Effect of acute bicarbonate administration on exercise responses of COPD patients

Patients with severe chronic obstructive pulmonary disease (COPD) are limited in their exercise tolerance by the level of ventilation (VE) they can sustain. We determined whether acutely increasing blood bicarbonate levels decreased acid stimulation to the respiratory chemoreceptors during exercise, thereby improving exercise tolerance. Responses were compared with those obtained during 100% O2 breathing (known to reduce VE in these patients) and to the responses of healthy young subjects. Participants were six patients with severe COPD (forced expired volume in 1 s = 31 +/- 11% predicted) but without chronic CO2 retention and 5 healthy young subjects. Each subject performed three incremental cycle ergometer exercise tests: 1) control, 2) after ingestion of 0.3 g.kg-1 of sodium bicarbonate and 3) while breathing 100% O2. During these tests VE was measured continuously and arterialized venous blood (patients) or arterial blood (healthy subjects) was sampled serially to assess acid base variables. Bicarbonate loading increased standard bicarbonate by 4-6 mmol.L-1 and this elevation persisted during exercise. In both groups, bicarbonate loading resulted in a substantially higher arterial pH; arterial PCO2 was either unchanged (healthy subjects) or mildly (averaging 5 torr) higher (COPD patients). However, in neither group did bicarbonate loading result in an altered VE response to exercise or an increase in exercise tolerance. In contrast, superimposing hyperoxia on bicarbonate ingestion yielded, on average, 24% reduction in VE and 50% increase in peak work rate in the patients (but not in the healthy young subjects). We conclude that acute bicarbonate loading is not an ergogenic aid in patients with severe COPD.     

The natural history of great toe amputations

The purpose of this study is to report the prevalence of reamputation following resection of the great toe and first ray in adults with diabetes. We abstracted the medical records of 90 diabetic great-toe and first-ray amputees admitted between 1981 and 1991. The most common etiologies of initial amputations were ulcer with soft tissue infection (39%), ulcer with osteomyelitis (32%), and puncture wounds (12%). Sixty percent of all patients had a second amputation, 21% had a third, and 7% had a fourth. Fifteen percent of the patients who had a second amputation had it contralaterally. Seventeen percent subsequently underwent a below-knee amputation and 11% had a Transmetatarsal amputation on the same extremity, 3% had a below-knee amputation, and 2% a transmetatarsal amputation contralaterally. The mean time from the first to the second amputation was approximately 10 months. The results of this study suggest that a large proportion of patients undergoing an amputation at the level of the great toe or first ray have subsequent amputations in the first year following the initial procedure. Additionally, it appears that the contralateral foot may be at significant risk for distal amputation following resection of the hallux or first day.     

Temporal expression of PTHrP during endochondral bone formation in mouse and intramembranous bone formation in an in vivo rabbit model

Expression of parathyroid hormone-related protein (PTHrP) messenger RNA (mRNA) and protein was investigated throughout the developmental progression of endochondral bone formation in mouse and intramembranous bone formation in an in vivo model in rabbit, using in situ hybridization and immunohistochemistry. Endochondral bone formation was investigated in a developing embryo, newborn, and adult mouse. In fetal long bones through to newborn (day 7), PTHrP mRNA and protein were consistently expressed in chondrocytes within the proliferative, transitional, and hypertrophic zones. In addition, high levels of PTHrP were also detected in osteoblasts on the surface of trabecular bone surfaces. Similarly, at the adult stage (week 7), PTHrP mRNA and protein were consistently expressed in chondrocytes at epiphyseal ends of the subarticular cartilage, within cortical periosteum, as well as in osteoblasts located at the metaphyseal trabecular bone surfaces. Using an in vivo intramembranous bone formation model in rabbits, expression of PTHrP mRNA and protein was demonstrated in preosteoblasts prior to trabecular bone formation (1-week bone harvest). As bone formed (2-, 3-, and 4-week bone tissue harvests), PTHrP mRNA and protein were highly expressed in actively synthesizing osteoblasts and in those osteocytes embedded within the superficial layers of the bone matrix. Lining osteoblasts and osteocytes buried deeply in the bone matrix displayed weak or no signal for PTHrP. The pattern of spatial and temporal expression of PTHrP demonstrated in cartilage cells and osteoblasts in the two systems suggests an important role of PTHrP in both endochondral and intramembranous bone formation.     

Transduction of envelope stress in Escherichia coli by the Cpx two-component system

Disruption of normal protein trafficking in the Escherichia coli cell envelope (inner membrane, periplasm, outer membrane) can activate two parallel, but distinct, signal transduction pathways. This activation stimulates the expression of a number of genes whose products function to fold or degrade the mislocalized proteins. One of these signal transduction pathways is a two-component regulatory system comprised of the histidine kinase CpxA and the response regulator, CpxR. In this study we characterized gain-of-function Cpx* mutants in order to learn more about Cpx signal transduction. Sequencing demonstrated that the cpx* mutations cluster in either the periplasmic, the transmembrane, or the H-box domain of CpxA. Intriguingly, most of the periplasmic cpx* gain-of-function mutations cluster in the central region of this domain, and one encodes a deletion of 32 amino acids. Strains harboring these mutations are rendered insensitive to a normally activating signal. In vivo and in vitro characterization of maltose-binding-protein fusions between the wild-type CpxA and a representative cpx* mutant, CpxA101, showed that the mutant CpxA is altered in phosphotransfer reactions with CpxR. Specifically, while both CpxA and CpxA101 function as autokinases and CpxR kinases, CpxA101 is devoid of a CpxR-P phosphatase activity normally present in the wild-type protein. Taken together, the data support a model for Cpx-mediated signal transduction in which the kinase/phosphatase ratio is elevated by stress. Further, the sequence and phenotypes of periplasmic cpx* mutations suggest that interactions with a periplasmic signaling molecule may normally dictate a decreased kinase/phosphatase ratio under nonstress conditions.     

Human monocyte-derived macrophages express an approximately 120-kD Ox-LDL binding protein with strong identity to CD68

A protein that specifically binds oxidized LDL (Ox-LDL) has recently been characterized in mouse peritoneal macrophages and identified as macrosialin, a protein with a molecular weight of 95 kD. First, the present work shows that human monocyte-derived macrophages express a membrane protein with a molecular weight of approximately 120 kD that selectively binds Ox-LDL. Second, we tested whether this approximately 120-kD Ox-LDL binding protein had any relation to CD68, the human homologue of macrosialin. The following evidence was obtained to support the role of CD68 as an Ox-LDL binding protein: (1) Ligand blots with Ox-LDL and Western blots with Ki-M6, an anti-human CD68 monoclonal antibody, revealed a single band with a molecular weight of approximately 120 kD under reducing and nonreducing condition. (2) The expression patterns of the approximately 120-kD Ox-LDL binding membrane protein and of CD68 paralleled each other during monocyte/macrophage differentiation. (3) Digestion with N-glycosidase F demonstrated that both CD68 and the Ox-LDL binding protein are glycoproteins; both showed a similar shift of approximately 18 kD in apparent molecular weight. (4) CD68, probed with monoclonal antibody Ki-M6, and the approximately 120-kD Ox-LDL binding protein were coprecipitated with EMB11, another anti-CD68 antibody. About 5000 molecules of CD68 are expressed on the cell surface of human macrophages. Ligation of 125I-Ki-M6 to cells leads to its internalization and degradation. This capacity would be sufficient to allow for the specific uptake and degradation of Ox-LDL. Taken together, these data support a role for CD68 as a specific Ox-LDL binding protein in human monocyte-derived macrophages.     

Detection of flunixin in greyhound urine by a kinetic enzyme-linked immunosorbent assay

Anxiety levels in a sample of 65 long-term cancer survivors were assessed in a study of the effects of a planned discharge from an oncology clinic. Thirty-one percent of patients scored > or = 8, and 12% > or = 11 on the anxiety subscale of the Hospital Anxiety and Depression Scale (HADS), indicating that anxiety rates in patients in long-standing remission do not greatly differ from patients with active disease. Despite the provision of continued support and guaranteed fast-access return to the clinic if necessary, 28% of patients refused to be discharged. Fear that recurrence would not be detected was the reason most frequently cited. Seventy-five percent of these patients were HADS anxiety cases. A second assessment 4-5 months later of the 41 patients who were discharged showed a slight, but non-significant increase in anxiety rates suggesting that anxiety in cancer survivors may be persistent and not related to clinic attendance.     

The supportive care needs of newly diagnosed cancer patients attending a regional cancer center

BACKGROUND: The objective of this study was to examine the physical and emotional health status, self-perceived problems, and needs of newly diagnosed cancer patients to determine and plan supportive care strategies. METHODS: A cross-sectional survey of newly diagnosed cancer patients attending a regional cancer center during a 6-month period was performed. Patients with breast, colorectal, head and neck, lung, and prostate carcinoma as well as nonmelanoma of the skin were selected randomly. Patients were interviewed prior to their first appointment at the clinic. Physical health status was assessed using the Symptom Distress Scale, psychologic health status was assessed with the General Health Questionnaire (GHQ), day-to-day functioning with the Rapid Disability Scale, and social support with the modified Sarason's Social Support Scale. Perceived needs were assessed in a number of ways, including identification of patients' specific social concerns and informational needs, and by asking them to list their current problems or concerns. RESULTS: Of 156 eligible patients, 134 completed the interview. One hundred and twenty-nine patients (96%) reported current symptoms that included fatigue (66%), worried outlook (61%), difficulty sleeping (48%), and pain (42%). Forty-four patients (33%) were identified as psychologically distressed with a GHQ score of > or = 6. One hundred and fourteen patients (85%) had informational needs, 89 (66%) indicated > or = 1 social concerns, and 55 (41%) reported a need for assistance with day-to-day living. CONCLUSIONS: Patients with newly diagnosed cancer commonly report symptoms related to fatigue, pain, and psychologic distress. Other frequently reported issues relate to the need for information and social concerns regarding the patients' ability to take care of their home and maintain family and other relationships. Awareness of these issues is important for planning supportive care interventions for newly diagnosed cancer patients.