Characterization of major histocompatibility antigens on trinitrophenyl-modified cells.

Cell membrane proteins encoded for by the major histocompatibility complex (MHC)¹ are associated with the antigenic determinant(s) recognized on trinitrophenyl (TNP)-modified cells by syngeneic murine cytotoxic T lymphocytes and by hapten-reactive guinea pig T cells. To investigate the relationship of the TNP moiety on TNP-modified cells to these major histocompatibility antigens, peritoneal exudate cells or splenocytes from two inbred guinea pig strains and one inbred murine strain were TNP-modified, radioiodinated and lysed in detergent. TNP-derivatized proteins were then isolated using an anti-TNP immunoabsorbent, and the presence on TNP-derivatized histocompatibility antigens in the eluted proteins was determined by immunoprecipitation experiments and SDS-polyacrylamide gel electrophoretic analysis. Whereas most of the various histocompatibility antigens examined were found to be TNP-derivatized in amounts proportional to the degree of membrane protein derivation as a whole, only small amounts of TNP-modified strain 2 guinea pig Ia antigens were found, and no hapten-modified strain 13 guinea pig Ia antigens were detected. It is concluded that, in contrast to most MHC gene products, strain 13 Ia antigens are not derivatized on TNP-modified cells and, thus, represent an important exception demonstrating that histocompatibility antigens need not be directly TNP-derivatized for T cell recognition and activation.     

Collagenous spherulosis of the breast

Fifteen examples of a hitherto undescribed lesion, which we have designated "collagenous spherulosis," were encountered in breast tissue from women aged 39 to 55 years. The lesion, which was multifocal in eight cases, was an incidental microscopic finding involving lobular acini and ductules, and consisted of intraluminal clusters of eosinophilic spherules measuring approximately 20-100 mu in diameter. The spherules typically were found, and appeared to originate, within the spaces of fenestrated epitheliosis ("papillomatosis"). Special stains indicated that the spherules were collagen-rich, but also contained variable amounts of acidic mucin, PAS-positive, basement membrane-like material, and elastin. With immunoperoxidase staining, the cells immediately surrounding the spherules stained positively for actin, suggesting myoepithelial differentiation. Collagenous spherulosis was typically situated adjacent to, or encompassed by, other benign proliferative processes, including intraductal papillomas, sclerosing adenosis, and "infiltrating epitheliosis" (radial scars). Collagenous spherulosis is a clinically and histologically benign lesion that on microscopic examination has been confused with--and should be distinguished from--malignant lesions including adenoid cystic carcinoma of the breast and so-called intraductal signet-ring carcinoma.     

Doppler evaluation of blood flow of the lower limb

Regional blood flow measurement in the limbs (BFLL) is of special interest in order to evaluate the consequences of hypertension. The purpose of this study is to assess the interest of the Doppler ultrasound method in the BFLL measurement among normotensive or borderline hypertensives young male adults. BFLL reproducibility was evaluated among 23 healthy subjects aged 21 +/- 2 y, height 177 +/- 8 cm, weight 75 +/- 13 kg at day one (D1) and three day later (D3). Measurements were made basically after 20 minutes lying at rest and after cold pressor test (CPT). BFLL estimation depends on common femoral artery diameter (FAD) echographic measurement at the thigh root and on velocity time interval (VTI) calculation with pulsed wave doppler using controlled incident angle and sample volume. The following parameters were measured: mean arterial pressure (MAP) using Dinamap, heart rate (HR), FAD, common femoral artery cross sectorial area (A), VTI and peripheral arteriolar resistances (PAR). Basic and CPT results at D1 and D3 were compared using paired "t" test. Results: [table: see text] Comparisons between basic state and CPT demonstrate a significant decrease of VTI and BFLL, a significant increase of PAR. D remained unchanged. Doppler ultrasound method is easy to use. Systolic femoral volume measurement is relatively insensitive to small transducer positioning variations so that the method reproducibility is satisfactory.     

Surgical stimulation does not enhance ventilatory chemoreflexes during enflurane anaesthesia in man

To assess the impact of surgical stimulation on regulation of ventilation in anaesthetized man, we measured ventilation and the ventilatory responses to either hyperoxic hypercapnia or to isocapnic hypoxaemia in fifteen subjects anaesthetized with enflurane 1.1 MAC, just prior to and then during a surgical procedure. Anaesthesia alone reduced ventilation, increased Pa_co2 decreased the response to carbon dioxide and virtually abolished the response to hypoxaemia. The addition of operation at the same level of anaesthesia augmented ventilation and reduced Pa_co2 but did not improve the anaesthesia-induced impairment of the responses to hypercarbia and hypoxaemia. Over the range of PCO₂ and PO₂, values studied, the effects of surgery were constant and independent of chemical drive. A.M. Lam, M.D., Resident; J.L. Clement, R.N.; R.L. Knill, M.D., F.R.C.P.(C), Associate Professor; Department of Anaesthesia, University Hospital, University of Western Ontario, London, Canada. This work was supported by the Medical Research Council of Canada, Development Grant 150. Address reprint requests to Dr. R.L. Knill, Department of Anaesthesia, University Hospital, 339 Windermere Road, London, Ontario, Canada, N6A 5A5.     

Fibrosarcoma in Children: A Rare Tumour with Long-Term Survival even with Advanced Disease A Report of 3 Cases

Fibrosarcoma is a rare tumour in children. The potential of malignancy has been questioned. We present three cases of fibrosarcoma in children. The follow-up periods range from 10 to 37 years. The first patient had pulmonary metastases at the time of diagnosis in 1958. The primary tumour in fossa ischio-rectalis was resected in 1960. Lung metastases were resected in 1960 and 1989. Radiotherapy was given in 1992. He is still alive with metastases 37 years after the first manifestation of disease. The second patient had a primary tumour and several local recurrences in the mandible. He is alive without evidence of disease 4 years after resection of pulmonary metastases and 21 years after resection of the primary tumour. The third patient has no signs of recurrence or metastasic spread 10 years after a wide excision of subcutanous tumours of the left upper arm. The cases demonstrate a special tumour-entity of low-grade malignancy, which show a good prognosis and a wide spectrum of biological behaviour.     

Pediatric liver transplantation: from the full-size liver graft to reduced, split, and living related liver transplantation

Between 1984 and 1996, the authors performed 499 liver transplants in 416 children less than 15 years old. The overall patient survival at 10 years was 76.5%. It was 71.3% for the 209 children grafted in 1984–1990; 78.5% for biliary atresia (n =?286), 87.3% for metabolic diseases (n?=?59), and 72.7% for acute liver failure (n?=?22). The 5-year survival was 73.6% for the 209 children grafted in 1984–1990 and 85% for the 206 grafted in 1991–1996. Scarcity of size-matched donors led to the development of innovative techniques: 174 children who electively received a reduced liver as a first graft in our center had a 5-year survival of 76% while 168 who received a full-size graft had a survival of 85% (NS). Results of the European Split Liver Registry showed 6-month graft survival similar to results obtained with full-size grafts collected by the European Liver Transplant Registry. Extensive use of these techniques allowed the mortality while waiting to be reduced from 16.5% in 1984–1990 to 10% in 1991–1992. It rose again to 17% in 1993, leading the authors to develop a program of living related liver transplantation (LRLT). The legal and ethical aspects are analyzed. Between July 1993 and October 1997, the authors performed 53 LRLTs with 90% survival. In elective cases, a detailed analysis was made of the 45 children listed for LRLT between July 1993 and March 1997 and the 79 registered on the cadaveric waiting list during the same period. Mortality while waiting was 2% and 14.5% for the LRLT and cadaveric lists, respectively. The retransplantation rate was 4.6% and 16.1% for LRLT and cadaveric transplants, respectively. Overall post-transplant survival was 88% and 82% for children who received a LRLT or a cadaveric graft, respectively. Overall survival from the date of registration was 86% and 70% (P?<?0.05) for LRLT or cadaveric LT respectively. The 2-year post-transplant survival in children less than 1?year of age at transplantation was 88.8% and 80.3% with a LRLT or cadaveric graft, respectively; patient survival after 3 months post-transplant was 95.8% and 91.9% for stable children waiting at home, 93.7% and 93.7% in children hospitalized for complications of their disease, and 89.5% and 77.7% for children hospitalized in an intensive care unit at the time of transplantation for children who received a LRLT or cadaveric graft, respectively. It is concluded that LRLT seems to be justified for multidisciplinary teams having a large experience with reduced and split liver grafting.     

Spinal sources of noxious visceral and noxious deep somatic afferent drive onto the ventrolateral periaqueductal gray of the rat

Studies utilizing the expression of Fos protein as a marker of neuronal activation have revealed that pain of deep somatic or visceral origin selectively activates the ventrolateral periaqueductal gray (vlPAG). Previous anatomical tracing studies revealed that spinal afferents to the vlPAG arose from the superficial and deep dorsal horn and nucleus of the dorsolateral funiculus at all spinal segmental levels, with approximately 50% of vlPAG-projecting spinal neurons found within the upper cervical spinal cord. This study utilized detection of Fos protein to determine the specific populations of vlPAG-projecting spinal neurons activated by noxious deep somatic or noxious visceral stimulation. Pain of cardiac or peritoneal (i.e., visceral) origin activated neurons in the superficial and deep dorsal horn and nucleus of the dorsolateral funiculus of the thoracic cord, whereas pain of hindlimb (i.e., deep somatic) origin activated neurons in the same laminar regions but in the lumbosacral cord. Each of these deep noxious manipulations also activated neurons in the superficial and deep dorsal horn and nucleus of the dorsolateral funiculus of the upper cervical spinal cord. In a second set of experiments, the combination of retrograde tracing and Fos immunohistochemistry revealed that vlPAG-projecting spinal neurons activated by deep somatic pain were located in both the upper cervical and lumbosacral cord, whereas those activated by visceral pain were restricted to the thoracic spinal cord. Thus pain arising from visceral versus deep somatic body regions influences neural activity within the vlPAG via distinct spinal pathways. The findings also highlight the potential significance of the upper cervical cord in integrating pain arising from deep structures throughout the body.     

A Longitudinal Cohort Study of Youth Mental Health and Substance use Before and During the COVID-19 Pandemic in Ontario,Canada: An Exploratory Analysis

BackgroundYouth mental health appears to have been negatively impacted by the COVID-19 pandemic. The impact on substance use is less clear, as is the impact on subgroups of youth, including those with pre-existing mental health or substance use challenges.ObjectiveThis hypothesis-generating study examines the longitudinal evolution of youth mental health and substance use from before the COVID-19 pandemic to over one year into the pandemic among youth with pre-existing mental health or substance use challenges.MethodA total of 168 youth aged 14–24 participated. Participants provided sociodemographic data, as well as internalizing disorder, externalizing disorder, and substance use data prior to the pandemic’s onset, then every two months between April 2020–2021. Linear mixed models and Generalized Estimating Equations were used to analyze the effect of time on mental health and substance use. Exploratory analyses were conducted to examine interactions with sociodemographic and clinical characteristics.ResultsThere was no change in internalizing or externalizing disorder scores from prior to the pandemic to any point throughout the first year of the pandemic. Substance use scores during the pandemic declined compared to pre-pandemic scores. Exploratory analyses suggest that students appear to have experienced more mental health repercussions than non-students; other sociodemographic and clinical characteristics did not appear to be associated with mental health or substance use trajectories.ConclusionsWhile mental health remained stable and substance use declined from before the COVID-19 pandemic to during the pandemic among youth with pre-existing mental health challenges, some youth experienced greater challenges than others. Longitudinal monitoring among various population subgroups is crucial to identifying higher risk populations. This information is needed to provide empirical evidence to inform future research directions.