Assessing heart disease using a novel magnetocardiography device.

The aim of this paper is to present the use of a portable, unshielded magnetocardiograph (MCG) and identify key characteristics of MCG scans that could be used in future studies to identify parameters that are sensitive to cardiac pathology. We recruited 50 patients with confirmed myocardial infarction (MI) within the past 12 weeks and 46 volunteers with no history of cardiac disease. A set of 38 parameters were extracted from MCG features including both signals from the sensor array and from magnetic images obtained from the device and principal component analysis was used to concentrate the information contained in these parameters into uncorrelated predictors. Linear fits of these parameters were then used to examine the ability of MCG to distinguish between sub-groups of patients. In the first instance, the primary aim of this study was to ensure that MCG has a basic ability to separate a highly polarised patient group (young controls from post infarction patients) and to identify parameters that could be used in future studies to build a formal diagnostic tool kit. Parameters that parameterised left ventricular ejection fraction (LVEF) were identified and an example is presented to show differential low and high ejection fractions.

Identification of biomarkers indicative of barotrauma and recovery in black rockfish Sebastes melanops.

A Sebastes-specific complementary DNA (cDNA) microarray was developed to identify potential biomarkers involved in the capture stress and recovery of Sebastes species if they are assisted in returning to their original depth of capture following barotrauma. Black rockfish Sebastes melanops were exposed to simulated decompression from 450 kPa (c. 35 m depth) (which resulted in barotrauma) and subsequent recompression. Sebastes melanops were sampled for liver tissue at days 3, 15 and 31 post-barotrauma. Potential candidate genes were identified from the microarray and then quantitative real-time PCR (qrt-PCR) was used to validate expression levels in biological replicates. Six potential biomarkers associated with the innate immune system were identified that were up-regulated in liver tissue at 3 days post-barotrauma: complement C1q-like protein 2, complement component C3, complement regulatory plasma protein, serum amyloid A-5, c-type lysozyme and hepcidin precursor type I. In addition, complement c1q was correlated to the presence of a ruptured swimbladder, providing further support that this gene may be a good biomarker of injury and recovery. Immune genes were no longer up-regulated at day 31 post-barotrauma, a good indication of recovery in S. melanops.

Clinical utility of routine pre-operative axillary ultrasound and fine needle aspiration cytology in patient selection for sentinel lymph node biopsy.

In patients with operable breast cancer, pre-operative evaluation of the axilla may be of use in the selection of appropriate axillary surgery. Pre-operative axillary ultrasound (US) and fine needle aspiration cytology (FNAC) assessments have become routine practice in many breast units, although the evidence base is still gathering. This study assessed the clinical utility of US+/-FNAC in patient selection for either axillary node clearance (ANC) or sentinel lymph node biopsy (SLNB) in patients undergoing surgery for operable breast cancer. Over a two-year period, 348 patients with a clinically negative axilla underwent axillary US. 67 patients with suspicious nodes on US also underwent FNAC. The sensitivity and specificity of axillary investigations to determine nodal involvement were 56% (confidence interval: 47-64%) and 90% (84-93%) for US alone, and 76% (61-87%) and 100% (65-100%) for FNAC combined with US, respectively. With a positive US, the post-test probability was 78%. A negative US carried a post-test probability of 25%. When FNAC was positive, the post-test probability was greater than unity. A negative FNAC yielded a post-test probability of 52%. All patients with positive FNAC and most patients with suspicious US were listed for axillary node clearance (ANC) after consideration at the multi-disciplinary team (MDT) meeting. With pre-operative axillary US+/-FNAC, 20% of patients were saved a potential second axillary procedure, facilitating a reduction in the overall re-operation rate to 12%. In this study, a positive pre-operative US+/-FNAC directs patients towards ANC. When the result is negative, other clinico-pathological factors need to be taken into account in the selection of the appropriate axillary procedure.

Recovery potential of black rockfish, Sebastes melanops Girard, recompressed following barotrauma.

Overfished species of rockfish, Sebastes spp., from the Northeast Pacific experience high bycatch mortality because of 'barotrauma', a condition induced from the rapid change in pressure during capture. Field experiments show that it may be possible for rockfish to recover from barotrauma if quickly recompressed; however, no work has followed the physiological recovery of rockfish after recompression or determined whether it is possible for rockfish to survive barotrauma in the long term. Barotrauma was induced in adult black rockfish, Sebastes melanops Girard, from a simulated depth of 35 m, followed by recompression. Blood and selected tissues (eye, heart ventricle, head kidney, liver, rete mirabile and gonad) were sampled at days 3, 15 and 31 post-recompression to evaluate the tissue- and physiologic-level response during recovery. No mortality from barotrauma occurred during the experiments, and feeding resumed in 80% of both treatment and control fish. The primary injury in treatment fish was the presence of a ruptured swimbladder and/or a ruptured tunica externa (outer layer of swimbladder), which was slow to heal. Blood plasma was analysed for glucose, sodium, chloride, potassium, calcium, phosphorus, insulin-like growth factor-1 and cortisol. Plasma analyses indicated no strong effects because of barotrauma, suggesting overall handling stress outweighed any effect from barotrauma. Rockfish with ruptured swimbladders may face compromised competency in the wild; however, it appears the majority of black rockfish decompressed from 35 m have a high potential for recovery if recompressed immediately after capture. This research suggests recompression could be a valuable bycatch mortality reduction tool for rockfish in recreational fisheries.

Prognostic value of C-reactive protein in HIV-infected patients with Pneumocystis jirovecii pneumonia.

C-reactive protein (CRP) is a sensitive marker of inflammation and tissue damage. We aimed to describe CRP responses in HIV-infected patients presenting with Pneumocystis pneumonia (PCP), bacterial pneumonia (BP) and pulmonary tuberculosis (TB) and, in patients with PCP, to identify if elevated CRP has prognostic significance. Data obtained by case-note review of consecutive HIV-infected adults with acute respiratory episodes included admission CRP (elevated >5 mg/L), haemoglobin, white blood count, CD4 count and partial pressure of oxygen in the blood (PaO(2)), presence of pulmonary co-pathology/intercurrent infection and outcome (survival). Median (range) CRP in patients with BP = 120 mg/L (<5-620 mg/L), TB = 44 mg/L (<5-256.3 mg/L) and PCP = 35 mg/L (<5-254 mg/L). CRP was elevated in 93/103 (90.3%) patients with PCP; six patients died; and all had an elevated CRP. PaO(2) and CRP values were associated as follows: average CRP levels declined by 10% (95% confidence interval [CI] 0.20%) per kPa increase in PaO(2) = 0.002. Factors associated with death were higher CRP, odds ratio (OR) (95% CI) = 5.30 (1.61 to 17.51) per 100 mg/L increase, P = 0.006 and haemoglobin, OR (95% CI) = 0.52 (0.29 to 0.93) per g/dL, P = 0.033. CRP is elevated in the majority of HIV-infected patients with PCP, BP and TB. Admission CRP measurement lacks specificity, but in PCP elevations of CRP are associated with disease severity (PaO(2)) and poor outcome and might be used prognostically, together with other mortality risk factors; further prospective evaluation is needed.

Early intramedullary nailing in an animal model of a heavily contaminated fracture of the tibia.

An ovine model was developed to study the outcome following intramedullary nailing of a heavily contaminated fracture. Animals in the control group received no treatment directed at controlling infection, whereas those in the treatment group received wound debridement, lavage and the use of appropriate systemic antibiotics. Despite this, infection developed at the osteotomy site and along the entire length of the implant in all animals in both groups. It was felt that standard methods of wound management might be inadequate when applied at the time of intramedullary nailing since the spread of contamination following the use of reamers was demonstrated in all animals. Results from this study support the clinical impression that heavily contaminated fractures should not be treated by primary intramedullary nailing.

Phyllodes tumours.

Phyllodes tumours are rare fibroepithelial lesions that account for less than 1% of all breast neoplasms. With the non-operative management of fibroadenomas widely adopted, the importance of phyllodes tumours today lies in the need to differentiate them from other benign breast lesions. All breast lumps should be triple assessed and the diagnosis of a phyllodes tumour considered in women, particularly over the age of 35 years, who present with a rapidly growing "benign" breast lump. Treatment can be by either wide excision or mastectomy provided histologically clear specimen margins are ensured. Nodal metastases are rare and routine axillary dissection is not recommended. Few reliable clinical and histological prognostic factors have been identified. Local recurrence occurs in approximately 15% of patients and is more common after incomplete excision. It can usually be controlled by further surgery. Repeated local recurrence has been reported without the development of distant metastases or reduced survival. Approximately 20% of patients with malignant phyllodes tumours develop distant metastases. Long term survival with distant metastases is rare. The role of chemotherapy, radiotherapy, and hormonal manipulation in both the adjuvant and palliative settings remain to be defined.

Why should diagnostic benign breast biopsies weight less than twenty grams?

To reduce the cosmetic deformity resulting from diagnostic biopsies, current breast screening guidelines recommend that 80% of biopsy specimens that subsequently prove to be benign should weigh less than 20 g. The relationship between specimen weight and cosmesis is unknown and evidence to support a 20 g upper limit is lacking. Patient satisfaction following all benign biopsies weighing more than 20 g (n = 49) and a random sample of 30 of those weighing less than 20 g (n = 103) performed by one screening unit, over a 6 year period, was assessed by a postal questionnaire. Overall, 32% of patients were unhappy with the cosmetic outcome of their surgery. Patient dissatisfaction appeared to increase with specimen weight (6/23 [26%] < 20 g versus 13/36 [36%] > 20 g) but no statistically significant relationship between weight and cosmesis was apparent (P = 0.57). Reducing benign breast biopsy specimen weights to a minimum is a desirable objective. However, the current quality standard is not evidence-based, is too stringent and should be revised. Strategies need to be introduced to improve patient satisfaction following breast wire-localisation biopsies. In particular, patients should be counselled pre-operatively regarding possible adverse cosmetic outcome.

Experimental models of gram-negative sepsis.

BACKGROUND: The mortality rate from sepsis has improved little over the past two decades. One reason for this has been the use of flawed or inappropriate experimental models in preclinical sepsis studies. METHODS: A literature review of animal models of sepsis was performed following a Medline search based on the following medical subject headings: disease models, endotoxin, inflammation, peritonitis and sepsis. Additional references were identified from the papers identified in the search. RESULTS AND CONCLUSION: Many animal models of sepsis have been described but none has proved to be superior. Extrapolation of results from endotoxicosis or bacterial infusion models should be regarded with caution. Peritonitis models should be accepted as the 'gold standard' but the use of appropriate virulent bacterial species needs to be ensured. A standardized panel of animal models for the preclinical assessment of immunomodulatory agents should be established, including at least one immuno- suppressed model to simulate the immunocompromised patient with sepsis. A uniform and valid definition of sepsis applicable to both small and large animal species is required.

A porcine model of sepsis resulting from the combined insults of hemorrhage and peritonitis.

The physiological responses to either hemorrhage or sepsis have been well documented, however, their simultaneous delivery, as often seen in penetrating trauma, has not been extensively studied. A terminally-anesthetized porcine model of fixed-volume hemorrhage combined with intraperitoneal sepsis was developed. Large White pigs (45-60 kg) were bled 40% of blood volume and peritonitis was induced using an E. coil (O18:K1:H7) culture. Three groups of animals were sequentially studied. Group A (n = 8) received 10(8) bacteria, and Groups B (n = 4) and C (n = 5) received 10(10) organisms. All animals were maintained on a 2.5 mL/kg/h infusion of 0.9% saline. Group C was autotransfused at 1 h. Animals were monitored for up to 24 h. Cardiovascular features of hypovolemia were recorded in all animals. Animals in Group A improved clinically with little microbiological evidence of systemic sepsis. Group B showed rapid cardiovascular collapse, early E. coil-positive blood cultures, and an early rise in serum TNF-alpha levels. Autotransfusion of Group C significantly improved cardiopulmonary parameters, acid-base status, and survival. A reproducible model of hemorrhage and peritonitis, appropriate for abdominal trauma, which allows investigation of resuscitative and pharmacological interventions has been characterized.

Pentoxifylline fails to improve organ dysfunction and survival when used in the resuscitation of a porcine model of haemorrhage and abdominal sepsis.

Pentoxifylline is a phosphodiesterase inhibitor, known to suppress tumour necrosis factor-alpha production and improve cardiopulmonary parameters and survival in animal models of sepsis. Using a porcine model of abdominal trauma resulting from the combined insults of haemorrhage and infection, a randomised placebo-controlled trial was conducted of pentoxifylline (20 mg/kg bolus followed by 20 mg/kg infusion over 1 h) administered in addition to a colloid resuscitation regimen. Female Large White pigs (45-60 kg) were bled 40% of their blood volume and peritonitis was induced using E. coli (O18: K1: H7) in an autoclaved faecal suspension. Animals were resuscitated with either colloid alone (n=5) or colloid plus pentoxifylline (n=5). Pentoxifylline attenuated increases in mean arterial and pulmonary artery pressures and reduced both systemic and pulmonary vascular resistance. It worsened the lactic acidosis associated with 'septic shock' and failed to reduce serum TNF-alpha levels. Pentoxifylline, in the high doses used in this study, does not have a role as an adjunct to resuscitation in this clinically relevant model of trauma.

Serving people with developmental disabilities in Medicaid managed care.

Concurrent with the sweeping changes in health care during the past decade, particularly in Medicaid financed health care, has been the reshaping of social policy toward people with developmental disabilities. The extent to which managed care entities match the themes now driving social services for people with mental retardation and other developmental disabilities (cerebral palsy, autism, etc.) is the extent to which they will be successful in serving this unique group of consumers of managed health care. The authors suggest a number of considerations for managed care organizations that increasingly serve significant numbers of this population.

Fibrinogen-impregnated collagen as a combined haemostatic agent and antibiotic delivery system in a porcine model of splenic trauma.

OBJECTIVE: To assess the effect of rifampicin on the haemostatic function of a fibrinogen-impregnated collagen fleece. DESIGN: Laboratory experiment. SETTING: Government research establishment, UK. MATERIAL: Six Large White pigs. INTERVENTIONS: Four 5 cm incisions were made in the spleen of each animal. Three of the wounds were each covered with a sheet of either dry, saline-soaked or rifampicin-soaked fibrinogen-impregnated collagen. MAIN OUTCOME MEASURES: The bleeding time and blood loss from each wound was recorded. Systemic serum rifampicin concentrations were measured using a Staphylococcus aureus inhibition assay. RESULTS: Dry fibrinogen-impregnated collagen resulted in significantly less blood loss (112 (21) compared with 39 (13)ml, p < 0.05) and shorter bleeding time (16 (2) compared with 9 (1) min, p < 0.01) than in untreated control wounds. Pre-soaking in saline or rifampicin solution had no significant effect on its haemostatic function. Rifampicin concentrations above the minimum inhibitory concentration were recorded in the systemic circulation 45 minutes after injury and persisted for the duration of the experiment. CONCLUSIONS: Fibrinogen-impregnated collagen is an effective haemostatic agent in splenic trauma that may be of use for both the local and systemic delivery of antibiotics.

Contamination of the medullary canal following pin-tract infection.

We developed an ovine model of an external-fixator pin-tract infection. With use of a novel method of tissue sampling, infection of the medullary canal was confirmed in all (10 of 10) external-fixator pins that were contaminated with Staphylococcus aureus after they were inserted. In addition, all (five of five) adjacent, uncontaminated pins became infected. We demonstrated that pin-tract infection can be difficult to diagnose clinically, despite gross infection of the tract, and that bacteria can spread within the medulla. Three of the infected pins (20%) did not appear clinically infected, were not loose, and were normal on radiographs after 1 week. Staphylococcus aureus was isolated from the medulla around all 15 pin tracts, and nine other organisms were isolated from the tracts. Despite the presence of infection, the majority of the pins remained well fixed in the bone after 2 weeks.

Differences in the metabolism of postprandial lipoproteins after a high-monounsaturated-fat versus a high-carbohydrate diet in patients with type 1 diabetes mellitus.

There is little information comparing the effects of a high-monounsaturated (Mono)-fat versus a high-carbohydrate (CHO) diet in patients with type 1 diabetes mellitus. In the present study, the effects of these diets on a number of metabolic parameters were compared. Seventeen normolipidemic, nonobese patients with type 1 diabetes were provided with the diets for 4 weeks each in a randomized, crossover design. The percentages of Mono fat of the two diets were 25 Mono versus 9 CHO, with a corresponding total fat content of 40% versus 24% and a total CHO content of 45% versus 61%. At the end of each dietary period, parameters of glycemic control, coagulation factors, and fasting and postprandial lipoproteins were assessed. There were no differences in weight, glycemia, insulin dose, fasting lipid profile, or coagulation factors between the two diets. However, the metabolism of postprandial lipoproteins after a fat load differed; viz, after the Mono diet compared with the CHO diet, mean plasma triglyceride levels over 10 hours were higher (P=.0025, by repeated-measures ANOVA). The levels of triglyceride (P=.0045) and retinyl esters (P=.0046) in chylomicrons (Sf>400) and chylomicron remnants (Sf 100 to 400) (P=.0047 and P=.043, respectively), and the total particle number (apolipoprotein B levels) in chylomicron remnants (P=.001) and small, very low density lipoprotein (Sf 20 to 100, P=.016) were also higher. Our data suggest that in patients with type 1 diabetes, a CHO diet might be preferable to a Mono diet, since adherence to the former results in a lower number of circulating postprandial lipoprotein particles that are potentially atherogenic.