A population-based study of the epidemiology of pancreatic cancer: a brief report.

OBJECTIVE: Administrative data are used to describe the pancreatic cancer (pcc) population. The analysis examines demographic details, incidence, site, survival, and factors influencing mortality in a cohort of individuals diagnosed with pcc. METHODS: Incident cases of pcc diagnosed in Ontario between 1 January 2004 and 31 December 2011 were extracted from the Ontario Cancer Registry. They were linked by encrypted health card number to several administrative databases to obtain demographic and mortality information. Descriptive, bivariate, and survival analyses were conducted. RESULTS: During the period of interest, 9221 new cases of pcc (4548 in men, 4673 in women) were diagnosed, for an age-adjusted standardized annual incidence in the range of 8.6-9.5 per 100,000 population. Mean age at diagnosis was 70.3 ± 12.5 years (standard deviation). Five-year survival was 7.2% (12.8% for those <60 years of age and 3.6% for those >80 years of age). Survival varied by sex, older age, rural residence, lower income, site of involvement in the pancreas, and presence of comorbidity. CONCLUSIONS: The mortality rate in pcc is exceptionally high. With an increasing incidence and a mortality positively associated with age, additional support will be needed for this highly fatal disease as demographics in Ontario continue to trend toward a higher proportion of older individuals.

Health system costs for stage-specific breast cancer: a population-based approach.

OBJECTIVE: The objective of the present analysis was to determine the publicly funded health care costs associated with the care of breast cancer (bca) patients by disease stage. METHODS: Incident cases of female invasive bca (2005-2009) were extracted from the Ontario Cancer Registry and linked to administrative datasets from the publicly funded system. The type and use of health care services were stratified by disease stage over the first 2 years after diagnosis. Mean costs and costs by type of clinical resource used in the care of bca patients were compared with costs for a matched control group. The attributable cost for the 2-year time horizon was determined in 2008 Canadian dollars. RESULTS: This cohort study involved 39,655 patients with bca and 190,520 control subjects. The average age in those groups was 61.1 and 60.9 years respectively. Most bca patients were classified as either stage i (34.4%) or stage ii (31.8%). Of the bca cohort, 8% died within the first 2 years after diagnosis. The overall mean cost per bca case from a public payer perspective in the first 2 years after diagnosis was $41,686. Over the 2-year time horizon, the mean cost increased by stage: i, $29,938; ii, $46,893; iii, $65,369; and iv, $66,627. The attributable cost of bca was $31,732. Cost drivers were cancer clinic visits, physician billings, and hospitalizations. CONCLUSIONS: Costs of care increased by stage of bca. Cost drivers were cancer clinic visits, physician billings, and hospitalizations. These data will assist planning and decision-making for the use of limited health care resources.

The role of attentional focus in plyometric training.

AIM: The purpose of this study was to examine how focusing attention during nine weeks of plyometric training influence jumping performance. It was hypothesized that participants utilizing an external focus of attention during practice would produce greater improvements in jumping behavior compared to participants practicing in the internal and control conditions. METHODS: Thirty-six untrained but physically active male college students were randomly assigned to 1 of 3 plyometric groups with a different focus of attention: external (EXF; N.=12), internal (INF; N.=12), and control (CON; N.=12). All participants subsequently participated in the same an 9-week periodized training program. Standing long jump (SLJ), countermovement jump (CMJ) and drop jump (DJ) were tested pre- and posttraining intervention. RESULTS: The EXF group exhibited greater improvement (P<0.05) in jumping distance for SLJ and height for CMJ than both the INF and CON groups, while the enhancement in jumping height for DJ was not superior (P<0.05) in the EXF group in comparison with the INF and CON groups. However, the CON group showed a greater increase (P<0.05) in jumping height for DJ than the INF group. The EXF group increased the range of knee flexion (KF), whereas both the INF and CON groups decreased the KF during the CMJ. Additionally, only the CON group reduced KF during the execution of the DJ. The EXF group (P<0.05) increased contact time, whereas both the INF and CON groups decreased (P<0.05) contact time in DJ. The EXF group had significantly (P<0.05) greater vertical ground reaction force in CMJ and DJ when compared with the INF and CON groups. CONCLUSION: These results suggest that the external focus of attention during plyometric training may provide a greater stimulus to jump performance in slow stretch shortening cycle (SSC) tasks by producing greater force than adopting the internal and no specific focus.

Population-based home care services in breast cancer: utilization and costs.

OBJECTIVE: To determine utilization and costs of home care services (hcs) for individuals with a diagnosis of breast cancer (bc). METHODS: Incident cases of invasive bc in women were extracted from the Ontario Cancer Registry (2005-2009) and linked with other Ontario health care administrative databases. Control patients were selected from the population of women never diagnosed with any type of cancer. The types and proportions of hcs used were determined and stratified by disease stage. Attributable home care utilization and costs for bc patients were determined. Factors associated with hcs costs were assessed using regression analysis. RESULTS: Among the 39,656 bc and 198,280 control patients identified (median age: 61.6 years for both), 75.4% of bc patients used hcs (62.1% stage i; 85.7% stage ii; 94.6% stage iii; 79.1% stage iv) compared with 14.6% of control patients. The number of hcs used per patient-year were significantly higher for the bc patients than for the control patients (14.97 vs. 6.13, p < 0.01), resulting in higher costs per patient-year ($1,210 vs. $325; $885 attributable cost to bc, p < 0.01). The number of hcs utilized and the associated costs increased as the bc stage increased. In contrast, hcs costs decreased as income increased and as previous health care exposure decreased. INTERPRETATION: Patients with bc used twice as many hcs, resulting in costs that were almost 4 times those observed in a matched control group. Less than an additional $1000 per bc patient per year were spent on hcs utilization in the study population.

Synthesis and Screening of Novel Peptides on Human Pancreatic Islets for Type 1 Diabetes Therapies.

Type 1 diabetic patients characteristically exhibit a loss of insulin production, leading to chronic hyperglycemia and related complications. Herein we describe the design, synthesis and screening of novel oligopeptides for their potential to enhance the secretion of insulin from human pancreatic islets. The investigation of these compounds, based off the patented INGAP-PP sequence, aims to identify the peptide features key to maximizing insulin secretion.Clinical Relevance - This report describes the relative efficacy of selected novel compounds for potential Type 1 Diabetes Therapy. Tested on live human pancreatic islets, the compounds are evaluated for their enhancing/inhibitory effect on the secretion of insulin. These studies pave the way for future targeted drug therapies.

Template requirements for in vivo replication of adenovirus DNA.

The adenovirus (Ad) DNA origin of replication was defined through an analysis of the DNA sequences necessary for the replication of plasmid DNAs with purified viral and cellular proteins. Results from several laboratories have shown that the origin consists of two functionally distinct domains: a 10-base-pair sequence present in the inverted terminal repetition (ITR) of all human serotypes and an adjacent sequence constituting the binding site for a cellular protein, nuclear factor I. To determine whether the same nucleotide sequences are necessary for origin function in vivo, we developed an assay for the replication of plasmid DNAs transfected into Ad5-infected cells. The assay is similar to that described by Hay et al. (J. Mol. Biol. 175:493-510, 1984). With this assay, plasmid DNA replication is dependent upon prior infection of cells with virus and only occurs with linear DNA molecules containing viral terminal sequences at each end. Replicated DNA is resistant to digestion with lambda-exonuclease, suggesting that a protein is covalently bound at both termini. A plasmid containing only the first 67 base pairs of the Ad2 ITR replicates as well as plasmids containing the entire ITR. Deletions or point mutations which reduce the binding of nuclear factor I to DNA in vitro reduce the efficiency of plasmid replication in vivo. A point mutation within the 10-base-pair conserved sequence has a similar effect upon replication. These results suggest that the two sequence domains of the Ad origin identified by in vitro studies are in fact important for viral DNA replication in infected cells. In addition, we found that two separate point mutations which lie outside these two sequence domains, and which have little or no effect upon DNA replication in vitro, also reduce the apparent efficiency of plasmid replication in vivo. Thus, there may be elements of the Ad DNA origin of replication which have not yet been identified by in vitro studies.

Telemedicine and telepresence for trauma and emergency care management.

The use of telemedicine is long-standing, but only in recent years has it been applied to the specialities of trauma, emergency care, and surgery. Despite being relatively new, the concept of teletrauma, telepresence, and telesurgery is evolving and is being integrated into modern care of trauma and surgical patients. This paper will address the current applications of telemedicine and telepresence to trauma and emergency care as the new frontiers of telemedicine application. The University Medical Center and the Arizona Telemedicine Program (ATP) in Tucson, Arizona have two functional teletrauma and emergency telemedicine programs and one ad-hoc program, the mobile telemedicine program. The Southern Arizona Telemedicine and Telepresence (SATT) program is an inter-hospital telemedicine program, while the Tucson ER-link is a link between prehospital and emergency room system, and both are built upon a successful existing award winning ATP and the technical infrastructure of the city of Tucson. These two programs represent examples of integrated and collaborative community approaches to solving the lack of trauma and emergency care issue in the region. These networks will not only be used by trauma, but also by all other medical disciplines, and as such have become an example of innovation and dedication to trauma care. The first case of trauma managed over the telemedicine trauma program or "teletrauma" was that of an 18-month-old girl who was the only survival of a car crash with three fatalities. The success of this case and the pilot project of SATT that ensued led to the development of a regional teletrauma program serving close to 1.5 million people. The telepresence of the trauma surgeon, through teletrauma, has infused confidence among local doctors and communities and is being used to identify knowledge gaps of rural health care providers and the needs for instituting new outreach educational programs.

Giant electron-hole transport asymmetry in ultra-short quantum transistors.

Making use of bipolar transport in single-wall carbon nanotube quantum transistors would permit a single device to operate as both a quantum dot and a ballistic conductor or as two quantum dots with different charging energies. Here we report ultra-clean 10 to 100 nm scale suspended nanotube transistors with a large electron-hole transport asymmetry. The devices consist of naked nanotube channels contacted with sections of tube under annealed gold. The annealed gold acts as an n-doping top gate, allowing coherent quantum transport, and can create nanometre-sharp barriers. These tunnel barriers define a single quantum dot whose charging energies to add an electron or a hole are vastly different (e-h charging energy asymmetry). We parameterize the e-h transport asymmetry by the ratio of the hole and electron charging energies ηe-h. This asymmetry is maximized for short channels and small band gap tubes. In a small band gap device, we demonstrate the fabrication of a dual functionality quantum device acting as a quantum dot for holes and a much longer quantum bus for electrons. In a 14 nm-long channel, ηe-h reaches up to 2.6 for a device with a band gap of 270 meV. The charging energies in this device exceed 100 meV.

Digital ischemia and gangrene preceding renal neoplasm. An association with sarcomatoid adenocarcinoma of the kidney.

A 63-year-old woman had acute onset of rapidly progressive Raynaud phenomenon and digital gangrene. Prior to the detection of a sarcomatoid renal carcinoma, prominemt hypergammaglobulinemia, microhematuria, and weight loss were noted. Following nephrectomy, the patient showed improvement of the Raynaud phenomenon, with complete healing of digital ulcers and decrease of gama-globulin levels. Immunofluroescence studies demonstrated substantial deposits of IgG that lined the tumor cells in a linear and diffuse pattern. Electron-dense deposits were seen in the endothelium of arterioles int the tumor by electron microscopy. These findings suggest that antibodies to tumor antigens may have participated in the induction of digital vasculitis and Raynaud phenomenon.

Homocysteinemia as a risk factor for atherosclerosis: a review.

Elevation in plasma homocysteine has been widely studied as an independent risk factor for atherosclerosis. Animal laboratory models have demonstrated rapid onset vascular lesions with homocysteine infusion. A large body of data indicates a consistent relationship between plasma homocysteine and symptomatic atherosclerotic disease involving the coronary, peripheral, and cerebral circulations. Elevated plasma homocysteine can be predictably normalized with oral folate in most patients. Despite the wealth of published clinical data on this topic, it is unknown if normalization of plasma homocysteine in patients with symptomatic atherosclerosis will prevent or arrest the disease process.

Treatment of experimental frostbite with intra-arterial sympathetic blocking drugs.

A number of experimental and clinical studies have shown that early regional surgical sympathectomy decreases tissue loss following frostbite, presumably by relieving vasospasm and increasing blood flow. This study was performed to determine if a decrease in tissue loss following a standard cold injury could be obtained following a regional "medical sympathectomy" achieved by the intra-arterial administration of sympathetic blocking drugs. A standard cold injury was produced in rabbits and the animals were divided into nine treatment groups. Various treatment modalities were evaluated, including rapid rewarming, intra-arterial reserpine and tolazoline, and intravenous low molecular weight dextran. In the slowly rewarmed animals, the usual clinic situation, the regional intra-arterial administration of reserpine and tolazoline significantly reduced tissue loss, equalling the results obtained in the rapidly rewarmed group. These results indicate that the early achievement of a regional "medical sympathectomy" may be of benefit in reducing tissue loss following frostbite in patients, especially in those in whom rapid rewarming cannot be performed.

Pharmacologic treatment of intermittent claudication.

Twenty-six patients with severe short-distance claudication underwent a 24-week, randomized, double-blind, parallel-group evaluation of the efficacy of pentoxifylline in the treatment of intermittent claudication. The primary variables analyzed were the initial and absolute claudication distances as determined by standardized treadmill walking. A statistically significant improvement in both parameters was present in the pentoxifylline-treated patients. Nausea was the only drug side effect noted.

Alpha-adrenergic receptors in platelets from patients with Raynaud's syndrome.

The pathophysiologic basis for spastic Raynaud's syndrome remains undefined but may be related to altered adrenergic activity. The relationship between Raynaud's syndrome and alterations in adrenergic receptor populations was examined in the present study by evaluation of alpha 2-adrenergic receptors in platelets. Direct binding assays revealed 78 +/- 8 fm/mg protein of alpha 2-adrenergic receptors in the platelets from control subjects. Similar levels of alpha 2-adrenergic receptors were observed in patients with obstructive Raynaud's syndrome. In contrast, platelet alpha 2-adrenergic receptor levels were significantly elevated (182 +/- 15 fm/mg protein) in the platelets from patients with spastic Raynaud's syndrome. These results indicate the presence of an altered alpha 2-adrenergic receptor population in the platelets from patients with spastic Raynaud's syndrome, which may be related to the vasospasm experienced by these patients.

Congenital venous valvular aplasia of the lower extremities.

A 10-year-old girl had bilateral, symmetrical swelling of the lower extremities, which had been present since the age of 1 year. Noninvasive vascular laboratory measurements of the ambulatory venous pressure, venous recovery time, and maximum venous outflow revealed profound bilateral lower extremity venous valvular incompetence. Duplex imaging of the veins of the lower extremities demonstrated no evidence of thrombosis, and no venous valves could be imaged. On phlebography, the patient was found to have no venous valves in the superficial and deep systems of the leg. We conclude that congenital absence of the venous valves of the lower extremities is almost certainly underdiagnosed and that the vascular laboratory can accurately and easily differentiate between lymphedema and venous valvular imcompetence. Such differentiation may have therapeutic implications.

Intermittent subclavian venous obstruction: utility of venous pressure gradients.

A 22-year-old-man with intermittent obstruction of the subclavian vein at the thoracic outlet was evaluated by a pullback venous pressure gradient measurement and phlebography. The use of venous pressure gradient measurement allowed precise definition of the site of venous obstruction in the thoracic outlet and guided appropriate surgical therapy. The gradient information is of potential importance as many normal individuals have positional phlebographic venous compression at the thoracic outlet. Early identification of subclavian compression syndromes may avoid venous thrombosis with its attendant morbidity.

Fifteen-year results of ambulatory compression therapy for chronic venous ulcers.

A nonoperative approach to venous stasis ulceration of the lower extremity, consisting of initial bedrest, ulcer cleansing, dressing changes, and ambulatory elastic compression stocking therapy, has been maintained for over 15 years. All patients had class III, severe chronic venous insufficiency. One hundred five of 113 patients (93%) experienced complete ulcer healing in a mean of 5.3 months. One hundred two patients were compliant with elastic compression stockings, and 11 patients were noncompliant. Complete ulcer healing occurred in 99 of 102 patients (97%) who were compliant versus six of 11 patients (55%) who were noncompliant (p less than 0.0001). The influence of noncompliance, previous venous ulceration, previous venous surgery, previous known deep venous thrombosis, peripheral arterial insufficiency (ankle brachial systolic blood pressure index less than or equal to 0.60), pretreatment ulcer duration, ulcer size, age, sex, diabetes, smoking, and photoplethysmography venous refill time on ulcer healing was determined by logistic regression analysis. Only noncompliance with elastic compression stockings (p less than 0.0001) and a pretreatment ulcer duration of more than 9 months (p = 0.02) significantly decreased initial ulcer healing. Posthealing follow-up was available in 73 patients for a mean of 30 months. Fifty-eight patients (79%) continued to be compliant with stockings; 15 patients were noncompliant. Total ulcer recurrence in patients who were compliant was 16%. Five-year lifetable recurrence was 29%. All patients who were noncompliant had recurrent ulceration by 36 months. Previous ulceration, previous venous surgery, and peripheral arterial insufficiency had no effect on ulcer recurrence (p greater than 0.05).

Supraceliac aortofemoral bypass.

Increasing numbers of patients with aortoiliac disease are seen with contraindications to standard infrarenal aortofemoral reconstruction. Although axillofemoral bypass is possible in these patients, the decreased patency rate associated with this operation makes alternate procedures desirable. This report details our experience with prosthetic bypass from the supraceliac aorta to the femoral arteries in seven patients with limb-threatening ischemia of the lower extremity, all of whom had undergone multiple previous aortic operations. The operations were performed through thoracoabdominal or flank incision, and the preferred graft configuration consisted of a single Dacron tube from the aorta to the left groin with a standard subcutaneous femorofemoral graft to the right groin. No surgical deaths occurred. At 3 1/2 years' mean follow-up, there has been one graft limb occlusion that resulted in amputation for an overall life table patency and limb salvage rate of 93%. We conclude that supraceliac to femoral artery bypass is a useful procedure for the treatment of patients who have had multiple previous aortic reconstructions fail.

Carcinoid tumor of the gallbladder: laparoscopic resection and review of the literature.

A 75-year-old woman with mild elevation of liver function test results was found to have an asymptomatic mass localized to the gallbladder by computed tomographic scan and ultrasonography. Endoscopic retrograde cholangiopancreatography revealed a fixed 2 x 4 cm filling defect in the gallbladder wall, consistent with a gallbladder neoplasm. The gallbladder and intramural neoplasm were excised successfully by use of uncomplicated laparoscopic cholecystectomy. Pathologic analysis revealed a carcinoid tumor of the gallbladder. All previously reported gallbladder carcinoid tumors in the Western literature are reviewed. Laparoscopic cholecystectomy has potential for application for the treatment of selected gallbladder neoplasms, with special preoperative assessment and intraoperative considerations being important.

Change in hepatic gene expression after shock/resuscitation.

In response to specific stresses, such as a heat pulse or the sequence of hypoxia-reoxygenation, each isolated cell (prokaryotic and eukaryotic) that has been studied characteristically alters gene expression to synthesize a set of proteins (heat-shock proteins) that are important for intracellular homeostasis. To determine whether a corresponding response occurs within parenchymal cells in vivo when subjected to the complex stress of circulatory shock, liver biopsy specimens were obtained from a swine model of cardiogenic shock before and after shock/resuscitation. With use of complementary DNA prepared from post-shock/resuscitation messenger RNA, a library was constructed and screened for differential gene expression. Of 32/4000 clones initially screened as positive for induction after shock/resuscitation, six were confirmed positive by Northern blot analysis. The nucleotide sequences of two of these six have been determined, and one has been unambiguously identified as metallothionein.

The diagnosis and treatment of Raynaud's phenomenon.

Twenty-five patients with Raynaud's phenomenon, including 20 with associated diseases and five with primary Raynaud's disease, were evaluated with sequential determinations of digital temperature recovery time after cold exposure and magnification hand arteriography before and after cold exposure and before and after intra-arterial reserpine. A variety of immunologic screening tests were performed, and the clinical response to oral guanethidine of phenoxybenzamine was determined. Temperature recovery time was prolonged in all but two patients with Raynaud's phenomenon before treatment. Arteriography revealed luminal obstruction of variable degree in all but two patients with Raynaud's phenomenon but not in those with Raynaud's disease. Radiographic vasospasm was noted in all patients. Patients with Raynaud's symptoms had a markedly greater vasospastic response to cold exposure than did three control patients without Raynaud's symptoms. Arteriography 48 hours after intra-arterial reserpine repeat revealed decreased vasospasm and a decreased vasospastic response to cold in most patients. A variety of serum protein and serologic aberrations were detected, with only eight patients being free of immunologic abnormalities, Nineteen patients were treated with guanethidine alone, three with guanethidine-phenoxybenzamine combination, and one with phenoxybenzamine alone. Good or excellent clinical results were noted in 19 of the 23 patients treated, with an average follow-up to date of 12 months.