Insulin secretion stimulated by allogeneic lymphocytes in an inbred strain of mice.

Effects of intraperitoneal injection of allogeneic lymphocytes on insulin secretion were studied in incubated pancreas slices from BALB/c mice. Injection of allogeneic lymphocytes from C57BL/6J (H2b) mice increased insulin secretion, both in basal and 11-mM glucose-stimulated conditions. This effect was only present when at least 5 X 10(6) or 1 X 10(6) cells were injected (in basal and stimulated conditions, respectively). Glucose-induced insulin secretion (3.3-27.5 mM) was significantly increased in pancreata from mice injected with allogeneic lymphocytes. No effect was observed when glucose was not included in the incubation medium. Intraperitoneal injection of Dextran 70 produced no change in glucose-elicited insulin secretion. There were no differences in glucagon and somatostatin (SRIF) secretion obtained from pancreas of mice injected with allogeneic or syngeneic lymphocytes. Injection of allogeneic cells increases insulin secretion (basal and both phases of 11 mM glucose-stimulated secretion). Puromycin significantly inhibited the second phase of insulin secretion. These results suggest that: Injection of allogeneic lymphocytes raises both basal and glucose-stimulated insulin secretion. This effect seems to be connected with the major histocompatibility complex, and to be related to the number of allogeneic cells injected. Injection of allogeneic lymphocytes seems to sensitize the beta cell response to glucose stimulus. Neither glucagon nor SRIF secretion are altered by alloantigen injection. The stimulatory effect of allogeneic lymphocytes is related, at least in part, to insulin synthesis.

Integrin-mediated adhesion of endothelial cells induces JAK2 and STAT5A activation: role in the control of c-fos gene expression.

Integrin-mediated adhesion induces several signaling pathways leading to regulation of gene transcription, control of cell cycle entry and survival from apoptosis. Here we investigate the involvement of the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway in integrin-mediated signaling. Plating primary human endothelial cells from umbilical cord and the human endothelial cell line ECV304 on matrix proteins or on antibody to beta1- or alphav-integrin subunits induces transient tyrosine phosphorylation of JAK2 and STAT5A. Consistent with a role for the JAK/STAT pathway in regulation of gene transcription, adhesion to matrix proteins leads to the formation of STAT5A-containing complexes with the serum-inducible element of c-fos promoter. Stable expression of a dominant negative form of STAT5A in NIH3T3 cells reduces fibronectin-induced c-fos mRNA expression, indicating the involvement of STAT5A in integrin-mediated c-fos transcription. Thus these data present a new integrin-dependent signaling mechanism involving the JAK/STAT pathway in response to cell-matrix interaction.

Oncological results of oncoplastic breast-conserving surgery: Long term follow-up of a large series at a single institution: A matched-cohort analysis.

PURPOSE: Oncoplastic surgery is a well-established discipline that combines conserving treatment for breast cancer with immediate plastic reconstruction. Although widely practiced, the oncologic outcomes of this combined approach are reported only in small series. The aim of the present paper is to assess the safety of oncoplastic surgery for invasive primary breast cancer. METHODS: We compared 454 consecutive patients who underwent an oncoplastic approach between 2000 and 2008 for primary invasive breast tumors (study group) with twice the number of patients who received conservation alone in the same interval time (control group). Disease free survival and overall survival were estimated using the Kaplan-Meier method. The log-rank test was used to assess differences between groups. RESULTS: The median follow-up was 7.2 years. The overall survival is similar within the two groups, being 91.4% and 91.3% at 10-yr in the study group and in the control group respectively. The disease free survival is slightly lower in the oncoplastic group (69 vs.73.1% at 10-yr). The difference is not statistically significant. DISCUSSION: We have compared a large series of primary breast cancer patients that have undergone oncoplastic surgery (454) with a control group (908) and they were followed for a prolonged period of time. It provides the best available evidence to suggest that oncoplastic surgery is a safe and reliable treatment option for the managing of invasive breast cancer.

Increased monocyte procoagulant activity (tissue factor) in patients with essential mixed cryoglobulinemia.

Procoagulant activity (PCA) of peripheral blood mononuclear cells was studied in vitro in 14 consecutive patients with essential mixed cryoglobulinemia (EMC). Mononuclear cells tested immediately after isolation expressed significantly higher PCA than cells from a matched control group (P less than 0.01). PCA generated by patients' cells after incubation at 37 degrees C for four hours without any stimulant was significantly higher than that produced by control cells (P less than 0.001). Lower mononuclear cell PCA was observed in the subgroup of patients treated with low doses of prednisone than in untreated patients. In two patients given high-dosage prednisone, cell PCA was markedly reduced. These findings suggest that mononuclear cells may be activated for PCA production in vivo by cryoglobulins or other unknown stimuli. Mononuclear phagocytes, by producing PCA in vivo, might be directly implicated in the local fibrin deposition in tissue lesions of EMC.

Actin cytoskeleton organization in response to integrin-mediated adhesion.

Cell matrix adhesion regulates actin cytoskeleton organization through distinct steps, from formation of filopodia and lamellipodia in the early phases of cell adhesion to organization of focal adhesions and stress fibers in fully adherent cells. In this review, we follow the events induced by integrin-mediated adhesion, such as activation of GTPases Cdc42 and Rac and their effectors and their role in actin polymerization leading to formation of lamellipodia and filopodia and cell spreading. We also show that actin stress fiber and focal adhesion formation following adhesion requires cooperation between integrin-mediated signaling and additional stimuli, including activation of PKC, Rho GTPases, and PTKs such as p125Fak and Src.

Automatic processing, code dissimilarity, and the efficiency of successive memory searches.

Two experiments examined the effects of automatic processing and code dissimilarity on the performance of successive memory searches through a single memory set having the same or different kinds of information (i.e., verbal and spatial). The results of both experiments showed that the total time to complete the successive searches was less when automatic processing was involved compared with when both searches required controlled processing. Performance of the successive searches improved substantially with practice. Both experiments also showed an asymmetrical temporal interference between the two searches. Aspects of the to-be-performed second search did not affect first-search reaction times (RTs), but performing the first search did affect the second-search RTs. The interfering effect of the first search was greatest when controlled processes that used the same code were required for both searches, whether the code was verbal or spatial. Several interpretations are offered for the interference generated by the first search. The joint effects of automatic processing and code dissimilarity are also discussed.

Learning curve for translaryngeal tracheotomy in head and neck surgery.

OBJECTIVES: Translaryngeal tracheotomy (TLT) is a widely accepted procedure in intensive-care units for its simplicity of execution, low morbidity, rapid wound closure after cannula removal, good esthetic results, and lack of long-term sequelae. The aim of this study was to evaluate the feasibility and use of adopting TLT in patients with cancer undergoing major head and neck surgery. STUDY DESIGN: Prospective analysis of learning curve and incidence of complications in 41 patients with cancer who underwent TLT at the Division of Head and Neck Surgery of the European Institute of Oncology from November 1997 to June 1999. METHODS: Patient characteristics, pathology, anatomic characteristics of the neck, and surgical short-term and long-term complications were noted. The patients were divided into consecutive groups of six or seven patients, and time trends in occurrence of complications and time to execute the procedure were assessed. RESULTS: TLT performance time decreased from 50 minutes in the first seven patients to 24 minutes in the last group. The technique was easy to perform and safe, with only two minor complications during surgery. However, minor complications occurred in three and major complications in 17 patients in the days immediately following surgery, almost entirely attributable to lack of counter-cannula and stylet. CONCLUSIONS: In view of the high proportion of major complications, TLT using the presently available kit is unsuitable for major head and neck surgery. However, the considerable advantages of the technique would recommend it as a valid alternative to surgical tracheotomy if the kit included a counter-cannula and stylet.

Cerebral ischemia after venous air embolism in the absence of intracardiac defects.

Cerebral air embolism occurred in a patient undergoing posterior fossa surgery performed in the sitting position for acoustic neuroma removal. The patient experienced two episodes of venous air embolism, as evidenced by precordial Doppler, end-tidal carbon dioxide reduction, and oxygen desaturation. In both cases, air was aspirated from the central venous catheter; during the second episode there was arterial hypotension and electrocardiogram changes, and air bubbles were visualized in the cerebellar arteries. The patient did not regain consciousness after surgery and developed early tonic-clonic convulsions and electroencephalogram status epilepticus, which was treated with barbiturate coma. Intracardiac septal defects were not detected by transesophageal echocardiography, and computerized tomography of the brain demonstrated multifocal discrete ischemic areas in the cerebral hemispheres. The patient died 6 days after surgery without having regained consciousness. This case appears to represent the occurrence of transpulmonary passage of venous air embolism.

Combined lung volume reduction surgery and thoracic aortic aneurysm resection.

Postoperative improvement of respiratory function has been reported with lung volume reduction surgery (LVRS) in patients with severe emphysema. Since smoking is an established risk factor for lung cancer, vascular diseases and emphysema, it is not infrequent to find these diseases associated in the same patient. Combined treatment of lung cancer and emphysema has already been reported. Surgical treatment of vascular diseases in emphysematous patients could also benefit from the application of LVRS techniques. We report resection of an aortic aneurysm combined with LVRS in a patient with concomitant thoracic aortic aneurysm and severe emphysema. Respiratory function improved in the postoperative period.

Endometrial cells of the "lower uterine segment" (LUS) in cervical smears obtained by endocervical brushings: a source of potential diagnostic pitfall.

The use of endocervical brushes has led to a generous sampling of both endocervical and "lower uterine segment" (LUS) cells. To an unfamiliar eye, the large fragments of endometrial tissue from the LUS may lead to misinterpretation as endometriosis or glandular malignancy, as happened in our institution when the use of endocervical brush and recognition of LUS cells in cervical smears were limited. Eight cases, cytologically interpreted as such, were proven to be benign following cervical biopsy or endometrial curettage. The nature of LUS cells was recognized only on retrospective review of this cytologic material. However, in recent years, routine use of the endocervical brush resulted in an influx of similar cases referred by the cytotechnologists to the pathologist as glandular atypia. Thus, to get familiarized with the cytomorphology of LUS cells and its diagnostic pitfalls, a prospective study was undertaken. This entailed a review of 62,187 consecutive cervicovaginal smears (women of post-hysterectomy status were excluded) received within a 12-mo period (July 1, 1992-June 30, 1993). A total of 344 smears (0.55%) showed large tissue fragments of branching tubular endometrial glands with and without surrounding stroma. Patients ranged from 14-82 yr of age. History of cervical cone biopsy was noted in nine patients (2.6%). Repeat cervical smear or concurrent endometrial or endocervical biopsy available in 84 patients (24.4%) were negative. LUS cells may be mistaken for endometriosis, epithelial glandular atypia, as well as carcinoma of both endocervical and endometrial origin. In addition to glandular abnormality, LUS cells may also be misinterpreted as that of squamous intraepithelial lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Internal and external distraction in the control of cold-pressor pain as a function of hypnotizability.

The effectiveness of different pain-distraction tasks was compared as a function of level of hypnotizability, using the cold-pressor pain-testing procedure. Selected high, medium, or low hypnotizable participants first underwent a 1-minute baseline immersion of a hand in ice water, with periodic pain ratings. Independent groups were then given 4-minute test immersions under one of five conditions. Analgesia suggestion and guided imagery were conceived to be internal distractors, whereas word memory and pursuit-rotor tasks were external distractors. Placebo-control groups were given permission to let their minds wander. All four experimental treatments reduced pain significantly for highly hypnotizable participants, compared to the control group, whereas none of the experimental treatments were effective for low hypnotizables. The different treatment instructions did not produce different preimmersion anxiety state ratings, so the treatment effects on pain ratings could not be explained in terms of their effects on anxiety. It appears that high hypnotizables are more effective than low hypnotizables at diverting attention to control pain, regardless of whether internal or external distractor tasks are used. Treatment effects on pain ratings did not change between 1 and 4 minutes of test immersion.

[Prognostic factors in chronic lymphatic leukemia]. / Fattori prognostici nella leucemia linfatica cronica.

The analysis of our case histories aims at verifying if the immunological phenotype of the leukaemic lymphocyte B, essential diagnostic element, can have prognostic meaning and integrate the known methods of staging. We tested peripheral blood and samples of bone marrow at the cytofluorimeter with techniques of immunofluorescence. We considered the density of the sIg, lymphocytic doubling time (LDT), clusters of designation 23 (CD23), as immunological marker of activation, we also documented a relationship between these indicators and the classic clinical stage. We observed that the chronic lymphocytic leukaemia (CLL) in the stage B and C have generally sIg at high density, correlated to a short time of lymphocytic doubling, and that in the group with a low risk (stage A) the low density of sIg is correlated with a long time of doubling, index of the growth of tumoral bulk. The activation marker (CD23) shows a positive prognostic meaning, as it is more expressed in CLL at a low density of sIg and present in larger quantity in the initial clinical stage. We defined a classic immunophenotypic pattern for the CLL-B with positivity of CD5, sIg at a low density, Ag of activation highly positive related to a history of favourable disease; while an immunologic structure with CD5 negativity, less activated and more differentiated phenotype (CD23 low expression, high density sIg) seems to define a more severe prognosis.

Safety of fat grafting in secondary breast reconstruction after cancer.

BACKGROUND: Fat grafting is largely used to correct soft-tissue defects in any region of the human body. This study analysed its safety when the technique is used to correct defects after breast-cancer reconstruction. METHODS: A total of 158 patients who underwent 194 breast fat grafting procedures were analysed. Almost all patients (98%) had a personal history of breast cancer: conservative surgery or mastectomy with breast reconstruction. In all cases, fat grafting was performed according to the Coleman's technique by a single surgeon. RESULTS: Immediate complications included liponecrosis and infection in seven cases (3.6%) that required only daily dressings and oral antibiotics administration. In cases of fat grafting after conservative surgery, only four patients (5.9%) showed minor alterations in the postoperative mammograms, consisting of the appearance of benign images. CONCLUSION: Breast fat grafting can be a good solution to repair defects after breast-cancer treatment and reconstruction, and can reduce the indication for more extensive surgeries such as myocutaneous flaps. Postoperative complication rates are very low and there is little alteration in follow-up mammograms. Two points remain unclear--how much of the fat is absorbed after grafting and the potential risk of local 'dormant' tumour cells being stimulated to induce a local recurrence.

Opportunities in IT Support of Workflow & Information Flow in the Emergency Department Digital Imaging Process.

The goal of this study is to examine workflow and information flow in the emergency department (ED) digital imaging process to identify features of an optimized system. Radiological imaging (x-rays, CT scans, etc) is unique in the ED setting, as the need for fast turn-around time and interactive communication between radiologists and emergency physicians is different than that of most other healthcare settings. The information technology systems which are used by both radiologists and emergency physicians to support these processes have been designed with a focus on the routine workflow of radiologists. We report the results of 14 hours of naturalistic observations of the use of digital imaging systems by a total of 22 ED and radiology staff. A hierarchical task analysis and an information process diagram are presented, and disparate theories that groups in the system have about other groups were discovered, particularly in the communication of clinical information.