Lateral habenula integration of proactive and retroactive information mediates behavioral flexibility.

The lateral habenula (LHb) is known to play an important role in signaling aversive or adverse events that have happened or are predicted by cues under Pavlovian conditions. In rodents, it is also required for behavioral flexibility when changes in reward outcomes signal that strategies should be changed. It is not known whether the LHb also controls appetitive behaviors when an animal is able to utilize external cues proactively to guide upcoming decisions. In order to test this, male Long-Evans rats were trained to switch between two arms of a figure eight maze based on the tone presented prior to the choice. Importantly, the tones were switched every three to six trials so rats were able establish a response pattern before being required to switch. This caused rats to rely on both proactive (tones) and retroactive information (reward feedback) to guide behavior. Inactivation of the LHb with the GABA agonists baclofen and muscimol impaired overall performance by increasing both errors when the tones are switched (switch errors) as well as on subsequent trials (perseverative errors) indicating that both proactive and retroactive information are utilized by the LHb to guide behavioral flexibility. Once a correct choice was made in a given block, LHb inactivated rats did not make more errors than controls. A control study revealed that the LHb is not required for tone or reward magnitude discrimination per se. These results demonstrate for the first time that the LHb contributes to behavioral flexibility through utilizing both proactive and retroactive information when performing appetitive tasks.

Comparison of a point of care device against current laboratory methodology using citrated and EDTA samples for the determination of D-dimers in the exclusion of proximal deep vein thrombosis.

UNLABELLED: D-dimer estimation is a routine part of diagnostic algorithms for the exclusion of venous thromboembolism (VTE). We evaluated a point of care device, Biosite Triage (Inverness Medical UK, Cheshire, UK) for the estimation of D-dimers in both samples taken into citrate and EDTA against our routine laboratory D-dimer (Liatest D-dimer, Diagnostica Stago, Reading, UK) performed on the STA-R Evolution. With informed consent, 102 consecutive patients presenting with possible deep vein thrombosis (DVT) were enrolled and D-dimers along with Wells scores and compression ultrasonography (CUS) were recorded. Using the manufacturers' recommended cut offs of 500 microg/l fibrinogen equivalent units and 400 microg/l for the Stago and Triage, respectively, sensitivity, specificity, positive and negative predictive values were calculated. These were 1.00, 0.42, 0.17, and 1.00 for the Triage machine using citrate samples, 1.00, 0.32, 0.14, and 1.00 using EDTA samples and 1.00, 0.29, 0.16, and 1.00 for the Stago Liatest assay, respectively. Three patients had significantly higher results for the Stago Liatest D-dimer assay compared with the Biosite Triage device although ultrasound scans were negative. CONCLUSION: The Biosite Triage D-dimer assay performed on either citrate or EDTA samples is comparable with the Stago Liatest laboratory D-dimer assay when used in conjunction with clinical pretest probability scoring and CUS for the exclusion of DVT.

Comparison of an immuno-turbidometric method (STalia D-DI) with an established enzyme linked fluorescent assay (VIDAS) D-dimer for the exclusion of venous thromboembolism.

The use of d-dimer tests for the exclusion of venous thromboembolism is an important advance in clinical practice and also has economic benefits. The Stalia D-Di (Diagnostica Stago, Asnieres, France) is a semi automated system for the quantification of d-dimer using an immuno-turbidometric method incorporating a suspension of latex microparticles coated with two different monoclonal antibodies specifically targeted against human d-dimer fragments. Results are available rapidly in <10 min compared with 35 min for the established VIDAS D-dimer automated enzyme-linked immunosorbent assay (ELISA, BioMerieux, Basingstoke, UK). During November and December 2005, 100 consecutive patients attending the outpatient deep venous thrombosis (DVT) clinic were tested using the VIDAS D-dimer as part of the routine DVT investigation. Using the same samples, D-dimer estimation was also performed on the STalia D-Di for comparison. Across a wide range of data (Vidas 83-5656) and (STali <200->4000), there was good agreement between the two methods. Using cutoff's of 500 microg/l fibrinogen equivalent units (Keeling et al., 1999), 42% (42/100) patients were negative (<500) and 46% (46/100) were positive (>500) on both systems. Six per cent (6/100) were positive on the Vidas but negative on the STalia and another 6% (6/100) were positive on the STalia but negative on the Vidas. In conclusion, 88% (88/100) of patients showed agreement and in the other 12% (12/100), one had a DVT as identified by Compression ultrasonography (CUS). In this study, there were seven patients with a DVT as identified by CUS and they all scored as 'likely' on a pretest clinical probability score and so negative D-dimer would not be used clinically to rule out the disease. The Vidas is a well established instrument for D-dimer measurement in outpatient DVT clinics, and in this small study the STalia compares very well and therefore would fit into an outpatient setting for D-dimer measurement. But ideally a larger study would be required before implementing new methodology in a clinical setting.

Ovarian mucinous carcinoids including some with a carcinomatous component: a report of 17 cases.

Only rare primary mucinous (goblet cell) carcinoids of the ovary have been reported, and their clinicopathologic features have not been well delineated. The authors studied 17 examples from patients 14 to 74 years of age. The clinical presentations were similar to those of ovarian neoplasms in general. The tumors ranged from 0.8 to 30 cm in diameter. In six cases the tumor was in the wall of a mature cystic teratoma, appearing grossly as solid nodules or areas of thickening in four of them, six tumors were entirely solid, and five were solid associated with other types of cystic tumor. The tumors were divided into three groups on the basis of their microscopic features. Six neoplasms, designated "well differentiated," were composed of small glands, many of which floated in pools of mucin. The glands were lined by goblet cells and columnar cells, some of which were of neuroendocrine type. Three tumors, designated "atypical," were characterized by crowded glands, some of which were confluent, small islands with a cribriform pattern, and scattered microcystic glands. The glands were lined by cuboidal to columnar cells, some of them neuroendocrine, admixed with goblet cells. Eight tumors, designated "carcinoma arising in mucinous carcinoid," contained islands and larger nodules of tumor cells, or closely packed glands, as well as single cells, mainly of the signet ring cell type. Most of the cells were devoid of mucin and were severely atypical with marked mitotic activity. Necrosis was present in all eight tumors. Seven of the eight tumors with a carcinomatous component contained at least minor foci of well-differentiated mucinous carcinoid; the eighth contained only foci of atypical mucinous carcinoid. The neuroendocrine nature of a variable proportion of the cells in all three groups was demonstrated by staining for neuroendocrine markers. The mucinous nature of other cells was confirmed by mucicarmine or Alcian blue stains. The ovary contained an intrinsic component of trabecular and insular carcinoid, and of strumal carcinoid in one case each, an adjacent mature cystic teratoma in six cases, mucinous cystadenocarcinoma in three cases, and borderline mucinous cystic tumor, borderline Brenner tumor, and epidermoid cyst in one case each. Fifteen tumors were stage I, one was stage II, and one was stage III. The last two tumors had a carcinomatous component. Follow-up data were available for 15 patients; 12 were alive and free of tumor 2.3 to 14 years (average, 4.7 years) after the ovarian tumor was excised. One patient, whose tumor had a carcinomatous component, died 3 years postoperatively of unrelated causes. Two patients, both of whom had a carcinomatous component in their tumor, died 9 and 12 months postoperatively. Primary mucinous carcinoids must be distinguished from metastatic mucinous carcinoid tumors from the appendix or elsewhere. Features supporting an ovarian origin are the additional presence in the specimen of teratoma or an ovarian surface epithelial tumor, an absence of blood vessel or lymphatic space invasion, and confinement to a single ovary. Similar features help to distinguish mucinous carcinoids from Krukenberg tumors. Mucinous carcinoids should also be distinguished from strumal carcinoids, which can contain mucinous glands, and insular carcinoid tumors that arise rarely in the wall of a mucinous cystic neoplasm. Although the number of cases in this series is small, the follow-up data suggest that the degree of differentiation, particularly the presence of frank carcinoma, is an important prognostic factor.

Radiation-induced pseudocarcinomatous proliferations of the urinary bladder: a report of 4 cases.

Four cases of radiation cystitis that caused diagnostic difficulty because of an epithelial proliferation with architectural complexity and reactive cytologic atypia are described. The patients, 2 male, 2 female, were from 43 to 77 years of age. Two presented with hematuria. Cystoscopy disclosed abnormalities in 3 patients. Microscopic examination showed irregularly shaped and arranged aggregates of epithelial cells in the upper and mid zones of the lamina propria. The cells, which typically showed at least mild, and sometimes severe, pleomorphism, were usually transitional, but squamous differentiation was seen focally in 3 cases. Ulceration of the overlying epithelium was present in all cases and was prominent and associated with conspicuous fibrin and hemorrhage in one of them. Edema of the lamina propria was present in 3 cases, whereas lamina propria fibrosis and chronic inflammation were present in all cases. The presence in all 4 cases of vascular ectasia and other changes characteristic of radiation injury, such as atypical fibroblasts, prompted investigation of the clinical history in 2 cases in which the pathologist was unaware that the patient had received radiation. Pseudocarcinomatous proliferations in the bladder caused by radiation injury have received limited attention in the literature. Our cases illustrate the potential diagnostic errors with which these lesions may be associated.

Superficial endometriosis of the uterine cervix: a report of 20 cases of a process that may be confused with endocervical glandular dysplasia or adenocarcinoma in situ.

Twenty cases of superficial endometriosis of the uterine cervix that occurred in patients from 20 to 51 (mean 37.1) years of age are described. The majority of the cases were seen in consultation and were usually referred because of diagnostic problems; endocervical glandular dysplasia, adenocarcinoma in situ, or rarely invasive adenocarcinoma were a frequent consideration of the contributor. The endometriosis was almost always an incidental microscopic finding. The endometriotic foci were usually confined to the superficial third of the cervical wall, but in one case there was also involvement of the middle third of the cervical wall. Deep cervical endometriosis was not present in any case. The endometriotic glands were typically evenly spaced and were surrounded at least focally by endometriotic stroma in all cases. The endometriotic stromal cells, however, were significantly obscured by inflammatory cells (two cases), inflammatory cells and hemorrhage (two cases), hemorrhage (four cases), and in one case by smooth muscle metaplasia causing initial failure to recognize the stromal component of the process. The presence of mitotic figures in the glandular epithelium contributed to an initial diagnosis of a premalignant or malignant glandular lesion being made or seriously entertained in 10 cases. Awareness that mitotic figures may be conspicuous in endometriosis from women of reproductive age, the usually bland cytologic features of the endometriotic epithelium, and the presence of associated endometrial stromal cells all facilitate establishing the correct diagnosis.

Identification of Mutations in the Human Factor VII Gene.

It has been recognized from the early 1800s that activation of coagulation can be initiated by the exposure of subendothelial layers (tissue factor), but it was the 1940s before factor VII (FVII) was included in this event (1,2). The discovery of hemophilia A and B supported the hypothesis that the intrinsic pathway incorporating factors VIII and IX was more important in hemostasis (3,4). More recently the extrinsic pathway (incorporating FVII) has been the focus of attention by activating both arms of the coagulation cascade via its action upon factors IX and X (5).

The status of age: preliminary results.

This study tested the hypothesis that there is an inverted U curve of status or prestige across the lifespan in Western culture. Although several theorists have suggested that young and old persons are accorded less status than the middle-aged, almost no empirical evidence exists on this subject. The factorial survey method was used to measure perceptions of the status of ages 5 to 100 for men and women. A set of 28 age by sex profiles were rated by 334 students. Ratings were made on a 7-point category scale. The data fit the theoretical predictions extremely well, with one notable exception. Very high ratings were given to 100-year-old people by almost half of the respondents. This anomaly was probably due to the rarity of centenarians.

New bacteriophage typing system for Yersinia enterocolitica, Yersinia kristensenii, Yersinia frederiksenii, and Yersinia intermedia: correlation with serotyping, biotyping, and antibiotic susceptibility.

Yersinia enterocolitica is listed as a single species in Bergey's Manual of Determinative Bacteriology, but has recently been split into "true" Y. enterocolitica, Y. kristensenii, Y. intermedia, and Y. frederiksenii. From 48 bacteriophages isolated from raw sewage, 24 were chosen as being the most useful for differentiating strains within the four Yersinia species. The composite set of 24 phages typed 92% of 236 Y. enterocolitica strains, 100% of 16 Y. kristensenii strains, 97% of 29 Y. frederiksenii strains, and 90% of 20 Y. intermedia strains. The most common phage type in any of the groups contained 22% of the strains tested, but most of the phage types contained greater than 5% of the strains. The new typing schema was tested in three outbreaks of Y. enterocolitica, and the results agreed well with serotyping and epidemiological findings. In the same outbreaks, biotyping (API 20E profiles; Analytab Products, Plainview, N.Y.) and antibiograms were less reliable markers and probably should be used only in conjunction with serotyping or phage typing or both. Caution should be used in identifying cultures of Y. frederiksenii and Y. intermedia with the API 20E system, since the tests at 37 degrees C for L-rhamnose and melibiose fermentation are often delayed past 24 h, which is the cut-off point for the final reading in the API system. There were distinct differences in the susceptibilities of Y. enterocolitica and Y. kristensenii to ampicillin, carbenicillin, and cephalothin, which adds further support for classifying the latter as a separate species.

Drug-induced depression and attempted suicide.

Sixty-eight patients who had attempted suicide were matched with non-suicidal patients with similar diagnoses to assess the extent to which excessive drug ingestion by the suicidal group might have contributed to their behaviour. It was found that the suicidal patients were consuming more drugs, particularly those of a potentially depressing kind. The implications of this finding are discussed.

Smoking and other factors affecting the conservative management of peripheral vascular disease.

Three hundred and ninety patients with peripheral vascular disease, who were neither eligible for, nor fit to undergo, surgery, have been studied in a prospective trial to assess the effectiveness of adequate active conservative therapy. These patients were followed up from 4 to 72 months, the duration of the average follow-up being 24 months. There was a 72% over-all improvement rate. The most striking feature of the trial was the correlation between smoking and failure to improve.

The use of mortality data in setting priorities for disease prevention.

The examination of specific disease mortality by five-year age groups helps identify health problems as problems of people and how they live. Traditional methods of examining data in broad classifications tend to obscure etiological factors and the importance of behaviour. Violence, a major cause of death in young adults, gives way to so-called diseases of indulgence in middle age, especially among men who have a much higher death rate than women. Male life expectancy at age 40 has increased only marginally in the past 40 years. Health-related human behaviour must be considered within an ecological framework since social, cultural and physical environmental differences as well as personal factors influence life-style. The responsibility for prevention rests more with the individual and society at large than with health workers. Probability tables, Health Hazard Appraisal (a system of personal risk assessment) and personal counselling can reinforce healthful life-styles and help correct hazardous ones.