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Human postmortem tissue: what quality markers matter?

Postmortem human brain tissue is used for the study of many different brain diseases. A key factor in conducting postmortem research is the quality of the tissue. Unlike animal tissue, whose condition at death can be controlled and influenced, human tissue can only be collected naturalistically. This introduces potential confounds, based both on pre- and postmortem conditions, that may influence the quality of tissue and its ability to yield accurate results. The traditionally recognized confounds that reduce tissue quality are agonal factors (e.g., coma, hypoxia, hyperpyrexia at the time of death), and long postmortem interval (PMI). We measured tissue quality parameters in over 100 postmortem cases collected from different sources and correlated them with RNA quality (as indicated by the RNA Integrity Number (RIN)) and with protein quality (as measured by the level of representative proteins). Our results show that the most sensible indicator of tissue quality is RIN and that there is a good correlation between RIN and the pH. No correlation developed between protein levels and the aforementioned factors. Moreover, even when RNA was degraded, the protein levels remained stable. However, these correlations did not prove true under all circumstances (e.g., thawed tissue, surgical tissue), that yielded unexpected quality indicators. These data also suggest that cases whose source was a Medical Examiner's office represent high tissue quality.

Adult↗

Increased plasma concentration of epidermal growth factor in female patients with non-toxic nodular goitre.

OBJECTIVE: Epidermal growth factor (EGF) is believed to be one of the most potent growth factors for the thyroid gland. DESIGN AND METHODS: We tested plasma EGF concentrations (radioreceptor method) in patients with non-toxic nodular goitre (NNG). Blood samples from patients with NNG were collected on the day before the surgery, during subtotal thyroidectomy (sTx)--from peripheral and thyroid veins, on the 3rd day after sTx, 3 months after sTx, and 9 months after the surgery. RESULTS: Before the operation, the mean plasma EGF concentration in 50 women with NNG was significantly higher (1.16 +/- 0.69 ng/ml; mean +/- S.E.) than that in 32 control female patients subjected subsequently to other (non-thyroid) operations (0.41 +/- 0.27 ng/ml; P < 0.001), and that in 20 healthy women (0.35 +/- 0.11 ng/ml; P < 0.001), both of which groups were without goitre or had a small non-toxic diffuse goitre. The surgical treatment of NNG resulted in a significant reduction in plasma EGF 3 months after sTx (0.56 +/- 0.22 ng/ml). A further slight decrease was observed 9 months after sTx (0.44 +/- 0.14 ng/ml). CONCLUSIONS: Our observations confirm the assumption that EGF may participate in the process of goitre formation in human subjects. However, the source of EGF involved in this process remains unclear. Some findings could suggest that plasma EGF, which was increased in patients with NNG, may be of non-thyroid origin; however, the majority of our observations strongly stress the significance of an intact thyroid in the preservation of an unchanged EGF value, suggesting a role of locally produced EGF in the pathogenesis of NNG.

Adult↗

Perioperative fractionated high-dose rate brachytherapy in the treatment of soft tissue sarcomas.

The purpose of the study was to investigate the viability of perioperative fractionated high dose rate brachytherapy (HDR BT) for primary and reccurent soft tissue sarcomas (STS). From February 1998 through June 2002, 21 adult patients, 11 females and 10 males with either low grade or high grade soft tissue sarcomas were treated by perioperative HDR BT. Surgical margin was negative in 10 cases, close in 4 and positive in 4 in cases. In 3 cases it was not described. BT was used as a part of primary treatment in 10 cases and for the treatment of reccurent tumor in 11 cases. The localisation of the tumor was the extremity in 16 patients and the trunk in 5 patients. Ten patients were treated with HDR BT alone (total mean dose 40 Gy) and 11 were treated with combination of external beam radiotherapy (EBRT) (40-50 Gy) and brachytherapy (total mean dose 24 Gy). Hyperfractionation 2.4-3 Gy twice daily at 10 mm from the source was used for BT. Follow-up periods were between 7--48 months (median: 20 months). Local control in patients treated pro primary STS was 100%.The pulmonal metastases were a cause of death in one case, one patient was alive with dissemination and one patient was disease free after salvage surgery and chemotherapy for lung metastases. Local control was achieved only in 3 of 11 patients treated for reccurent tumor (27%). Six patients were disease free after salvage surgery, 2 patients died of disease progression, one patient died of toxicity of chemotherapy without evidence of disease and 2 patients are alive with distant metastases. Local control was achieved in 5 of 11 (45%) patients with positive, close or not stated surgical margin and in 5 of 10 (50%) patients with negative margin. Local control was 100% in patients treated by EBRT + BT, but only 20% in patients treated by BT alone. No infection or delayed wound healing has occurred after BT. Soft tissue necrosis was seen in 4 cases, subcutanous fistula in one case and peripheral nerve palsy in one case. Despite small number of patients and short follow up our study suggest that perioperative HDR BT is easy and promissing when used as a part of primary treatment for STS. The treatment results for recurrence are poor and in a lot of cases radical surgical approach should have been considered for the salvage.

Adult↗

Hybrid surgical angiogenesis: omentopexy can enhance myocardial angiogenesis induced by cell therapy.

BACKGROUND: The conditions at the injection site are important in cell transplantation for severe ischemic heart disease. The omentum is both a well-vascularized tissue and a source of angiogenic factors. We examined the effectiveness of autologous bone marrow-derived mononuclear cells (BM-MNCs) with or without omentopexy in a large animal model. METHODS: Myocardial infarction was generated in the lateral wall by ligation of coronary artery branches in miniswine. Animals received BM-MNC injection with or without omentopexy. Controls received saline only. Three weeks after surgery, regional myocardial blood flow and contractility were measured, and density of arterioles was evaluated immunohistologically. Angiography and postmortem examinations were performed to determine collateral communication. RESULTS: Regional myocardial contractility was significantly improved by BM-MNC transplantation both with and without omentopexy (0.29 +/- 0.02 vs 0.11 +/- 0.03, p < 0.01, 0.30 +/- 0.02 vs 0.12 +/- 0.01, p < 0.01, respectively). Relative regional myocardial blood flow in the combined omentopexy group was significantly higher than the controls both at rest (1.05 +/- 0.11 vs 0.57 +/- 0.07, p < 0.01) and under stress (1.09 +/- 0.08 vs 0.40 +/- 0.10, p < 0.01). The number of arterioles (< 50 microm) in both groups were higher than the controls (88.1 +/- 5.00 vs 38.1 +/- 8.99, p < 0.01 and 109.2 +/- 9.91 vs 38.1 +/- 8.99, p < 0.01, respectively). The number of large arterioles (> 50 microm) in the combined omentopexy group was significantly higher than in both BM-MNC alone (26.9 +/- 2.4 vs 17.6 +/- 1.8, p = 0.011) and controls (26.9 +/- 2.4 vs 10.0 +/- 1.3, p < 0.01). Collateral communication between the omentum and myocardium was demonstrated by angiography and postmortem injection. CONCLUSIONS: The BM-MNC transplantation may attenuate cardiac contractile dysfunction, and omentopexy may enhance angiogenesis induced by BM-MNC transplantation.

Angiography↗

Haemostasis in laparoscopy.

OBJECTIVE: Adequate haemostasis is essential for advanced laparoscopic procedures since uncontrolled bleeding may cause significant complications and even required converting to laparotomy to obtain sufficient haemostasis. The aim of this review is to give insight into the most important tools and strategies to achieve sufficient haemostasis during advanced urologic laparoscopy. METHODS AND RESULTS: Lowering the risk of haemorrhage may be achieved primarily by proper case selection, resulting in adequate laparoscopic preparation and dissection technique or the use of local compression by sponge stick to control local bleeding. For early bleeding control, laparoscopic clip appliers, staplers and suturing techniques may be utilised. Various energy sources such as monopolar and bipolar electrocautery, argon beam coagulators, laser or ultrasonic dissectors and topical sealing agents can be used to augment natural haemostasis. CONCLUSIONS: A wide armamentarium for achieving haemostasis during laparoscopy is available. Consequently, laparoscopic surgeons must have detailed knowledge of the physical concepts of each surgical instrument or energy source and of proper use of tissue sealants for obtaining sufficient haemostasis. This knowledge will improve postoperative outcome, increase patient safety and guide laparoscopic techniques to further perspectives.

Catheterization↗

Impact of endoscopic therapy on outcome of operation for bleeding peptic ulcers.

Since elective surgery for bleeding peptic ulcer disease has declined, the surgical opinion is that patients who undergo emergency operation have more advanced disease and possibly a poorer outcome. We examined current mortality for surgical correction of upper gastrointestinal (UGI) bleeding from peptic ulcer disease. Between July 1, 1986, and December 31, 1990, 1,213 patients had esophagogastroduodenoscopy for UGI bleeding (659 with peptic ulcer disease, 219 with gastroesophageal varices, 152 with esophagitis, 83 with other causes, and 100 with no source found). Of 110 patients with peptic ulcer disease treated by endoscopic methods, bleeding was controlled in 90, and 20 required operation for failed endoscopic control. Another 22 patients had primary operation for exigent bleeding with diagnostic endoscopy only. The overall results in our series compared favorably with two pre-therapeutic endoscopy index series (Nottingham, 1982; University of Pittsburgh, 1982). Our operation rate was 6%, with a mortality rate of 7%, compared with operation rates of 15% to 27%, with mortality rates of 21% to 22% in the historical control series. In conclusion, we found that: (1) endoscopic control of UGI bleeding from peptic ulcer disease has decreased the incidence of operation compared with historical series; (2) overall operative mortality is decreasing; and (3) the major postoperative complication is rebleeding.

Adult↗

Postmastectomy radiation therapy: A surgical perspective.

Controversy exists about whether postmastectomy radiotherapy prolongs survival or is merely of benefit to maintain local control. Surgical series of patients treated by radical or modified radical mastectomy alone show locoregional failure rates ranging from 4% to 26%. The likelihood of involvement of supraclavicular and internal mammary nodal metastases increases as the extent of axillary nodal involvement increases. Adjuvant systemic therapy appears to have limited impact on the incidence of locoregional failure. Untreated nodal disease is a potential source of tumor dissemination and provides a biological rationale for a survival benefit for irradiation.

Breast Neoplasms↗

Possible sources of neuroprotection following subretinal silicon chip implantation in RCS rats.

Current retinal prosthetics are designed to stimulate existing neural circuits in diseased retinas to create a visual signal. However, implantation of retinal prosthetics may create a neurotrophic environment that also leads to improvements in visual function. Possible sources of increased neuroprotective effects on the retina may arise from electrical activity generated by the prosthetic, mechanical injury due to surgical implantation, and/or presence of a chronic foreign body. This study evaluates these three neuroprotective sources by implanting Royal College of Surgeons (RCS) rats, a model of retinitis pigmentosa, with a subretinal implant at an early stage of photoreceptor degeneration. Treatment groups included rats implanted with active and inactive devices, as well as sham-operated. These groups were compared to unoperated controls. Evaluation of retinal function throughout an 18 week post-implantation period demonstrated transient functional improvements in eyes implanted with an inactive device at 6, 12 and 14 weeks post-implantation. However, the number of photoreceptors located directly over or around the implant or sham incision was significantly increased in eyes implanted with an active or inactive device or sham-operated. These results indicate that in the RCS rat localized neuroprotection of photoreceptors from mechanical injury or a chronic foreign body may provide similar results to subretinal electrical stimulation at the current output evaluated here.

Animals↗

Clinical detection and movement recognition of neuro signals.

Neuro signal has many more advantages than myoelectricity in providing information for prosthesis control, and can be an ideal source for developing new prosthesis. In this work, by implanting intrafascicular electrode clinically in the amputee's upper extremity, collective signals from fascicules of three main nerves (radial nerve, ulnar nerve and medium nerve) were successfully detected with sufficient fidelity and without infection. Initial analysis of features under different actions was performed and movement recognition of detected samples was attempted. Singular value decomposition features (SVD) extracted from wavelet coefficients were used as inputs for neural network classifier to predict amputee's movement intentions. The whole training rate was up to 80.94% and the test rate was 56.87% without over-training. This result gives inspiring prospect that collective signals from fascicules of the three main nerves are feasible sources for controlling prosthesis. Ways for improving accuracy in developing prosthesis controlled by neuro signals are discussed in the end.

Amputation, Surgical↗

An outbreak of Staphylococcus aureus in a pediatric cardiothoracic surgery unit.

OBJECTIVE: To investigate an outbreak of Staphylococcus aureus surgical-site infections. DESIGN: Case-control study. SETTING: Pediatric cardiothoracic surgery service of a tertiary-care university medical center. METHOD: Molecular typing was used to identify healthcare workers who carried the epidemic strain. RESULTS: Three children acquired surgical-site infections caused by a single strain of S. aureus. Fourteen (25%) of the staff members in the operating room and 17 (11%) on nursing units carried the epidemic strain (P = .01). A case-control study identified 4 healthcare workers who were associated statistically with the outbreak, 2 of whom (a cardiothoracic surgeon and a perfusionist) carried the epidemic strain in their nares. The surgeon also carried the epidemic strain on his hands. Each staff member who carried the epidemic strain was treated with mupirocin; those carrying the strain on their hands were required to wash their hands with chlorhexidine. The surgeon was not allowed to perform surgery until 2 of his hand cultures did not grow S. aureus. CONCLUSIONS: Only three children were infected with the epidemic strain, but it was disseminated widely among staff who cared for children who underwent cardiothoracic surgery. No additional cases were identified after staff members who carried the epidemic strain were decolonized. Both classic epidemiologic methods and molecular typing techniques were necessary to identify the source and extent of this outbreak.

Carrier State↗

An evaluation of completeness of tuberculosis notification in the United Kingdom.

BACKGROUND: There has been a resurgence of tuberculosis worldwide, mainly in developing countries but also affecting the United Kingdom (UK), and other Western countries. The control of tuberculosis is dependent on early identification of cases and timely notification to public health departments to ensure appropriate treatment of cases and screening of contacts. Tuberculosis is compulsorily notifiable in the UK, and the doctor making or suspecting the diagnosis is legally responsible for notification. There is evidence of under-reporting of tuberculosis. This has implications for the control of tuberculosis as a disproportionate number of people who become infected are the most vulnerable in society, and are less likely to be identified and notified to the public health system. These include the poor, the homeless, refugees and ethnic minorities. METHOD: This study was a critical literature review on completeness of tuberculosis notification within the UK National Health Service (NHS) context. The review also identified data sources associated with reporting completeness and assessed whether studies corrected for undercount using capture-recapture (CR) methodology. Studies were included if they assessed completeness of tuberculosis notification quantitatively. The outcome measure used was notification completeness expressed between 0% and 100% of a defined denominator, or in numbers not notified where the denominator was unknown. RESULTS: Seven studies that met the inclusion and exclusion criteria were identified through electronic and manual search of published and unpublished literature. One study used CR methodology. Analysis of the seven studies showed that undernotification varied from 7% to 27% in studies that had a denominator; and 38%-49% extra cases were identified in studies which examined specific data sources like pathology reports or prescriptions for anti-tuberculosis drugs. Cases notified were more likely to have positive microbiology than cases not notified which were more likely to have positive histopathology or be surgical in-patients. Collation of prescription data of two or more anti-tuberculosis drugs increases case ascertainment of tuberculosis. CONCLUSION: The reporting of tuberculosis is incomplete in the UK, although notification is a statutory requirement. Undernotification leads to an underestimation of the disease burden and hinders implementation of appropriate prevention and control strategies. The notification system needs to be strengthened to include education and training of all sub-specialities involved in diagnosis and treatment of tuberculosis.

Disease Notification↗

Universal precautions to prevent HIV transmission to health care workers: an economic analysis.

The universal precautions recommended by the US Centers for Disease Control (CDC), Atlanta, for the prevention of HIV (human immunodeficiency virus) transmission to health care workers are widely accepted, despite little documentation of their effectiveness and efficiency. We reviewed the evidence on the risk of HIV transmission to hospital workers and the effectiveness of the universal precautions. We also evaluated the costs of implementing the recommendations in a 450-bed acute care teaching hospital in Hamilton, Ont. On the basis of aggregated results from six prospective studies the risk of HIV seroconversion among hospital workers after a needlestick injury involving a patient known to have AIDS (acquired immune deficiency syndrome) is 0.36% (upper 95% confidence limit 0.67%); the risk after skin and mucous membrane exposure to blood or other body fluids of AIDS patients is 0% (upper 95% confidence limit 0.38%). We estimated that 0.038 cases of HIV seroconversion would be prevented annually in the study hospital if the CDC recommendations were followed. The incremental cost of implementing the universal precautions was estimated to be about $315,000 per year, or over $8 million per case of HIV seroconversion prevented. If all HIV-infected workers were assumed to have AIDS within 10 years of infection the of the program would be about $565,000 per life-year saved. When less conservative, more probable assumptions were applied the best estimate of the implementation cost was $128,862,000 per case of HIV seroconversion prevented. The universal precautions implemented in the study hospital were not found to be efficacious or cost-effective. To minimize the already small risk of HIV transmission in hospitals the sources of risk of percutaneous injury should be better defined and the design of percutaneous lines, needles and surgical equipment as well as techniques improved. Preventive measures recommended on the basis of demonstrated efficacy and aimed at routes of exposure that represent true risk are needed.

Acquired Immunodeficiency Syndrome↗

Management of non-small cell lung cancer with direct mediastinal involvement.

The results of surgical treatment were analyzed for 102 patients with non-small cell lung cancer invading the mediastinum by direct extension (T3 and T4), but those who had N2 disease were excluded to eliminate the adverse prognostic effect of this nodal subset. The histologic type was squamous cell carcinoma in 55 patients, adenocarcinoma in 40, and large cell carcinoma in 7. There were 58 T3 tumors invading the mediastinal pleura or fat, phrenic nerve, vagus nerve, pericardium, or pulmonary vessels and 44 T4 lesions invading the aorta, vena cava, esophagus, trachea, spine, or atrium. Resection included lobectomy (33 patients), pneumonectomy (32 patients), and limited resection (6 patients). Complete resection was possible in 46 patients and incomplete or no resection was possible in 56. The interstitial implantation of radioactive sources to control residual tumor also was undertaken in 43 patients. The operative mortality was 6%. The overall survival (Kaplan-Meier) was 19% at 5 years (median survival time, 18 months). Factors found to be significantly affect survival were complete resectability and the histologic type. With complete resection, the 5-year survival was 30% (p = 0.005). The 5-year survival in patients with adenocarcinoma or large-cell carcinoma was 30%, compared with 14% in patients with squamous cell carcinoma (p = 0.002). The extent of mediastinal involvement (T3 versus T4) influenced resectability and survival, and this approached statistical significance (p = 0.055). We conclude that most patients with non-small cell carcinoma and mediastinal invasion do poorly with primary surgical treatment.

Adult↗

Visual function of police officers who have undergone refractive surgery.

INTRODUCTION: The visual acuity and contrast sensitivity of police recruits and officers was evaluated in both normal and dim illumination conditions to determine whether officers who have had refractive surgery have compromised night vision. METHODS: The control group consisted of 76 officers and recruits who have not had refractive surgery and the refractive surgery group consisted of 22 officers and recruits who had refractive surgery. Visual acuity and contrast sensitivity were measured under both room illumination and dim illumination. The room illumination test series included high contrast acuity, low contrast acuity and Pelli-Robson contrast sensitivity. The dim illumination test series included high contrast acuity, low contrast acuity, Pelli-Robson contrast sensitivity, license plate number acuity (with and without glare) and the Mesotest. RESULTS: The general findings were that the refractive surgery group had lower acuity scores on low contrast targets in both room and dim light levels along with a reduction in the Mesotest scores with a glare source compared to the control group. CONCLUSIONS: Although refractive surgery police recruits and officers had reduced performance on some vision tests, these reductions were small and it is unlikely that their performance on vision related tasks would be compromised, on average. The major concern is the small number of refractive surgery candidates whose results were well outside the range of the non-surgical candidates. Their vision may be unacceptable for policing.

Adult↗

Condyloma acuminata: an unusual presentation of child abuse.

Condyloma acuminata seen in childhood is a disease not well recognized as a sign of child abuse. These viral lesions are often diagnosed and treated without regard to their venereal mode of transmission. Four infants and children with condyloma acuminata ranging in age from 14 mo to 11 yr required surgical management. Two required multiple procedures for control of the lesions. Indications for surgical treatment include large, recurrent, or refractory lesions, as well as the need for histologic identification and acquiring tissue for immunotherapy when necessary. The follow-up care is often difficult because of the socioeconomic structure of the involved families. Careful and persistent medical and social care is necessary to adequately treat the disease and remove the source of infection and to protect children from sexual abuse.

Child↗

A new technique of brachytherapy for malignant gliomas with caesium-137: a new method utilizing a remote afterloading system.

Failure of conventional treatment to cure malignant gliomas has stimulated interest in various forms of brachytherapy. We describe a new method of using intracranial radiation utilizing a remotely-controlled afterloading system with a modified endotracheal tube as the applicator. The system used is the Selectron LDM/MDR (Nucleotron) which is a sophisticated machine widely available at radiotherapy centres and primarily used to treat gynaecological malignancies. It uses Caesium-137 in the form of spherical pellets in a linear source train within a sealed system. The applicator is implanted at the time of surgical resection. The inflated balloon stabilises the applicator and allows a suitable dose distribution at a distance from the source train to be achieved. Details of the implantation and radiation procedures as well as the dosimetry calculation are presented. The advantages are simplicity of use, the elimination of radiation risk to personnel and the combination of cytoreduction and applicator implantation in one surgical procedure.

Brachytherapy↗

Exclusion of elderly women from published randomized trials of stress incontinence surgery.

OBJECTIVE: More than 20,000 women, aged 70 years or older, undergo surgery for stress urinary incontinence each year. Our objective was to review the published randomized trials of the surgical treatment of stress urinary incontinence and estimate the proportion of women 70 years or older enrolled in those trials. DATA SOURCES: MEDLINE and Cochrane Databases of Clinical Trials were searched from January 1966 through December 2003 with the terms "urinary incontinence," "stress incontinence," "urethropexy," "needle suspension," "pubovaginal sling," "tension-free vaginal tape," "urethral injection," "collagen injection," "anterior colporrhaphy," and "clinical trial," "controlled trial," or "randomized trial" as both subject headings and words contained in article titles. We supplemented this search with manual searches of meta-analyses and review articles from 2000 to 2003. METHODS OF STUDY SELECTION: All studies that included at least one group undergoing an invasive treatment for stress incontinence (including urethral bulking injections) were reviewed. We excluded reports without sufficient data to estimate the number of women aged 70 and older who participated, those published only in abstract form, and those studies in languages other than English, French, German, Italian, or Spanish. Twenty studies met our inclusion criteria. TABULATION, INTEGRATION, AND RESULTS: The number of women aged 70 or older in each study was estimated using the demographic data provided. The median percentage of subjects aged 70 or older was 3.8% (interquartile range 0.37-15%). There was no significant difference in the proportion of subjects 70 years of age or older based on the year of publication. CONCLUSION: Our review of the published literature suggests that elderly women are underrepresented in clinical trials of stress incontinence surgery. Efforts should be made to include more elderly women in clinical trials of stress incontinence surgery.

Aged↗

A review of mechanical adjuncts in wound healing: hydrotherapy, ultrasound, negative pressure therapy, hyperbaric oxygen, and electrostimulation.

Chronic or non-healing wounds may develop in the setting of many diseases and are the source of considerable morbidity as well as health costs. These wounds demand an aggressive, multifactorial approach including surgical debridement, revascularization, antibiotics and dressings. In addition several adjuvant treatment methods have been developed to further stimulate healing. Whirlpool, although used frequently, has not been proven to be of benefit. However, pulsed lavage does show a promising future. Ultrasound has demonstrated beneficial effects but further controlled studies are needed. Subatmospheric pressure therapy is associated with few complications and is fast becoming a mainstay of adjuvant therapy. Hyperbaric oxygen therapy has been shown to be effective for many types of wounds. Unfortunately, cost and access to chambers may prohibit its use on a routine basis. Finally, electrostimulation may be one of the up and coming therapies for the future. Though, more studies are needed to determine the mode of delivery for various types of wounds.

Electric Stimulation Therapy↗