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PubMed1994

Quantitative single-photon emission computed tomography: basics and clinical considerations.

Although quantitative single-photon emission computed tomography (SPECT) has been the goal of much research effort for a number of years, only recently has it received wide interest, especially for clinical applications. It has been increasingly recognized that the achievement of quantitative SPECT will increase the accuracy of measurements, such as dimensions of specific regions of interest, absolute amount of radioactivity, and dosimetry calculations, and substantially reduce reconstruction image artifacts and distortions, thus, greatly improving clinical diagnosis. This article provides a review of the definition of terms, major factors affecting SPECT quantitation and their degrading effects on SPECT image quality, and methods to compensate for these effects. Compensation methods include those that make certain approximations for ease of implementation and those that provide more accurate compensation by modeling the imaging process more exactly, usually at the cost of increased complexity and computational requirements. Different reconstruction and compensation methods may be compared through the use of phantom cardiac and brain SPECT studies. The clinical efficacy of the methods may be demonstrated by applying them to a clinical thallium-201 myocardial perfusion SPECT study. The results clearly demonstrate that, by modeling the imaging process and/or image degrading factors three-dimensionally, quantitative reconstruction and compensation methods provide the best image quality and quantitative accuracy. Important research efforts and developmental work being conducted currently to bring quantitative SPECT into routine clinical use are also discussed.

Humans↗
PubMed1978

Similarity of clinical and laboratory results obtained with microporous teflon membrane oxygenator and bubble-film hybrid oxygenator.

For 80 elective clinical cardiopulmonary bypasses we alternately used either a commercial microporous Teflon membrane oxygenator or a commercial hybrid bubble-film oxygenator. Setup time was a little longer with the membrane unit (20 minutes), but priming volume (2,250 ml) was the same. No problems were encountered with the hybrid oxygenator. However, despite our monitoring of additional variables, including shim and inlet pressure and recirculation flow, gas exchange abnormalities were encountered in 5 patients on whom the membrane oxygenator was used; in 4 of these cases the abnormalities were encountered prior to our recognition of the potential for occasional internal shunting with this device. There were no hospital deaths. When the two groups, matched except for oxygenator selection, were compared, there were no significant differences clinically or hematologically. For cardiopulmonary bypass of 2 hours or less, both oxygenators studied are definite improvements over previous silicone membrane and high-gas-flow bubble oxygenators. However, lower cost and reduced complexity favor the hybrid oxygenator.

Blood Glucose↗
PubMed1997

Total arteriovenous CO2 removal: simplifying extracorporeal support for respiratory failure.

BACKGROUND: To reduce the complexity, complications, and cost of conventional extracorporeal membrane oxygenation, we have developed a technique of simplified arteriovenous extracorporeal CO2 removal (AVCO2R) with a low-resistance membrane gas exchanger for total CO2 removal to provide lung rest in the setting of severe respiratory failure. METHODS: We initially used AVCO2R in healthy animals to quantify the gas exchange capabilities of the system and establish ventilator management protocols for the subsequent studies of AVCO2R in a large animal model of respiratory failure secondary to a severe smoke inhalation injury. RESULTS: In healthy sheep the maximum spontaneous arteriovenous flow ranged from 1,350 to 1,500 mL/min, whereas CO2 removal plateaued at a blood flow of approximately 1,000 mL/min in which 112 +/- 3 mL/min CO2 was removed, allowing an 84% reduction in the minute ventilation of from 6.9 +/- 0.8 L/min to 1.1 +/- 0.4 L/min (p < 0.01) without triggering hypercapnia. A subsequent reduction in extracorporeal flow at a reduced minute volume led to the development of hypercapnia only if it decreased to less than 500 mL/min. We also applied AVCO2R in mechanically ventilated sheep with a severe smoke inhalation injury and removed 95% (111 +/- 4 mL/min) of the total CO2 production. This allowed the minute ventilation to be reduced by 95% and the peak inspiratory pressures by 52% (both p < 0.05) over 6 hours and produced no adverse hemodynamic effects. The partial pressure of arterial oxygen was maintained above 100 mm Hg at a maximally reduced minute volume. The mean AVCO2R flow was 1,213 +/- 29 mL/min, averaging 27% +/- 1% of the cardiac output. CONCLUSIONS: We conclude that AVCO2R in a simple arteriovenous shunt is a less complicated technique than extracorporeal membrane oxygenation and is capable of total CO2 removal that allows a significant reduction in the minute ventilation and peak airway pressure during severe respiratory failure.

Animals↗
PubMed2002

Antibiotic therapy--managing odontogenic infections.

Several pharmaceuticals have been developed in the past 10 years that have made a significant impact on the health of the human race. There have been few advances, however, that have proved more efficacious than the pharmacotherapies we have had available for many decades for the treatment of odontogenic infections. Many new antibiotics/antimicrobials have been developed, but none have been determined to be of significant benefit to replace or supplant the use of penicillins for the management of orofacial infections caused by pathogens in and around the oral cavity. Judicious use of antibiotics in conjunction with surgical therapy is the most appropriate method to treat odontogenic infections. Using the antibiotic "du jour," many times promoted by pharmaceutical representatives, results in costly and unnecessary complexity of care. A return to the basics is indicated for the antibiotic management of odontogenic infections.

Abscess↗
PubMed1991

The role of superovulation with menotropins in ovulatory infertility: a review.

The risks of menotropin therapy (ovarian hyperstimulation syndrome, multiple gestation, adnexal torsion) are well known and have been previously described. Superovulation should not be considered for the indications described herein until more traditional therapies for infertility have been tried and found unsuccessful and sufficient time has elapsed for conception to occur. The cost of superovulation is high: the medications are expensive, frequent E2 monitoring and US studies are costly, and pregnancy complications relating to the higher rate of pregnancy loss and multiple gestation may add substantially to the overall cost. Yet, compared with IVF and GIFT, superovulation cycles combined with IUI cost between one third to one sixth that of an IVF cycle. Protocols involving combined CC/hMG/hCG, which reduce the total number of ampules of Pergonal needed per cycle and still provide multiple follicular development, may further reduce costs. There is a growing consensus that superovulation-IUI protocols should be attempted before GIFT and IVF in couples with normal pelvic viscera. There is little doubt that IVF and GIFT cycles are more costly, stressful, and complex. No comparative data have clearly shown IVF and GIFT to be superior to superovulation protocols in ovulatory women with normal pelvic anatomy. In the only study examining this issue published to date, Kaplan et al. retrospectively analyzed all GIFT and superovulation/IUI cycles at a single university center and found GIFT to be three times more efficient. However, the inherent limitations of a nonrandomized, nonprospective study of this kind are obvious as these authors have suggested. Therefore, it may be wise to consider the use of superovulation before assisted reproductive technologies until this issue is settled. It would be interesting to determine if the high PRs reported for couples with unexplained infertility or mild endometriosis in IVF and GIFT cycles in some centers not incorporating superovulation/IUI protocols would hold up if such an approach was routinely followed. Despite the increasing acceptance of superovulation protocols, we must be aware that many of the studies suggesting a role of hMG in treating ovulatory infertile women with normal pelvic anatomy suffer from deficiencies in experimental design. In a payor-driven system, such as in the United States, the difficulties in designing and carrying out scientifically sound clinical studies examining infertility therapies are obvious. The lack of federal or outside funding for the study of infertility issues contributes to the problem. It is our hope that better designed studies examining the role of superovulation in the treatment of ovulatory infertile women with normal pelvic anatomy will be forthcoming.

Female↗
PubMed2000

Three-year outcome of a progressive treatment program for erectile dysfunction with intracavernous injections of vasoactive drugs.

OBJECTIVES: To perform a comparative evaluation and follow-up of patients with erectile dysfunction (ED) who were treated with intracavernous injection of vasoactive drugs, starting with simple drugs and advancing to complex combinations. METHODS: The study included 625 patients, 26 to 85 years old, with ED. Four intracavernous injection protocols were used: protocol 1, papaverine plus phentolamine; protocol 2, prostaglandin E(1); protocol 3, papaverine, phentolamine, and prostaglandin E(1); and protocol 4, atropine sulfate, papaverine, phentolamine, and prostaglandin E(1). A positive response was defined as an erection sufficient for penetration. Patients for whom the basic protocol failed were successively switched to the more advanced protocols until a positive response was achieved. RESULTS: A positive response was achieved by 415 (66.4%) of the 625 patients given protocol 1; 75 (36%) of the remaining 210 patients given protocol 2; 98 (72.6%) of the 135 patients given protocol 3; and 22 (59.5%) of 37 patients given protocol 4. All four protocols failed in only 15 patients (2. 4%). At the 3-year follow-up visit (n = 610), 349 had achieved coitus, 65 (10.6%) without an injection and 202 (33.1%) with an injection. Eighty-two patients sometimes performed coitus without an injection. Sixty-three patients (10.3%) abandoned the program because of marital or health problems; 198 asked to be switched to Viagra during the follow-up period, and 120 returned to the program. CONCLUSIONS: Overall, our progressive treatment yielded a high positive response rate (97.6%), with 57.2% achieving successful coitus on follow-up. The main advantage of the program is that it spares patients who are responsive earlier from using more complex, painful, and costly drugs.

Adult↗
PubMed2006

Fluorescence versus conventional sputum smear microscopy for tuberculosis: a systematic review.

Most of the world's tuberculosis cases occur in low-income and middle-income countries, where sputum microscopy with a conventional light microscope is the primary method for diagnosing pulmonary tuberculosis. A major shortcoming of conventional microscopy is its relatively low sensitivity compared with culture, especially in patients co-infected with HIV. In high-income countries, fluorescence microscopy rather than conventional microscopy is the standard diagnostic method. Fluorescence microscopy is credited with increased sensitivity and lower work effort, but there is concern that specificity may be lower. We did a systematic review to summarise the accuracy of fluorescence microscopy compared with conventional microscopy. By searching many databases and contacting experts, we identified 45 relevant studies. Sensitivity, specificity, and incremental yield were the outcomes of interest. The results suggest that, overall, fluorescence microscopy is more sensitive than conventional microscopy, and has similar specificity. There is insufficient evidence to determine the value of fluorescence microscopy in HIV-infected individuals. The results of this review provide a point of reference, quantifying the potential benefit of fluorescence microscopy, with which the increased cost and technical complexity of the method can be compared to determine the possible value of the method under programme conditions.

Cytodiagnosis↗
PubMed1992

Clinical PET scanning. A "short-lived" orphan.

Positron emission tomography (PET) is a method of nuclear medicine imaging that uses short-lived radiopharmaceuticals to detect and quantify the metabolic abnormalities of disease processes. PET initially was developed in a research environment as a research tool; data from these research studies resulted in the gradual recognition that PET studies would be useful for various routine clinical applications. The diffusion of PET into clinical practice has been slow in comparison with other new imaging methods (e.g., magnetic resonance imaging). This slow diffusion is attributable to several factors, including the complexity and high cost of PET, the uncertain role of the U.S. Food and Drug Administration in regulating the radiopharmaceuticals that are produced and used on-site for PET studies, and the apparent slow pace at which the Health Care Financing Administration and other third-party payers are developing policies for reimbursing for PET.

Centers for Medicare and Medicaid Services, U.S.↗
PubMed2004

A blood-brain barrier disruption model eliminating the hemodynamic effect of ketamine.

OBJECTIVE: We propose a simple modification to an established blood-brain barrier disruption (BBBD) animal model that allows us to use ketamine/xylazine as the anaesthetic agent, therefore decreasing the complexity and the cost of the model, while maintaining similar efficiency. METHODS: Sixty-two Long Evans rats were anaesthetized by intraperitoneal injection of ketamine/xylazine. Osmotic BBBD was performed by administering 25% mannitol into the internal carotid artery in a retrograde fashion from the external carotid. The infusion rate of mannitol, as well as the duration was adjusted in a stepwise fashion to identify optimal parameters for BBBD and minimize complications. As a supplementary step to previously reported models, a vascular clip was applied to the common carotid artery prior to the infusion of mannitol, therefore isolating our model system from the depressant hemodynamic effects of ketamine/xylazine. Evans blue dye was used to control for BBBD intensity. RESULTS: Using this model at an initial infusion rate of 0.15 ml/sec, a significant incidence of brain hemorrhage (75%) and a death rate of 62.5% were observed. Decreasing the infusion rate in a stepwise fashion, 0.08 ml/sec was found to produce optimal BBBD, as demonstrated by Evans blue staining. At this rate, 6/7 animals depicted grade II staining, whereas one animal depicted grade IV. CONCLUSION: The application of a clip to the common carotid artery prior to mannitol infusion allowed us to isolate the cerebral circulation from the depressant hemodynamic effects of ketamine/xylazine. This supplementary step produced consistent and efficient BBBD in our animal model.

Adrenergic alpha-Agonists↗
PubMed1999

Population newborn screening for inherited metabolic disease: current UK perspectives.

Some of the generally accepted criteria for screening programmes are inappropriate for newborn metabolic screening as they ignore the family dimension and the importance of timely genetic information. Uncritical application of such criteria creates special difficulties for screening by tandem mass spectrometry, which can detect a range diseases with widely different natural histories and responsiveness to treatment. Further difficulties arise from increasing demands for direct proof of the effects of screening on long-term morbidity and mortality. The randomized controlled trial is held to be the gold standard, but for ethical and practical reasons it will be impossible to achieve for such relatively rare diseases. This approach also oversimplifies the complex matrix of costs and benefits of newborn metabolic screening. A more workable approach could involve Bayesian synthesis, combining quantitative performance data from carefully designed prospective pilot studies of screening with existing experience of the natural history, diagnosis, and management of the individual disorders concerned.

Humans↗
PubMed2002

The functional relationships of medical schools and health services.

Medical schools need good functional relationships with the health systems in which their students, graduates and staff will learn and work. With increasing complexity and rising costs of health delivery the 2 types of organisation have become more interdependent but not always as collaborating partners. Recent changes in the organisation of undergraduate medical education have been reactive to re-structuring of health services. For example, traditional teaching hospitals have become more specialised and less suitable for general medical education. While this has helped to decentralise medical education into appropriate clinical environments, these and other changes have generally been adaptive to the health systems rather than being instigated by the medical schools for educational reasons. This discussion paper examines the nature of the relationships and their contributory elements. A taxonomy of functional relationships is proposed with primary categories of (i) autonomy (ii) contiguity (iii) interdependence (iv) collaboration, and (v) obligation. It is suggested that medical schools should become more assertive in application of their creative talents and educational resources throughout the environment in which their graduates will use their medical skills, and in which they will work with other health care professionals.

Alberta↗
PubMed2003

Bilirubin rinse: A simple protectant against the rat liver graft injury mimicking heme oxygenase-1 preconditioning.

Heme oxygenase (HO)-1 preconditioning through genetic or pharmacologic interventions was shown experimentally to improve posttransplant outcome of liver grafts. However, its clinical application requires careful consideration because of the complexity and economic costs of the procedures. This study aimed to examine if graft preconditioning with HO-1 could be substituted by a simple treatment with heme-degrading products such as bilirubin. Rats were pretreated with or without hemin, an HO-1 inducer for preconditioning. Their livers were harvested as grafts in University of Wisconsin (UW) solution for 16 hours at 4 degrees C and followed by reperfusion ex vivo or by transplantation in vivo. The control grafts were also treated with a rinse buffer containing varied concentrations of unconjugated bilirubin with different time intervals. The HO-1-preconditioned grafts ex vivo exhibited a marked improvement of bile output and cell injury that was cancelled by blocking HO with zinc protoporphyrin-IX. The aggravation of the graft viability by the inhibitor was repressed by supplementation of bilirubin but not by that of carbon monoxide. Furthermore, a short-term rinse treatment with micromolar levels of bilirubin attenuated biliary dysfunction and cell injury of the grafts both ex vivo and in vivo even without HO-1 preconditioning. The protective effects of HO-1 preconditioning or bilirubin rinse appeared to involve its inhibitory effects on lipid peroxidation in hepatocytes. In conclusion, these results suggest that bilirubin rinse serves as a simple strategy to ameliorate hyperacute oxidative stress and hepatobiliary dysfunction of the transplanted grafts, mimicking effects of HO-1-mediated preconditioning.

Adenosine↗
PubMed2003

[The potential and the limits of photodynamic therapy - a review].

BACKGROUND: The spectrum of possible treatments for choroidal neovascularisation has been considerably increased with the introduction of photodynamic therapy. On the other hand the technical complexity and high cost associated with this new method require a pinpointed and dedicated application to achieve not only treatment benefits for the patients, but also not to exceed the available resources. This focussed application of the new treatment method can only be performed if the basics of diagnosis, indication, treatment and follow-up care are sufficiently known and used. MATERIAL, METHODS AND RESULTS: The standard treatment protocol, the results of published clinical trials as well as many published clinical observations are presented and discussed. CONCLUSIONS: Photodynamic therapy with verteporfin can prevent massive loss of vision in many cases of subfoveal choroidal neovascularisation, but the treatment outcome depends on many factors, the most important being the underlying disease process. Hence, indication for photodynamic therapy should adhere to the published treatment guidelines. In the future, additional medications or alterations of the treatment protocol might improve treatment outcome.

Aged↗
PubMed2006

Label-free detection of DNA hybridization using carbon nanotube network field-effect transistors.

We report carbon nanotube network field-effect transistors (NTNFETs) that function as selective detectors of DNA immobilization and hybridization. NTNFETs with immobilized synthetic oligonucleotides have been shown to specifically recognize target DNA sequences, including H63D single-nucleotide polymorphism (SNP) discrimination in the HFE gene, responsible for hereditary hemochromatosis. The electronic responses of NTNFETs upon single-stranded DNA immobilization and subsequent DNA hybridization events were confirmed by using fluorescence-labeled oligonucleotides and then were further explored for label-free DNA detection at picomolar to micromolar concentrations. We have also observed a strong effect of DNA counterions on the electronic response, thus suggesting a charge-based mechanism of DNA detection using NTNFET devices. Implementation of label-free electronic detection assays using NTNFETs constitutes an important step toward low-cost, low-complexity, highly sensitive and accurate molecular diagnostics.

Alleles↗
PubMed1999

Relation between spinal load factors and the high-risk probability of occupational low-back disorder.

Spinal compression is traditionally assumed the principal biomechanical mechanism associated with occupationally related low-back disorders (LBD). However, there is little conclusive evidence demonstrating that compression is related to occupational LBD. The objective of this research was to examine whether axial compression in the lumbar spine can predict the probability that a lifting task should be classified as high risk for LBD. Furthermore, the improvement in predictive ability was examined when analyses include 3-D, dynamic biomechanical factors. Ten experienced warehouse workers transferred 12 pallet loads of boxes in a simulation of warehouse working conditions. Biomechanical estimates of 2-D static and 3-D dynamic spinal compression, shear loads and tissue strains were achieved from the subjects during each lifting exertion. Each lift was also assessed for probability of high LBD risk classification. Regression analyses were performed to examine the relationship between biomechanical and epidemiological factors. Results indicate 2-D static estimates of spinal compression describe approximately 13% of the probability of high LBD risk variability. Dynamic estimates of spinal compression describe > 44% of the variability. A multifactor regression model including 3-D spinal loads and tissue strains further improved the predictive ability, but the improvement was not statistically significant. This research demonstrates the biomechanical source of low-back pain is dynamic, multifaceted and multidimensional. Significant improvements in ergonomics assessments can be achieved by examining interactions of dynamic biomechanical factors. Unfortunately, this improved predictive ability is generated at the high cost of computational complexity. However, less realistic biomechanical representations may ignore the injury mechanisms associated with the greater number of workplace injuries. Thus, improved understanding of the dynamic biomechanical interactions influencing the tolerance and injury mechanisms of the spine may permit more accurate assessments of workplace injury factors associated with LBD and reduced incidence of occupationally related low-back pain.

Adult↗
PubMed1994

A screening algorithm to identify clinically significant changes in neuropsychological functions in the Diabetes Control and Complications Trial. DCCT Research Group.

Neuropsychological (NP) evaluations provide an accepted means of monitoring safety in multi-center long-term medical trials. However, using neuropsychologists to review test protocols and rate level of clinical impairment can be a costly and logistically complex undertaking. To facilitate that process, the DCCT Research Group developed a computerized screening strategy that utilized statistical models to identify individuals with possible cognitive deterioration. Two hundred and eight subjects with insulin-dependent diabetes mellitus were assessed twice, 2 years apart, with an extensive battery of NP tests, and the results were rated by expert clinicians. Multiple logistic regression was used to develop a statistical model to predict clinically significant NP worsening (as determined by clinical raters) on the basis of changes in scores (year 2--baseline) derived from the actual tests. A subsequent performance evaluation with an additional 1087 subjects demonstrated that the computerized algorithm was highly successful in identifying individuals with significantly worsened NP performance. Despite a high false positive rate, the algorithm can achieve an 80-90% reduction in the number of cases requiring evaluation by expert neuropsychologists.

Adolescent↗
PubMed1999

Hospice care for injection drug using AIDS patients.

Injection drug use now accounts for the majority of new AIDS cases. Treatment for these patients is both more complex and more costly than for other AIDS patients as the factors associated with drug use are obstacles to treatment. Using data from a national survey of hospices, the findings from this study indicated that resources, hospice size, years in operation, and the Medicaid waiver were associated with hospice involvement with these patients. Staff training and supports are important factors in adequately dealing with the issues that these patients present.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Improving accrual into cancer clinical trials.

It is thought by some that there are inadequate patient entries on high priority national cancer treatment protocols, resulting in intolerable delays in addressing crucial research issues. The North Central Cancer Treatment Group in Rochester, Minnesota generated a questionnaire with possible impediments to patient treatment entry as well as suggested measures for approving accrual. Of 334 questionnaires, 63% were completed and returned by medical oncologists, radiation therapists, surgeons and nurse/data managers. The most frequently listed impediments included patients' advanced age or fragility, inadequate health insurance, and excess travel distance. Protocol concerns included too many tests that were too complex and too costly. Practice concerns included physicians too busy and inadequate help. Suggestions toward improving patient accrual included subsidizing drugs, subsidizing nonessential tests for patient care, and increasing funding for support personnel. Popular suggestions for education efforts included teaching the importance of clinical trials, emphasizing personal benefit to the patient and recognition of physicians and institutions participating. It was felt that protocols should be simplified, be more consistent with practice, and be more flexible. These considerations are relevant not only in the interests of more effective clinical research but also in the interests of appropriate education of residents and oncology fellows involved in clinical trials.

Clinical Protocols↗