The course of severe foot infection in patients with diabetes.

Infection of the foot is a limb threatening condition for patients with diabetes mellitus. Identification of patients with diabetes and severe infection of the foot most likely to benefit from early revascularization or major amputation would improve the results of a treatment policy to prevent limb loss and avoid futile delays in amputation. During a nine year period, 79 diabetic patients underwent emergency procedures for severe infection of the foot during the initial hospitalization period. None of the patients underwent arterial reconstruction. Eventually, 21 of the patients required a major amputation, eight during the initial hospitalization and 13 on a subsequent admission. Stepwise discriminant analysis of clinical independent variables revealed that the patients most likely to require a major amputation during the initial hospitalization were those with an absent dorsalis pedis pulse and a polymicrobial infection (p = 0.018). The overall amputation rate (immediate or subsequent amputation) was higher for patients of either sex with nonpalpable pedal pulses when compared with those with at least one palpable pulse (p less than 0.05). Males who were not dependent on insulin had the highest risk of overall limb loss (p = 0.01). Patients undergoing delayed amputation required a significantly higher number (p = 0.01) of readmissions to the hospital for recurrent infection of the foot than those who did not undergo amputation. Data in the current study suggest that early major amputation in a subset of patients would prevent delay in the rehabilitation process of the amputee, decrease long term morbidity and reduce health care cost. An aggressive policy of early revascularization in patients with a pulse deficit may reduce the amputation rate in those with diabetes with severe infection of the foot.     

The adverse impact of cytomegalovirus infection on clinical outcome in cyclosporine-prednisone treated renal allograft recipients

Cytomegalovirus (CMV) infection was diagnosed in 28% (n = 144) of 516 renal allograft recipients treated with cyclosporine-prednisone (CsA-Pred) immunosuppressive therapy. The majority of infections produced either asymptomatic (n = 37) or mild-to-moderate (n = 75) clinical disease, while 10% were lethal (n = 14). Transplantation from a seropositive donor to a seronegative recipient was associated with an increased incidence of (CMV) infection but did not predispose to more severe clinical disease. Similarly, donor source (cadaver [CAD] vs. living-related donor [LRD]), age greater than or equal to 45 years, and antecedent pulse steroid therapy for the treatment of acute rejection were not correlated with clinically more severe disease. An increase in serum creatinine to greater than or equal to 25% of preinfection nadir values occurred in association with CMV infection in 106 patients, returning to nadir values or below in 74.5% of these individuals. CMV infection did not impact on actual patient survival among recipients of LRD or CAD allografts or on actual 1-year HLA-haploidentical or HLA-identical LRD graft survival. In contrast, actual 1-year cadaveric graft survival was significantly lower among CMV-infected (n = 95) vs. uninfected (n = 198) patients (75.8% vs. 87.8%, P = .01). In association with the finding of reduced actual 1-year CAD graft survival, CMV-infected patients were found to be more predisposed to develop acute rejection episodes. Of the CMV-infected CAD graft recipients, 48.4% developed greater than or equal to 1 acute rejection episode during the first year following transplantation vs. 25.3% of their uninfected counterparts (P less than .001). The impact of CMV infection in CsA-Pred treated renal transplant recipients does not differ substantially from that reported historically in association with prednisone-azathioprine immunosuppressive therapy.     

Secreted peptides as regulators of neuron-glia and glia-glia interactions in the developing nervous system

Secreted peptides of the nervous system help to regulate neuron-glia and glia-glia interactions during development. These regulatory factors, referred to as glia-promoting factors (GPFs), act on specific classes of glia and include oligodendroglia-stimulating peptides, interleukin-1 (IL-1), colony-stimulating factors (CSF), and fibroblast growth factor (FGF). The maturity of secretory and target cells determines, in part, the ability of a factor to influence glial proliferation, activation, or differentiation. During neural development, GPFs help to control such fundamentally important events as cell movement, neurite outgrowth, and myelination.     

Measurement of immunoreactive myelin basic protein peptide (45-89) in cerebrospinal fluid

To measure myelin basic protein (MBP)-like material in cerebrospinal fluid, we compared two radioimmunoassays, both using the same antiserum to MBP but one using peptide (45-89) as the radioligand and standard (peptide assay), and the other using purified MBP as the radioligand and standard (MBP assay), with respect to their diagnostic sensitivity. Cerebrospinal fluid specimens from 185 patients with definite multiple sclerosis (MS) (n = 27), possible MS (n = 63), probable MS (n = 24), and other neurological disease (n = 71) were analyzed using both assays. The diagnostic sensitivity of the peptide assay was significantly better than that of the MBP assay in those with definite MS (sensitivity 59% and 30%, respectively); there was no significant difference in specificity. The peptide assay also showed better correlation with disease activity than the MBP assay: 14 patients classified as having active MS showed significantly higher sensitivity (78.6% versus 38%, p less than 0.04) when compared to patients with inactive disease. The MBP assay showed no significant difference between these two groups. Besides the increase in sensitivity, the actual molar concentrations of immunoreactive MBP detected using this peptide assay were considerably higher than those found using the MBP assay. These results show that the use of MBP antisera capable of recognizing epitopes present in the carboxyl half of MBP peptide (45-89) results in more sensitive detection of immunoreactive MBP when used with MBP peptide (45-89) as radiolabeled ligand in the assay.     

DRGs, orthopedic surgery, and age at an academic medical center

The federal Medicare Diagnostic Related Group (DRG) hospital reimbursement system has been on line for 5 years. Hospitals contend that profit margins have dropped to dangerously low levels, due to the federal DRG Prospective Payment System. The authors analyzed all orthopedic surgical admissions to a large academic medical center under DRG reimbursement and characterized patients by age, resource utilization, and outcome. Total costs for the 1,040 orthopedic patients analyzed during a 15-month period added up to $9,718,800. Mean hospital cost per patient, mean hospital length of stay, percent outliers, and mortality generally increased with age. All age categories of patients 65 years of age and above generated financial losses under DRGs. Older orthopedic patients consumed a disproportionately larger share of resources than younger patients, and were more frequent users of the SICU and blood. The current DRG reimbursement scheme may be inequitable in relation to the older orthopedic surgery patient. If these findings are demonstrated at other medical centers, older orthopedic surgical patients could be limited in both their access and quality of care in the future.     

Actions of the phorbol ester, PMA, on ATP-induced fluctuations in cytoplasmic calcium in single isolated bovine aortic endothelial cells.

Agonist-evoked rises in [Ca2+]i were recorded from single bovine aortic endothelial cells in the middle of confluent monolayers by dual-wavelength microspectrofluorimetry. Low doses of ATP (1-5 microM) induced a transient rise in [Ca2+]i followed by a maintained plateau phase upon which were superimposed irregular fluctuations in [Ca2+]i. The mechanism underlying these fluctuations is not known. Addition of the phorbol ester, phorbol 12-myristate 13-acetate (PMA), to single cells displaying ATP-induced fluctuations reduced the amplitude and frequency of these fluctuations but the maintained plateau phase was unaffected. Elevation of intracellular cAMP by activation of adenylate cyclase with forskolin, or application of dibutyryl cAMP did not affect the ATP-induced fluctuations. These results suggest a possible role for the diacylglycerol limb of the phosphoinositide hydrolysis pathway, via activation of protein kinase C, but not cAMP, in the mechanism responsible for generating ATP-induced fluctuations in [Ca2+]i.     

Fat embolism after liposuction

We present a case of adult respiratory distress syndrome (ARDS) after extensive liposuction. On the basis of fever, tachypnea, hypoxia, and ARDS occurring within 48 hours after surgery without evidence of cardiogenic pulmonary edema or sepsis, the etiology is believed to be fat embolism. Although liposuction is generally an effective and safe procedure, awareness of this life-threatening complication is important in order to institute prompt and appropriate treatment. Fat embolism must be differentiated from thromboembolism, as the treatment is different, and heparin is not indicated. It is recommended that training standards and guidelines be devised in order to reduce morbidity and mortality associated with this procedure.     

The effect of TNFa on bradykinin receptor binding, phosphatidylinositol turnover and cell growth in human A431 epidermoid carcinoma cells.

In this study, we examined the effect of TNFa on bradykinin (BK) B2 receptor binding and function in human A431 epidermoid carcinoma cells. [3H]BK binds to a single class of receptors on A431 cells in a saturable and reversible manner. A binding affinity (KD) of 3.0 +/- 0.3 nM (n = 4) and a Bmax of 151 +/- 14 fmols/10(6) cells, representing approximately 90,000 BK receptors per cell, was observed. The rank order of potency for BK agonist peptides indicates that the A431 BK receptor appears to be of the B2 subtype. When A431 cells were incubated with TNFa (10 ng/ml) for 48 h prior to BK binding, a significant decrease in the number of BK receptors compared to control was observed. TNFa did not influence the affinity of BK binding to A431 cells and direct addition of TNFa to the binding assay did not effect BK binding. BK-stimulated IP1 formation appeared to be increased in TNFa treated cells compared to control whereas histamine-stimulated IP1 formation was not influenced. Both control and TNFa treated cells were greater than 95% viable. However, TNFa treated cells were blocked in the G1 phase of the cell cycle resulting in a decrease in DNA synthesis. This may be one mechanism for the TNFa-induced decrease in BK receptors in A431 cells.