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Biomedical subjects

K A Nelson

Publications and source records attributed to K A Nelson.

At least 19 recordsLinked to original sources

Tracking the motion of charges in a terahertz light field by femtosecond X-ray diffraction.

In condensed matter, light propagation near resonances is described in terms of polaritons, electro-mechanical excitations in which the time-dependent electric field is coupled to the oscillation of charged masses. This description underpins our understanding of the macroscopic optical properties of solids, liquids and plasmas, as well as of their dispersion with frequency. In ferroelectric materials, terahertz radiation propagates by driving infrared-active lattice vibrations, resulting in phonon-polariton waves. Electro-optic sampling with femtosecond optical pulses can measure the time-dependent electrical polarization, providing a phase-sensitive analogue to optical Raman scattering. Here we use femtosecond time-resolved X-ray diffraction, a phase-sensitive analogue to inelastic X-ray scattering, to measure the corresponding displacements of ions in ferroelectric lithium tantalate, LiTaO(3). Amplitude and phase of all degrees of freedom in a light field are thus directly measured in the time domain. Notably, extension of other X-ray techniques to the femtosecond timescale (for example, magnetic or anomalous scattering) would allow for studies in complex systems, where electric fields couple to multiple degrees of freedom.

Journal Article↗

Metrics for negative-refractive-index materials.

The importance of loss in the field solution for left-handed media, and in particular, the impact on what would otherwise be a purely evanescent field, is addressed. Using an equivalent electric current source, field solutions are constructed in semi-infinite and finite thickness left-handed media. In the slab case, field growth and power dissipation metrics with uniform amplitude and uniform power excitation, respectively, provide a means to evaluate the potential of a left-handed material lens. Power dissipation suggests that field growth will be adversely impacted.

Journal Article↗

Evaluation of nutritional status in advanced metastatic cancer.

Consecutive cancer referrals to a palliative medicine program were evaluated to assess nutritional status using a standard protocol. The study included 352 patients (180 men, 172 women; median age 61 years, range 22-94 years). The most common diagnosis was lung cancer. All had metastatic disease, 139 with gastrointestinal involvement. The most common gastrointestinal symptoms were weight loss ( n=307), anorexia ( n=285), and early satiety ( n=243). Of those with any weight loss, 71% had lost >or0% of their pre-illness weight. The most common factor identified which might have contributed to weight loss was hypophagia ( n=275/307). Men had lost weight more often and to a greater extent than women. Triceps skinfold (TSF) was measured in 337: 51% had values that suggested severe fat deficiency. Upper mid-arm muscle area (AMA) was measured in 349: 30% had evidence of significant muscle mass reduction. The body mass index (BMI) was normal or increased in most patients. Calculated resting energy expenditure (REE) ( n=324) was high in 41%. C-reactive protein was elevated in 74% of those measured ( n=50). We conclude that: (1).most of this group of cancer patients referred to palliative medicine had severe weight loss; (2).there was a gender difference in the severity and type of weight loss; (3).males lost more weight overall and more muscle than females; (4).males with any degree of weight loss had a higher REE than females; (5).a significant correlation existed between the time from diagnosis to death and the severity of weight loss in the prior month; (6).BMI was normal in most patients, suggesting precancer diagnosis obesity; and (7).both TSF and AMA correlated well with body composition of both fat and protein as determined by bioelectrical impedance.

Adult↗

Induction of donor-specific tolerance to islet allografts in nonhuman primates.

Pancreatic tissue grafting is by far the most physiological therapeutic solution to the insulin deficiency of diabetes. Recent clinical trials have indicated somewhat successful use of nonsteroidal immunosuppressive regimens and a successful nonhuman primate trial using CD154 for costimulation blockade was reported. However, these protocols need to be replaced with safe and efficacious ones in which long-term allotolerance would make these treatments routine in a clinical setting. With the specific objective of testing whether peripheral infusions of stem cells or stem cell fractions in conjunction with islet allografting would induce allograft tolerance, we have established a macaque diabetic model. The macaques were rendered diabetic by streptozotocin and required daily doses of insulin to maintain lower blood glucose levels. The diabetic macaques then received islets and stem cells from unrelated and MHC-mismatched donors without any immunosuppression. In our initial analysis, 5 of 7 macaques that received stem cell infusions at the time of islet allografting have shown allograft survival longer than the group of macaques that received islets without the stem cell infusion. One of these five macaques has been normoglycemic for 10 months, with no exogenous insulin. This macaque received stem cell population enriched for CD34+ cells with depletion of CD18 cells, which have shown low or no allostimulatory potential in mixed lymphocyte cultures. Increased levels in insulin and C-peptide levels were shown in the macaques after islet transplantation.

Animals↗

Induction of islet allotolerance in nonhuman primates.

Recent clinical trials have pioneered the successful use of a nonsteroidal immunosuppressive regimen and established a basis for application in a routine clinical setting. In this study, a single islet transplant was not sufficient to regulate blood glucose levels, and a second transplant became necessary. A similar observation was made in our macaque islet transplant study, where animals after the second transplantation have shown trends towards normoglycemia in the presence of mycophenolate mofetil. All five animals that received the second transplant have shown an initial rise in C peptide levels, which rapidly decreased as we tapered the MMF dose from 20 mg/kg BID to 5 mg/kg SID. Two animals of the five that were preconditioned with MMF one week prior to transplantation have shown significantly higher C peptide levels. We believe that it is very important to understand the relationship between the first graft failure and subsequent islet allograft success. Since graft success did not correlate with number of transplanted islets, the correction of blood glucose levels toward normoglycemia after the second transplantation suggests a mechanism by which the allotolerance to second transplant is facilitated by the first islet transplantation. These initial observations suggest approaches to "tolerize" the recipient to accept the second-transplant islets (a) through preconditioning the animal to improve the rate of success for the first transplant or (b) through tolerization to islets in the first transplant to facilitate better engraftment of the second-transplant islets.

Animals↗

The gastrointestinal symptoms of advanced cancer.

The commonest gastrointestinal (GI) symptoms in advanced cancer are reviewed with reference to definition, pathophysiology, etiology, prevalence, severity, and management. Observation or reporting of such symptoms must lead to consideration of the multi-faceted pathophysiology. Careful assessment and an analytical detailed approach are the keystones of effective management.

Age Factors↗

Hydromorphone: pharmacology and clinical applications in cancer patients.

Hydromorphone is a more potent opioid analgesic than morphine and is used for moderate to severe pain. It can be administered by injection, by infusion, by mouth, and rectally. Oral bioavailability is low. The kidney excretes hydromorphone and its metabolites. Some metabolites may have greater analgesic activity than hydromorphone itself but are unlikely to contribute to the pharmacological activity of hydromorphone. With the exception of pruritus, sedation and nausea and vomiting, which may occur less after hydromorphone than after morphine, the side-effects of these drugs are similar. On a milligram basis hydromorphone is five times as potent as morphine when given by the oral route, and 8.5 times as potent as morphine when given intravenously.

Analgesics, Opioid↗

Music therapy in palliative medicine.

A partnership between The Cleveland Clinic Foundation and The Cleveland Music School Settlement has resulted in music therapy becoming a standard part of the care in our palliative medicine inpatient unit. This paper describes a music therapy program and its impact on patients, their families, and staff. A service delivery model is suggested for implementation and integration of music therapy within palliative medicine. Specific music therapy interventions, evaluation and documentation techniques are also mentioned. A description of patient and family responses to music therapy, staff satisfaction, and effectiveness of interventions is presented.

Humans↗

Important drugs for cough in advanced cancer.

Cough is a defense mechanism that prevents the entry of noxious materials into the respiratory system and clears foreign materials and excess secretions from the lungs and respiratory tract. In advanced cancer, it is a common symptom that interferes with the patient's daily activity and quality of life. Empiric treatment with antitussive agents is often needed. Two classes of antitussive drugs are available: (1) centrally acting: (a) opioids and (b) non-opioids; (2) peripherally acting: (a) directly and (b) indirectly. Antitussive availability varies widely around the world. Many antitussives, such as benzonatate, codeine, hydrocodone, and dextromethorphan, were extensively studied in the acute and chronic cough settings and showed relatively high efficacy and safety profiles. Benzonatate, clobutinol, dihydrocodeine, hydrocodone, and levodropropizine were the only antitussives specifically studied in cancer and advanced cancer cough. They all have shown to be effective and safe in recommended daily dose for cough. In advanced cancer the patient's current medications, previous antitussive use, the availability of routes of administration, any history of drug abuse, the presence of other symptoms and other factors, all have a role in the selection of antitussives for prescription. A good knowledge of the pharmacokinetics, dosage, efficacy, and side effects of the available antitussives provides for better management.

Antitussive Agents↗

Modern management of the cancer anorexia-cachexia syndrome.

The cancer anorexia-cachexia syndrome is common, occurring in 80% of patients with advanced-stage cancer, and it is one of the most frequent causes of death in patients with cancer. It is a complex problem involving abnormalities in protein, carbohydrate, and fat metabolism. Tumors have both direct and indirect effects that result in anorexia and weight loss. The disease burden does not necessarily correlate with the degree of cachexia. In addition to the physical manifestations, the resulting abnormalities have a significant psychologic effect on patients and their families. Although there is no treatment to reverse the process, pharmacologic and nonpharmacologic measures can enhance food intake and improve quality of life.

Anorexia↗

Infectious complications of advanced cancer.

We present a retrospective study of the frequency, pattern, and management of infections in advanced cancer. Three hundred ninety-three patients were admitted to an acute care palliative medicine unit in an 8-month period for evaluation and palliation of cancer-related symptoms and complications. One hundred fifteen had at least one positive bacteriological culture, and 100 of these patients were evaluable. One hundred fifty-two infections and 192 isolates were identified. Sixty-eight patients had polymicrobial infections. Sixty-six patients had urinary tract infections. Forty-one were found to have multisystemic infections. Eighty-one had invasive devices; 32 had more than one invasive device. Fifty-three were taking corticosteroids at the time of infection. Only 3 were neutropenic. Urinary tract infections were significantly more common in those taking corticosteroids. The median duration of antibiotic treatment was 11 days and the median hospital stay, 14 days. Twenty-eight patients died in the hospital; 10 of those who died had lung cancer, which was a statistically significant observation. In conclusion, infections are an underrecognized but common complication in nonneutropenic hospitalized patients with advanced solid tumors. Urinary tract infections appear to be associated with the use of corticosteroids. Lung cancer patients are at greater risk for fatal infections. Infections increase morbidity in debilitated patients with solid tumors, are a frequent cause of hospital admission, and are associated with significant mortality.

Adult↗

Psychostimulants in supportive care.

Psychostimulant medications have been used clinically and investigated in psychiatric populations, the medically ill, cancer patients and healthy people. This article discusses the pharmacology of dextroamphetamine, methylphenidate, pemoline (and other psychostimulants such as caffeine and ephedrine), their use in general medicine and cancer care, side effects, and abuse potential. Therapeutic use in children is addressed only insofar as it illustrates facets of their use in adults.

Adult↗

Modern management of the cancer anorexia-cachexia syndrome.

The cancer anorexia-cachexia syndrome is common, occurring in 80% of patients with advanced-stage cancer, and it is one of the most frequent causes of death in patients with cancer. It is a complex problem involving abnormalities in protein, carbohydrate, and fat metabolism. Tumors have both direct and indirect effects that result in anorexia and weight loss. The disease burden does not necessarily correlate with the degree of cachexia. In addition to the physical manifestations, the resulting abnormalities have a significant psychologic effect on patients and their families. Although there is no treatment to reverse the process, pharmacologic and nonpharmacologic measures can enhance food intake and improve quality of life.

Anorexia↗

Use of an HBV-DNA hybridization assay in the evaluation of equivocal hepatitis B virus tests in solid organ donors.

CONTEXT: Serological markers for the hepatitis B virus are routinely used in the evaluation of potential organ donors. However, serological tests can be associated with significant false or equivocal results and may not be indicative of the true risk of hepatitis B infection. Studies have recently questioned the significance of an isolated hepatitis B core antibody test in evaluating the suitability of solid organs for transplantation. The ability to detect hepatitis B virus DNA may prove useful when the diagnosis of hepatitis B infection is in doubt. DESIGN: Serum samples from 16 donors with equivocal or positive hepatitis B core antibody and/or hepatitis B surface antigen serological screening tests were retrospectively tested for the presence of hepatitis B DNA. Any available follow-up data on the placement of organs from these donors was obtained. RESULTS: One of the 16 (6.3%) donors tested positive for the presence of hepatitis B DNA, but organs from this donor were not recovered or transplanted. Follow-up on 14 organs recovered and transplanted from 6 donors in this group did not show clinical and/or laboratory evidence of hepatitis B infection in the recipients. CONCLUSIONS: In our donor population, there was a low incidence (6.3%) of donors with equivocal or positive hepatitis B core antibody and/or hepatitis B surface antigen serological screening tests who subsequently demonstrated the presence of detectable hepatitis B DNA. Posttransplantation follow-up of the recipients of 14 recovered organs failed to demonstrate any cases of posttransplant hepatitis B infection.

DNA, Viral↗

Common symptoms in advanced cancer.

The relief of physical and psychological symptoms is an essential part of palliative care. Advanced cancer is an acute process; because the clinical picture changes rapidly, symptoms must be reassessed regularly, and a careful history is essential. Defining the relationship of the symptoms to the disease can defuse fear and encourage a sense of control in patients and their families. We review the pathophysiology, causes, prevalence, consequence, and management of common symptoms in advanced cancer.

Disease Progression↗

Common complications of advanced cancer.

Complications due to cancer and its treatment are common and increase in incidence and severity as the disease progresses. Central nervous system complications affect 15% to 20% of patients, and up to 75% have bone metastases at some point during the disease process. Endocrine abnormalities include hypercalcemia, adrenal insufficiency, and inappropriate antidiuretic syndrome. Hematologic disorders, malignant effusions, and gastrointestinal (GI) problems may cause significant morbidity.

Disease Progression↗

The cancer anorexia-cachexia syndrome.

The cancer anorexia-cachexia syndrome is one of the most common causes of death among cancer patients and is present in 80% at death. It is a complex example of metabolic chaos effecting protein, carbohydrate, and fat metabolism. Tumors produce both direct and indirect abnormalities, resulting in anorexia and weight loss. The disease burden does not correlate with the degree of cachexia. Although there is no treatment to control or reverse the process, appetite stimulants may promote increased food intake and enhance quality of life.

Cachexia↗

The dying cancer patient.

Cancer patients often die with serious unrelieved symptoms causing a distressing death for them and needless added suffering for their families. Many physicians have not been trained to care for the dying patient. This chapter reviews the common symptoms and describes the methods to control them and support the patient and family through this difficult time. These symptoms are so characteristic of the dying process that all physicians should recognize them, be skilled in providing appropriate care, and prepare for problems that may arise.

Attitude to Death↗