A new look at the supposed risks of early institutional rearing.

The main focus is on the assessment of the effects of early institutional care and compares three longitudinal studies from Romania, Greece and Hong Kong/China. The findings have been strikingly contrasting. The review asks if the risks are dependent on whether or not the institutional rearing is accompanied by gross pervasive deprivation (as it was in Romania) and investigates the methodological issues to explore the causal influence of the outcomes. Evidence is considered on changing institutional practices and the benefits of doing so. Comparison is made between institutions with major deprivation and those without global deprivation. A small number of studies are discussed that look at direct comparisons between institutional and community care. The empirical and conceptual implications of the findings are discussed.

Effects of radiotherapy on different histopathological types of rectal carcinoma.

BACKGROUND: Down staging by pre-operative chemoradiotherapy is currently considered part of the standard therapeutic approach to rectal carcinoma. The aim of this study was to assess the response to chemoradiotherapy of different histopathological types of rectal carcinoma with emphasis on the mucinous variant. METHOD: Between 1997 and 2002, 71 patients who received pre-operative chemoradiotherapy followed by surgery for rectal carcinoma were enrolled in the study. Staging of the rectal carcinoma was performed according to transrectal ultrasound findings (TN score) prior to the chemoradiotherapy. The chemoradiotherapy was followed by radical resection with mesorectal excision. All surgical specimens were examined by a single pathologist (MB). Pathological TN staging was assessed and tumour regression was graded according to a standard method (TRG1, complete response - TRG5 no response). Tumours were classified as mucinous or nonmucinous according to pre- and post-operative biopsy and specimen histopathological types. TN score change and TRG differences between groups were assessed. RESULTS: Tumour regression was seen after chemoradiotherapy in 94.4% of the patients, while in 5.6% of the patients no response was found. The change in TN score and TRG were correlated. Higher TRG was associated with a smaller decrease in TN staging. TRG was significantly lower in the nonmucinous compared to the mucinous group and the decrease in TN grade was significantly larger in the nonmucinous group. CONCLUSION: Mucinous carcinoma was associated with a lower response to pre-operative chemo-radiotherapy in this group of rectal carcinoma patients. Further studies are needed to determine its prognostic value.

Double stapled ileal pouch anal anastomosis (DS-IPAA) for mucosal ulcerative colitis (MUC): is there a correlation between the tissue type in the circular stapler donuts and in follow-up biopsy?

PURPOSE: This study aims to assess the correlation between the tissue types found in the circular stapler donut at the time of initial double-stapled ileal pouch-anal anastomosis (DS-IPAA) and during subsequent periodic routine random biopsy. Secondarily, we sought to assess the risk of dysplasia, carcinoma or mucosal ulcerative colitis (MUC) recurrence in the retained mucosa. METHODS: The pathology reports of 91 patients (48 males, 43 females) who were operated upon for MUC from September 1988 to June 1997 and were reviewed and had two follow up visits for biopsy. The histological features of the distal donuts and biopsies of retained mucosa obtained at yearly interval follow-up were assessed in order to determine the epithelial tissue type (columnar, transitional and squamous), inflammation, recurrence of MUC and presence of dysplasia or malignancy. RESULTS: Median age at surgery was 43 (range 15-71) years and duration of MUC was 9.6 (range 0.3-42) years prior to surgery. The anastomosis was performed at a median height of 1.0 (range 0-2.5) cm cephalad to the dentate line and biopsy follow-up was undertaken at median 34 (range 2-110) months after DS-IPAA. The distal donuts were analysed in all cases, as were 305 follow-up biopsies (median 3.4; range 1-7 per patient). Although columnar epithelium (CE) was found in 62 (68%) donuts, it was absent on follow-up biopsy in 16 (26%) of these patients. Conversely, although no CE was identified in 29 (32%) donuts, it was identified in 11 (38%) of these patients during follow-up biopsy. CE in the donut was a significant predictor of CE in subsequent biopsies (P = 0.0012). The histological features consistent with MUC were seen in the biopsies from the retained mucosa in 15 (16%) patients from 0.3 to 7.6 years after DS-IPAA. While eight (9%) patients exhibited dysplasia or adenocarcinoma in the excised colon or rectum, none of the patients had either dysplastic changes or carcinoma within the retained mucosal biopsies. CONCLUSION: The correlation between CE in the circular stapler donut and at follow-up biopsy was high. However since CE developed in some patients in whom no CE was present in the distal donuts, regardless of the epithelial tissue type finding at the time of DS-IPAA, periodic follow-up biopsy should be obtained.

Laboratory ascertainment of Cryptosporidium and local authority policies for investigating sporadic cases of cryptosporidiosis in two regions of the United Kingdom.

To discover laboratory ascertainment and reporting practice for cases of cryptosporidiosis in two health authority regions, we surveyed laboratories serving Wales and the North West of England for faecal screening policies and methods for detection of Cryptosporidium. Forty-eight of the 49 laboratories responded, of which 39 (81%) screen all stool specimens from symptomatic individuals for Cryptosporidium and 9 (19%) screen selected specimens. Although laboratory screening is more complete than has been reported in other regions, we identified discrepancies where patient age was used as a selection criterion, and we make suggestions to amend this. Forty-two (88%) responding laboratories report confirmed cases to the regional Communicable Disease Surveillance Centre (CDSC) and 45 (94%) report to the local authority environmental health department. We also surveyed local authorities in both regions for policy and practice concerning the investigation of reported cases of cryptosporidiosis in the same regions. All 59 local authorities responded, of which 57 (97%) investigate cases by completion of an exposure questionnaire as well as providing advice on the prevention of spread of infection. Variation in case ascertainment may influence perception of incidence, clusters and outbreaks of cases of cryptosporidiosis.

Variability in serotonin and enterochromaffin cells in patients with colonic inertia and idiopathic diarrhoea as compared to normal controls.

AIM: To evaluate differences in distribution, density and staining intensity of enterochromaffin cells (EC) and serotonin cells (SC) in the colonic mucosa of patients with colonic inertia (CI), idiopathic diarrhoea (ID) and a control group. METHODS: Three groups were studied: 19 patients' colons after subtotal colectomy for CI, and 17 patients' biopsies for diarrhoea (>3 bowel movements/day) with histological findings of normal mucosa (excluding microscopic, eosinophillic and collagenous colitis). The third group included 15 patients who underwent colonoscopy and biopsy for indications other than constipation, inflammatory bowel disease, diarrhoea or neoplasm (control group). Specimen blocks were obtained in each case from the right and left colon. Immunohistochemical staining for EC and SC were done on 4 micro m sections from Hollandes fixed, paraffin embedded tissues with primary rabbit antibody against chromagranin A or serotonin, and biotynylated secondary antibody and enzyme labelled streptavidin. RESULTS: The number of EC in the mucosa of the left colon in patients with CI (16.8 +/- 10.2) and ID (19.9 +/- 9.7) were significantly higher than they were on the right side (CI: 9.4 +/- 6.0, ID: 12.1 +/- 5.3). However, there were no significant differences between the left and right sides in the control group (L: 10.3 +/- 5.3; R: 13.4 +/- 7.6). Although the quantity of EC in the left colon in both patients with CI (P < 0.05) and ID (P < 0.01) were significantly higher than in the controls, there was no significant difference between CI and ID. In both the right and left colon, the percentage of EC with low positive density was significantly higher (P < 0.01) while those cells with moderate or low staining intensity were significantly lower in patients with CI than in either patients with ID or control group. In patients with CI, the quantity of SC in the mucosa of the left colon (12.1 +/- 6.4) was higher than in the right (CI: 7.9 +/- 3.6; control 4.6 +/- 3.3; ID 4.6 +/- 2.9) (P = 0.0057). In contrast there was no significant difference in SC in either the ID or control groups. The quantity of SC in both sides of the colon was significantly higher both in patients with CI as compared to the control group (P < 0.01) and patients with CI vs. patients with ID (L = P < 0.01; R = P < 0.05). There was a significantly positive correlation between the numbers of EC and SC in patients with CI (L: r = 0.5425, P < 0.05; R: r = 0.745, P < 0.01). CONCLUSION: In patients with CI, EC increases possibly due to an increase in SC. Conversely, in patients with ID, the EC increase results from peptides other than SC. Our results suggest that different aetiological factors contribute to ID and CI.

Altered serotonin immunoreactivities in the left colon of patients with colonic inertia.

BACKGROUND: Serotonin is an important positive regulator of colonic motility and transit. Its quantity and distribution in the left colon could be abnormal in patients with colonic inertia (CI) and contribute to the disease. AIM: To evaluate serotonin positive cells and immuno-reactivities in the mucosa, submucosa and muscularis propria of the left colon from patients with CI was compared to a control group. PATIENTS AND METHODS: Nineteen patients who underwent subtotal colecotomy for CI were assessed. The control group consisted of 15 patients who underwent left hemicolectomy for colonic cancer; histologically normal tissue specimens were used. Immunohistochemical staining for serotonin was performed. In the mucosa, the average number of serotonin positive cells per microscopic field (200 x ) was determined. The positively stained area (square pixels) in the mucosa, submucosa and muscularis propria per microscopic field (200 x ) was calculated utilizing a computer image analysis program. RESULTS: In the mucosa, both the number of serotonin positive cells and positively stained area were significantly higher in the patient group than in controls (P < 0.05). The difference in serotonin positive area in the submucosa in the CI group compared to the control group was not statistically significant. There was a very significant correlation between the serotonin positive area in the submucosa and muscularis propria in controls (r=0.65, p < 0.01), but not in patients with CI. CONCLUSION: The increased serotonin level in patients with CI may contribute to the disease or be an adaptive response to some other pathology. The lack of a positive correlation in serotonin levels between the submucosa and muscularis propria in CI patients suggests that the coordinated distribution of serotonin may be disrupted in CI.

Loss of heterozygosity and HIV infection in patients with anal squamous-cell carcinoma.

PURPOSE: This study was designed to determine whether loss of heterozygosity and/or microsatellite instability correlate with HIV infection and tumor recurrence after chemoradiation therapy in patients with squamous-cell carcinoma of the anus. BACKGROUND: The molecular mechanisms leading to the progression of HIV-related squamous-cell carcinoma of the anus are poorly understood. In particular, genetic alterations responsible for resistance to chemoradiation have important clinical and functional implications. METHODS: In a case-control study, we analyzed normal and tumor DNA samples of four patients with squamous-cell carcinoma of the anus who were successfully treated with chemoradiotherapy and four patients with radio-resistant squamous-cell carcinoma of the anus who required abdominoperineal resection for local recurrence. To determine the presence of microsatellite instability, we used the reference panel of five pairs of microsatellite primers recommended for colorectal cancer specimens. These include the microsatellite markers BAT25, BAT26, D5S346 (APC), D2S123 (hMSH2), and D17S250 (P53). In addition, we used microsatellite markers for loss of heterozygosity analyses that were tightly linked to tumor suppressor genes. These included D3S1611 (hMLH1), D17S513 (P53), D18S46 and 18qTA (DCC/SMAD4), D5S107 (APC), and CA5 (hMSH2). RESULTS: There were two HIV-positive and two HIV-negative patients in each group. Three HIV-positive patients (one in the chemoradiotherapy group and two in the nonchemoradiotherapy group) demonstrated loss of heterozygosity. In the chemoradiotherapy group, one HIV-positive patient demonstrated loss of heterozygosity at the hMLH1 locus. In the nonchemoradiotherapy group, two HIV-positive patients exhibited a total of four instances of loss of heterozygosity. One tumor had loss of heterozygosity at hMSH2 and DCC/SMAD4; another tumor demonstrated loss of heterozygosity at hMSH2 and APC. Microsatellite instability-low was found in two HIV-positive patients. No instances of loss of heterozygosity and microsatellite instability were detected in HIV-negative patients. CONCLUSION: Loss of heterozygosity and microsatellite instability, which reflect inactivation of tumor-suppressor genes and genomic instability, occur with increased frequency in HIV-associated squamous-cell carcinoma. These data demonstrate for the first time evidence of loss of heterozygosity at the APC and DCC/SMAD4 gene loci in anal carcinoma. Although the findings presented here need to be expanded in a larger study, the recurrent loss of heterozygosity at D2S123, which was demonstrated in HIV-positive patients with radio-resistant squamous-cell carcinoma of the anus, is notable.

In vitro and in vivo binding of snowdrop (Galanthus nivalis agglutinin; GNA) and jackbean (Canavalia ensiformis; Con A) lectins within tomato moth (Lacanobia oleracea) larvae; mechanisms of insecticidal action.

When fed in semi-artificial diet the lectins from snowdrop (Galanthus nivalis: GNA: mannose-specific) and jackbean (Canavalia ensiformis: Con A: specific for glucose and mannose) were shown to accumulate in vivo in the guts, malpighian tubules and haemolymph of Lacanobia oleracea (tomato moth) larvae. Con A, but not GNA, also accumulated in the fat bodies of lectin-fed larvae. The presence of glycoproteins which bind to both lectins in vitro was confirmed using labelled lectins to probe blots of polypeptides extracted from larval tissues. Immunolocalisation studies revealed a similar pattern of GNA and Con A binding along the digestive tract with binding concentrated in midgut sections. Binding of lectins to microvilli appeared to lead to transport of the proteins into cells of the gut and malpighian tubules. These results suggested that both lectins are able to exert systemic effects via transport from the gut contents to the haemolymph across the gut epithelium. The delivery of GNA and Con A to the haemolymph was shown to be dependent on their functional integrity by feeding larvae diets containing denatured lectins. Con A, but not GNA, was shown to persist in gut and fat body tissue of lectin-fed larvae chased with control diet for three days. Con A also shows more extensive binding to larval tissues in vitro than GNA, and these two factors are suggested to contribute to the higher levels of toxicity shown by Con A, relative to GNA, in previous long term bioassays.

Risk of invasive meningococcal disease among school workers in Cheshire, United Kingdom.

We have demonstrated an increased risk of invasive meningococcal disease among school workers in Cheshire, United Kingdom, compared with other adults in that area (relative risk, 6.0; 95% confidence interval, 2.75--13.07). If this trend is observed elsewhere in the United Kingdom, it may have policy implications for the prevention of such disease in this group of individuals.

Selective imidazoline I2 ligands do not show antidepressant-like activity in the forced swim test in mice.

Clonidine is an adrenergic agonist with high affinity for alpha2 adrenoceptors that also has affinity for imidazoline receptors. Clonidine has previously been shown to reduce immobility in the forced swim test (FST) in mice. In the present study, this effect was blocked by idazoxan (0.06 mg/kg s.c.) and by yohimbine (1.0 mg/kg s.c.) suggesting that clonidine's effects in this test are mediated via its action at alpha2 sites. Imidazoline I2 site ligands have been shown to inhibit monoamine oxidase and thus may also have antidepressant activity. Three compounds with selective affinity for I2 receptors (BU224, BU239, BDF 8082) were also tested in the FST. These compounds showed no activity either alone or in combination with a subthreshold dose of imipramine in the FST. These results suggest that I2 receptor ligands do not show antidepressant-like activity in the FST in mice. Furthermore the activity of the mixed alpha2/I1 agonist clonidine is most likely to be due to its action at alpha2 sites.

Reparative changes and the false-positive/false-negative Papanicolaou test: a study from the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology .

CONTEXT: Reparative changes can be a diagnostic challenge on Papanicolaou tests and must be distinguished from epithelial cell abnormalities. Both squamous intraepithelial lesions (SIL) and carcinoma may be underdiagnosed as repair. This study examines laboratory and cytologist performance in the diagnosis of repair. OBJECTIVES: To determine if laboratories and cytologists can consistently distinguish reparative changes from SIL and carcinoma and to document how often SIL and carcinoma are mistaken for repair in a standardized educational slide program. DESIGN: Results for reparative changes, SIL, and carcinoma slides from the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology for 1998 were analyzed. Only results from validated referenced slide responses were used. RESULTS: The concordancy rate for reparative-change slides, that is, any response of within normal limits or benign cellular changes, ranged from 91% to 94% for cytotechnologist, pathologist, and laboratory responses. False-negative rates for squamous carcinoma and adenocarcinoma, high-grade SIL, and low-grade SIL ranged from 0.47% to 5.41%; the proportion of false-negative diagnoses of reparative changes ranged from 24% to 62% of all discordant responses. CONCLUSIONS: Of all benign cellular changes and within normal limits categories in the Interlaboratory Comparison Program in Cervicovaginal Cytology, repair most often elicits a false-positive laboratory response. Underdiagnosing epithelial abnormalities as repair is also a source of false-negative Papanicolaou test results.

Synthesis and DNA-binding properties of dinuclear platinum(II)-amine complexes of 1,7-dicarba-closo-dodecaborane(12).

The first examples of platinum(II)-amine complexes containing a dicarba-closo-dodecaborane(12) (carborane) moiety are described; preliminary in vitro DNA-binding experiments indicate that the complexes are capable of targetting plasmid DNA.

A lead cancer nurse role at Birmingham Children's Hospital National Health Service Trust.

This paper reports on an innovative scheme and course developed as part of a Lead Cancer Nurse role based at the Birmingham Children's Hospital NHS Trust, UK. In doing so issues are raised which may be helpful to others should they consider adopting a similar scheme and the possibilities of the scope of the role are highlighted.

Enterochromaffin and serotonin cells are abnormal for patients with colonic inertia.

PURPOSE: In recent studies, serotonin and several gut peptides have been shown to serve as regulators of colonic transit. Thus, the distribution, density, and intensity of cells secreting serotonin or certain gut peptides could be abnormal in patients with colonic inertia. The aim of this study was to evaluate the distribution, density, and staining intensity of enterochromaffin and serotonin cells in the colonic mucosa of patients with colonic inertia compared with a control group. METHODS: Between 1993 and 1998 tissue blocks from the right and left side of the colon were obtained in 19 consecutive patients (18 females; mean age, 43.7 +/- 11.5 years) who underwent subtotal colectomy for colonic inertia. The control group consisted of colonoscopic biopsies from the right and left colon of 15 patients (all females; mean age, 52.7 +/- 16.5 years) for indications other then constipation, inflammatory bowel diseases, or carcinoma. Immunocytochemical staining of enterochromaffin and serotonin cells were performed on 4 microm tissue sections with the primary rabbit antibody against chromogranin A or serotonin, and the biotinylated secondary antibody and enzyme-labeled-streptavidin. The average cell number per microscopic field (x200) was calculated and the proportion of cells with various staining distribution was expressed as the percentage of the entire positive cell population as low, moderate, and high intensity. Student's t-test and chi-squared test were used for statistical analysis, with significance level set at P < 0.05. RESULTS: The quantity of both enterochromaffin cells (16.8 +/- 10.2) and serotonin cells (12.1 +/- 6.4) in the mucosa of the left colon in patients with colonic inertia was significantly higher when compared with the right side of the colon (enterochromaffin cells, 9.4 +/- 6.0; serotonin cells, 7.8 +/- 3.6; P < 0.01). The percentage of both types of cells with low staining intensity was increased, whereas the cells with high and moderate staining intensity were decreased (P < 0.01) in the left colon as compared with the right. The number of enterochromaffin cells in left-sided colonic mucosa was significantly higher in the colonic inertia group than in the control group (16.8 +/- 10.1 vs. 10.4 +/- 6.0; P < 0.05). Moreover, the numbers of serotonin cells in both the right and left colon was also significantly higher in the colonic inertia group than in the control group (right, 7.8 +/- 3.6 vs. 4.1 +/- 2.4; left, 12.1 +/- 6.4 vs. 5.8 +/- 3.7; P < 0.01). In both sides of the colon, the percentage of enterochromaffin and serotonin cells with low staining was significantly higher, whereas percentage of those cells with high or moderate staining was significantly lower in the colonic inertia group than in the control group. In the colonic inertia group there was a significantly positive correlation between numbers of enterochromaffin and serotonin cells (right side, P < 0.01; left side, P < 0.05). CONCLUSION: In patients with colonic inertia, the number of both enterochromaffin and serotonin cells are significantly increased in the colonic mucosa, especially in the left colon. As indicated by staining distribution, enterochromaffin and serotonin cells contain significantly less hormone than do the same cells in the control group.

Atypical epithelial cells and specimen adequacy: current laboratory practices of participants in the college of American pathologists interlaboratory comparison program in cervicovaginal cytology.

CONTEXT: The Bethesda System for reporting cervical/vaginal cytologic diagnoses introduced terminology for atypical squamous and glandular cells and categories for specimen adequacy. OBJECTIVES: To analyze current laboratory reporting practices and compare trends to previous surveys. DESIGN: Questionnaire surveys were mailed to 2000 laboratories in 1996 and 1997. PARTICIPANTS: Laboratories enrolled in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology. MAIN OUTCOME MEASURES: Laboratory policies, criteria, and reporting rates for Bethesda System categories. RESULTS: The 1996 specimen adequacy survey had 1166 respondents, and 768 laboratories returned the 1997 questionnaire focusing on atypical squamous cells of undetermined significance (ASCUS) and glandular cells of undetermined significance (AGUS). Nearly all laboratories (92%) routinely reported specimen adequacy, an increase from the 66% rate in 1991. The median rate for unsatisfactory specimens was 0.5% (mean 0.95%), and the median rate for the satisfactory but limited category was 5.8% (mean 9.3%). The Bethesda criteria for designating a specimen unsatisfactory were used by more than 90% of laboratories. Nearly all laboratories (97%) used the term ASCUS in 1997, and more than 80% of laboratories used the Bethesda criteria for this category. Median reporting rates for epithelial abnormalities were as follows: ASCUS, 4.5%; AGUS, 0.3%; low-grade squamous intraepithelial lesion (SIL), 1.6%; and high-grade SIL, 0.5%. The median ASCUS/SIL ratio was 2.0, with 80% of laboratories reporting ratios between 0.64 and 4.23. The median ASCUS rate and ASCUS/SIL ratio were higher than 1993 survey results. Nearly all laboratories attempted follow-up studies on patients with abnormal cytology results, and midsized laboratories achieved the highest rates of follow-up. Median rates of abnormalities following an ASCUS or AGUS diagnosis were 20% and 15%, respectively. Laboratory respondents commonly used written recommendations in ASCUS/AGUS reports. CONCLUSIONS: Most laboratories that responded to the surveys had adopted Bethesda terminology and criteria for specimen adequacy and ASCUS/AGUS. Reporting rates for SIL and adequacy categories have remained stable, but median ASCUS rates and ASCUS/SIL ratios are higher than in 1993. The AGUS category is reported infrequently, but can be associated with significant pathology.

Snowdrop lectin (GNA) has no acute toxic effects on a beneficial insect predator, the 2-spot ladybird (Adalia bipunctata L.).

Two-spot ladybird (Adalia bipunctata L.) larvae were fed on aphids (Myzus persicae (Sulz.)) which had been loaded with snowdrop lectin (Galanthus nivalis agglutinin; GNA) by feeding on artificial diet containing the protein. Treatment with GNA significantly decreased the growth of aphids. No acute toxicity of GNA-containing aphids towards the ladybird larvae was observed, although there were small effects on development. When fed a fixed number of aphids, larvae exposed to GNA spent longer in the 4th instar, taking 6 extra days to reach pupation; however, retardation of development was not observed in ladybird larvae fed equal weights of aphids. Ladybird larvae fed GNA-containing aphids were found to be 8-15% smaller than controls, but ate a significantly greater number of aphids (approx. 40% to pupation). GNA was shown to be present on the microvilli of the midgut brush border membrane and within gut epithelial cells in ladybird larvae fed on GNA-dosed aphids, although disruption of the brush border was not observed. It is hypothesised that GNA does not have significant direct toxic or adverse effects on developing ladybird larvae, but that the effects observed may be due to the fact that the aphids fed on GNA are compromised and are thus a suboptimal food.