Defective positioning in granulomas but not lung-homing limits CD4 T-cell interactions with Mycobacterium tuberculosis-infected macrophages in rhesus macaques.

Protection against Mycobacterium tuberculosis (Mtb) infection requires CD4 T cells to migrate into the lung and interact with infected macrophages. In mice, less-differentiated CXCR3+ CD4 T cells migrate into the lung and suppress growth of Mtb, whereas CX3CR1+ terminally differentiated Th1 cells accumulate in the blood vasculature and do not control pulmonary infection. Here we examine CD4 T-cell differentiation and lung homing during primary Mtb infection of rhesus macaques. Mtb-specific CD4 T cells simultaneously appeared in the airways and blood ∼21-28 days post exposure, indicating that recently primed effectors are quickly recruited into the lungs after entering circulation. Mtb-specific CD4 T cells in granulomas display a tissue-parenchymal CXCR3+CX3CR1-PD-1hiCTLA-4+ phenotype. However, most granuloma CD4 T cells are found within the outer lymphocyte cuff and few localize to the myeloid cell core containing the bacilli. Using the intravascular stain approach, we find essentially all Mtb-specific CD4 T cells in granulomas have extravasated across the vascular endothelium into the parenchyma. Therefore, it is unlikely to be that lung-homing defects introduced by terminal differentiation limit the migration of CD4 T cells into granulomas following primary Mtb infection of macaques. However, intralesional positioning defects within the granuloma may pose a major barrier to T-cell-mediated immunity during tuberculosis.

[Problematic of reoperations for persisting and recurrent primary hyperparathyroidism]. / Problematika reoperací pro perzistující a rekurentní primární hyperparatyreózu.

Surgery provides final therapy for patients with primary hyperparathyroidism. Once the diagnosis is established, the outcome of surgery depends on the surgeon's experience and judgment. Our experience with 523 procedures (including 31 reoperations) performed from the beginning of 1994 to the end of 2004, have proved that complicated cases, including reoperations, should be concentrated in clinics with sufficient surgcial experience, rating hundreds of the cases.

[Surgical intraduodenal drainage of bile duct: an introductory report]. / Operacyjny dodwunastniczy drenaz drogi zólciowej--doniesienie wstepne.

UNLABELLED: Reconstructing operations, performed on extrahepatic bile ducts, usually need protection of anastomosis by means of drainage. Classic Kehr's drainage is loaded with the risk of complications. Since 1993 the authors have been applying the alter way of drainage: an intraduodenal drainage by endoprothesis Y (DEY). Endoscopical removal of the drain was performed in 3-4 months after the operation. This way of drainage was used between III 1993--V 1997 in 23 patients. We did not observed any complications or pancreas reactions. Clinical control of patients was made after operation with ECW. In 4 cases the results of treatment were unsuccessful. In other 16 patients results of performed operations were favourable. CONCLUSION: Proposed way of protection of bile duct's reconstruction's site using DEY decreases the number of complications connected with classic Kehr's drainage.

Modulation of rat cardiac sodium channel by the stimulatory G protein alpha subunit.

1. Modulation of cardiac sodium currents (INa) by the G protein stimulatory alpha subunit (Gsalpha) was studied using patch-clamp techniques on freshly dissociated rat ventricular myocytes. 2. Whole-cell recordings showed that stimulation of beta-adrenergic receptors with 10 microM isoprenaline (isoproterenol, ISO) enhanced INa by 68.4 +/- 9.6 % (mean +/- s.e.m.; n = 7, P < 0.05 vs. baseline). With the addition of 22 microgram ml-1 protein kinase A inhibitor (PKI) to the pipette solution, 10 microM ISO enhanced INa by 30.5 +/- 7.0 % (n = 7, P < 0.05 vs. baseline). With the pipette solution containing both PKI and 20 microgram ml-1 anti-Gsalpha IgG or 20 microgram ml-1 anti-Gsalpha IgG alone, 10 microM ISO produced no change in INa. 3. The effect of Gsalpha on INa was not due to changes in the steady-state activation or inactivation curves, the time course of current decay, the development of inactivation, or the recovery from inactivation. 4. Whole-cell INa was increased by 45.2 +/- 5.3% (n = 13, P < 0.05 vs. control) with pipette solution containing 1 microM Gsalpha27-42 peptide (amino acids 27-42 of rat brain Gsalpha) without altering the properties of Na+ channel kinetics. Furthermore, application of 1 nM Gsalpha27-42 to Na+ channels in inside-out macropatches increased the ensemble-averaged INa by 32.5 +/- 6.8 % (n = 8, P < 0.05 vs. baseline). The increase in INa was reversible upon Gsalpha27-42 peptide washout. Single channel experiments showed that the Gsalpha27-42 peptide did not alter the Na+ single channel current amplitude, the mean open time or the mean closed time, but increased the number of functional channels (N) in the patch. 5. Application of selected short amino acid segments (Gsalpha27-36, Gsalpha33-42 and Gsalpha30-39) of the 16 amino acid Gsalpha peptide (Gsalpha27-42 peptide) showed that only the C-terminal segment of this peptide (Gsalpha33-42) significantly increased INa in a dose-dependent fashion. These results show that cardiac INa is regulated by Gsalpha via a mechanism independent of PKA that results in an increase in the number of functional Na+ channels. In addition, a 10 residue domain (amino acids 33-42) near the N-terminus of Gsalpha is important in modulating cardiac Na+ channels.

Phosphorylation of tau at both Thr 231 and Ser 262 is required for maximal inhibition of its binding to microtubules.

The paired helical filaments (PHFs) found in Alzheimer's disease (AD) brains are composed primarily of the microtubule-associated protein tau. PHF-tau is in a hyperphosphorylated state and is unable to promote microtubule assembly. We investigated whether the inhibition of tau binding to microtubules is increased when tau is phosphorylated by different kinases in combination with GSK-3. We found that when tau was first phosphorylated by A-kinase, C-kinase, cdk5, or CaM kinase II and then by GSK-3, its binding to microtubules was inhibited by 45, 61, 78, and 79%, respectively. Further, the kinase combinations cdk5/GSK-3 and CaM kinase II/GSK-3 rapidly phosphorylated the sites Thr 231 and Ser 235. When these sites were individually replaced by Ala and the phosphorylation experiments repeated, tau binding to microtubules was inhibited by 54 and 71%, respectively. By comparison, when Ser 262 was replaced by Ala, tau binding to microtubules was inhibited by only 8% after phosphorylation by CaM kinase II. From these observations we estimate that the phosphorylation of Thr 231, Ser 235, and Ser 262 contributes approximately 26, approximately 9, and approximately 33%, respectively, of the overall inhibition of tau binding to microtubules. Together, our results indicate that the binding of tau to microtubules is controlled by the phosphorylation of several sites, among which are Thr 231, Ser 235, and Ser 262.

ARISE: a method for engaging reluctant alcohol- and drug-dependent individuals in treatment. Albany-Rochester Interventional Sequence for Engagement.

A method, the Albany-Rochester Interventional Sequence for Engagement (ARISE), is described for engaging highly ambivalent alcohol- and/or drug-dependent individuals in treatment. A three stage interventional sequence is presented, which begins when a family member or concerned other contacts a treatment program regarding a substance abuser who needs help. At that point a process is set in motion for collaboration with significant others toward client enrollment. Staff move to the next stage in a graduated operating procedure if initial, less demanding efforts do not succeed. The final stage, if needed, is a modified Johnson Institute Intervention. The overall procedure is designed to maximize the probability of patient recruitment, while minimizing the amount of time and energy required of staff. The method compares favorably with results obtained with other approaches, such as coercion (legal, employer) and client self-referral.

Predicting readmission to the psychiatric hospital in a managed care environment: implications for quality indicators.

OBJECTIVE: This study examined predictors of hospital readmission to determine whether readmissions can serve as a quality indicator for an inpatient psychiatric service. METHOD: A series of 255 patients consecutively admitted to any of seven psychiatric hospitals in a regional managed care program were followed to determine whether they were readmitted within 6 months of discharge. Case managers assessed patients with the use of a reliable outcome management/decision support system designed for acute psychiatric services. RESULTS: Patients with greater impairment in self-care, more severe symptoms, and more persistent illnesses were more likely to be readmitted than other patients. Suicidal patients were less likely to be readmitted. There was no evidence to suggest that poor hospital outcome or premature discharge was associated with readmission either within 30 days or within 6 months. CONCLUSIONS: Although patients at risk for hospital admission can be identified, it does not appear that the success of the hospital intervention per se influences the likelihood of readmission. Use of readmission rates as quality indicators for hospital care providers is not recommended.

[Comparison of early results for pancreato-jejunal and pancreato-gastric anastomosis after pancreatoduodenectomy]. / Porównanie wczesnych wyników zespolenia trzustkowo-jelitowego i trzustkowo-zoladkowego po wycieciu glowy trzustki wraz z dwunastnica.

The aim of the study was to compare two types of anastomosis of the pancreatic stump with the digestive tract after pancreatoduodenectomy. 64 patients have been studied. Eighteen of them underwent pancreatoduodenectomy followed by the anastomosis of the pancreatic stump with the posterior wall of the stomach, in 46 patients pancreato-jejunal anastomosis has been done. Short term results of those two types of anastomosis did not differ significantly. Pancreato-gastric anastomosis seems to be technically easier, can be endoscopically controlled and does not impair recovery of gastric motility.

[Biostatic endoprosthesis of the esophagus for prevention of leakage and stenosis at the site of anastomosis]. / Biostatyczna endoproteza przelyku w zapobieganiu nieszczelnosci oraz zwezeniu w miejscu zespolenia.

The authors present the results of using endoprosthesis made of bowine fascia which was conserved in special way. The endoprosthesis was used to cure salivary fistula in the place of anastomosis oesophagus with its replacement of the neck. The endoprosthesis was used to prevent leakness or stenosis in difficult operative circumstances and to pass the substitutive oesophagus in non-anatomical way. Prophylactic using of the endoprosthesis in technical difficulties caused by operative circumstances prevents leakness and stenosis in the place of anastomosis.

[Reoperation after gastroesophageal reflux surgery]. / Reoperace po operacích pro gastroezofageální reflux.

In a group of 19 patients reoperated after a primary operation on account of gastrooesophageal reflux the authors demonstrate that the reason for reoperation can be either a relapse of the reflux or also other complaints (most frequently dysphagia). The selection of a suitable operation is strictly individual. Cases of a short oesophagus are most difficult to resolve. The decisive factor is a correct surgical approach-laparotomy or thoracotomy.

[Zenker's diverticulum]. / Zenkeruv divertikl.

In the course of 10 years 72 patients with an oesophageal diverticulum were operated, incl. 56 with a Zenker diverticulum. The incidence of operative and postoperative complications declined markedly after the introduction of peroperative fibroscopy and the use of fine absorbable atraumatic fibres, in indicated cases also puncture pharyngostomy was used. The authors did not record practically any relapses of diverticula, 81.4% of the patients are after a long-term follow up free from complaints.

[Caroli's disease]. / Caroliho nemoc.

As compared with the past Caroli's disease will be more frequently diagnosed due to new examination methods. In case of clinical manifestation when the disease is confined to one lobe the possibility of lobectomy should be considered, as it is the method of choice as regards the surgical approach. It is important to emphasize the possible concurrent presence of cystic degeneration of the extrahepatic biliary pathways and renal cystosis, the possible occurrence and risk of development of cholangiocarcinoma which increases with advancing age.

[Surgical treatment of esophageal reflux disease associated with a short esophagus]. / Chirurgické osetrení refluxní nemoci jícnu pri krátkém jícnu.

Supradiaphragmatic fundoplication is effective therapy of complicated GER with a feasible morbidity and low mortality. These favourable results moreover do not apply to patients with primary oesophagitis but to a small percentage of patients suffering either from severe transmural oesophagitis or previous unsuccessful fundoplication. Under these conditions surgery is difficult regardless of the selected technique. An alternative possibility of supradiaphragmatic fundoplication in short oesophagus is Collis gastroplasty and fundoplication. The authors recorded good results of this operation/4, 12/. It may be, however, assumed that, at least in patients after previous fundoplication, mobilization of the oral portion of the stomach is associated either a further alteration of its blood supply and thus the risk of ischaemia of the "neo-oesophageal" suture. Supradiaphragmatic fundoplication is thus in the author's opinion the most effective therapeutic method in oesophagitis, performed on account of gastroesophageal reflux in short oesophagus.

[Carcinoma of the cervical esophagus]. / Karcinom krcního jícnu.

Resection of carcinoma of the cervical portion of the oesophagus, if it is to be radical surgery, calls as a rule for concurrent laryngectomy. Patients with severe dysphagia accept gladly even this variant of surgery. In the authors' opinion it is safest to replace the extirpated oesophagus by the colon on a vascular pedicle of the left colic arteries. In some instances in that case even the caecum remains vital. Perspectively the method of choice of a resected cervical oesophagus will be replacement by an isolated jejunal loop.

Molecular characterization of the minimal protease resistant tau unit of the Alzheimer's disease paired helical filament.

The Alzheimer's disease paired helical filament (PHF), after digestion with Pronase, retains its characteristic morphological features. We term this the protease resistant core PHF. A 12 kDa tau fragment can be released from the core as an essentially pure preparation. Sequence analysis of this fragment revealed six distinct N-termini beginning in the repeat region of tau. The precise C-terminus is unknown, but the fragment is approximately 100 residues long. A monoclonal antibody, mAb 423, which recognizes the core PHF and the 12 kDa tau fragment, does not recognize normal full-length tau. We describe cDNA synthesis and expression of candidate 12 kDa tau analogues which permit the mapping of the mAb 423 epitope. mAb 423 recognizes all and only those analogues which terminate at Glu391, which lies beyond the homology repeat region. Addition or removal of a single residue at the C-terminus abolishes immunoreactivity. Therefore, mAb 423, together with knowledge of the N-terminus, can be used to measure the precise extent of 12 kDa PHF core tau fragment which we term the minimal protease resistant tau unit of the core PHF. This unit is 93-95 residues long, which is equivalent to three repeats, but is 14-16 residues out of phase with respect to the maximum homology organization of the repeat region. mAb 423 labels isolated PHFs prior to Pronase digestion and intracellular granular and neurofibrillary degeneration in Alzheimer's disease tissues. The constraints which determine endogenous truncation at Glu391 appear to be characteristic of an assembled configuration of tau, either within the PHF or its precursor.

[Problems in perineal wound healing after abdominoperineal excision of the rectum per primam]. / K problematice hojení perineální rány po abdominoperineální exstirpaci konecníku per primam.

The authors analyze different methods of treatment of perineal wounds after abdominoperineal extirpation of the rectum. They do not recommend for wider use the method of filling the cavity with an omental flap or loops of the small intestine. They consider haemostatic tamponades of the perineal cavity as obsolete in view of the large number of postoperative infectious complications. In their trials they used as a filling absorbable polymer. They elaborated a method of lavage drainage of the perineal wound which, in view of the favourable results achieved, is considered the method of choice.

[Removal of pulmonary metastases using the Nd:YAG laser]. / Odstranení matastáz plic Nd:YAG laserem.

The authors submit a case-history on their first successful application of a Nd:YAG laser in pulmonary surgery. They operated a 17-year-old boy with metastases of a synovial sarcoma in both wings of the lungs. First the boy was operated on the left side by the classical technique, half a year later the authors used a Nd:YAG laser on the right side. By means of the laser four metastases were removed. The postoperative course was without complications. One month after operation the patient was discharged from the care of oncologists and was free of complaints. The authors compare the surgical techniques and the postoperative course of the patient. A Nd:YAG laser is a suitable supplement of the equipment of pulmonary surgeons. Since the described case the authors used the laser in same indication in another three patients.