Nutritional status and wound severity of overweight and obese patients with venous leg ulcers: A pilot study

Obesity is a chronic disease that is linked to the presence of numerous chronic illnesses, including venous disease. Venous disease can lead to chronic wounds, which may be exacerbated by vitamin, mineral, and macro-nutritional deficiencies. A cross-sectional observational design was used to examine the nutritional status of patients with chronic venous leg ulcers (VLUs) who are overweight or obese and to explore the relationship between nutritional status and severity of venous ulceration. Nutritional status was evaluated using anthropometric measurements, nutrient analysis from a 3-day dietary intake log, serum albumin, vitamins A and C, and zinc levels. Wound severity was assessed using the Leg Ulcer Measurement Tool (LUMT). Eight patients participated; six patients were men, and all eight patients were more than 50 years of age. Patients had an average daily caloric intake below their estimated caloric need. When compared with recommended daily intake levels, dietary nutrient intake was suboptimal for protein, vitamin C, and zinc. Serum levels were below normal for at least one of these nutrients in six patients. A positive correlation was found only between serum albumin, average daily intake, and percent recommended daily intake of protein (r(s) = 0.93, P = .003). An inverse relationship was found between LUMT score and serum vitamin A levels (r(s) = -0.83, P = .01), and a positive correlation was observed between LUMT score and serum vitamin C (r(s) = 0.74, P = .04). No clear relationships were shown among serum zinc, albumin, and LUMT scores. Overweight and obese patients with VLU show nutritional deficits that are similar to those of the broader population of patients with leg ulcers. The relationships found between vitamins A and C and leg ulcer severity warrant further exploration. The nutritional differences in the study need to be examined in a larger sample of overweight and normal-weight patients to determine whether overweight patients are at greater risk for prolonged VLU because of poor nutrition than non-overweight patients.     

Fast neutron therapy for malignant astrocytomas

The treatment of supratentorial malignant gliomas has continued to be a major problem for neurosurgeons and oncologists. Post-operative conventional radiotherapy is known to prolong survival and to enhance the quality of life. Local persistence of tumor kills the majority of patients. Fast neutron irradiation is being utilized to treat malignant gliomas based on its reputed radiobiological advantages for treatment of large tumors and the encouraging preliminary reports showing tumor eradication in post-radiation biopsy and autopsy specimens. This paper reviews the results of fast neutron irradiation alone and in combination with photons and hypoxic cell sensitizers. Survival comparisons do not show any superiority for neutrons compared to conventional radiation. However, post-neutron radiation tissue samples have shown less agressive and minimal residual tumor in many instances. At the same time radiation necrosis has emerged as a significant problem. In summary, even though neutron irradiation can eradicate malignant gliomas a therapeutic window has yet to be identified. Address for offprints: Neutron Therapy Facility, MS-301, P.O. Box 500, Batavia, IL 60510, USA     

Effects of an augmented postoperative fluid protocol on wound healing in cardiac surgery patients.

BACKGROUND: Cardiac surgery patients are vulnerable to hypoperfusion postoperatively and often have subcutaneous tissue oxygen tension less than 50 mm Hg. Hypovolemia most likely contributes to this hypoperfusion and may lead to impaired wound healing. OBJECTIVES: To determine if a modified postoperative fluid replacement protocol would result in improved tissue oxygen tension, blood flow, and healing in cardiothoracic surgery patients. METHODS: A total of 166 cardiac surgery patients, 18 to 90 years old, participated in a randomized, 2-group, repeated-measures study. The experimental group received fluid augmentation during the first 36 hours after surgery; the control group received standard postoperative replacement fluids. Subcutaneous tissue oxygen tension and temperature were measured 8, 18, and 36 hours after surgery. Tissue cellularity and accumulation of hydroxyproline were evaluated in tissue obtained from subcutaneous expanded polytetrafluoroethylene tubes. Wound complications were evaluated by using the ASEPSIS Wound Scoring System. RESULTS: Tissue oxygen levels, tissue cellularity, and accumulation of hydroxyproline were similar in the 2 groups. A negative correlation (P = .01) existed between higher tissue oxygen values and lower (better) ASEPSIS leg wound scores. More than 80% of the patients had tissue oxygen levels of 50 mm Hg or less at each time of measure. Many values were 30 to 40 mm Hg less than the ideal for control of bacteria and healing. CONCLUSIONS: The frequency of low oxygen levels is consistent with data from earlier studies. Determination of other interventions to improve subcutaneous tissue perfusion in cardiac surgery patients is needed.     

Quantitative Comparison of Active and Latent Tuberculosis in the Cynomolgus Macaque Model

We previously described that low-dose Mycobacterium tuberculosis infection in cynomolgus macaques results in a spectrum of disease similar to that of human infection: primary disease, latent infection, and reactivation tuberculosis (S. V. Capuano III, D. A. Croix, S. Pawar, A. Zinovik, A. Myers, P. L. Lin, S. Bissel, C. Fuhrman, E. Klein, and J. L. Flynn, Infect. Immun. 71:5831-5844, 2003). This is the only established model of latent infection, and it provides a unique opportunity to understand host and pathogen differences across of range of disease states. Here, we provide a more extensive and detailed characterization of the gross pathology, microscopic histopathology, and immunologic characteristics of monkeys in each clinical disease category. The data underscore the similarities between human and nonhuman primate M. tuberculosis infection. Furthermore, we describe novel methods of quantifying gross pathology and bacterial burden that distinguish between active disease and latent infection, and we extend the usefulness of this model for comparative studies. Early in infection, an abnormal chest X ray, M. tuberculosis growth by gastric aspirate, and increased mycobacterium-specific gamma interferon (IFN-γ) in peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage (BAL) cells were associated with the development of active disease. At necropsy, disease was quantified with respect to pathology and bacterial numbers. Microscopically, a spectrum of granuloma types are seen and differ with disease type. At necropsy, monkeys with active disease had more lung T cells and more IFN-γ from PBMC, BAL, and mediastinal lymph nodes than monkeys with latent infection. Finally, we have observed a spectrum of disease not only in monkeys with active disease but also in those with latent infection that provides insight into human latent tuberculosis.Mycobacterium tuberculosis is a remarkably successful human pathogen. Infection, usually via the respiratory route, results in primary tuberculosis or latent infection. Primary tuberculosis, defined as active disease within 2 years of the initial infection, is likely the result of a failure of the host immune response to control the infection. In this case, the initial infection can progress rapidly or slowly but causes contagious, active tuberculosis. Primary disease occurs in ∼5 to 10% of infected individuals (30). In contrast, most persons control the initial infection but apparently do not eliminate the bacteria completely. This asymptomatic condition is termed latent infection and is not considered to be contagious. A small percentage (5 to 10%) of latently infected persons reactivate during the course of a lifetime, resulting in active disease (reactivation). In humans, reactivation rates are increased in the setting of immune suppression, including human immunodeficiency virus (HIV) coinfection (30), aging (34), and tumor necrosis factor (TNF) neutralization (15, 24).The factors that dictate the outcome of M. tuberculosis infection in humans are not well understood. Studies of murine models have identified T cells, particularly CD4 T cells, as important in the control of initial and chronic infection. The cytokines gamma interferon (IFN-γ), interleukin-12 (IL-12), and TNF also have been shown to be crucial for the control of infection. IFN-γ is necessary for the activation of macrophages, and TNF has multiple functions in the immune response to M. tuberculosis (reviewed in reference 6). This is recapitulated in human studies, in which TNF neutralization (15, 24) and HIV infection (either as the direct loss of CD4 T cells or another immunologic perturbation) (30) has been associated with increased susceptibility to tuberculosis.Although the mouse model has been instrumental in defining several important aspects of the immune response to M. tuberculosis, infection in the mouse is progressive and ultimately leads to death. Mice control initial infection and a state of chronic infection ensues that is characterized by slowly advancing pathology, although the progression of disease is determined in part by the mouse strain used and the inoculating dose. Regardless, the mouse is not a model of latent infection. Mice also lack the organizational characteristics of human granulomas and do not have hypoxic granulomas, which are seen in humans and our model (32). Human granulomas have much more structured architecture, often with caseous necrosis in the center, and can be surrounded by a peripheral rim of fibrosis. Other animal models can display more human-like granulomas, such as the guinea pig and the rabbit, but latent infection has not been demonstrated in either of these animal models and immunology tools are limited.We previously reported that cynomolgus macaques infected with a low dose of M. tuberculosis either develop primary tuberculosis or have latent infection (3). To validate our clinical classification of disease states and quantify the outcome of infection, here we perform an in-depth comparison of monkeys with active and latent disease, and we demonstrate significant differences between these two clinically determined infection states with respect to gross and microscopic histopathology, bacterial numbers, and immune responses. There is a spectrum of disease in active tuberculosis and also in the subclinical state that is classified as latent infection. This is an effective model for understanding the events that predict disease outcome and for investigating therapies for active and latent tuberculosis and reactivation from latent infection. The close similarities between human and nonhuman primates with M. tuberculosis infection provide an excellent model for the study of tuberculosis. We demonstrate here that the outcomes of infection and amount of disease now can be quantified, allowing an analysis of monkey groups that will be useful when using this model to study immune interventions or drugs.     

Tumor necrosis factor neutralization results in disseminated disease in acute and latent Mycobacterium tuberculosis infection with normal granuloma structure in a cynomolgus macaque model

Objective

An increased risk of tuberculosis has been documented in humans treated with tumor necrosis factor α (TNFα)–neutralizing agents. In murine models, impaired signaling by TNF causes exacerbation of both acute and chronic infection associated with aberrant granuloma formation and maintenance. This study was undertaken to investigate immune modulation in the setting of TNF neutralization in primary and latent tuberculosis in a non‐human primate model.

Methods

Cynomolgus macaques 4 years of age or older were infected with Mycobacterium tuberculosis and subjected to clinical, microbiologic, immunologic, and radiographic examinations. Monkeys were classified as having active or latent disease 6–8 months after infection, based on clinical criteria. Monkeys used in acute infection studies were randomized to receive either adalimumab (prior to and during infection) or no treatment. Monkeys with latent infection that were randomized to receive TNF‐neutralizing agent were given either an inhibitor of soluble TNF, recombinant methionyl human soluble TNF receptor I (p55‐TNFRI), or adalimumab. Control monkeys with latent infection were given no treatment or saline. Data from previously studied monkeys with active or latent disease were also used for comparison.

Results

Administration of TNF‐neutralizing agents prior to M tuberculosis infection resulted in fulminant and disseminated disease by 8 weeks after infection. Neutralization of TNF in latently infected cynomolgus macaques caused reactivation in a majority of animals as determined by gross pathologic examination and bacterial burden. A spectrum of dissemination was noted, including extrapulmonary disease. Surprisingly, monkeys that developed primary and reactivation tuberculosis after TNF neutralization had similar granuloma structure and composition to that of control monkeys with active disease. TNF neutralization was associated with increased levels of interleukin‐12, decreased levels of CCL4, increased chemokine receptor expression, and reduced mycobacteria‐induced interferon‐γ production in blood but not in the affected mediastinal lymph nodes. Finally, the first signs of reactivation often occurred in thoracic lymph nodes.

Conclusion

These findings have important clinical implications for determining the mechanism of TNF neutralization–related tuberculosis.

     

Professional strategies in work-related practice: an exploration of occupational and physical therapy roles and approaches.

Both occupational and physical therapy have historical roots in worker rehabilitation; however, the core philosophies and areas of expertise of these professions suggest there may be inherent differences in the ways each approaches therapeutic intervention. This study surveyed 600 occupational and physical therapists in the United States to determine the nature and scope of work-related practice, and the degree to which occupation-based strategies are used by either profession. The overall response rate was 54% (n = 324), and 76% of respondents (n = 246) were actively engaged in providing work-related services. Results indicate that both professions provide all services commonly associated with work-related therapy in almost equal proportions. Few significant differences were identified between the professions in terms of approaches to therapy, and findings did not reveal the use of occupation-based interventions to any greater degree by occupational therapists.