Citations

In gene-targeted mouse models for cystic fibrosis (CF), the disease is mainly manifested by mucus obstruction in the intestine. To explore the mucus composition, mucins insoluble and soluble in 6M guanidinium chloride were purified by three rounds of isopycnic ultracentrifugation from the small and large intestines of CF mice (Cftrm1UNC/Cftrm1UNC) and compared with wild-type mice. The amino acid composition was typical of that for mucins and showed increased amounts of the insoluble (2.5-fold increase) and soluble (7-fold increase) mucins in the small intestine of the CF mice compared with wild-type mice. Mucins from the large intestine of both wild-type and CF mice showed a high but constant level of fucosylation. In contrast, the insoluble and soluble mucins of the small intestine in CF mice revealed a large increase in fucose, whereas those of wild-type mice contained only small amounts of fucose. This increased fucosylation was analysed by releasing the O-linked oligosaccharides followed by GC-MS. NMR spectroscopy revealed that the increased fucosylation was due to an increased expression of blood group H epitopes (Fucα1-2Gal-). Northern-blot analysis, using a probe for the murine Fucα1-2 fucosyltransferase (Fut2), showed an up-regulation of this mRNA in the small intestine of the CF mice, suggesting that this enzyme is responsible for the observed increase in blood group H-type glycosylation. The reason for this up-regulation could be a direct or indirect effect of a non-functional CF transmembrane conductance regulator (CFTR) caused by the absence of CFTR channel.

Background— Stenting-related myocardial injury has been recognized as a frequent and prognostically important event, the extent of which depends on microcirculatory impairment in association with platelet aggregation, inflammation, and increased oxidative stress. Recent studies underscored the non–lipid-lowering effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) with antithrombotic, antiinflammatory, and antioxidative aspects. Thus, we tested the hypothesis that preprocedural statin therapy is associated with a reduction in the extent of stenting-related myocardial injury. Methods and Results— We stratified 296 consecutive patients who were undergoing stenting of a de novo stenosis according to the preprocedural status of statin therapy (229 statin-treated and 67 control patients). Incidence of periprocedural myocardial injury was assessed by analysis of creatine kinase (CK; upper limit of normal [ULN] 70 IU/L for women, 80 IU/L for men) and cardiac troponin T (cTnT; bedside test; threshold 0.1 ng/mL) before and 6, 12, and 24 hours after the intervention. Relative to control patients, the incidence of CK elevation >3× ULN was more than 90% lower in statin-treated patients (0.4% versus 6.0%, P =0.01). Statin therapy was the only factor independently associated with a lower risk of CK elevation >3× ULN (OR: 0.08, 95% CI: 0.01 to 0.75; P =0.03). The overall incidences of CK and cardiac troponin T elevation were slightly lower in statin-treated than in control patients (14.4% versus 20.9%, P =0.3, and 17.9% versus 22.4%, P =0.5, respectively). Conclusions— Preprocedural statin therapy is associated with a reduction in the incidence of larger-sized, stenting-related myocardial infarctions. Prospective, randomized trials are warranted to further assess this cardioprotective effect of statins in coronary intervention.

ABSTRACTOn viral infection, infected cells can become the target of host immune responses or can go through a programmed cell death process, called apoptosis, as a defense mechanism to limit the ability of the virus to replicate. To prevent this, viruses have evolved elaborate mechanisms to subvert the apoptotic process. Here, we report the identification of a novel antiapoptotic K7 protein of Kaposi's sarcoma-associated herpesvirus (KSHV) which expresses during lytic replication. The KSHV K7 gene encodes a small mitochondrial membrane protein, and its expression efficiently inhibits apoptosis induced by a variety of apoptogenic agents. The yeast two-hybrid screen has demonstrated that K7 targets cellular calcium-modulating cyclophilin ligand (CAML), a protein that regulates the intracellular Ca2+concentration. Similar to CAML, K7 expression significantly enhances the kinetics and amplitudes of the increase in intracellular Ca2+concentration on apoptotic stimulus. Mutational analysis showed that K7 interaction with CAML is required for its function in the inhibition of apoptosis. This indicates that K7 targets cellular CAML to increase the cytosolic Ca2+response, which consequently protects cells from mitochondrial damage and apoptosis. This is a novel viral antiapoptosis strategy where the KSHV mitochondrial K7 protein targets a cellular Ca2+-modulating protein to confer resistance to apoptosis, which allows completion of the viral lytic replication and, eventually, maintenance of persistent infection in infected host.

Studies of patient satisfaction are continually needed to provide feedback to the medical community about rapidly changing telemedicine technology. We accumulated data during 1998 from geriatric patients living in a retirement community based on their experience with telemedicine (one encounter a week for eight weeks). Responses to the items on a Likert scale were generally positive. A similar study was conducted with random patients at the same site two and a half years later. The results were once again positive and appeared to show an even better response than those obtained in the previous study. Thus, although the pilot study was small (20 patients, 18 reporting), this trend may reflect an increased acceptance of telemedicine applications among geriatric patients. Larger studies are needed to substantiate this claim.

Abstract Spigelian hernia is a rare partial abdominal wall defect. The frequent lack of physical findings along with vague associated abdominal complaints makes the diagnosis elusive. A retrospective review of Mayo Clinic patients was performed to find all patients who had undergone surgical repair of a Spigelian hernia from 1976 to 1997. Patients were scrutinized for presentation, work‐up, therapy, and outcome. The goal of this study was to obtain long‐term outcome. The study was set in a tertiary referral center. There were 76 patients in whom 81 Spigelian hernias were repaired. Symptoms most commonly included an intermittent mass (n = 29), pain (n = 20), pain with a mass (n = 22), and bowel obstruction (n = 5). Five patients were asymptomatic. Preoperative imaging was performed in 21 patients and correctly diagnosed the hernia in 15. Spigelian hernias were repaired by primary suture closure (n = 75), mesh (n = 5), and laparoscopic (n = 1) techniques. Eight patients (10%) required emergent operations. Thirteen hernias (17%) were found to be incarcerated at the time of the operation. Overall mean follow‐up for the 76 patients was 8 years, with three hernia recurrences identified. Spigelian hernia is rare and requires a high index of suspicion given the lack of consistent symptoms and signs. An astute physician may couple a proper history and physical examination with preoperative imaging to secure the diagnosis. Mesh and laparoscopic repairs are viable alternatives to the durable results of standard primary closure. Given the high rate of incarceration/strangulation, the diagnosis of Spigelian hernia is an indication for surgical repair.

The trend toward limited exploration for primary hyperparathyroidism (1° HPT) has stemmed from advances in sestamibi scanning, gamma probe technology, and intraoperative parathyroid hormone monitoring (iPTH). Prior to widespread application, directed parathyroidectomy must be shown to meet the high standards of conventional cervical exploration. In this prospective, nonrandomized trial, results of parathyroidectomy utilizing the gamma probe, iPTH, or neither technique were evaluated. Altogether, 150 patients underwent parathyroidectomy utilizing the gamma probe (n = 50), iPTH (n = 50), or neither technique (n = 50). Each group was evaluated for operating time, length of hospitalization, cure rate, morbidity, mortality, and cost. A telephone survey was conducted with 25 patients in each group (n = 75) to address patient satisfaction. The gamma probe localized the abnormal gland in 66% of patients and confirmed cure intraoperatively in 84%. In the iPTH group, a more than 50% decrease from baseline occurred in 98%. The mean operating times were 76, 84, and 90 minutes, respectively (p = 0.16); and the mean length of hospitalization was 1 day. The biochemical cure rates were 98%, 100%, and 96%, respectively (p = 0.17). Total costs were $4476, $3918, and $3905, respectively. A total of 96% of patients in all three groups were "very satisfied" with their surgical procedure. Directed parathyroidectomy utilizing the gamma probe or iPTH assay does not significantly alter the operating time, length of hospitalization, cure rate, morbidity, mortality, or patient satisfaction when compared to conventional exploration in our practice. The probe is more expensive and was not a consistently reliable tool for localizing parathyroid pathology. PTH monitoring reliably predicts cure intraoperatively.

It is uncertain whether more extensive primary surgery and increasing use of radioiodine remnant ablation (RRA) for papillary thyroid carcinoma (PTC) have resulted in improved rates of cause‐specific mortality (CSM) and tumor recurrence (TR). Details of the initial presentation, therapy, and outcome of 2444 PTC patients consecutively treated during 1940–1999 were recorded in a computerized database. Patients were followed for more than 43,000 patient‐years. The 25‐year rates for CSM and TR were 5% and 14%, respectively. Temporal trends were analyzed for six decades. During the six decades, the proportion with initial MACIS (distant Metastasis, patient Age, Completeness of resection, local Invasion, and tumor Size) scores <6 were 77%, 82%, 84%, 86%, 85%, and 82%, respectively (p = 0.06). Lobectomy accounted for 70% of initial procedures during 1940–1949 and 22% during 1950–1959; during 1960–1999 bilateral lobar resection (BLR) accounted for 91% of surgeries (p <0.001). RRA after BLR was performed during 1950–1969 in 3% but increased to 18%, 57%, and 46% in successive decades (p <0.001). The 40‐year rates for CSM and TR during 1940–1949 were significantly higher (p = 0.002) than during 1950–1999. During the last 50 years the 10‐year CSM and TR rates for the 2286 cases did not significantly change with successive decades. Moreover, the 10‐year rates for CSM and TR were not significantly improved during the last five decades of the study, either for the 1917 MACIS <6 patients or the 369 MACIS ? 6 patients. Increasing use of RRA has not apparently improved the already excellent outcome, achieved before 1970, in low risk (MACIS <6) PTC patients managed by near‐total thyroidectomy and conservative nodal excision.

Abstract Background Digitalis has a long history in the treatment of heart failure but its effects on cardiac hemodynamics and neurohormonal modulation are not well characterized. Aims The purpose of this study was to evaluate the relationship between atrial natriuretic peptide (ANP) and the hemodynamic responses to acute digitalis administration in patients with normal and impaired left ventricular function (LVD). Methods and Results Thirty patients were enrolled in the study, 20 with LVD (LVEF-22±8%) and 10 control subjects (LVEF-77±10%). Hemodynamics and plasma ANP concentrations were measured supine and with leg elevation before and after digitalis. In patients with normal ventricular function, the hemodynamic stress of leg elevation in the pre-digitalis state resulted in significant (P&lt;0.05) increases in PAWP and MPAP. Digitalis administration in the supine position produced reductions in heart rate, PAWP, MPAP and CI; SVR was increased. In LVD patients leg elevation further increased PAWP, RAP and MPAP. Digitalis in the supine position, however, reduced RAP, MPAP and PAWP and increased CI. These improved hemodynamics were preserved during the stress of leg elevation. Leg elevation following digitalis resulted in increased ANP concentrations despite decreased cardiac filling pressures. Conclusions Acute digitalis administration results in hemodynamic improvement in LVD patients which may in part result from digitalis stimulated release of myocardial ANP under conditions of hemodynamic stress.