The tolerogenic peptide hCDR1 immunomodulates cytokine and regulatory molecule gene expression in blood mononuclear cells of primary Sjogren's syndrome patients.

Primary Sjogren's syndrome (pSS) is an autoimmune disease characterized by lymphocytic infiltration of exocrine glands. We investigated whether the tolerogenic peptide, hCDR1, that ameliorates lupus manifestations would have beneficial effects on pSS as well. The in vitro effects of hCDR1 on gene expression of pro-inflammatory cytokines and regulatory molecules were tested in peripheral blood mononuclear cells (PBMC) of 16 pSS patients. hCDR1, but not a control peptide, significantly reduced gene expression of IL-1ß, TNF-α, MX-1 and BlyS and up-regulated immunosuppressive (TGF-ß, FOXP3) molecules in PBMC of pSS patients. hCDR1 did not affect gene expression in patients with rheumatoid arthritis and anti-phospholipid syndrome. Further, hCDR1 up-regulated the expression of Indoleamine 2,3-dioxygenase (IDO) via elevation of TGF-ß. IDO inhibition led to a significant decrease in the expression of FOXP3 which is crucial for the induction of T regulatory cells. Thus, hCDR1 is potential candidate for the specific treatment of pSS patients.

Roxithromycin Pharmacokinetics in Hospitalized Geriatric Patients: Oral Administration of Whole Versus Crushed Tablets.

BACKGROUND: Drug administration as tablets to debilitated elderly patients in crushed form can modify the pharmacokinetic characteristics of the active components. Only scarce information is available on the pharmacokinetics when administered in such form. The aim of this study was to evaluate the pharmacokinetics of roxithromycin administered in crushed form and to compare it with the pharmacokinetics of a group of geriatric patients receiving it in the conventional tablet form. METHODS: Twenty patients from the acute ward of the Shmuel Harofeh Geriatric Medical Center in stable, clinical, and hemodynamic condition were studied. Patients in group 1 (n = 10) received medications orally in tablet form. Group 2 (n = 10) included age- and disease-matched patients from the same department, who received oral roxithromycin in crushed tablet form. The mean daily dose was the same in both groups: 300 mg (150 mg twice daily). The patients received the drug for 3 days before the initiation of the study. Blood samples for determination of the roxithromycin concentration were taken at the baseline, 1 hour before the drug administration, and at 1, 3, 4, 6, 8, and 10 hours after drug administration. Roxithromycin concentration was measured by a liquid chromatography-tandem mass spectrometry method. RESULTS: Pharmacokinetic parameters of roxithromycin were significantly different between the 2 groups: the Cmin and Cmax were significantly higher, the tmax significantly longer, AUC0-10 larger, and CL/F smaller in group 2. CONCLUSIONS: Roxithromycin pharmacokinetic parameters were significantly different between the 2 patient groups resulting in higher drug serum concentrations in the crushed tablets group. The impact of the increased drug exposure is unclear.

Pharmacokinetics of ciprofloxacin in hospitalized geriatric patients: comparison between nasogastric tube and oral administration.

OBJECTIVES: Drug administration to debilitated elderly patients on enteral feeding through a nasogastric tube (NGT) can modify the pharmacokinetic characteristics of the drug and influence its therapeutic blood concentration. The aim of this study was to evaluate the pharmacokinetics of ciprofloxacin administered through an NGT and to compare it with those of a group of patients receiving the drug orally. METHODS: Twenty patients in stable clinical and hemodynamic condition from the long-term care ward of a geriatric multilevel hospital were studied. Patients in group 1 (n = 10) had oropharyngeal dysphagia and received food and medications, including ciprofloxacin, by NGT. Group 2 (n = 10) included age- and disease-matched orally fed patients from the same department receiving ciprofloxacin orally. Blood samples for ciprofloxacin concentration were taken at steady state, before drug administration, time 0, and at 1, 2, 3, 4, 6, 8, and 10 hours after drug administration. Ciprofloxacin was measured using liquid chromatography with tandem mass spectrometric detection. The mean daily dose was the same in both the groups: 1000 mg (500 mg twice daily). RESULTS: Pharmacokinetic parameters of ciprofloxacin were not significantly different between the 2 groups: trough concentrations were 1.24 ± 0.95 µg/mL (0.25-3.67 µg/mL) versus 1.30 ± 0.61 µg/mL (0.21-2.36 µg/mL) (P = 0.76); Cmax 3.30 ± 2.16 µg/mL (1.54-8.62 µg/mL) versus 4.24 ± 1.99 µg/mL (2.24-9.02 µg/mL) (P = 0.356); tmax 2.8 ± 1.5 versus 3.1 ± 2.8 hours (P = 0.799); and AUC0-10 20.2 ± 12.1 µg·h·mL (9-51.07 µg·h·mL) versus 24.4 ± 13.0 µg·h·mL (5.57-52.48 µg·h·mL) (P = 0.493), in the oral fed versus NGT, respectively. CONCLUSIONS: Ciprofloxacin pharmacokinetic parameters are not significantly different between patients receiving the drug through NGT compared with those who received it orally, and therefore, in frail elderly patients, this route of administration can be considered.

Increased incidence of pathological and clinical prostate cancer with age: age related alterations of local immune surveillance.

PURPOSE: The incidence of prostate cancer dramatically increases with age. The etiology still awaits elucidation, and the question as to why it is so prominently a disease of aging remains unanswered. We offer an explanation by suggesting an age related deficient immune surveillance. MATERIALS AND METHODS: Reports published in the scientific literature with relevance to cancer and immunity, immune senescence, blood-prostate barrier and immune privilege were identified using MEDLINE. RESULTS: The existence of a blood-prostate barrier is a fair assumption, and the prostate may be considered an immune privileged site. With aging the prostate, a priori immunologically under surveilled, probably becomes more and more so. There is impaired function, transmigration and probably penetration into the gland of natural killer and other immune competent cells due to the onset of immune senescence coupled with impaired diapedesis and possible age related alterations in the blood-prostate barrier. CONCLUSIONS: Apparently, with aging the immune surveillance of the already immune privileged prostate is progressively and further affected. This condition may result in the inability of the gland to eradicate emergent malignant cells.

Management of adverse clinical events by duty physicians in a nursing home.

BACKGROUND AND AIMS: The nature of adverse clinical events (ACE) during duty hours (16:00-08:00 and holidays), as well as the way they are addressed by duty physicians (DP) in a nursing home (NH) are the subject of this study. METHODS: Data, including medical details concerning ACEs and the resultant referrals to hospital, were collected prospectively during 183 consecutive days in a 90-bed NH. RESULTS: Ninety-six residents experienced 370 ACEs, representing an average of one for every 44.5 patient days. The highest rate of events was during evening hours (18:00-21:00). The most prevalent ACE was fever (32%). Most cases (53%) were treated by the DPs on site. No intervention was needed in 19% of cases, whereas 28% of ACEs (104 cases) were referred to the Emergency Room (ER) of a general hospital. Sixty-six percent of these were actually admitted. The rate of ER referral of residents was one for every 158 patient days. About 40% of the referred patients had been discharged from hospital the previous week. High fever was the commonest cause for referral: 47%. During the working hours of the study period, the rate of referral by the staff physician was only 1 for every 915 patient days. Only 17% of these had high fever. CONCLUSIONS: Evening rounds by staff physicians, strengthening of working relations with hospital physicians, as well as fostering intravenous treatment in NHs, are suggested as means for reducing hospital transfers. A standardized method for the reporting of ACEs and referrals to hospitals should be adopted in order to facilitate comparisons between NHs and to evaluate its use as a quality indicator.

Therapeutic drug monitoring of theophylline in frail elderly patients: oral compared with nasogastric tube administration.

SUMMARY: Treating debilitated elderly patients through nasogastric tube (NGT) can change the pharmacokinetic characteristics of drugs, mainly those that are slow released (SR). The purpose of this study was to compare pharmacokinetic parameters between patients who receive SR theophylline orally and those who receive it through NGT. PATIENTS AND METHODS: The authors studied elderly patients in the geriatric ward receiving SR theophylline for chronic obstructive lung disease. In 17 patients fed by NGT (group I), theophylline was removed from the capsule and mixed with 10 mL of water. Group II included 15 patients who swallowed the drug orally. Theophylline blood levels were measured, as were peak concentration (C(max) ), time to peak (T(max) ), and area under the serum concentration-time curves (AUC). RESULTS: The mean daily dose was not statistically different between the two groups: 320 +/- 130 (200-500) mg/d in group I and 360 +/- 85 (200-500) mg/d in group II, given twice daily. All pharmacokinetic measurements were lower in group I as compared with group II: trough theophylline blood levels were 3.78 +/- 3.2 (0.5-10.77) microg/mL versus 8.63 +/- 4.6 (0-15.61) microg/mL ( P= 0.002); C(max) was 6.53 +/- 4.1 (1.3-13.33) microg/mL versus 10.51 +/- 3.30 (4.3-16.28) microg/mL (P = 0.0058), and AUC was 50.04 +/- 38.59 (11-112) microg/h/mL versus 80.37 +/- 28.8 (23-148) microg/h/ml (P = 0.024). CONCLUSIONS Patients receiving the drug through NGT had variability and unexpectedly low blood levels. Therefore, the pharmacokinetic parameters of SR preparations should be evaluated before their administration through NGT.