Specialized nutritional support in respiratory disease

Nutritional status in patients with respiratory disease is discussed and nutritional support and pharmacotherapy considerations in these patients are reviewed. Undernutrition is common among patients with respiratory disease and can lead to decreased respiratory muscle mass and ventilatory drive. Both overfeeding and underfeeding can adversely affect patient outcome. Specialized nutrition-support regimens for patients with respiratory disease should include carbohydrate doses below the maximal oxidative rates for glucose and fat emulsion as a daily continuous infusion. Early enteral feeding may be beneficial. Respiratory quotient, oxygen consumption, and carbon dioxide production are useful measurements in providing optimal nutrition support. Pharmacotherapeutic measures, such as gastrointestinal-tract decontamination and growth-hormone administration, are being investigated in these patients as adjunctive therapy. Nutrition-support regimens for patients with respiratory disease should be carefully designed and monitored to avoid further compromising respiratory function and to reduce the risk of infection.     

Permissive underfeeding

Dietary manipulation may influence outcome after infection and injury by altering production of inflammatory mediators and disease activity. Restricted nutrient intake may have beneficial effects on life-span, development of degenerative disease, autoimmune processes, renal injury, susceptibility to infection, and survival rate after infection. Nutritional therapies that serve to maximize nitrogen balance may adversely affect the host response to injury, especially when given in excess of energy and protein needs. The optimal calorie/protein intake during different phases of critical illness remains to be established. However, a short period of restricted intake may be beneficial.     

Cortical blindness

Nutritional support is indicated when cirrhotic patients undergo surgery because they are malnourished, hypercatabolic and immunocompromised. However, the choice of nutrient may be problematic as the liver itself is the central organ of protein, fat and glucose metabolism. Branched chain amino acid-enriched solution may be the choice of protein source, as it is anticatabolic and it stimulates liver regeneration. Excessive glucose is undesirable as it may suppress endogenous fat utilization, which may be the preferred pathway of metabolism after hepatectomy. Medium chain triglycerides are preferred to long chain triglycerides as they are readily utilized and are not deposited in the liver; however, the tendency of cirrhotic patients to accumulate free fatty acids and glycerol after infusion of triglycerides dictates their use intermittently. Clinical studies have shown that perioperative nutritional support is beneficial in cirrhotic patients undergoing major hepatectomy or liver transplantation. The judicious choice of nutrient, care of the catheter and a limitation of the fluid infused are all prerequisites for the efficient use of perioperative nutritional support, which is complementary to a technically perfect operation.     

Malignant tracheoesophageal fistula in patients with esophageal cancer

BACKGROUND: Patients with esophageal cancer and a malignant tracheoesophageal fistula (TEF) have an extremely poor prognosis. Additionally, these patients often are denied treatment with radiation therapy because there is concern that these treatments may increase the size and associated problems of the TEF. METHODS: To determine the appropriate treatment (use of radiation therapy) for patients with esophageal cancer and malignant TEF, a review was performed of all such cases seen at the Mayo Clinic between 1971 and 1991. RESULTS: Between 1971 and 1991, 41 patients with malignant TEF arising as a result of esophageal cancer were seen at the Mayo Clinic in Rochester. Twenty-eight of these cancers were locally recurrent, and this group of patients had a uniformly poor outcome (median survival time, 1.4 months). Thirteen patients had a malignant TEF and had not received previous treatment for their esophageal cancer. The median survival length was 4 months for this group of patients. Of the 41 patients in this study, 10 received radiation therapy for their malignant TEF (30-66 Gy). The median survival length of this group of patients was 4.8 months. Six of these 10 patients died of metastatic disease (median survival length, 9 months), and there was no evidence of progression of the local tumor. Four of these 10 patients died of local progression of the malignancy (median survival length, 3 months). CONCLUSIONS: Radiation therapy did not increase the severity of the TEF. The authors conclude that radiation therapy can be administered safely in patients with TEF resulting from esophageal cancer. In some patients, radiation treatment may contribute to stabilization of the local tumor process (60% of patients treated with radiation therapy died of metastatic disease without local progression of tumor); however, all patients in this study eventually died of esophageal cancer.     

Energy balance in critical illness

Energy balance is the difference between energy consumed and total energy expended. Over a given period of time it expresses how much the body stores of fat, carbohydrate and protein will change. For the critically-ill patient, who characteristically exhibits raised energy expenditure and proteolysis of skeletal muscle, energy balance information is valuable because underfeeding or overfeeding may compromise recovery. However, there are formidable difficulties in measuring energy balance in these patients. While energy intake can be accurately recorded in the intensive care setting, the measurement of total energy expenditure is problematic. Widely used approaches, such as direct calorimetry or doubly-labelled water, are not applicable to the critically ill patient. Energy balance was determined over periods of 5-10 d in patients in intensive care by measuring changes in the fat, protein and carbohydrate stores of the body. Changes in total body fat were positively correlated with energy balance over the 5 d study periods in patients with severe sepsis (n 24, r 0.56, P = 0.004) or major trauma (n 24, r 0.70, P < 0.0001). Fat oxidation occurred in patients whose energy intake was insufficient to achieve energy balance. Changes in body protein were independent of energy balance. These results are consistent with those of other researchers who have estimated total energy requirements from measurements of O2 consumption and CO2 production. In critically-ill patients achievement of positive non-protein energy balance or total energy balance does not prevent negative N balance. Nutritional therapy for these patients may in the future focus on glycaemic control with insulin and specialised supplements rather than on energy balance per se.     

The progression of chronic renal disease: immunological, nutritional and intrinsic renal mechanisms

The majority of patients with any initial renal insult show progression of renal damage over time. The histological end-result is often the same, whatever the initial lesion, and consists of an increase in extracellular matrix (ECM) and ultimately glomerulosclerosis. The clinical rate of progression correlates mainly with the degree of interstitial, rather than with that of glomerular damage. The main culprits for the ultimate interstitial damage and the rate of progression of renal disease, are the type and degree of the initial (e.g. immunological) insult and the magnitude of the proteinuria. Hypertension (intraglomerular) is an independent risk factor. Control of hypertension with angiotension converting enzyme (ACE) inhibitors or angiotensin II (AII) receptor blockers, reduction of protein and fat intake, anti-oxidative therapy and a variety of experimental measures reduce the progression of renal damage in animal experiments. Some of these interventions have also been shown to be beneficial in a number of controlled clinical studies, in well-defined renal disease entities in humans. These new data provide insight into the pathogenesis of chronic renal damage and raise the hope that in the not too far future, effective strategies can be devised to attenuate the progression of acquired renal disease.     

Respiratory syncytial virus infection in childhood

Respiratory syncytial virus is the most frequent cause of respiratory tract infections in infants and is responsible for annual winter epidemics of acute bronchiolitis. Over the last decades medical therapy has remained unchanged and controversial, despite intensive research. Inhaled bronchodilators are often not effective and should be discontinued if no beneficial response can be documented. Steroids and ribavirin are not indicated in previously healthy infants with acute RSV bronchiolitis. There is some evidence, however, that certain risk groups may benefit from their use. With good supportive care the mortality from RSV infection is now low. Postinfectious alterations in lung function are usually transient and reversible. High-risk infants can be protected from severe RSV infections by monthly infusions of RSV immune globulins. This treatment modality has, however, not gained wide acceptance because of the benign nature of the disease and the high costs and side effects of regular immune globulin infusions. An international consensus statement on the treatment of RSV bronchiolitis may help to reduce the wide differences in clinical practice.     

Lung cancer and chronic obstructive pulmonary disease

Spirometry can predict lung health and monitor disease and response to therapy. This noninvasive test can and should be done regularly by primary care providers. It can identify patients at risk for lung cancer as well as heart attack and stroke. Patients with abnormal spirometric findings can be warned that airflow obstruction has begun, which may provide the motivation to quit smoking. Abnormal spirometry measurements correlate with all-cause mortality. Approaches to early diagnosis of lung cancer continue to expand. For example, use of the new fluorescent bronchoscope can increase diagnostic accuracy in lung cancer by highlighting lesions that are malignant or likely to be malignant. For now, however, identification of airflow obstruction with spirometry and follow-up with sputum cytology provide the widest benefit.     

The long-term course of carcinoma in situ of the uterine cervix

The malignant potential of carcinoma in situ (CIS) of the uterine cervix has been the subject of great controversy. Despite refinements and additions to knowledge in this area, few reports on the long-term course of the disease have appeared in the past decade. Recent developments in diagnostic and therapeutic techniques coupled with changes in the patient population with this disease have prompted renewed interest in conservative management. Results of long-term observation of a group of patients followed initially without ablative therapy are reported. The data indicate that CIS of the uterine cervix is not the inevitably progressive disease that it has been considered to be. Unequivocal invasive cancer develops in only a small percentage of cases and can be controlled, if not cured, by current therapeutic modalities. The intraepithelial lesion, however, tends to persist despite conization, and eventually requires ablative therapy in most cases. Conservative procedures should be regarded as temporizing, at least until their long-term benefits can be recorded.     

Determination of energy window width and position for the triple energy window (TEW) scatter compensation method

Phytoestrogens are naturally occurring plant compounds which have oestrogenic and/or anti-oestrogenic activity. They are present in many human foodstuffs including beans, sprouts, cabbage, spinach, soyabean, grains and hops. The main classes are the isoflavones, coumestans and lignans. This review assesses the evidence that these substances may have adverse and/or beneficial impacts on the risk of several hormone-dependent diseases in humans. Evidence from studies of various animal species has demonstrated that ingestion of high levels of phytoestrogens can produce adverse effects on reproductive endpoints including fertility. Studies in laboratory animals have also shown that exposure to high doses of phytoestrogens during development can adversely affect brain differentiation and reproductive development in rodents, but may also have possible beneficial effects. In humans, there is a lack of information concerning the possible effects of high doses of phytoestrogens in infants and this should be addressed as a matter of priority so that any risks (or benefits) can be established. In adults, no current data exist to suggest that consumption of phytoestrogens at the levels normally encountered in the diet is likely to be harmful. Epidemiological studies suggest that foodstuffs containing phytoestrogens may have a beneficial role in protecting against a number of chronic diseases and conditions. For cancer of the prostate, colon, rectum, stomach and lung, the evidence is most consistent for a protective effect resulting from a high intake of grains, legumes, fruits and vegetables; it is not possible to identify particular food types or components that may be responsible. Dietary intervention studies indicate that in women soya and linseed may have beneficial effects on the risk of breast cancer and may help to alleviate postmenopausal symptoms. For osteoporosis, tentative evidence suggests phytoestrogens may have similar effects in maintaining bone density to those of the related pharmaceutical compound ipriflavone. Soya also appears to have beneficial effects on blood lipids which may help to reduce the risk of cardiovascular disease and atherosclerosis. Generally, however, little evidence exists to link these effects directly to phytoestrogens; many other components of soya and linseed are biologically active in various experimental systems and may be responsible for the observed effects in humans. It is concluded that dietary phytoestrogens may have a role in the prevention of several types of chronic disease including certain cancers. However, at present the evidence is not sufficient to recommend particular dietary practices or changes. Encouraging findings from laboratory and clinical studies indicate the need for further research to clarify the biological activities of phytoestrogens in humans.     

Novel systems for controlled delivery of macromolecules

Gene therapy promises new treatments for human disease by alterations in the DNA content of tissues. Methods for efficient and stable introduction of genes into target cells in the body are critically important in this effort. Researchers and physicians now have many years of experience with synthetic polymers for controlled drug delivery; many of these polymers can also be used to deliver macromolecules at controlled rates to tissues. This article reviews the use of polymers in controlled protein delivery and suggests ways that polymer delivery systems may be useful in the delivery of gene transfer agents.     

New therapies in the treatment of malignant pleural mesothelioma

It can be safely stated that currently there exists no standard therapy for malignant mesothelioma. The "standard" methods of chemotherapy, radiation therapy, and surgery have all been used with little improvement in overall survival. Trimodality therapy that involves a combination of all three standard treatment modalities has been shown to improve survival in selected patients. New and innovative treatment strategies clearly are needed for a disease which, because of the disappointment with standard therapy, is most commonly approached with only palliative intent. The location of this malignancy and its tendency to remain localized make it an ideal target for intracavitary approaches using photodynamic therapy, targeted cytokines, and gene therapy. Strategies using modulation of the immune system in an attempt to elicit a specific response to the tumor have been combined with chemotherapy to optimize response. Lessons learned from treating this localized malignancy with novel therapies may have much broader implications for other tumors in which systemic disease predominates.     

A phase I study of high-dose tamoxifen for the treatment of refractory malignant gliomas of childhood

Recent studies have indicated that the proliferation of malignant gliomas is in part dependent on excessive activation of protein kinase C (PKC)-mediated pathways. Conversely, inhibiting PKC may provide a novel approach for blocking glioma growth. The antiestrogen tamoxifen, a moderately potent PKC inhibitor, has been shown in vitro to block the proliferation of malignant glioma cell lines at concentrations several-fold higher than those typically attained during the treatment of breast cancer; such serum concentrations may be achieved with doses > 40 mg/m2 b.i.d. The safety and efficacy of these high doses for producing disease control in patients with malignant gliomas has recently been noted anecdotally, although a rigorous study of this agent has been lacking. To address this issue, we examined the safety and efficacy of high-dose tamoxifen in a series of children with malignant gliomas that had progressed after conventional therapy. An initial group was treated with 60 mg/m2 p.o. b.i.d. and a second group with 100 mg/m2 b.i.d. Steady-state serum tamoxifen and metabolite levels were measured in most patients. Toxicity with the regimen was minimal; two patients treated at the higher dose required reduction to the lower dose because of asymptomatic prolongation of the QT interval on an electrocardiogram. Although none of the patients exhibited clear-cut tumor regression, 4 of 14 patients had stabilization of previously progressive disease for at least 3 months; the longest survivor lived for 17 months after beginning tamoxifen. The moderate efficacy of this agent in otherwise end-stage disease coupled with its low toxicity and the relative ease of oral administration provides a rationale for proceeding with larger studies of this agent in patients with malignant gliomas, possibly as a means for potentiating the effects of conventional chemotherapeutic agents, which to date have shown limited efficacy in the treatment of these tumors.     

Web technology for emergency medicine and secure transmission of electronic patient records

Animals with cardiac disease can have a variety of nutritional alterations for which interventional nutrition can be beneficial. Deviation from optimal body weight, both obesity and cachexia, is a common problem in cardiac patients and adversely affects the animal. Methods for maintaining optimal weight are important for good quality of life in dogs and cats with cardiac disease. Providing proper diets to prevent excess intake of sodium and chloride also is important, but severe salt restriction may not be necessary until later stages of disease. Certain nutrient deficiencies may play a role in the pathogenesis or complications of cardiac disease, but nutrients also may have effects on cardiac disease which are above and beyond their nutritional effects (nutritional pharmacology). Supplementation of nutrients such as taurine, carnitine, coenzyme Q10, and omega-3 polyunsaturated fatty acids may have benefits in dogs or cats with cardiac disease through a number of different mechanisms. By addressing each of these areas maintaining optimal weight, avoiding nutritional deficiencies and excesses, and providing the benefits of nutritional pharmacology, optimal patient management can be achieved.     

Therapy of Crohn's disease in childhood

The aim of therapy in Crohn's disease in childhood is to induce and to maintain a remission of disease activity so that normal growth and development of the child may occur. Enteral nutrition may now be recommended as the first-line treatment for most children with Crohn's disease. However, the evidence for remission is better for children with Crohn's disease of the small intestine rather than of the large intestine. There is evidence that amino acid feeds (elemental), whole protein (polymeric) and protein hydrolysate feeds (semi-elemental) may all be successful. Such a therapeutic approach can lead to healing of the mucosa and down-regulation of inflammation. However, in some cases surgery is required, particularly in children with growth failure and delayed puberty. Drug therapy also continues to have a role in therapy especially with severe colonic disease.     

Dyskeratosis congenita: multisystemic disorder with special consideration of immunologic aspects. A review of the literature

Dyskeratosis congenita (DC) is a rare, predominantly X-linked multisystemic disorder. It demonstrates a wide spectrum of clinical manifestations and typically presents with dermatologic symptoms during the first decade of life. This review of the literature points out the importance of hematologic and immunologic alterations in defining the course and prognosis of the disease process. Pancytopenia as well as the humoral and cellular disturbances in immunologic functions associated with this disease complex may lead to severe infections that represent the main cause of death. The pathogenesis of DC is still unclear and a curative therapy is presently lacking. Recent reports suggest that a beneficial effect may be observed in the administration of hematopoietic growth factors (G-CSF, GM-CSF) for patients with DC and neutropenia.     

Antidiarrheal agents for the management of treatment-related diarrhea in cancer patients

The efficacy and use of antidiarrheal agents in patients who diarrhea associated with cancer treatments are reviewed. Diarrhea is common in cancer patients and may interfere with cancer treatment. Diarrhea may be induced by chemotherapy, radiation therapy, surgery, graft-versus-hot disease (GVHD) or infection after bone marrow transplantation, and other causes. The general goal of antidiarrheal therapy is to reduce fluid loss in the stool by inhibiting intestinal secretion, promoting absorption, and decreasing intestinal motility. Antidiarrheal agents may be classified as intestinal transit inhibitors, intraluminal agents, proabsorptive agents, and antisecretory drugs. Opiate agonists are the most commonly used intestinal transit inhibitors; they can be effective in treating cancer treatment-related diarrheas but must be used cautiously. Intraluminal agents include clays, activated charcoal, and cholestyramine; these adsorbents and other binding resins can interfere with the absorption of orally administered antidiarrheals and other drugs and are unlikely candidates for use in most cases of diarrhea in cancer patients. Clonidine, a proabsorptive agent, should be used only in patients with secretory diarrhea refractory to opiate agonist treatment. Octreotide is an antisecretory drug that has shown considerable efficacy in clinical trails as a treatment for diarrhea caused by chemotherapy of GVHD; its use for radiation therapy-induced diarrhea, although not studied clinically, is nevertheless an option. In general, opiate agonists and octreotide appears to offer the most efficacy and flexibility. Opiate agonists and octreotide are effective agents for cancer treatment-related diarrhea.     

Alcoholic liver disease. Treatment strategies for the potentially reversible stages

Even modest alcohol ingestion can increase the risk of steatosis, and long-term, excessive consumption can lead to alcoholic hepatitis and eventually cirrhosis. Most patients with clinically significant alcoholic liver disease have histologic findings typical of all three conditions. The only clearly beneficial treatment is abstinence from alcohol. Abstinence in combination with proper nutrition and general supportive care is state of the art. Steatosis is reversible upon withdrawal of alcohol, but alcoholic hepatitis can persist even with abstinence and may progress to cirrhosis. Corticosteroid therapy may reduce short-term mortality rates in patients with moderate or severe alcoholic hepatitis who have hepatic encephalopathy but no evidence of infection or gastrointestinal bleeding. Treatment with colchicine may decrease the risk of cirrhosis; however, once cirrhosis has developed, the liver damage is irreversible. The prognosis is improved with abstinence, but complications (e.g., ascites, gastrointestinal bleeding) often occur. Liver transplantation may be considered in patients with severe complications.     

Treatment of thoracic malignancy accompanied with cardiovascular disease

We treated 10 cases of thoracic malignancy accompanied with cardiovascular disease. Among thoracic malignancy, 7 cases were lung cancer and 3 were esophageal cancer. Accompanied cardiovascular diseases were ischemic heart disease (2 cases), valvular disease (3 cases), WPW syndrome (1 case), aortic aneurysm (4 cases). The mean age was 66, ranged from 51 to 79. The simultaneous occurrence of the two lesions were observed in 6 cases and thoracic malignancy was diagnosed after a varying interval of time following surgery of cardiovascular disease in 4 cases. In cases of thoracic malignancy accompanied with heart disease, the treatment of heart disease should precede the operation of malignant disease to reduce the risk of surgery. For the patient with esophageal cancer, posterior mediastinal esophagostomy should be applied who may have heart surgery in future. In cases of coexisting malignancy and aortic aneurysm, the priority of treatment should be determined considering the size of aneurysm. If the transverse diameter of aneurysm is larger than 7 cm, there is a high risk of rupture, so surgery for the aneurysm precedes operation of malignant diseases. It is desirable to avoid concomitant operation of malignancy and cardiovascular disease.