Hospital life: avoiding negative attitudes

The population of Milton Keynes continues to grow and with it the need for more facilities in its recently opened community hospital. But how can the hospital cope now that Buckinghamshire AHA has put staff replacements under an embargo? Alison Hyde finds out how the staff are facing up to disappointed hopes, delayed plans and an establishment level which is one third under target.     

Mecca and the unbelievers

Wallingford Community Hospital was an experiment by the then Oxford Regional Hospital Board to make available to general practitioners the facilities and skills which a community hospital could provide. It included many additional responsibilities for the GP.     

Survival and developmental disability in infants with birth weights of 501 to 800 grams, born between 1979 and 1994

OBJECTIVE: Because the survival rate has increased for extremely low birth weight neonates, many have raised the concern that the rate of developmental disability among survivors will also increase. To address this concern, we analyzed changes over time in survival and major neurosensory impairment in a sample of extremely low birth weight infants born between July 1, 1979, and June 30, 1994. METHODS: The study sample included 513 infants with birth weights of 501 to 800 g who were cared for in either of the two neonatal intensive care units that serve a 17-county region in northwest North Carolina and who were born to mothers residing in that region. At 1 year of age (corrected for gestation), survivors were examined by a pediatrician and were tested using the Bayley Scales of Infant Development. Major neurosensory impairment was defined as cerebral palsy, a Bayley Mental Developmental Index <68, or blindness. A total of 209/216 (97%) of survivors were examined at 1 year of age. Epoch of birth was defined as follows: epoch 1, July 1, 1979 to June 30, 1984; epoch 2, July 1, 1984 to June 30, 1989; and epoch 3, July 1, 1989 to June 30, 1994. RESULTS: Survival rates for epochs 1, 2, and 3 were, respectively, 24/120 (20%), 63/175 (36%), and 129/218 (59%). In contrast, the proportions with a major neurosensory impairment did not increase over time; rates for successive epochs were 6/24 (25%), 17/61 (28%), and 26/124 (21%). Rates of cerebral palsy were 3/24 (13%), 12/61 (20%), and 9/124 (7%); rates of delayed mental development were 4/24 (17%), 12/61 (20%), and 17/124 (14%); and rates of blindness were 2/24 (8%), 0/62, and 5/124 (4%), respectively. CONCLUSIONS: This analysis suggests that the increasing survival of extremely low birth weight neonates since the late 1970s has not resulted in an increased rate of major developmental problems identifiable at 1 year of age.     

Topographic projection from the optic tectum to the auditory space map in the inferior colliculus of the barn owl

In the barn owl (Tyto alba), the external nucleus of the inferior colliculus (ICX) contains a map of auditory space that is calibrated by visual experience. The source of the visually based instructive signal to the ICX is unknown. Injections of biotinylated dextran amine and Fluoro-Gold in the ICX retrogradely labelled neurons in layers 8-15 of the ipsilateral optic tectum (OT) that could carry this instructive signal. This projection was point-to-point and in register with the feed-forward, auditory projection from the ICX to the OT. Most labelled neurons were in layers 10-11, and most were bipolar. Tripolar, multipolar, and unipolar neurons were also observed. Multipolar neurons had dendrites that were oriented parallel to the tectal laminae. In contrast, most labelled bipolar and tripolar neurons had dendrites oriented perpendicular to the tectal laminae, extending superficially into the retino-recipient laminae and deep into the auditory recipient laminae. Therefore, these neurons were positioned to receive both visual and auditory information from particular locations in space. Biocytin injected into the superficial layers of the OT labelled bouton-laden axons in the ICX. These axons were generally finer than, but had similar bouton densities as, feed-forward auditory fibers in the ICX, labelled by injections of biocytin into the central nucleus of the inferior colliculus (ICC). These data demonstrate a point-to-point projection from the OT to the ICX that could provide a spatial template for calibrating the auditory space map in the ICX.     

Verhandlungen der American Dermatological Association 1898

Archives of Dermatological Research -     

A histology-based model for predicting microsatellite instability in colorectal cancers

Identifying colorectal cancers (CRCs) with high levels of microsatellite instability (MSI-H) is clinically important. MSI-H is a positive prognostic marker for CRC, a predictive marker for resistance to standard 5-fluorouracil-based adjuvant chemotherapy, and an important feature for identifying individuals and families with Lynch syndrome. Our aim was to compare and improve upon the existing predictive pathology models for MSI-H CRCs. We tested 2 existing models used to predict MSI-H tumors, (1) Revised Bethesda Guidelines and (2) MsPath, in our population-based cohort of CRCs diagnosed less than 75 years from Newfoundland (N=710). We also scored additional histologic features not described in the other models. From this analysis, we developed a model for the prediction of MSI-H CRCs; Pathologic Role in Determination of Instability in Colorectal Tumors (PREDICT). An independent pathologist validated this model in a second cohort of all CRCs (N=276). Tumor histology was a better predictor of MSI status than was personal and family history of cancer. MsPath identified MSI-H CRCs with a sensitivity of 92.1% and a specificity of 37.8%, whereas the Revised Bethesda Guidelines had a sensitivity of 81.3% and a specificity of 39.5%. PREDICT included some new histology features, including peritumoral lymphocytic reaction and increased proportion of plasma cells in the tumor stroma. PREDICT was superior to both existing models in the development cohort with a sensitivity of 97.4% and a specificity of 53.9%. In the validation cohort, sensitivity was 96.9% and specificity 76.6%. We conclude that PREDICT is a good predictor of MSI-H CRC.     

Long-term protection of hematopoiesis against the cytotoxic effects of multiple doses of nitrosourea by retrovirus-mediated expression of human O6-alkylguanine-DNA-alkyltransferase

A human O6-alkylguanine-DNA-alkyltransferase (ATase) cDNA-containing retrovirus was used to infect murine long-term primary bone marrow cultures. High levels of ATase expression were obtained, and colony- forming cells of the granulocyte-macrophage lineage from the cultures transduced with the human ATase retrovirus were three times more resistant to the alkylating agent, N-methyl-N-nitrosourea (MNU), than control cultures. Furthermore, expression of the human ATase protected long-term hematopoiesis, measured as the output of progenitor cells to the nonadherent fraction of the culture, against the cytotoxic effects of repeated exposures to MNU. These results clearly show that a human ATase cDNA-containing retrovirus can be used to infect long-term primary bone marrow cultures and that this attenuates their sensitivity to nitrosoureas.     

CALLA-positive myeloma: an aggressive subtype with poor survival

Detailed immunotyping was carried out on 21 direct myeloma bone marrow aspirates and eight human myeloma cell lines. Four previously untreated common acute lymphoblastic leukemia antigen (CALLA)-positive myeloma patients were identified and six of eight cell lines (75%) were also positive. CALLA positivity, as part of an immature B phenotype, was found to correlate with very aggressive clinical disease: median survival six months v 56 months for the CALLA-negative group.