T1-weighted sequences. MATERIALS AND METHODS: One hundred hip MRA examinations performed at 3 T were identified retrospectively. Each study was reviewed by a musculoskeletal radiologist using either the T2-weighted sequences only (without gadolinium-based contrast agent [GBCA] effect) or the entire examination, including T1-weighted sequences (with GBCA effect). Receiver operating characteristic (ROC) curves were calculated for both groups and compared within a non-inferiority framework, using - 0.10 as the limit of non-inferiority. RESULTS: For labral tears, the difference area under the curve (AUC) was -0.004 (95% confidence interval [CI]: -0.064-0.056, p=0.90). For acetabular cartilage lesions, the difference AUC was 0.011 (95% CI: -0.073-0.096, p=0.79). For femoral cartilage lesions, the difference AUC was -0.059 (95% CI: -0.206-0.087, p=0.43). CONCLUSION: T2-weighted sequences alone were not inferior in diagnostic accuracy compared with the full examination (including T1-weighted sequences with intra-articular GBCA) in detecting acetabular cartilage lesions and labral tears. Further study with prospective comparison of saline injectate to GBCA-containing injectate may help clarify the necessity of continued GBCA use in MRA of the hip.

An immunomodulatory feed additive enhances in vitro viral vaccine recall antigen responses in dairy heifers.

Enhancing immunological responses to vaccination is an important goal in many herd health management systems. OmniGen-AF®(OG) is an immunomodulatory feed additive that has been shown to enhance innate immune function in ruminants and its effects on adaptive immunity require additional study. The objective of this study was to evaluate post-vaccine antibody titers and circulating cellular memory development in heifers fed OG and administered a commercially available modified-live bovine respiratory disease (BRD) vaccine. Twenty-four Holstein heifers were assigned to one of two diets for 170 days: Control TMR (CON; n = 11), or TMR plus OG (TRT; 9 g/100 kg BW/day; n = 13). Samples for hematology, serology, and cellular assays were collected on D-110, 0, 21, 42, and 60 of the trial. Heifers were administered two priming doses of a modified-live BRD vaccine, with a third dose given on D0. There were no significant differences in total WBC and absolute number or the percentage of circulating lymphocytes, monocytes, neutrophils, RBC, or platelets on D-110 through D21. On D42 and D60, CON had significantly higher numbers of lymphocytes. On D0, mean serum neutralizing (SN) titer to BHV-1 was significantly higher for CON compared to TRT. SN titers were not significantly different between CON and TRT at any other time point for BHV-1, BVDV type 1, or BVDV type 2. TRT mounted a significantly stronger recall proliferative response to 0.5 multiplicity of infection (MOI) of BHV-1, BVDV type 1 and BVDV type 2 on D42 and D60; 0.25 MOI of BVDV type 1 on D21 and D42; and 0.25 MOI BVDV type 2 on D42 compared to CON. IL-4 production induced by 0.5 and 1.0 MOI BHV-1 (D42 and D60); 0.25 MOI of BVDV type 1 (D21); and 0.25 and 0.5 MOI of BVDV type 2 (D60) were significantly higher for TRT than CON. IL-17 production induced by 0.25 MOI of BVDV type 1 was significantly higher on D60 for TRT compared to CON. IFN-gamma and IL-10 were not significantly different between treatments. These data indicate feeding OG has a beneficial effect on responses to vaccine antigens in Holstein dairy heifers.

A new conjugate vaccine against pneumococcal disease.

Streptococcus pneumoniae (pneumococcus) is a major cause of morbidity and mortality, particularly among infants and children. Pneumococcal 7-valent conjugate vaccine (PNCRM7) is the first conjugate vaccine known to prevent most invasive pneumococcal disease in infants and children. PNCRM7, which has a favorable safety profile, provides protection against invasive disease caused by antibiotic-resistant strains of S. pneumoniae, and the vaccine has demonstrated a significant impact on otitis media recurrence. Routine immunization with this vaccine should substantially reduce morbidity and mortality and improve the quality of life for infants, children, and their families.

MR imaging of nontraumatic brachial plexopathies: frequency and spectrum of findings.

Magnetic resonance imaging is the method of choice for evaluating patients with a nontraumatic brachial plexopathy. Although there is a wide range of disease processes that may cause a brachial plexopathy, radiation fibrosis, primary and metastatic lung cancer, and metastatic breast cancer account for almost three-fourths of the causes. Radiation fibrosis, the most common cause in our series, may occur several months to years after the completion of therapy. Findings of radiation fibrosis include (a) thickening and diffuse enhancement of the brachial plexus without a focal mass and (b) soft-tissue changes with low signal intensity on both T1- and T2-weighted images. Lung cancer arising in the lung apex may invade the lower portion of the brachial plexus. Many tumors may metastasize to the brachial plexus, causing a brachial plexopathy. Breast cancer is the most likely to metastasize because major lymphatic drainage routes for the breast course through the apex of the axilla.

Effects of indirect light and propranolol on melatonin levels in normal human subjects.

An indirect lighting protocol was developed to measure nocturnal melatonin suppression by light in normal human subjects. Goals were to minimize both discomfort due to staring intensely at a bright light source, and behavioral variation due to wandering gaze. Subjects sat with a bank of five full-spectrum light sources placed behind them. Lights reflecting off the surfaces before each subject produced a hemisphere of light that measured 500 lx +/- 5%. Subjects retired to bed in darkness by midnight and then sat in the hemisphere of light from 02.00 h to 04.00 h. Blood for melatonin was drawn at 20-30-min intervals from midnight to 06.00 h. Plasma melatonin was measured by radioimmunoassay. The indirect lighting protocol was used to compare the effects of 500 lx light to dark (21 subjects) and to study varying light intensities from 300 to 2000 lx (7 subjects). We studied the effects of the sitting posture in very dim light of 20-30 lx (6 subjects). We also studied the effects of propranolol plus dark and propranolol plus 500 lx light on melatonin levels. Subjects received placebo, 10 mg propranolol or 40 mg propranolol orally at 23.00 h, and were then exposed to either the dark or light condition. Melatonin levels obtained with the indirect lighting protocol were consistent with studies using direct lighting; light of 500 lx significantly suppressed nocturnal melatonin and suppression was dose related between 300 and 2000 lx. Sitting in dim light had no significant effect on melatonin suppression when compared with the supine posture in the dark in six subjects. Propranolol caused a dose-dependent decrease in melatonin levels in both the dark and the light. There was no relationship between suppression of melatonin by propranolol and suppression by light.

Single rope tree swing injuries among children.

OBJECTIVE: To examine the scope and severity of injuries sustained from falls from single rope tree swings among children. METHODS: Twenty-six children formed the basis of this retrospective study. Patients were divided into three groups based on the estimated distance of their fall (one, two, or three stories). Data were analyzed with respect to mechanism of injury, age, gender, length of hospital stay, injury severity score, number and type of injuries, and mortality. RESULTS: Eighteen patients fell from ropes, and 8 from vines (all onto packed dirt). Fourteen falls occurred from one story or less, 8 from two stories, and 4 from three stories. One death occurred from intracranial injury following a two-story fall. No difference in age, gender, injury severity score, or length of hospital stay with respect to the height of the fall was observed. Falls from lower heights resulted in equally severe injuries as falls from higher heights. Overall, head trauma was the most common injury (58%) followed by long bone fractures (42%), axial skeletal fractures (23%), and intra-abdominal visceral injuries (8%). CONCLUSIONS: The present study demonstrated that recreational single rope tree swing injuries among children resulted in significant morbidity regardless of the height of the fall. This activity carries a substantial risk for serious injury. The mechanism of injury, clinical data, and the importance of medical awareness and patient education are emphasized.

Intraductal papillary-mucinous tumors of the pancreas: clinicopathologic features, outcome, and nomenclature. Members of the Pancreas Clinic, and Pancreatic Surgeons of Mayo Clinic.

BACKGROUND & AIMS: Intraductal papillary-mucinous tumor (IPMT) of the pancreatic ducts is increasingly recognized. This study investigated if clinical, imaging, or, histological features predicated outcome, formulated a treatment algorithm, and clarified relationships among IPMT, mucinous cystic neoplasms of the pancreas (MCN), and chronic pancreatitis. METHODS: The medical records, radiographs, and pathological specimens of 15 patients with IPMT (dilated main pancreatic duct or branch ducts with mucin overproduction) who were evaluated between October 1983 and January 1994 were reviewed. RESULTS: One patient had hepatic metastases. Fourteen underwent an operation (6 distal pancreatectomy, 4 total pancreatectomy, and 4 pancreaticoduodenectomy); all had dysplastic intraductal epithelium and chronic pancreatitis, whereas 3 had invasive adenocarcinoma. After a median of 25 months, 10 patients were alive; 3 of 4 with malignant and 2 of 11 with benign IPMT died (P < 0.05). Patients with or without carcinoma had similar clinical and radiographic features. A clinical diagnosis of chronic pancreatitis had been made in 9 patients with benign IMPT and in none with malignant IPMT (P < 0.05). CONCLUSIONS: IPMT is a dysplastic and likely precancerous lesion that is frequently diagnosed as chronic pancreatitis and is separate from MCN. Because it is not possible to distinguish noninvasive from invasive IPMT preoperatively, complete surgical excision of the dysplastic process is our treatment of choice whenever appropriate.

Evaluation of cyropreserved internal thoracic artery as an alternative coronary graft: evidence for preserved functional, metabolic and structural integrity.

The internal thoracic artery (ITA) is the conduit of choice for coronary artery bypass grafting (CABG). This study, utilizing a canine model, evaluates cryopreserved ITA. Sixteen ITAs were harvested and cryopreserved according to United CryoInstitute protocol. Test conduits, 5 cm long and 4 mm mean diameter, were anastomosed to the ligated carotid artery of an unmatched mongrel recipient, above and below the site of native artery ligation. Graft patency was assessed by angiography at 14 days (early) and 980 days (late) postoperatively. Catheterization of the 16 vessels identified three (18%) early and one (6%) late graft occlusion. Ninety days postoperatively, each dog was killed and the graft harvested for histopathological and functional evaluation. Morphologic evaluation, using conventional staining, showed preserved cellular structure, decrease in smooth muscle cells and distorted endothelial layer. Immunocytochemistry, using an antibody against prostacyclin (PGI2), detected PGI2 immunoactivity in the ITA smooth muscle cells. An in vitro assay performed on the arterial rings confirmed preserved functional integrity of the vascular endothelium and smooth muscle. These findings suggest that cryopreserved ITA may have potential as a substitute graft, in devising conduit strategies for primary or reoperative coronary bypass surgery.

Efficacy of combined coronary revascularization and valve procedures in octogenarians.

From January 1982 to October 1991, 42 consecutive patients 80 years of age and older underwent a combined cardiac procedure with coronary revascularization and valve repair or replacement. There were 20 women and 22 men. Mean age at operation was 82.8 years (range, 80 to 89.7 years). Twenty-seven patients (64%) were in New York Heart Association (NYHA) functional class III or IV preoperatively. Six patients (14.3%) had undergone previous cardiac procedures. There were six hospital deaths (14.3%). The only significant preoperative risk factor identified for the event hospital death was aortic insufficiency (p = 0.005). The 36 hospital survivors were followed up at a mean of 21.1 months after hospital discharge. There were nine (21%) late deaths occurring at a mean of 21.3 months postoperatively: two from acute myocardial infarctions and seven from chronic heart failure. Survival analysis indicated that higher preoperative NYHA class (p = 0.0003), hypertension (p = 0.015), hypercholesterolemia (p = 0.03), and elevated left atrial/left ventricular gradient (p = 0.04) were incremental risk factors for overall mortality. The actuarial survival at 40 months was 51.9%, with no significant difference as compared with an age-, sex-, and race-matched population. Of the 27 late survivors, 26 were in NYHA class I or II. We conclude that octogenarians may undergo complex cardiac surgical procedures with an expectation of an acceptable mortality rate and significant improvement in their functional status. These results must be taken into consideration in light of reported strategies to ameliorate health-care costs by limiting availability of complex medical care to the elderly.

Comparison of low-pressure versus standard-pressure fixation Carpentier-Edwards bioprosthesis.

Intermediate-phase clinical results of 51 low-pressure (LP) and 234 standard-pressure (SP) fixation porcine Carpentier-Edwards (CE) valves implanted between 1977 and 1991 were compared for valve-related events. Group similarities included New York Heart Association functional class, ejection fraction, and sex. Patients with SP valves were younger (mean age, 58 versus 68 years; p = 0.0001). There were 20 in-hospital deaths (8.6%) in the SP valve group and 5 (9.8%) in the LP valve group (p = 0.79). Follow-up was 99%, with a mean of 104 months in the SP valve group versus 55 months in the SP valve group (p = 0.0001). The actuarial survival rate was 48.2% and 22.3% at 10 and 15 years, respectively, in the SP valve group and 34.1% at 10 years in the LP valve group (p = 0.42). Freedom from events at 5, 10, and 15 years in the SP valve group and at 5 years in the LP valve group was as follows: for late valve-related events, 86.3%, 51.4% and 20.2%, respectively, in the SP valve group versus 85% in the LP valve group (p = 0.44); for valve-related death, 96.4%, 93.6%, and 87.3% in the SP valve group versus 100% in the LP valve group (p = 0.20); for structural valve failure, 96%, 68%, and 35% in the SP valve group versus 100% in the LP valve group (p = 0.09); and for reoperation, 95%, 61%, and 30% in the SP valve group versus 92% in the LP valve group (p = 0.82). In conclusion, this study revealed no significant statistical difference between LP and SP valves. In the LP valve group, structural valve failure/valve-related death was not observed, perhaps indicating a more favorable result. Absolute verification of this trend awaits long-term follow-up.

Normothermic retrograde cardioplegia is effective in patients with left ventricular hypertrophy. A prospective and randomized study.

Twenty patients with left ventricular hypertrophy (LVH) undergoing isolated aortic valve replacement were prospectively randomized to receive either continuous retrograde normothermic (n = 8) or intermittent retrograde hypothermic (n = 12) methods of myocardial protection. Biopsies of the left ventricular septum were evaluated for ultrastructure and assayed for ATP. There was no mortality, no requirement for intra-aortic balloon pump nor neurological events in any of the patients from either group. Myocardial ATP (warm 23.2 +/- 1.8 nmol/mg protein; cold 22.4 +/- 1.2 nmol/mg protein; p = 0.72) and myocardial CPK-MB (warm 43.6 +/- 5.2 U/l; cold 39.0 +/- 2.5 U/l; p = 0.67) were not significantly different. Ultrastructure was generally well preserved in the biopsies from both groups, with the exception of one patient in the normothermic group. Systemic lactate sampled after 40 minutes of cardiopulmonary bypass was significantly higher in the normothermic group (warm 3.4 +/- 0.27 mmol/l; cold 2.3 +/- 0.21 mmol/l; p = 0.01), however, the myocardial lactate production was not significantly different between the two groups (extraction ratio; warm 0.01 +/- 0.3; cold 0.13 +/- 0.1; p = 0.45). We conclude that the continuous normothermic retrograde method of myocardial protection is effective in patients with left ventricular hypertrophy; however, the higher systemic lactate levels using this technique raises concerns regarding the adequacy of systemic perfusion at 37 degrees C.

The impact of aprotinin on coronary artery bypass graft patency.

STUDY DESIGN: Aprotinin has recently been shown to reduce postoperative bleeding and transfusion requirements associated with coronary artery bypass grafting. One concern with its use, however, is that it may have a deleterious effect on graft patency because it promotes hemostasis. Forty-seven patients undergoing coronary artery bypass. Forty-seven patients undergoing coronary artery bypass grafting were enrolled in a prospective, randomized double-blind trial of aprotinin to determine the effect of this agent on postoperative bleeding, transfusion requirements, renal function, and graft patency. The study group was comprised of the 32 patients who underwent technically adequate ultrafast CT scans 6 to 8 weeks postoperatively to determine graft patency. Sixteen patients received aprotinin (aprotinin group) and 16 received placebo (control group). RESULTS: Demographic and operative descriptors were comparable between groups. Postoperative mediastinal and chest tube drainage in the aprotinin group was significantly less than that in the control group (722 vs 1,540 mL; p = 0.0006) and the mean blood transfusion requirements were less, but this did not reach significance (125 vs 297 mL; p = 0.42). Analysis of graft patency by patients revealed that 5 patients in the aprotinin group (31%) had at least one occluded graft, while none of the patients in the control group had an occluded graft (p = 0.04). Analysis by graft revealed that 38 of 43 grafts placed in the aprotinin group were patent, while all 38 grafts placed in the placebo group were patent (88.4 vs 100%; p = 0.057). There was no difference in the incidence of myocardial infarction, renal dysfunction or hematologic indexes at discharge between the groups, or evidence of other thrombotic complications. CONCLUSION: We conclude that high-dose aprotinin is effective in reducing hemorrhage after coronary artery bypass grafting. However, its routine use should be approached cautiously due to its possible adverse effects on graft patency.

Early and late-phase events after valve replacement with the St. Jude Medical prosthesis in 1200 patients.

From May 1982 to August 1991, 1200 patients underwent valve replacement with the St. Jude Medical (St. Jude Medical, Inc., St. Paul, Minn.) valve: 615 men (51%) and 585 women, mean age 58 years. Preoperatively, 830 patients (69%) were in functional class III or IV. A total of 611 patients (51%) had the aortic valve replaced, 490 (41%) the mitral valve, 2 (0.2%) the tricuspid valve, and 97 (8%) multiple valves. There were 81 hospital deaths (6.8%). Risk factors included older age (p = 0.0001), female gender (p = 0.02), higher preoperative left ventricular end-diastolic pressure (p = 0.05), previous cardiac operation (p = 0.003), longer aortic crossclamp time (p = 0.0001), and longer cardiopulmonary bypass time (p = 0.0001). Follow-up was 98% complete (3153 patient-years). There were 152 late deaths; 32 (21%) were considered valve-related: six thromboembolism, four valve thrombosis, five anticoagulant-related hemorrhage, eight prosthetic valve endocarditis, one paravalvular leak, and seven sudden death. The 5-year actuarial survival was 75%. Risk factors for late death included older age (p = 0.03), lower preoperative ejection fraction (p = 0.005), longer aortic crossclamp time (p = 0.001), longer cardiopulmonary bypass time (p = 0.0001), previous cardiac operation (p = 0.02), and higher preoperative functional class (p = 0.0001). Actuarial freedom at 5 years from major thromboembolic events and anticoagulant-related hemorrhage was 97% and 95%, respectively. This value for valve thrombosis was 99%, for reoperation 96%, for prosthetic valve endocarditis 98%, and for paravalvular leak 96%. Actuarial freedom from all valve-related events and valve-related death at 5 years was 74% and 94%, respectively. We conclude that the low incidence of valve-related events and low mortality supports the continued use of the St. Jude Medical valve.

Chronic type A aortic dissection: an unusual complication of cocaine inhalation.

Acute aortic pathology temporally related to cocaine inhalation may lead to frank rupture or acute aortic dissection. This is a report of an unusual case of a 43-year-old man who presented 9 weeks after experiencing a tearing sensation in his chest while smoking cocaine. The diagnosis was chronic type A aortic dissection with 4+ aortic insufficiency. The successful surgical management included resuspension of the aortic valve and placement of a Dacron tube graft in the ascending aorta such that flow was maintained distally in both the true and false lumens.

Prophylactic procainamide for prevention of atrial fibrillation after coronary artery bypass grafting: a prospective, double-blind, randomized, placebo-controlled pilot study.

OBJECTIVE: To evaluate the effect of prophylactic procainamide on the frequency of postoperative atrial fibrillation in patients undergoing myocardial revascularization. DESIGN: Prospective, randomized, double-blind, placebo-controlled pilot study. SETTING: Surgical intensive care unit and wards at a university hospital affiliate. PATIENTS: A total of 46 patients undergoing myocardial revascularization. INTERVENTIONS: Twenty-two patients received procainamide (procainamide group) and 24 patients received placebo (control group). Procainamide was administered to the procainamide group within 1 hr of the patient's arrival in the intensive care unit and consisted of an intravenous loading dose (12 mg/kg) followed by a maintenance dose (2 mg/min) of procainamide. The control group received a similar volume of placebo. When the patient was able to take oral medication, the study drug was administered orally in a weight-adjusted dosage. MEASUREMENTS: Electrocardiograms (EKGs) were continuously monitored. Procainamide and N-acetyl procainamide serum concentrations were measured, and the dosages in the procainamide group were adjusted by an independent observer. The study drug was continued for 5 days or until an event occurred that resulted in dismissal from the study. MAIN RESULTS: The procainamide group and control group had similar preoperative demographic descriptors and operative variables, except for the mean left ventricular ejection fraction, which was lower in the control group than in the procainamide group (60% vs. 68%, p = .03 [Wilcoxon rank-sum test]). There were no hospital deaths. The number of episodes of postoperative atrial fibrillation was significantly reduced in the procainamide group (5 episodes in 129 patient days at risk [3.9%/day at risk]) compared with the control group (17 episodes in 161 patient days at risk [10.6%/day at risk], p = .04 [Fisher's exact test]). Complication rates were similar in both groups. CONCLUSIONS: In a pilot trial, prophylactic procainamide reduced the number of episodes of atrial fibrillation in patients after coronary artery bypass grafting. Procainamide also decreased the number of patients who experienced postoperative atrial fibrillation. However, due to the small sample size, this latter difference was not statistically significant. Further studies are needed to confirm this encouraging trend.

The impact of intraoperative autotransfusion on cardiac surgery. A prospective randomized double-blind study.

The effect of intraoperative autotransfusion during coronary artery bypass grafting was studied in a randomized double-blind trial involving 38 patients. Nineteen patients had the collected RBCs washed and autotransfused (autotransfusion group), while the remaining patients had their washed cells discarded (control group). Postoperative hemoglobin and hematocrit values were similar. Exposure to banked blood was markedly decreased in the autotransfusion group compared with the control group. In addition, the mean volume of banked packed RBCs transfused per patient was significantly less in the autotransfusion group compared with the control group. Platelet utilization also was markedly decreased in the autotransfusion group. Cryoprecipitate and fresh frozen plasma utilization also was less in the autotransfusion group than in the control group, but this did not reach statistical significance. We conclude that the intraoperative use of autotransfusion decreases the volume of homologous blood products transfused, which results in reduced exposure of the patients to banked blood products.