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Objectives. To identify epidemiological, clinical and laboratory characteristics of juvenile dermatomyositis (JDM) in a national multi-centre cohort of patients, and to review recent changes in the understanding of management and prognosis in the light of these data. Methods. All children with idiopathic inflammatory myositis recruited to the Juvenile Dermatomyositis National Registry and Repository (UK and Ireland) were included. Features at presentation, and later in disease, were assessed and evaluated. A total of 63 out of 175 children with a new diagnosis of myositis were recruited at the time of diagnosis and followed prospectively. Out of the 175 children, 122 diagnosed prior to 2000 were recruited retrospectively, with subsequent data collected prospectively. Results. One patient died (0.7%), which is equivalent to one death per 465 patient years. Data were available at the time of analysis on 151 registered patients. The most common presenting features were characteristic rash, weakness, tiredness, Gottron’s patches and myalgia. Muscle biopsy, magnetic resonance imaging and muscle enzymes were frequently, but not always, abnormal. Muscle enzymes and erythrocyte sedimentation rate were not useful markers of disease activity. Conclusions. The JDM National Registry and Repository captures data on a significant cohort of children with inflammatory myositis. The current study reports the largest European cohort of children with dermatomyositis to date. This powerful resource will help improve our understanding of this rare disease. Prospective data collection will allow a fuller analysis of poor prognostic features, impact of therapy, and variable outcome of childhood myositis.

Background Isolated hip disease in the context of chronic childhood inflammatory arthritis is uncommon. This paper reports 14 children who presented to the rheumatology and orthopaedic departments of our hospitals with severe hip symptoms, and who continued to have primarily hip disease throughout their clinical course. Our aim was to characterize and present the relevant demographic, clinical, investigational, treatment and outcome data from the above cohort. Methods All paediatric cases with the diagnosis of protrusio acetabuli, Otto pelvis or idiopathic chondrolysis who were seen in the past 15 yr at Great Ormond Hospital and Middlesex Hospital in London were identified and their case notes were searched retrospectively for relevant information. Results In 11 cases, the disease progressed to involve no joints other than the contralateral hip. None were considered to have a specific subtype of juvenile idiopathic arthritis (JIA) and all tested were negative for HLA-B27. Elevation of serum inflammatory markers was variable. Protrusio acetabuli was the predominant radiological feature. There were definite inflammatory changes on the gadolinium-enhanced magnetic resonance imaging study in all patients who had this procedure performed (seven cases). Microbiological investigations were all consistently negative. Severe hip disease resulted in considerable ongoing symptoms and disability. Six cases were treated with disease-modifying anti-rheumatic drugs. Total hip replacement has been required in four patients to date, with major functional improvement. Conclusions These cases represent severe and disabling primary hip disease with considerable clinical and investigational inflammatory features. Such a mode of presentation has not been described previously in the context of childhood chronic inflammatory arthritides, and may represent a separate oligoarthritis subtype of JIA.

We have studied immune reconstitution in a patient with paediatric-onset polyarteritis nodosa treated with high-dose immunosuppressive agents followed by stem cell rescue. The patient developed several new autoimmune phenomena over the 18 months after immunosuppression and stem cell rescue. Flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR) heteroduplex and isotype-specific RT-PCR analysis of immunoglobulin expression showed that the T- and B-cell repertoires were highly restricted in the first few months after treatment. The dominant T-cell clones seen after reconstitution were persistently expanded, were different from those which could be demonstrated before autologous stem cell transplantation, and were in the CD8(+) population. Our data also show that 12 months after treatment these expanded T-cell clones were within the CD45RA(+) population, suggesting that reversion from the CD45RO(+) to the CD45RA(+) phenotype had occurred in vivo.

AIMS To review the precipitating events, clinical features, treatment, and outcome of macrophage activation syndrome (MAS). METHODS Retrospective review of cases of MAS from a prospectively collected database of children with rheumatic diseases from 1980 to 2000. RESULTS Nine patients (eight girls) were considered to have evidence of MAS. The primary diagnosis was systemic onset juvenile idiopathic arthritis in seven, enthesitis related arthritis in one, and chronic infantile neurological cutaneous articular syndrome in one. Mean age of onset was 5.7 years, and duration prior to MAS, 4.2 years. No medication was identified as a trigger. Eight had infections prior to MAS; specific infectious agents were identified in four. High grade fever, new onset hepatosplenomegaly, and lymphadenopathy were common clinical features. Platelet counts fell dramatically, from an average of 346 to 99 × 10 9 /l. Mean erythrocyte sedimentation rate (in three patients) fell from 115 to 28 mm/h. Eight had abnormal liver function during the disease course, and six had coagulopathy. Bone marrow examination supported the diagnosis with definite haemophagocytosis in four of seven. All received high dose steroids (eight intravenous, one oral), five cyclosporin, two cyclophosphamide, and one antithymocyte globulin. Two of three patients with significant renal impairment died. CONCLUSION MAS is a rare and potentially fatal complication of childhood rheumatic disorders. Most of our patients were female, and most cases were preceded by infection. Bone marrow studies support the diagnosis. Deranged renal function may be a poor prognostic sign. Aggressive early therapy is essential. Key messages MAS is a rare complication of childhood rheumatic disease It is a potentially fulminant disorder, which may occur as part of the initial presentation of the rheumatic disease An infective trigger may herald the onset of this complication in predisposed patients Differentiation from a disease flare may be difficult, but is critical to ensure optimal outcome An early and dramatic fall in platelet count is characteristic, with changes in WBC and haemoglobin being more variable early and common Elevation in transaminases and coagulation abnormalities may not be present at onset of MAS Bone marrow examination is supportive, but false negative reports occur as a result of sampling errors or the subtle nature of the disease Multisystem involvement is a poor prognostic sign

Objective: To describe recent trends in television tip over-related injuries among children aged 0–9 years, and to compare injury rates with sales of newer digital televisions. Methods: Digital television sales data were obtained from marketing data provided by the Television Bureau of Advertising. Data regarding television tip over-related injuries among children aged 0–9 years were obtained from the 1998–2007 National Electronic Injury Surveillance System. A Wald χ 2 test, estimated from logistic analysis, was used to determine whether the distribution of injury types differed by age group. Pearson’s correlation was used to estimate the association between digital television sales and television tip over-related injuries. Results: An estimated 42 122 (95% CI 35 199 to 49 122) injuries from television tip-overs were treated in US emergency departments from 1998 to 2007. The injury rate was highest for children aged 1–4 years (18.6/100 000). A majority of injuries (63.9%) involved the head and neck for children under 1 year of age, while a higher proportion of injuries among children aged 1–4 involved the hip and lower extremity (42.9% and 31.0%, respectively), and shoulder and upper extremity (16.8%) for children aged 5–9. A strong, positive correlation was observed between television sales and annual injury rates (r = 0.89, p Conclusion: Estimates of injury rates were similar to previously reported estimates, particularly for the increased proportion of head and neck injuries among very young children. While digital television sales were strongly correlated with increased injury rates, the lack of information regarding the type of television involved prevents inference regarding causation.

OBJECTIVES: Joint hypermobility (JH) or "ligamentous laxity" is felt to be an underlying risk factor for many types of musculoskeletal presentation in paediatrics, and joint hypermobility syndrome (JHS) describes such disorders where symptoms become chronic, often more generalized and associated with functional impairment. Clinical features are felt to have much in common with more severe disorders, including Ehlers-Danlos syndrome (EDS), osteogenesis imperfecta and Marfan syndrome, although this has not been formally studied in children. We defined the clinical characteristics of all patients with joint hypermobility-related presentations seen from 1999 to 2002 in a tertiary referral paediatric rheumatology unit. METHODS: Patients were identified and recruited from paediatric rheumatology clinic and ward, and a dedicated paediatric rheumatology hypermobility clinic at Great Ormond Street Hospital. Data were collected retrospectively on the patients from the paediatric rheumatology clinics (1999-2002) and prospectively on patients seen in the hypermobility clinic (2000-2002). Specifically, historical details of developmental milestones, musculoskeletal or soft tissue diagnoses and symptoms, and significant past medical history were recorded. Examination features sought included measurements of joint and soft tissue laxity, and associated conditions such as scoliosis, dysmorphic features, cardiac murmurs and eye problems. RESULTS: One hundred and twenty-five children (64 females) were included on whom sufficient clinical data could be identified and who had clinical problems ascribed to JH present for longer than 3 months. Sixty-four were from the paediatric rheumatology clinic and 61 from the hypermobility clinic. No differences were found in any of the measures between the two populations and results are presented in a combined fashion. Three-quarters of referrals came from paediatricians and general practitioners but in only 10% was hypermobility recognized as a possible cause of joint complaint. The average age at onset of symptoms was 6.2 yr and age at diagnosis 9.0 yr, indicating a 2- to 3-yr delay in diagnosis. The major presenting complaint was arthralgia in 74%, abnormal gait in 10%, apparent joint deformity in 10% and back pain in 6%. Mean age at first walking was 15.0 months; 48% were considered "clumsy" and 36% as having poor coordination in early childhood. Twelve per cent had "clicky" hips at birth and 4% actual congenital dislocatable hip. Urinary tract infections were present in 13 and 6% of the female and male cases, respectively. Thirteen and 14%, respectively, had speech and learning difficulties diagnosed. A history of recurrent joint sprains was seen in 20% and actual subluxation/dislocation of joints in 10%. Forty per cent had experienced problems with handwriting tasks, 48% had major limitations of school-based physical education activities, 67% other physical activities and 41% had missed significant periods of schooling because of symptoms. Forty-three per cent described a history of easy bruising. Examination revealed that 94% scored > or =4/9 on the Beighton scale for generalized hypermobility, with knees (92%), elbows (87%), wrists (82%), hand metacarpophalangeal joints (79%), and ankles (75%) being most frequently involved. CONCLUSIONS: JHS is poorly recognized in children with a long delay in the time to diagnosis. Although there is a referral bias towards joint symptoms, a surprisingly large proportion is associated with significant neuromuscular and motor development problems. Our patients with JHS also show many overlap features with genetic disorders such as EDS and Marfan syndrome. The delay in diagnosis results in poor control of pain and disruption of normal home life, schooling and physical activities. Knowledge of the diagnosis and simple interventions are likely to be highly effective in reducing the morbidity and cost to the health and social services.

Objectives. To assess the efficacy and safety of intravenous cyclophosphamide (CYP) used in severe and refractory juvenile dermatomyositis (JDM). Methods. Retrospective case note review of the outcome of 12 patients. Results. Assessment at 6 months of therapy in 10 of the 12 patients showed a significant improvement in muscle function as assessed by the Childhood Myositis Assessment Scale (CMAS) (P ¼ 0.012), muscle strength (P ¼ 0.008), global extramuscular disease score (P ¼ 0.008), skin disease severity (P ¼ 0.015) and lactate dehydrogenase (P ¼ 0.028). There were reductions in creatine kinase, alanine aminotransferase, prednisolone dose and ESR, but these did not reach statistical significance. Clinical improvement was maintained after CYP until the most recent follow-up (between 6 months and 7 yr) and no severe side-effects were seen. Reversible complications included lymphopenia, herpes zoster infections and alopecia. The median cumulative dose was 4.6 g/m 2 (range 3–9 g/m 2 ). The available evidence suggests that, at the doses required, risks of malignancy, infertility and gonadal failure are low. Two patients with severe treatment-resistant disease died after one dose of CYP, both of whom were ventilated prior to commencement of CYP and were thought to have died as a result of their severe disease process, and too early for clinical benefit to be obtained from the drug. Conclusions. In this cohort of children with severe and refractory JDM, CYP appeared to have provided major clinical benefit with no evidence of serious toxicity in the short term.

Central nervous system (CNS) complications are rarely reported in either juvenile or adult onset inflammatory myositides, such as dermatomyositis and polymyositis. We report two children, aged 4 and 10 yr respectively, with a diagnosis of juvenile dermatomyositis, both of whom subsequently developed clinical features of severe CNS involvement, possibly consistent with cerebral vasculopathy. One child died from apparent brainstem involvement; the other developed seizures, pseudoseizures and clinical depression which responded to aggressive immunosuppression. Although the vasculopathy or vasculitis underlying this disorder is known to have a systemic distribution, CNS involvement has rarely been reported and may be under-recognized.

Five patients with the 22q11 deletion syndrome (velocardiofacial syndrome) developed chronic inflammatory polyarticular arthritis. These new cases add to 8 previously reported and confirm the association. The arthritis in all cases was moderate to severe, but at least partially responsive to methotrexate and/or corticosteroids, and was clinically indistinguishable from juvenile idiopathic arthritis (JIA). Analysis of the total 13 patients indicates that 2 are rheumatoid factor positive, 6 are antinuclear antibody positive, 5 have subtle T cell deficiencies, and 6 have hypergammaglobulinemia. Of particular interest is the occurrence of IgA deficiency in 4 patients, including 2 from our own series. Although IgA deficiency is seen in both JIA (2-4%) and 22q11 deletion syndrome (2-4%), the prevalence of low IgA in this series (31%) is much greater than expected. This phenomenon and the true association of inflammatory arthritis and a chromosome deletion disorder provides further evidence of important genetic factors in the pathogenesis of JIA.

We describe 2 pediatric patients with sickle cell disease (SCD) who developed seropositive juvenile rheumatoid arthritis (JRA). Both patients have severe joint damage, the compound effect of both disease processes. The bone and cartilage destruction, which poses serious therapeutic challenges, highlights the difficulty of making a diagnosis of chronic inflammatory disease in the setting of SCD. There may be a correlation between increased levels of tumor necrosis factor-alpha in the synovial tissue of joints damaged by arthritis and local sickling. The resultant ischemia and corresponding inflammatory infiltrates could in turn worsen existing synovial proliferation and cartilage destruction as well as trigger further sickling.

To define the onset and duration of effect of the HLA alleles that are associated with disease susceptibility and protection in juvenile rheumatoid arthritis (JRA) and 2 of its subtypes.We typed 680 patients with JRA and 254 ethnically matched unrelated controls for HLA class I and II genes. The frequency of each allele was calculated for each of the age-at-onset, onset type, and sex categories and plotted against the allele frequency in the control population. Survival analysis (with onset of disease as the terminating event) was used to calculate the age by which 50% (St0.5) and 80% (St0.2) of the children with particular alleles and combinations of alleles develop disease. This allele-specific survival analysis also allowed for the comparison of the overall survival functions for the various JRA subtype and sex categories.Certain alleles are strongly associated with early susceptibility to pauciarticular JRA, including HLA-A2, DR8, DR5, and DPB1*0201. Fifty percent of the children carrying at least 1 of these alleles had disease onset prior to their third birthday. Among children who carried HLA-A2 and any 2 HLA-DR alleles (DR3, DR5, DR6, or DR8), the median age at the onset of pauciarticular disease was 2.7 years. Combinations of A2 and DPB1*0201 and one DR allele narrowed the window further to a median age at onset of 2.4 years. B27 and DR4 were associated with protection early in life but with increased risk later in childhood, with St0.5 values of 7.3 and 6.6 years, respectively, for pauciarticular JRA and St0.5 values of 10.2 and 10.7 years, respectively, for polyarticular JRA. Sex strongly influenced the age at which many of the alleles have their effect.These data define at what age and for how long various HLA alleles influence susceptibility and protection (window-of-effect) in patients with JRA. In addition, these data establish more clearly the boundaries of ages-at-onset for 2 of the subtypes of the disease.

To characterize synovial T cell infiltrate, in terms of CD4/CD8 ratio and level of activation of T cells, in juvenile rheumatoid arthritis (JRA) and juvenile spondyloarthropathy(JSpA), to correlate these findings with clinical outcomes of the different forms of disease, and to compare them with findings in adult RA synovium.We studied synovial tissue specimens from 22 individuals with childhood onset of chronic arthritis (12 polyarticular JRA, 5 pauciarticular JRA, 5 JSpA) and 4 with adult RA. Specimens were selected from an initial bank from 40 patients on the basis of significant inflammation on hematoxylin and eosin and CD3 and CD68 monoclonal antibody staining (T cells and macrophages, respectively). Indirect immunohistochemistry was used with monoclonal antibodies to CD3, CD4, CD8, and interleukin 2 receptor alpha to determine CD4/CD8 ratios and the levels of activation within the T cell subsets. The distribution of gamma delta T cells was also studied.Two patterns of T cell infiltration were seen. The majority of patients had lymphocytic aggregates associated with diffuse infiltrates; a few tissue specimens had diffuse infiltrates without aggregates. The CD4/CD8 ratio was significantly lower in pauciarticular course JRA than polyarticular JRA (p0.01) and RA (p0.05). Similarly patients with JSpA had a significantly lower CD4/CD8 ratio than patients with polyarticular JRA (P0.05). The level of T cell activation (CD3+IL-2R+) was significantly higher in pauciarticular compared with both polyarticular JRA (P0.01) and RA (p0.05). In general, higher levels of activation of CD8 cells than CD4 cells were seen, particularly in the pauciarticular JRA and JSpA groups. gamma delta T cells were prominent in 2 patients.Demonstrated differences in T cell subset distribution between types of childhood chronic arthritis at a histopathological level may reflect different pathogenic mechanisms.

Efforts to improve local control and survival by increasing the dose of once-daily radiation therapy beyond 70 Gray (Gy) for patients with malignant gliomas has yet been unsuccessful. Hyperfractionated radiation therapy (HF) should allow for delivery of a higher total dose without increasing normal tissue late effects, whereas accelerated hyperfractionated radiation therapy (AHF) may minimize tumor repopulation by shortening overall treatment time. The Radiation Therapy Oncology Group (RTOG) conducted a randomized Phase I/II study of escalating doses of HF and AHF either carmustine (bis-chlorethyl nitrosourea [BCNU]) fro adults with supratentorial glioblastoma multiforme (GBM) or anaplastic astrocytoma (AA). Primary study endpoints were overall survival and acute and chronic treatment-related toxicity.From 1983 to 1989, 786 patients with supratentorial gliomas (81% with GBM and 19% with AA) were stratified by histology, age, and performance status and randomized to receive partial brain irradiation, utilizing either HF (1.2 Gy twice daily to doses of 64.8, 72, 76.8, or 81.6 Gy) of AHF (1.6 Gy twice daily to doses of 48 or 54.4 Gy). All patients received carmustine. The distinction of pronistic factors was similar on all arms.There were 747 eligible and analyzable patients among 786 enrolled patients (95%). Two patients had a Grade 5 and 65 patients had a Grade 4 chemotherapy toxicity. Two patients in the 81.6 Gy arm experienced late Grade 4 radiation toxicity and there was 1 late radiation-associated death in the 54.4 Gy arm. The rate of Grade 3 of worse radiation toxicity at 5 years, calculated by the delivered does level, was 3% in the lowest total dose arms (48 and 54.4 Gy), 4% in the intermediate dose arms (64.8 and 72 Gy), and 5% in the highest dose arms (76.8 and 81.6 Gy) (p = 0.54). Survival rates at 2 and 5 years were: 21% and 11%, and 4%, respectively, for GBM patients. There were no significant differences between the treatment arms with regard to median survival time (MST), when analyzed by the originally assigned dose. The MST for all patients varied between 10.8 months and 12.7 months (P = 0.59); between 9.6 months and 11 months for patients with GBM (P = 0.43); and between 30.4 months and 85.8 months for patients with AA (P = 0.78). Analysis of the survival rates for all patients by dose received rather than by dose assigned revealed a 14% 5-year survival rate for the lower HF doses (64.8 and 73 Gy), 11% for the higher doses (76.8 and 81.6 Gy), and 10% for the AHF doses (48 and 54.4 Gy) (P = 0.1). The subgroup a AA patients had a better MST (49.9 months) in the lower received HF doses than in the higher HF doses (34.6 months) (P = 0.35). In contrast, GM patients who received the higher HF doses had survival superior to the patients in the AHF arms (MST of 11.6 months and 10.2 months, respectively, P = 0.04).The use of HF with BCNU and dose escalation up to 81.6 Gy is both feasible and tolerable, although late toxicity increases slightly with increasing dose. The best MST with the least toxicity were observed for AA in the lower received HF doses (72 and 64.8 Gy). Accordingly, 72 Gy in two 1.2 Gy fractions was used as the investigational arm of a completed Phase III trial (RTOG 90-06). In contrast, for GBM patients, longer survival times were noted in the higher received HF doses (78.6 and 81.6 Gy), suggesting the role for further dose escalation. The low toxicity rate with AHF arms suggest that further dose escalation is possible and is currently occurring in RTOG 94-11.

In adults, sensorineural hearing loss (SNHL) resulting from megavoltage temporal bone radiation therapy (RT) is dose dependent. A review of the literature reveals only two cases of pediatric SNHL after RT without chemotherapy. This report presents four cases of late onset, asymmetric SNHL after RT in children treated for posterior fossa tumors. The children were treated with surgical resection of the tumor, followed by RT of 50 to 54 gray and no chemotherapy. These children, without evidence of tumor recurrence, developed severe SNHL 18 to 36 months after the completion of RT. Although no definite audiometric pattern was seen, most of the patients had a predominately high frequency SNHL in the poorer hearing ear, and fluctuant hearing in the better ear, without evidence of osteoradionecrosis or otitic infection. A review of the literature suggests that injury to the outer hair cells and cochlear neurons of the basal turn of the cochlea are possible sources for the hearing loss. Pretreatment audiologic evaluation as well as a minimum of 3 years of evaluations following RT would be prudent.

Four children with prolonged emesis during brain tumor therapy were diagnosed with pancreatitis.All were exposed to medications or radiotherapy that potentially contributed to pancreatitis.Because recognition of pancreatitis may necessitate changes in supportive care, pancreatitis should be included in the differential diagnosis of vomiting in this population.

Meeting the demands of patients and the public for health information is now a recognised aim. Healthpoint is a community-based touch-screen public-access health information system which aims to make health information easily accessible by the public and to provide feedback information on this demand. We have assessed Healthpoint in an experiment in three parts. Part one was a survey of 13 Healthpoints for several weeks in various community sites in Glasgow, such as a shopping centre, supermarket, library, and pub, as well as health service sites such as out-patient department and general practice. The number of users and the topics chosen were recorded by the systems. Part two was a survey of ten Healthpoints in one town (Clydebank) over five months, which examined routine information recorded by the system, and interviews with an opportunistic sample of 300 weekday shoppers in the street and a random sample of 271 by telephone. Part three was a survey of one Healthpoint in a general practice for 36 weeks using routine recording by the system and a postal survey of a systematic sample of 250 attenders. Seventy five (25%) out of 300 in the street survey and 45 (22%) of the telephone sample who had visited a site where there was a Healthpoint had used it. Overall, 17% of the telephone sample had used it. Seventy three (27%) out of 200 general practice attenders had used Healthpoint.(ABSTRACT TRUNCATED AT 250 WORDS)

Seven hundred fifty-nine patients with Stage I/II breast cancer who were treated with mastectomy alone (558 patients) or breast-conserving surgery and tangential irradiation (201 patients) were evaluated. Median follow-up time was 34 months. Axillary node status showed differences between treatment groups. Seventy-two percent of patients undergoing lumpectomy and radiation therapy (Lx) versus 35% of patients in the mastectomy group were pathologically node-negative, 18% Lx versus 30% mastectomy alone had one to three nodes positive, and four or more positive axillary nodes were seen in 35% of mastectomy alone patients. Reflecting this trend, overall survival (P less than 0.007), time to locoregional failure (P less than 0.0005), and time to any failure (P less than 0.0001) favored Lx patients. Correcting for axillary node status, significant differences persisted only for node-negative patients. Median actuarial survival time was 73 months for the mastectomy alone group (196 patients) versus 120 months for the Lx group (144 patients) (P less than 0.02), with significant differences also noted in time to local failure (P less than 0.003) and time to any failure (P less than 0.001). Stratification according to primary tumor size in patients who were node-negative yielded marked differences in time to locoregional failure in T1 (less than 2 cm) (P less than 0.0006) presentations, with analysis approaching significance for T2 (2 to 5 cm) lesions (P less than 0.06). Disease-free interval was greater in node-negative Lx patients for both T1 (P less than 0.007) and T2 (P less than 0.05) presentations. Overall survival was not significantly different in node-negative Lx patients when primary tumor size was considered. Improved prognosis was identified in node-negative patients undergoing breast-conserving surgery and radiation therapy over mastectomy alone. Theoretical considerations included eradication of occult microscopic disease within the chest wall by tangential irradiation.

Selective inhibitors of the cyclic nucleotide phosphodiesterase (PDE) isoenzymes have been studied to assess the potential for such agents in the treatment of asthma. A novel selective PDE V inhibitor, SKF 96231, reversed the bronchoconstriction induced in anaesthetised guinea pigs by histamine, a thromboxane-mimetic or by ovalbumin challenge. There was no effect of SKF 96231 on heart rate or blood pressure in conscious dogs. Siguazodan (SKF 94836, a selective PDE III inhibitor) caused bronchodilation but also had cardiovascular effects in conscious dogs. Studies on the PDE profile of various inflammatory cells have indicated that inhibition of PDE IV would be beneficial in the treatment of the inflammatory aspects of asthma and this is briefly reviewed.

Twenty-three patients underwent craniotomies for brain malignancies. One hundred eleven fluorescein-stained and 75 nonstained tissue biopsies were obtained for histopathological examination using a special arc-lighting system connected to a conventional surgical headlight. Of the 75 nonstained specimens, 71 (94.7%) were negative for tumor and 4 demonstrated the presence of tumor. Ninety-four (84.7%) of the fluorescent tissues obtained were reported as having neoplasia and the remaining 17 showed characteristics consistent with necrotic tissue debris. All stained tissues obtained in this study demonstrated visible fluorescence within neoplastic tissue margins harboring abnormally permeable blood-brain barriers.

A morbidity and mortality study of workers at an alcohol manufacturing plant which included several weak acid isopropyl alcohol units and a strong acid ethanol unit is described. An excess mortality of upper respiratory cancer was found and associated with work on the strong acid ethanol unit. The strong acid ethanol process used resulted in high concentrations of diethyl sulfate, which has been shown to be carcinogenic in animals, and the unit, which closed on 1975, had significant opportunities for worker exposure to diethyl sulfate. These facts, plus previous reports of excess upper respiratory cancer on strong acid isopropyl alcohol units with similarly high concentrations of the animal carcinogen diisopropyl sulfate, lead to the tentative conclusion that diethyl sulfate was primarily responsible for the ethanol unit cancer cases. In the modern weak acid isopropyl alcohol plants, where only trace amounts of diisopropyl sulfate are present and exposures are much lower, the problems found on the old strong acid units do not exist.

Capillaries from cerebral white matter were isolated from normal humans and normal mice and from human astrocytomas (Grades II-IV) to investigate potential biochemical and ultrastructural differences between normal and neoplastic-derived microvessels. Capillaries from Grade III and IV astrocytomas averaged 55-fold higher in the concentration of total protein than capillaries from normal mouse and normal human cerebral tissues. Scanning electron microscopic examination revealed more bifurcations and fewer surface undulations in the capillaries derived from anaplastic astrocytomas than in capillaries derived from normal specimens. Sprouting configurations were detected in the capillaries from anaplastic astrocytomas. They measured 4 to 5 micron in diameter and manifested fewer surface undulations than capillaries from normal human white matter. The results of these preliminary investigations suggest early capillary growth from parent vessels in high-grade and highly vascularized astrocytomas.

This study further characterizes the morphological and in vitro properties of human neoplastic cells derived from one Grade IV cerebral astrocytoma and one Grade III cerebellar astrocytoma. Light microscopic observations performed weekly over a four month period revealed two morphologically indistinguishable cell populations in each of the tumor cultures. Scanning electron microscopy demonstrated the presence of microvilli, blegs, and ruffles on the cell surfaces of both tumors; however, these topographical features were more prominent in the cultures derived from the Grade III cerebellar astrocytoma. Scanning electron microscopy may provide a useful tool for the further morphologic classification of human astrocytomas.

Neutrophil chemotaxis was evaluated for five patients with a primary intracerebral malignancy. All patients had intratumor cysts and these fluids with corresponding serum and cerebrospinal fluid were tested for their chemotactic ability. The ability of cyst fluid to effect neutrophil chemotaxis was diminished in comparison to serum from either patients or control population. Cyst fluids had lower complement levels than serum and did not have a humoral chemotactic inhibitor. The neutrophils for both the patient and control groups had similar chemotaxis to a given chemotactic stimulus suggesting that this malignancy does not have an accompanying peripheral blood phagocytic cell chemotactic defect. Chemotaxis, the migration of phagocytic cells, is a fundamental requisite for the inflammatory and the immune response.

The trauma victim with a severe closed head injury, who requires general anesthesia for emergency repair of concomitant exigent major injuries, poses a clinical dilemma. During general anesthesia and during the immediate postoperative period, the status of the patient's central nervous system cannot be clinically monitored, and emergency cerebral arteriograms and/or CAT scans are not easily obtained. Under these circumstances, delays in the diagnosis of intracranial blood accumulations frequently occur, and occult cerebral edema often goes untreated. In an attempt to avoid these management problems, we have employed intraoperative intracranial pressure (ICP) monitoring in such patients, using a subarachnoid screw. Following placement of this screw, several clinical courses may occur: 1) The patient maintains a normal pressure; thus a significant mass lesion and/or cerebral edema requiring decompression is unlikely. 2) The patient's ICP is elevated but controlled by medical management. 3) The patient's ICP cannot be controlled below 20 to 25 mm Hg using medical management, and exploratory burr holes are made. 4) If intracranial blood is encountered during placement of the ICP monitor, immediate exploratory craniotomy is indicated.