Depletion of intracellular polyamines relieves inward rectification of potassium channels.

Two different approaches were used to examine the in vivo role of polyamines in causing inward rectification of potassium channels. In two-microelectrode voltage-clamp experiments, 24-hr incubation of Xenopus oocytes injected with 50 nl of difluoromethylornithine (5 mM) and methylglyoxal bis(guanylhydrazone) (1 mM) caused an approximate doubling of expressed Kir2.1 currents and relieved rectification by causing an approximately +10-mV shift of the voltage at which currents are half-maximally inhibited. Second, a putrescine auxotrophic, ornithine decarboxylase-deficient Chinese hamster ovary (O-CHO) cell line was stably transfected with the cDNA encoding Kir2.3. Withdrawal of putrescine from the medium led to rapid (1-day) loss of the instantaneous phase of Kir2.3 channel activation, consistent with a decline of intracellular putrescine levels. Four days after putrescine withdrawal, macroscopic conductance, assessed using an 86Rb+ flux assay, was approximately doubled, and this corresponded to a +30-mV shift of V1/2 of rectification. With increasing time after putrescine withdrawal, there was an increase in the slowest phase of current activation, corresponding to an increase in the spermine-to-spermidine ratio over time. These results provide direct evidence for a role of each polyamine in induction of rectification, and they further demonstrate that in vivo modulation of rectification is possible by manipulation of polyamine levels using genetic and pharmacological approaches.     

Changes in aqueous immunoglobulin and albumin levels following penetrating keratoplasty

The feline model of induced rejection of corneal allografts was employed to define the changes in the concentrations of immunoglobulins and albumin in the anterior chamber prior to, and concomitant with the rejection of the transplanted cornea. Fourteen animals received unilateral exchange corneal allografts. Aqueous humor obtained by anterior chamber paracentesis at regular intervals prior to and following the performance of the penetrating keratoplasties was analyzed for IgG, IgM and albumin concentrations using the micro enzyme-linked immunosorbant assay (ELISA). Two patterns of anterior chamber protein modulation were observed. Eight of the animals demonstrated a biphasic pattern in which both immunoglobulin and albumin concentrations were elevated two- to five-fold above presurgical values 14 days postkeratoplasty, returning to preoperative values by day 42. Three to 5 weeks after corneal rejection was induced increases in protein concentrations were observed that correlated with the appearance of clinical signs of rejection. A second, monophasic pattern of anterior chamber protein modulation following keratoplasty was observed in four of the animals. It was distinguishable from the biphasic pattern in that levels did not return to baseline values after the initial rise following keratoplasty until the rejection process was completed. The monophasic response was found to be characteristic of more rapid and vigorous corneal rejection. Examination of albumin to immunoglobulin ratios suggested that all changes in protein levels following keratoplasty were a result of increased influx of serum proteins into the anterior chamber, rather than due to local immunoglobulin synthesis.     

Characteristics of patients hospitalized with acute decompensated heart failure who are referred for hospice care

BACKGROUND: Hospice is a potential option for patients with end-stage heart failure whose symptoms and clinical status have progressed despite maximal medical therapy. However, little is known about hospice referral practices when patients are admitted because of acute decompensated heart failure. METHODS: Data from the Acute Decompensated Heart Failure Registry (ADHERE) were analyzed from October 1, 2001, to December 31, 2005, accounting for 182 898 patient episodes with known disposition from 307 hospitals. Demographic data, clinical characteristics, and medical management were compared in the group discharged to hospice vs patients discharged to home or to intermediate-care facilities. Hospitals, stratified by frequency of discharge of patients to hospice, were evaluated for adherence to performance measures. Temporal trends according to discharge category were analyzed using analysis of variance, and predictors of hospice referral were determined by multivariate analysis. RESULTS: The hospice cohort composed 1.6% (n = 3010) of the total sample. Patients referred to hospice were generally older, more likely to have been admitted because of antecedent heart failure in the preceding 6 months, more likely to receive intravenous inotropic therapy, less likely to receive angiotensin-converting enzyme inhibitors, and less likely to undergo a procedure (eg, dialysis or cardiac catheterization) during the hospitalization. The median rate of hospice referral increased from 0.8% in 2001 to 1.3% in 2005 (P < .008). Hospitals in the upper quartile of hospice referrals had comparable or higher rates of adherence to quality indicators for heart failure than did hospitals in the lowest quartile. Variables obtained at admission that were associated with hospice referral included older age (per 10-year increment; odds ratio [OR], 1.63; 95% confidence interval [CI], 1.57-1.68), lower serum sodium concentration (per 5-mEq/L [to convert to millimoles per liter, multiply by 1.0] increment; OR, 0.81; 95% CI, 0.78-0.83), lower systolic blood pressure (per 10-mm Hg increment; OR, 0.86; 95% CI, 0.85-0.88), higher serum urea nitrogen concentration (per 10-mg/dL to convert to millimoles per liter, multiply by 0.375] increment; OR, 1.20; 95% CI, 1.18-1.21), and absence of lipid-lowering drug therapy (use of drug OR, 0.69; 95% CI, 0.63-0.75). CONCLUSIONS: A small percentage of patients admitted to acute care hospitals with decompensated heart failure are referred to hospice at rates increasing with time. Hospitals that refer patients to hospice are more likely to be in compliance with heart failure performance measures. Further investigation is required to determine if the hospice option is appropriately selected and if it should be offered to a broader cohort of patients.     

Peculiarities of the surgical treatment of nasal septum perforations

The objective of the present study was the retrospective analysis of the results of nasal septum perforation (NSP) surgery. We report our experience with the operations on the perforated nasal septum based on the treatment of a total of 84 patients. Plastic repair of the perforated nasal septum was undertaken in 54 of them. The endonasal approach with the use of local tissue flaps was employed in 47 cases. Additional bucco-gingival flaps were used in another 4 patients and the open rhinoplastic approach in 3 cases. The complete closure of nasal septum perforations was achieved in 34 (63%) patients. The reduction of the size of perforations was documented in 17 (31%) patients whereas in the remaining three the perforation size slightly increased. The surgical technique and peculiarities of the postoperative management of the patients are described; the possible causes of NSP relapses following surgery are discussed.