Protein kinase C in platelets of depressed patients

Though described in 1769, the etiology of Zenker's diverticulum remains unclear. Various primary esophageal motor disorders have been proposed, but no consistent manometric pattern or anatomic etiology has been uniformly recognized. An association with clinical neurologic disease at our institution prompted a review of 12 cases of Zenker's diverticulum in patients over 60 years of age, treated in the last 8 years. Nine patients (75%) underwent cricopharyngeus myotomy and diverticulectomy, with uniformly good results. Ten patients (83%) had an associated neurologic disorder, substantiated by cranial CT or MRI, in most cases. A wide range of neurologic problems were identified, but a strong trend toward brainstem or basilar lesions was present. As expected, the etiology of the neurologic abnormality in most patients in this group was cerebrovascular disease, but two patients had peripheral neuropathies. We suggest that the etiology of Zenker's diverticulum in the elderly may be neurologic in origin. Esophageal motor disorders, including incomplete upper esophageal sphincter opening and increased hypopharyngeal pressures, which may result in Zenker's diverticulum, may be a manifestation of central or peripheral neurologic disease in the elderly.     

MMP and TIMP expression pattern in pleural effusions of different origins

The matrix metalloproteinases (MMP) are proteolytic enzymes that are essentially involved in the turnover of the extracellular matrix (ECM). Their activity is counterbalanced by specific antagonists, the tissue inhibitors of metalloproteinases (TIMP). In this study, we sought to analyze the expression of MMP and TIMP isoforms in pleural effusions from 88 patients. We compared MMP and TIMP isoform expression in transudates (n = 21) and exudates (n = 67), the latter divided into exudates of paraneoplastic (n = 46) or parainfectious (n = 21) origin. Zymographic and Western blot analyses revealed constant expression of interstitial collagenase (MMP-1), gelatinase-A (MMP-2), and TIMP-1 in all 88 samples. In contrast, analyses of gelatinase-B (MMP-9) demonstrated a specific expression pattern, with high expression in exudates and lack of expression in transudates. Neutrophil collagenase (MMP-8) was detected in trace amounts, and correlated with the number of neutrophils in the effusion. Low levels of TIMP-2 were detected only in exudates and not in transudates. Quantitative analysis of the expression ratio of gelatinase-B to gelatinase-A revealed statistically significant differences between effusions of different origin. The ratio was highest in exudates of paraneoplastic origin and lowest in transudates. Our data thus suggest that interstitial collagenase, gelatinase-A, and TIMP-1 play a role in homeostasis of the pleural space in vivo as constitutively expressed proteins, whereas gelatinase-B and TIMP-2 expression are induced in specific disease states. These observations contribute to the understanding of the pathophysiology of pleural effusions, and may help to characterize and possibly distinguish effusions of different origin.     

Pigmented epithelium sustains cell proliferation and decreases expression of opsins and acetylcholinesterase in reaggregated chicken retinospheroids

We investigated the effect of the retinal pigmented epithelium on cell proliferation and differentiation in rosetted retinospheroids, which are retina-like spheres reaggregated in the complete absence of retinal pigmented epithelium from dissociated retinal cells of 6-day-old chick embryos in a rotation culture system. In spheroids raised in the absence of retinal pigmented epithelium (controls), acetylcholinesterase was expressed in cells of an inner nuclear-like layer and their neuropil matrices. Moreover, the ratio between rods and cones was found to be approximately normal throughout the spheroid. When spheroids were cultured in the presence of retinal pigmented epithelium monolayers, cell proliferation in spheroids as determined by BrdU labelling was significantly increased and extended for 1 week, while acetylcholinesterase protein levels and specific activities in homogenates were decreased to approximately 30%. At the same time, opsin immunoreactivity was completely suppressed within the spheroid and appeared slowly in cells around its periphery; i.e. the proportion of rhodopsin-positive cells decreased from 14 to 3%. This study reveals that the retinal pigmented epithelium in vitro sustains cell proliferation but inhibits the differentiation of acetylcholinesterase-positive cells and of photoreceptors.     

The influence of bicarbonate supplementation on plasma levels of branched-chain amino acids in haemodialysis patients with metabolic acidosis

BACKGROUND: It has been hypothesized that correction of metabolic acidosis might improve the nutritional state of acidotic haemodialysis (HD) patients partly because of a reduced oxidation of branched-chain amino acids (BCAA). AIM: We investigated whether bicarbonate (Bic) supplementation in acidotic HD patients results in increased plasma levels of BCAA. METHODS: In a longitudinal study (run-in period, 2 months; study period, 6 months), the effect of Bic supplementation on plasma levels of BCAA was studied in 12 acidotic HD patients (7 men, 5 women, mean age 54 +/- 18 years) with a predialysis bicarbonate (Bic) concentration smaller or equal to 22 mmol/l. Bic was supplemented by increasing Bic concentration of the dialysate and by oral Bic supplementation. RESULTS: Predialysis Bic increased significantly during the study period (18.7 +/- 2.7 vs. 23.1 +/- 11.5 mmol/l). There was no change in nutritional parameters. However, plasma levels of the BCAA valine, leucine, and isoleucine increased significantly. CONCLUSIONS: In haemodialysis patients with metabolic acidosis, Bic supplementation over a 6-months period resulted in an increase in plasma levels of BCAA. Further study is needed to elucidate the mechanisms behind, and the clinical importance of the observed changes in plasma BCAA levels.     

HLA gene and haplotype frequencies in the North American population: the National Marrow Donor Program Donor Registry

BACKGROUND: As of May 1, 1995, the National Marrow Donor Program had a donor registry consisting of over 1.35 million HLA-typed volunteers recruited from most major cities and states in the United States. This registry represents the largest single HLA-typed pool of normal individuals in the world. METHODS: We analyzed the HLA-A, -B, -DR locus phenotypes of the National Marrow Donor Program donors in order to estimate gene and haplotype frequencies for major racial groups of the United States: Caucasian American, Asian American, African American, Latin American, and Native American. The large size of the database allowed us to calculate the frequencies of relatively rare antigens and haplotypes with more accuracy than previous studies. RESULTS: We observed 89,522 distinguishable HLA-A, -B phenotypes in 1,351,260 HLA-A, -B-typed donors and 302,867 distinguishable HLA-A, -B, -DR phenotypes in 406,503 HLA-A, -B, -DR-typed donors. Gene and haplotype frequencies differed remarkably among the five racial groups, with African Americans and Asian Americans having a large number of haplotypes that were specific to their racial groups, whereas Caucasian Americans, Latin Americans, and Native Americans shared a number of common haplotypes. CONCLUSIONS: These data represent an important resource for investigators in the fields of transplantation and population genetics. The gene and haplotype frequencies can be used to aid clinicians in advising patients about the probability of finding a match within a specific ethnic group, or to determine donor recruitment goals and strategies. The information is also a valuable resource for individuals who are interested in population genetics, selection and evolution of polymorphic human genes, and HLA-disease association.     

Unlike any other procedure

The paper presents several mnemonics to assist clinicians in recalling DSM-IV diagnostic criteria for personality disorders. The mnemonics are acronyms, and each letter is associated with a specific criterion. Each acronym reflects a facet of the related disorder; for example, the acronym for the diagnostic criteria for paranoid personality disorder is SUSPECT, and for histrionic personality disorder it is PRAISE ME. The mnemonics have been used to teach students and residents the conceptual nature of DSM-IV disorders and to help them remember the criteria.     

Long-term T cell memory requires the surface expression of self-peptide/major histocompatibility complex molecules

How memory T cells are maintained in vivo is poorly understood. To address this problem, a male-specific peptide (H-Y) was identified and used to activate female anti-H-Y T cells in vitro. Anti-H-Y T cells survived in vivo for at least 70 days in the absence of antigen. This persistence was not because of the intrinsic ability of memory T cells to survive in vivo. Instead, the survival and function of adoptively transferred memory cells was found to require transporter of antigen protein 1-dependent expression of self-peptide/major histocompatibility complex class I molecules in recipient animals. Therefore, it appears that the level of T cell receptor engagement provided by transporter of antigen protein 1-dependent, self-peptide/major histocompatibility complexes is sufficient to maintain the long-term survival and functional phenotype of memory cells in the absence of persistent antigen. These data suggest that positive selection plays a role not only in T cell development but also in the maintenance of T cell memory.     

Operative videothoracoscopy in the surgical treatment of penetrating firearms wounds of the chest

We prospectively analyzed our experience with operative videothoracoscopy (OVT) performed in a field military hospital in cases of penetrating firearms wounds of the thorax (PFAWT) sustained in Chechnya. From February to April 1996, we treated 206 wounded patients, of whom 37 (18.0%) had sustained chest injuries. PFAWT were present in 23 soldiers, accounting for 62.2% of all chest injuries. Twelve injuries were confined to the thorax, eight patients had associated injuries, and three soldiers had thoracoabdominal injuries. Nineteen patients had pleural drainage performed during medical evacuation. The thoracic injuries were right-sided (17), involved bullets or shell splinters (23); were through and through (16), represented solitary wounds (19), and were associated with internal organ injuries (21). Fifteen patients had indications for OVT when they were delivered from the battle-field 1.5 to 22 hours after injury. All patients manifested signs of hemorrhagic shock and hemodynamic instability. Indications for OVT were ongoing intrapleural bleeding (6), clotted hemothorax (6), or marked air leakage (3) preventing lung inflation with the OP-02 apparatus (field modification). OVT revealed 12 lung wounds, nine of which were multiple wounds, pleural bleeding in 6 patients, clotted hemothorax in 11 patients, and foreign bodies in 5 patients. Two patients underwent thoracotomy, one for suspicion of heart injury and the second because we could not adequately visualize and control bleeding revealed at OVT to be from the intercostal artery in the left costovertebral angle. Eight of 23 patients had no indication for operative videothoracoscopy and were managed with continued pleural aspiration and drug therapy. Wedge resection of the lung using an Endo-GIA-30 stapler was necessary in two patients because of parenchymal destruction and bleeding. Evacuation of clotted blood by fragmentation and aspiration was satisfactory in all cases. Satisfactory manual suturing of selected lung injuries was obtained largely with intracorporeal knot tying. The duration of the procedures ranged from 40 to 90 minutes. No morbidity nor mortality was encountered in patients undergoing OVT. Postoperative pain was minimized by using OVT placement of catheters in the chest wall soft tissue with local administration of 2% Trimecain. Patients were able to stand in 10 to 12 hours and to walk by the end of the first postoperative day. All patients who underwent OVT were evacuated without drains by the third or fourth postoperative day, all tolerating sitting and standing positions. We conclude that early OVT in the military field hospital for continued bleeding, clotted hemothorax, and continued major air leakage has several advantages in military patients with PFAWT: early definition and management of organ injury; identification and control of bleeding in most instances; earlier and more accurate assessment for thoracotomy; vigorous lavage and removal of projectiles such as bone fragments and evacuation of clotted hemothorax; early debridement with suture closure of the thoracic wall canal; and minimal postoperative pain with dramatically reduced suppurative sequelae and bronchopleural fistulae.     

Measurement of myocardial blood flow with oxygen-15 labelled water: comparison of different administration protocols

Positron emission tomography (PET) in conjunction with C15O2 or H215O can be used to measure myocardial blood flow (MBF) and tissue fraction (TF), i.e. the fraction of the tissue mass in the volume of the region of interest. However, with C15O2 inhalation, the tissue fraction in the septum is overestimated. Bolus injection of H215O together with arterial cannulation gives very precise results but is invasive. The purpose of this study was to develop a method which circumvents these problems. A four-parameter model with parameters for MBF, TF and spill-over fractions from both left and right ventricular cavities was developed. This method was compared with a three-parameter model (no right ventricular cavity spill-over) in both septal and non-septal regions of interest for three different administration protocols: bolus injection of H215O, infusion of H215O and inhalation of C15O2. It was found that MBF can be measured with intravenous administration of H215O without the requirement for arterial cannulation. The four-parameter protocol with bolus injection was stable in clinical studies. The four-parameter model proved essential for the septum, where it gave highly significantly better fits than did the three-parameter model (P<0.00003 in each of 15 subjects). Administration of H215O together with this four-parameter model also circumvented the problem of overestimation of TF in the septum seen with C15O2 inhalation. In addition, the radiation dose of H215O protocols is lower than that of C15O2 inhalation. Using a left atrial input curve instead of a left ventricular cavity input curve gave the same mean MBF and TF.