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Background: The enhanced recovery after surgery (ERAS) is nowadays a widely accepted multimodal programme of care in colorectal surgery, but still there is some reluctance in its application to very elderly patients. Aim: The aim of this study is to investigate short-term outcomes of laparoscopic resection for colorectal cancer in octogenarian patients within the ERAS programme. Methods: Data on 162 consecutive patients aged ≥ 80 years receiving elective minimally invasive colorectal resections within ERAS programme were collected in a multicentre, retrospective database in the period 2008–2017 in Italy. Univariate and multivariate analyses were performed to assess possible risk factors for poor clinical outcomes. Results: The postoperative minor morbidity rate (Clavien–Dindo 1 and 2) was 25.9%. The incidence of postoperative major morbidity rate (severe medical and surgical complications defined as Clavien–Dindo 3 and 4) accounted 6.1% and only 1.8% had an anastomotic leakage. Reoperation rate was 5.5%, perioperative 30-day mortality was 1.8%, and 30-day readmission rate was 6.8%. On average, patients were released after 6 days. A univariate analysis showed that possible risk factors for severe medical complications were: low preoperative albumin level, high Charlson Age Comorbidity Index Score and number of days in the intensive care unit (ICU); risk factors for severe surgical complications were: low preoperative albumin level; risk factors for late hospital discharge were: multivisceral resections, number of days in ICU and body mass index (BMI) > 25 kg/m2. The multivariate analysis confirmed a low level of preoperative albumin and a longer ICU stay as independent risk factors for both postoperative severe surgical complications and late hospital discharge. Discussion: The minimal invasive nature of the laparoscopic approach together with a multimodal analgesia therapy, the early resumption to oral diet and mobilisation could minimize the surgical stress and play an essential role in order to reduce medical morbidity in high-risk patients. Conclusion: Colorectal surgery within ERAS programme in octogenarians is a safe and flexible treatment in high-volume centres.

Grieco M. S. (1985) Corby: New Town planning and imbalanced development, Reg. Studies 19, 9-18. The object of this paper is to present an anatomy of the imbalanced development of Corby in the post-war period. The consequences of this imbalanced development, which caused a small Northamptonshire village to grow into a major steel town, are now reflected in the grim economic and social problems of Corby following on from the closure of major sections of the steel works. The paper focuses, in particular, on the role of planning in this failure. It is argued that the principle of balance which was at the heart of the New Town ideology found no place in the development of Corby New Town. Indeed, it is shown that the New Town status worked against regional and structural balance in Corby - a striking contrast with the common view of the role of New Towns. The paper concludes by drawing out the policy implications of this planning failure.

Two rat thyroid epithelial differentiated cell lines, PC Cl 3 and PC myc, were infected with the polyoma murine leukemia virus (PyMLV) carrying the Middle-T-antigen gene of polyomavirus. After infection, both cell lines acquired the typical markers of neoplastic transformation; however, the PC myc cells showed a greater malignant phenotype. Furthermore, the thyroid differentiated functions were completely suppressed in PC myc cells transformed by PyMLV, whereas they were, at least partially, retained in PC Cl 3 cells transformed by PyMLV, and in particular, thyroglobulin synthesis and secretion were not affected at all. Since no differences in the expression of the middle-T-antigen gene were observed in the two PyMLV-transformed cell lines, the different properties shown by these two infected cell lines must be ascribed to the expression of the c-myc oncogene.

Human erythrocytes bearing electroinserted full-length CD4 (RBC-CD4) can bind and fuse with a laboratory strain of human immunodeficiency virus type 1 (HIV-1) or with T cells infected by HIV-1. Here we show that RBC-CD4 neutralize primary HIV-1 strains in an assay of cocultivation of peripheral blood mononuclear cells (PBMC) from HIV-1- infected persons with uninfected PBMC. RBC-CD4 inhibited viral p24 core antigen accumulation in these cocultures up to 10,000-fold compared with RBC alone. Viral p24 accumulation was inhibited equally well when measured in culture supernatants or in call extracts. The inhibition was dose-dependent and long-lived. Two types of recombinant CD4 tested in parallel were largely ineffective. The neutralization of primary HIV- 1 by RBC-CD4 in vitro was demonstrated in PBMC cultures from 21 of a total of 23 patients tested at two independent sites. RBC-CD4 may offer a route to blocking HIV-1 infection in vivo.

A system of epithelial cells is described in which it is possible to study the number and the nature of genes capable of conferring the malignant phenotype. Two fully differentiated, hormone-responsive cell lines from rat thyroid glands are presented which are susceptible to one-step or two-step transformation upon infection with several murine acute retroviruses. After infection, both cell lines became independent from their thyrotropic hormone requirement for growth. However, complete transformation was achieved with one of the cell lines (FRTL-5 Cl 2), whereas the other cell line (PC Cl 3) failed to grow in agar and to give rise to tumors in vivo. The latter cell line was susceptible to complete transformation upon cooperation of the v-ras-Ha and the human c-myc oncogenes.

Non-thyroid neoplasia were analysed by Southern blot of genomic DNA and DNA prepared by reverse transcription and amplification by polymerase chain reaction (RT/PCR) for the activation of the RET oncogene. It is known that the rearrangement of RET occurs in about 10%-20% of human thyroid papillary carcinomas. None of 528 non-thyroid tumours showed rearrangement of the RET proto-oncogene, whereas three out of 30 thyroid papillary carcinomas were positive for RET activation. Therefore the activation of RET seems to be a somatic cell mutation specific to human thyroid carcinomas.

We have recently reported the activation of a new oncogene in human papillary thyroid carcinomas. This oncogene, named PTC, is a novel rearranged version of the ret proto-oncogene. In fact PTC is the product of the fusion of the tyrosine kinase domain of the ret proto-oncogene with the 5'-terminal region of another gene that we have named H4. The ret proto-oncogene shows a pattern of expression restricted to neuroendocrine tissue. Its fusion with H4 allows the expression of the activated form in thyroid papillary carcinomas. Therefore the detection of ret transcripts is a tool to investigate ret activation in thyroid neoplasms. Here we show the detection by in situ hybridisation, of activated ret transcripts in human thyroid papillary neoplasms that were positive for PTC activation by Southern blot analysis. We did not find any ret transcripts in papillary carcinomas negative for PTC activation, nor in normal thyroid and in non-papillary thyroid neoplasias.

Natural killer cell activity of peripheral blood mononuclear cells against K562 myeloid cells was studied in 8 normal heterosexual men, 5 healthy homosexual men, and 11 homosexual men with acquired immune deficiency syndrome. The overall natural killer cell activity was lower in healthy homosexual men and in homosexual men with acquired immune deficiency syndrome. Peripheral blood mononuclear cells from four normal heterosexual men were preincubated overnight in complete medium supplemented with various concentrations of lectin-free interleukin 2 lacking interferon. Cells from these cultures exhibited a dose-dependent augmentation of natural killer cell activity. Peripheral blood mononuclear cells obtained from 8 normal heterosexuals, 5 healthy homosexuals, and 11 homosexual men with acquired immune deficiency syndrome were preincubated overnight in complete medium supplemented with 20% interleukin 2. Natural killer cell activity cultured in 20% interleukin 2 increased to 78.4 +/- 8.4 (mean +/- standard deviation) from 30.8 +/- 11.0 in normal heterosexual men, to 68.3 +/- 17.6 from 16.8 +/- 13.6 in healthy homosexual men and to 49.3 +/- 15.3 from 11.6 +/- 6.1 in homosexual men with acquired immune deficiency syndrome at a 100:1 effector/target cell ratio. These results suggest that interleukin 2 is capable of directly stimulating natural cell-mediated cytotoxicity. Consideration of the use of interleukin 2 as a potential therapeutic agent to modify immune responses in disorders such as acquired immune deficiency syndrome appears warranted.

Levels of erythropoietin and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured in sera of 28 HIV-seronegative heterosexual non-intravenous drug using controls, 57 HIV-seronegative and 42 HIV-seropositive asymptomatic intravenous drug users (IVDU) and 36 HIV-seronegative and 36 HIV-seropositive homosexuals, 79 patients with lymphadenopathy, 11 patients with AIDS-related complex (ARC) and 110 patients with AIDS. Serum erythropoietin levels were significantly elevated in HIV-seronegative and HIV-seropositive asymptomatic homosexuals and in patients with lymphadenopathy, ARC and AIDS when compared to controls. However, in asymptomatic HIV-seronegative and HIV-seropositive IVDU the erythropoietin levels were not significantly different from the control group.GM-CSF mean levels in both HIV-seronegative and HIV-seropositive IVDU were elevated compared with the level in controls, whereas the mean levels in both the HIV-seronegative and HIV-seropositive homosexuals were decreased relative to the level in controls. GM-CSF levels in patients with lymphadenopathy, ARC and AIDS were not significantly different from the control value.It appears that male homosexuals have mildly increased erythropoietin levels which rise substantially with the development of ARC and AIDS, which suggests that AIDS patients have intact capacity to produce erythropoietin. In contrast, GM-CSF levels are increased in association with IVDU but are not increased in association with HIV infection including ARC or AIDS. The difference in circulating levels of erythropoietin and GM-CSF may reflect the tissue sources of erythropoietin predominantly in the kidney and GM-CSF being a product of the immunological and inflammatory systems.

Mice inoculated with an artificially constructed retrovirus carrying the middle T gene of polyomavirus develop acute myeloproliferative disease with severe thrombotic and hemorrhagic disorder and impaired platelet function. The megakaryocytic lineage appears to be a target for polyoma-murine leukemia virus infection and middle T gene expression. This newly described disease represents a unique model system for studying disorders of the megakaryocytic lineage.

RET/PTC is a transforming sequence created by the fusion of the tyrosine kinase domain of the RET protooncogene with the 5' end of the locus D10S170 designated by probe H4 and is frequently found activated in human papillary thyroid carcinomas. RET and D10S170 have been mapped to contiguous regions of the long arm of chromosome 10: q11.2 and q21, respectively. To identify the mechanism leading to the generation of the oncogenic sequence RET/PTC, a combined cytogenetic and molecular analysis of several cases of papillary thyroid carcinomas was done. In four cases the results indicated that these tumors had RET/PTC activation and a paracentric inversion of the long arm of chromosome 10, inv(10)(q11.2q21), with breakpoints coincident with the regions where RET and D10S170 are located. Therefore, a chromosome 10q inversion provides the structural basis for the D10S170-RET fusion that forms the hybrid transforming sequence RET/PTC.

Soluble CD8 levels in sera were quantitated in asymptomatic intravenous drug abusers, homosexuals, and patients with lymphadenopathy or acquired immunodeficiency syndrome. Soluble CD8 levels were elevated in human immunodeficiency virus-seronegative intravenous drug abusers and homosexuals, probably reflecting infections like cytomegalovirus. The sera of human immunodeficiency virus-seropositive groups of patients with human immunodeficiency virus infection also had elevated levels of soluble CD8, reflecting infections like cytomegalovirus and human immunodeficiency virus infection.

A chimeric expression vector which encoded for a molecule encompassing the extracellular domain of the epidermal growth factor (EGF) receptor (EGFR) and the intracellular domain of the ret kinase (EGFR/ret chimera) was generated. Upon ectopic expression in mammalian cells, the EGFR/ret chimera was correctly synthesized and transported to the cell surface, where it was shown capable of binding EGF and transducing an EGF-dependent signal intracellularly. Thus, the EGFR/ret chimera allows us to study the biological effects and biochemical activities of the ret kinase under controlled conditions of activation. Comparative analysis of the growth-promoting activity of the EGFR/ret chimera expressed in fibroblastic or hematopoietic cells revealed a biological phenotype clearly distinguishable from that of the EGFR, indicating that the two kinases couple with mitogenic pathways which are different to some extent. Analysis of biochemical pathways implicated in the transduction of mitogenic signals also evidenced significant differences between the ret kinase and other receptor tyrosine kinases. Thus, the sum of our results indicates the existence of a ret-specific pathway of mitogenic signaling.

Using DNA transfection analysis1on NIH3T3 cells2, activated human oncogenes have been isolated from a variety of fresh solid tumours3. Thyroid neoplasias show a wide range of lesions varying from slowly progressive well-differentiated tumours to anaplastic highly malignant neoplasms4. Therefore they represent an attractive model to investigate the role of oncogene activation in different stages of the neoplastic state. Here we report the detection of transforming activity in DNAs extracted from five thyroid papillary carcinomas and two of their respective lymph-nodal metastases.

CD4 antigen levels in sera from asymptomatic intravenous drug users and homosexuals and patients with lymphadenopathy, acquired immunodeficiency syndrome-related complex, or acquired immunodeficiency syndrome were quantitated. Like soluble CD8, CD4 antigen levels were elevated in human immunodeficiency virus-seronegative asymptomatic intravenous drug users and homosexuals, probably reflecting infections such as cytomegalovirus, Epstein-Barr virus, and hepatitis B virus infections. The sera from human immunodeficiency virus-seropositive groups of patients with human immunodeficiency virus infection also had elevated levels of CD4 antigen, presumably reflecting infections like cytomegalovirus and human immunodeficiency virus infections.

NF1 is associated with increased mortality not only from malignancy, but also from hypertension (H). The purpose of this study was to assess the prevalence of H in patients (pts) with NFl. We studied 71 NF1 pts (37M and 34F) with a mean age of 11 years (range 4–25 years). We measured blood pressure (BP) 3 times consecutively using a mercury sphygmomanometer. The mean measurements were taken as the office (O) BP. Each patient underwent a 24-h ambulatory BP monitoring (ABPM) by Spacelabs 90207 device, performed on regular school days with normal recreational activities. None of the children were taking any medication at the time of study. For each subject the following parameters were calculated: mean systolic BP (SBP) and diastolic BP (DBP), 24-h BP load, defined as the percentage of BP readings during a 24-h period that exceeded the age and sex-specific 95th percentile (P95). Pts with SBP and/or DBP > the P95 were submitted within 10 days to a second ABPM. When a tumor or a renovascular origin was suspected, a study of the plasmatic catecholamines, a nuclear magnetic resonance, a basal plasma renin activity/aldosteronemia and an echo-color-Doppler of renal arteries were performed. One patient was excluded from the study because <85% ABPM was valid. The mean 24h-SBP/DBP was respectively 118±8 and 71±5 mmHg. In 10 pts (14%) both ABPMs showed a SBP and/or DBP > P95 with a SBP and a DBP load > 69%. Four of these presented O-SBP and/or O-DBP values > P95. A Family history of H was present in 2 pts. The exams used to detect a tumoral or a renovascular origin of H, excluded secondary H in 4 of the 10 pts. This confirms the existence of H, especially secondary, in NF1 pts and the usefulness and acceptability of ABPM.