Residential facilities for mentally handicapped children: evaluation of a development project in Sheffield

Aspects of residential units provided for children under the Sheffield Development Project were studied. A variety of issues were raised which could be helpful in planning future services. The demand for places was considerably less than had been expected under the Project plans, and a greater than predicted proportion of the children had severe handicaps. Units had not specialized as intended, but had developed their own admission criteria. All unit heads felt smaller group sizes would have been preferable and most favoured smaller bedrooms. Fewer institutional staff management practices took place in the more domestic environments. Provision for outdoor play tended to be neglected.     

Serial processing and the "phonetic route:" lessons learned in the functional reorganization of deep dyslexia

A patient with chronic agrammatic Broca's aphasia presented with symptoms of deep dyslexia, in which it is presumed that phonologic processing of the written message is disrupted. Functional reorganization of the "nonlexical" or phonetic route of reading was undertaken according to principles of A. R. Luria, whereby the patient must learn consciously to control behaviors that had formerly been unconscious and automatic. This patient's responses in treatment made it clear that the phonetic route encompasses at least two dissociable functions, grapheme-phoneme conversion and sequential analysis. This is discussed in light of Luria's ideas regarding the functions of the precentral and postcentral regions of sensori-motor cortex.     

Surgical resection in the management of small cell carcinoma of the lung

In an attempt to define the role of initial surgical resection in patients with undifferentiated small cell carcinoma of the lung, we reviewed the experience of the Veterans Administration Surgical Oncology Group (VASOG). One hundred forty-eight patients with small cell carcinoma of the lung had undergone a potentially "curative" resection. This represented 4.7% of "curative" resections carried out in four major prospective adjuvant chemotherapy trials. In the early trials (101 patients), 16 patients (15.8%) died within the first 30 postoperative days. These patients have been excluded from the analysis of long-term survival, since in the more recent trials postoperative deaths were excluded prior to randomization. In the 132 patients remaining, the 5 year survival rate by the life-table method was 23.0%. The tumor of each was classified pathologically by the TNM system. Five-year survival rates for each category were as follows: T1 N0 M0 59.9%, T1 N1 M0 31.3%, T2 N0 M0 27.9%, T2 N1 M0 9.0%, and any T3 or N2 3.6%. The effect of postoperative adjuvant chemotherapy was evaluated in each of the trials. No beneficial effect of the adjuvant therapy was noted with a one or two course regimen of either nitrogen mustard or cyclophosphamide, but possible benefit, although not significant, was noted in a prolonged intermittent chemotherapy trial of cyclophosphamide either alone or alternating with methotrexate. In the most recent trial of prolonged intermittent courses of 1-(2-chlorethyl)-3-cyclohexyl-l-nitrosourea (CCNU) and hydroxyurea, a 5 year survival rate of 80.8% was noted in those receiving adjuvant chemotherapy as compared to a 38.1% in the control group. We conclude that resection is definitely indicated in patients with T1 N0 M0 lesions and probably indicated in those with T1 N1 M0 or T2 N0 M0 lesions. Primary surgical resection is contraindicated in patients with any other TNM category.     

Poor outlook for childhood acute lymphoblastic leukaemia with relapse.

Results of treatment in 72 children with a relapse of acute lymphoblastic leukaemia were analysed. A second remission was induced in 57 children (79%). Remission rates were significantly higher in males, and in patients with white cell counts less than 30 X 10(9)/L. The median duration of the second remission was only four months, and the median duration of survival from the time of relapse was nine months. The median duration of survival from the time of diagnosis was 27 months. Among children who suffered a relapse was a small group who had prolonged survival and prolonged second remissions. It is uncertain whether some of these may have a chance of "cure".     

Staff exposure to anaesthetic gases in theatre and non theatre areas

Environmental monitoring of anaesthetic gases was carried out in theatre areas in eight hospitals as well as in Delivery suites, radiology, radiotherapy and Dental suites. High staff exposures occurred in nontheatre areas although exposures in theatres were generally satisfactory. Environmental control measures are required where staff exposures exceed legal standards.     

Use of radiolabeled antibodies in the treatment of childhood acute leukemia

Abstract: Despite advances in therapy for acute leukemia, relapse continues to be the major cause of treatment failure. Hematopoietic stem cell transplant can rescue some patients after relapse, but the ability to escalate the intensity of preparative regimens is limited by toxicity to normal organs. Radiolabeled monoclonal antibodies against hematopoietic antigens have emerged as an alternative to deliver targeted supplemental radiation to sites of leukemic involvement while relatively sparing normal organs. This paper will review the rationale for using this approach, our current experience with radiolabeled anti-CD45 antibody, and the potential challenges encountered in treating children with radiolabeled antibodies.     

Neurocardiogenic syncope: a model for SIDS

A 5 1/2 month old male infant who had suffered three acute life threatening episodes was admitted for overnight sleep studies but was found dead after their completion while still in hospital. A necropsy classified the cause of death as sudden infant death syndrome (SIDS). The sleep studies had shown no periods of apnoea (> 20 seconds) or bradycardia (< 90 beats/min), and a rapid response to nasal occlusion (5 seconds). However, autonomic function during sleep was poor, with reduced heart rate variability (6 beats/min v control 24 beats/min, SD 6.2) and postural hypotension (a 12-14% fall in resting systolic blood pressure) associated with a fall in heart rate when tilted to a vertical position. Postural hypotension with bradycardia occurs in adults with unexplained syncopal episodes and is called a neurocardiac reflex. It involves poor vasomotor tone with peripheral pooling of blood, a consequent reduction in central venous return and cardiac distension, and in some individuals a neurally mediated bradycardia, as seen in this infant, rather than the expected tachycardia. A progressive bradycardia is the predominant mechanism of death seen in SIDS infants dying on cardiorespiratory monitors at home. This case suggests that a neurocardiac reflex occurs in infants, may have been involved in this infant's death, and deserves further study in the context of SIDS.     

Regulation of glucocorticoid receptor mRNA and heat shock protein 70 mRNA in the developing sheep brain

Fetal hypothalamo-pituitary-adrenal (HPA) activity increases dramatically at term in sheep, however, little is known about the regulation of glucocorticoid feedback in the developing brain. Heat shock protein 70 (hsp70) is closely associated with glucocorticoid actions within the cell. We hypothesized that there is a decrease in glucocorticoid negative feedback in the brain, near term, resulting from changes in the expression of glucocorticoid receptors (GR) and hsp70. Brains were removed at various stages of development. GR mRNA levels in the paraventricular nucleus (PVN) and cortex, and hsp70 mRNA in the PVN were determined by in situ hybridization. In the hippocampus, GR mRNA levels were measured by Northern analysis. In the PVN, GR mRNA was present by d60. GR mRNA levels reached a peak at d100-110, but then decreased significantly with progression of gestation, and were lowest at term. Hippocampal GR mRNA levels were highest on day 130 of gestation, decreasing to low levels at term. In the cerebral cortex, GR mRNA levels were expressed at high levels in all layers of the cortex by day 110 of gestation with levels decreasing to term. Hsp70 mRNA was present in both parvocellular and magnocellular regions of the PVN, and there was no significant change in late gestation. In conclusion, (1) The high levels of GR mRNA present in the PVN, hippocampus and cerebral cortex during fetal life are likely important in development of these structures at a time when circulating glucocorticoids are low. (2) Changes in GR mRNA levels in the PVN are not associated with alterations in the expression of hsp70. (3) The decrease in GR mRNA in the hippocampus and PVN in late gestation, at a time when fetal plasma cortisol is increasing, likely facilitates maintained hypothalamic drive to the pituitary corticotroph.