Host determinants in HIV infection and disease. Part 2: genetic factors and implications for antiretroviral therapeutics.

The course of HIV infection varies widely among individuals. Immunologic and genetic studies of long-term nonprogressors and exposed yet uninfected persons have helped to elucidate the mechanisms by which some persons are protected from HIV acquisition or have slow rates of disease progression. This two-part review describes what is currently known about host factors in HIV-1 infection. Studies for inclusion were identified by a systematic search of PubMed for English-language literature published from 1988 through June 2000. Abstracts of presentations at major meetings convened in 2000 were also included if appropriate. The first part of the review discussed cellular and humoral immunity to HIV infection. This second part describes genetic host factors-namely, inheritance of mutant chemokine receptors or ligands, such as CCR5-Delta32, CCR2-V64I, stromal cell-derived factor-1 3'alpha, and CCR5 promoter polymorphisms, as well as HLA type-that affect susceptibility to infection and subsequent clinical course. Soluble inhibitory factors, the cytokine milieu, and concomitant infections also affect outcome. Knowledge of host responses is increasingly being applied to new therapeutic strategies, including early treatment, immune modulation, structured treatment interruptions, therapeutic vaccination, and new chemotherapeutic agents, as well as to vaccine development.

Host determinants in HIV infection and disease. Part 1: cellular and humoral immune responses.

The course of HIV infection varies widely among individuals. Long-term nonprogressors or slow progressors may remain asymptomatic and have normal CD4 counts despite more than a decade of untreated HIV infection. In contrast, rapid progressors develop AIDS within 5 years. In addition, some persons remain uninfected despite repeated exposure to HIV. Immunologic and genetic studies of long-term nonprogressors and exposed yet uninfected persons, as well as data from studies of primary HIV infection, have helped to elucidate the mechanisms by which some persons are protected from HIV acquisition or have slow rates of disease progression. This review (the first of two parts) describes what is currently known about host factors in HIV-1 infection. Studies for inclusion were identified by a systematic search of PubMed for English-language literature published from 1988 through June 2000. Abstracts of presentations at major meetings convened in 2000 were also included if appropriate. Growing evidence suggests a crucial role of cytotoxic T cells and T-helper cells in controlling viremia, slowing disease progression, and perhaps preventing establishment of infection. Humoral and mucosal immunity, soluble inhibitory factors, the cytokine milieu, and concomitant infections also affect outcome. Genetic host factors, such as inheritance of mutant chemokine receptors or certain HLA types, affect susceptibility to infection and subsequent clinical course. The role of cellular and humoral immunity, mucosal immunity, and other local factors in determining the course of HIV infection is discussed.

The nurse's role in diarrhea management.

PURPOSE/OBJECTIVES: To discuss the causes, clinical manifestations, and consequences of diarrhea in the patient with cancer; to describe the oncology nurse's role in the assessment, management, and treatment of cancer-related diarrhea. DATA SOURCES: Synthesis of published peer-reviewed data, professional experience. DATA SYNTHESIS: The many causes of cancer-related diarrhea include specific types of cancer and specific anticancer treatment regimens (e.g., chemotherapy, radiotherapy). Poorly controlled diarrhea may result in a range of physiologic and psychological effects that extend beyond the patient to significant others and caregivers. Comprehensive assessment of diarrhea is the foundation for the appropriate use of pharmacologic and supportive therapies. CONCLUSIONS: Diarrhea, much like fatigue, is a symptom that only recently has become a focus of oncology nursing research and focused intervention. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses can significantly influence the quality of care given to patients who develop diarrhea as a symptom of cancer or as a sequela of cancer therapy. As such, oncology nurses are challenged to maintain current knowledge of the causes and available treatment strategies for cancer-related diarrhea. Nurses need to rely on their experiential skill and a working knowledge of published research to identify patients at risk. They also must communicate effectively with patients and caregivers in every practice setting about the nature of diarrhea and its causes, as well as develop appropriate interventions for each individual.

Physiologic mechanisms of nausea and vomiting in patients with cancer.

PURPOSE/OBJECTIVES: To review the current literature describing the multiple etiologies of nausea and vomiting in patients with cancer. DATA SOURCES: Reports of pertinent research, clinical articles, and book chapters. DATA SYNTHESIS: As a result of knowledge gained about the important role of serotonin in mediating the initial emetic response to antineoplastic drug administration, nurses have made tremendous strides in controlling acute chemotherapy-induced nausea and vomiting. The role of neurotransmitters other than serotonin in mediating the response of delayed or persistent nausea and vomiting remains unclear. Efforts continue to further describe the mechanisms and management of nausea and vomiting that occur as a result of other cancer-related conditions or treatments. CONCLUSIONS: A rational, often combinational approach to antiemetic therapy is derived from a working knowledge of the physiologic mechanisms associated with nausea and vomiting in patients with cancer. Assessment of the individual's precancer history and current physiologic and psychosocial status is the corner-stone of designing and providing effective therapies. IMPLICATIONS FOR NURSING PRACTICE: Understanding the physiologic mechanisms responsible for the cause and control of nausea and vomiting in patients with cancer facilitates creative use of drugs and nonpharmacologic strategies that are more likely to result in control of these distressing symptoms.

Coping with biotherapy: physiological and psychosocial concerns.

Cancer treatment with biological response modifier (BRM) therapies is characterized by many of the same issues observed with other modalities. Yet, the nurse caring for the patient receiving BRM therapy frequently is faced with the need to develop interventions that respect both the integrity of investigational studies and the patient's unique needs. Coping with BRM therapy is influenced by many factors. Several models may be used simultaneously to assess coping behaviors and to provide effective interventions. The goals of investigational therapy and the management of symptom distress influence the ability to cope with BRM therapy. The interruption or impediment of normal adult developmental activities also influences the individual's response to the psychological stressors associated with this cancer therapy. Consequently, the most significant challenge faced by anyone receiving cancer therapy is the same for the individual receiving BRM therapy--living with uncertainty.

Advances in the management of nausea and vomiting.

The successful management of cancer-related nausea and vomiting is dependent upon many factors. An understanding of the various pharmacologic and nonpharmacologic interventions serve as the foundation for symptom control. The most important variable, however, is the nurse's commitment to alleviate these symptoms. Such commitment requires flexibility, tenacity, and a willingness to serve as a patient advocate. Regardless of the care setting, the nurse remains in a pivotal position to facilitate the optimal management of symptoms. Tremendous opportunities exist for nurses to collaborate across a variety of settings in order to ensure continuity. Such continuity enhances patient care but most important assures individuals (and their significant others) that their history is known and that they do not have to fear poor emetic control because of caregiver ignorance. The ability to initiate or support behavioral interventions demonstrates the nurse's commitment to holistic care. Such holism is the foundation and reward of cancer nursing practice.

Influence of growth substrate on production of cellulase enzymes by Trichoderma harzianum E58.

Cellulase production by Trichoderma harzianum E58 grown on lactose and various cellulosic substrates such as Solka Floe, Avicel, and steamed aspenwood was investigated. The culture filtrates of T. harzianum E58 obtained after growth on these substrates were assayed for their cellulase activities and overall hydrolytic activities. The severity of the steaming conditions used for the aspenwood had a pronounced effect on the cellulolytic activity of the produced culture filtrates. Those substrates that were more readily hydrolyzed by the cellulase complex were the poorest substrates for inducing an active cellulase complex. Substrates such as acid-impregnated aspenwood and lactose induced a less hydrolytic efficient cellulase complex than more recalcitrant substrates such as microcrystalline cellulose.

Recycle of enzymes and substrate following enzymatic hydrolysis of steam-pretreated aspenwood.

The commercial production of chemicals and fuels from lignocellulosic residues by enzymatic means still requires considerable research on both the technical and economic aspects. Two technical problems that have been identified as requiring further research are the recycle of the enzymes used in hydrolysis and the reuse of the re calcitrant cellulose remaining after incomplete hydrolysis. Enzyme recycle is required to lower the cost of the enzymes, while the reuse of the spent cellulose will lower the feedstock cost. The conversion process studied was a combined enzymatic hydrolysis and fermentation (CHF) procedure that utilized the cellulolytic enzymes derived from the fungus Trichoderma harzianum E58 and the yeast Saccharomyces cerevisiae. The rate and extent of hydrolysis and ethanol production was monitored as was the activity and hydrolytic potential of the enzymes remaining in the filtrate after the hydrolysis period. When a commercial cellulose was used as the substrate for a routine 2-day CHF process, 60% of the original treated, water-extracted aspenwood was used as the substrate, only 13% of the original filter paper activity was detected after a similar procedure. The combination of 60% spent enzymes with 40% fresh enzymes resulted in the production of 30% less reducing sugars than the original enzyme mixture. Since 100% hydrolysis of the cellulose portion is seldom accomplished in an enzymatic hydrolysis pro cess, the residual cellulose was used as a substrate for the growth of T. harzianum E58 and production of celulolytic enzymes. The residue remaining after the CHF process was used as a substrate for the production of the cellulolytic enzymes. The production of enzymes from the residue of the Solka Floc hydrolysis was greater than the production of enzymes from the original Solka Floc.