How many people think they have hay fever, and what they do about it. Little is known about the number of people who perceive themselves to be sufferers of hay fever. This study investigated how many people between the ages of 15 and 59 years perceived themselves to be hay fever sufferers and how they treated themselves. The study was carried out in a general practice in Arnold, Nottingham, using a postal questionnaire, to which the response rate was 77% from a sample size of 1062. Of the 813 respondents, 232 (29%) claimed to have had hay fever within the last two years. The prevalence of hay fever decreased significantly with age, and was associated with a history of asthma. One hundred and twenty five sufferers (54%) used over the counter treatments for their hay fever, and one third of these said that they felt drowsy after using them. These findings point to the need for general practitioners to be aware that a number of people, more than has been indicated by previous surveys, perceive themselves to be hay fever sufferers and are prepared to treat themselves using over the counter preparations.


Prevalence of heart failure in three general practices in north west London. There is little recent information on the prevalence of heart failure in the United Kingdom. Assuming that patients with heart failure would be taking diuretic drugs all such patients were identified in three general practices in north west London. The practice records of these patients were examined to determine which patients had heart failure. Of the 30,204 patients served by the practices, 117 had heart failure, a prevalence of 3.9 per 1000 patients. The mean age of these patients was 74 years. The prevalence of heart failure among patients under 65 years of age was 0.6 per 1000 patients rising to 27.7 per 1000 among those aged 65 years and over. The aetiology of heart failure was considered to be coronary heart disease for 32% of patients, valve disease for 19%, hypertension for 6%, cor pulmonale for 4% and congenital heart disease for 2%. The aetiology for the remaining 37% of patients was unknown. Most patients were referred to hospital and only 20% had been treated solely by the general practitioner. An electrocardiogram and chest radiograph had been obtained for over 80% of patients but only 28% had an echocardiogram. Heart failure occurs primarily in elderly patients, and coronary heart disease is the dominant aetiological factor.


General practitioners' attendance at courses accredited for the postgraduate education allowance. An analysis was undertaken in the northern half of the South Western Regional Health Authority of general practitioners' attendance at courses accredited for the postgraduate educational allowance over one year. A total of 358 courses provided 2341 hours of accredited education and produced a total general practitioner attendance of 50,389 hours. The mean attendance per principal in the area was 49.2 hours although the region may be a net importer of attenders from outside the area. Of the 50,389 total hours of attendance, 28.3% were in health promotion, 48.2% in disease management and 23.5% in service management. Course provision and attendance varied considerably over the year. September, October and November accounted for 42.7% of the total hours of attendance, compared with 6.8% in June, July and August. Courses of two to four days or of one week duration accounted for 48.3% of total attendance hours; 10.1% of total attendance hours were at commercially organized courses and 5.6% at courses organized by practices. A total of 66.1% of attendance hours were in postgraduate centres and 6.8% in the practice. Courses with more than 30 participants accounted for 15.9% of courses attended. A total of 174 general practitioners and others organized courses, 21 of them influencing 33,521 hours of general practitioner education. The study shows that in this area, there was an encouraging provision, range and uptake of continuing education courses for general practitioners. The concentration of educational activities in postgraduate centres underlines the need for increased provision for developing educational skills for clinical tutors.


New strategies for higher professional education. Since the original recommendation in 1968 for a period of higher professional education, the development of this form of education has been slow. However, in 1990 a working party was established by the education division of the Royal College of General Practitioners to report on higher professional education. This paper describes some of the early work of the working party and its recommendations with particular emphasis on educational strategies, assessment and accreditation. A flexible, learner centred approach needs to be developed to encourage autonomy. Educational strategies are described which value previous experience and allow for a shift of responsibility for learning from the teacher to the learner.


Calcitonin gene-related peptide (CGRP)-immunoreactive nerves in the tracheal epithelium of rats: an immunohistochemical study by means of whole mount preparations. The airway mucosa is known to be densely supplied with several types of peptidergic nerve fibers. The distribution of the nerve fibers in a large extent of the mucosa, however, has been difficult to visualize by observation of conventional thin sections. In the present study, whole mount preparations of the rat tracheal mucosa were designed to demonstrate calcitonin gene-related peptide (CGRP)-containing nerves which are most predominant among peptidergic nerves in the trachea. The mucosal sheet of the trachea was separated from the cartilaginous base by means of dispase, a protease, to be processed to immunohistochemistry for CGRP. In the cartilaginous portion, thick nerve bundles immunoreactive for CGRP ran transversely between the cartilage rings, sending terminal branches toward the epithelium. In the membranous portion, immunoreactive nerve bundles were thinner than those in the cartilaginous portion and ran longitudinally. A very dense nerve plexus of CGRP-immunoreactive fibers was demonstrated to extend in the basal part of the epithelium; every epithelial cell appeared to contact more than one nerve fiber. Immunohistochemistry of the whole mount preparations also clearly demonstrated the distribution and entire shape of broncho-pulmonary paraneurons scattered in the epithelium. Ultrastructurally, the CGRP-immunoreactive intraepithelial nerves were found to lack myelin and Schwann sheaths, and to run through the bases of the epithelial cells; they were most frequently surrounded by the cytoplasmic processes of the epithelial cells. The present study demonstrates that immunohistochemistry of whole mount preparations is a useful tool to morphologically analyze neuronal and paraneuronal distribution throughout the tracheal epithelium.


The dependency of collagen fibrillogenesis in vitro on fibroblast culture conditions. Fibroblasts in mono- and multi-layers. The extracellular matrix produced by monolayer and tridimensional cultures of fibroblasts was investigated using histochemical and ultrastructural methods. In monolayer cultures, collagen and proteoglycans produced by fibroblasts could not be organized into morphologically recognizable structures. Tridimensional fibroblast cultures produced a well organized matrix with periodic, parallel ordered collagen fibrils of 50 nm diameter, criss-crossed by alcianophylic segments 6-10 nm thick in diameter and 100-300 nm in length, parallel to each other, perpendicular to the collagen fibrils and spaced 67 nm from each other. Some alcianophylic segments lay perpendicular to the above described ones, with maximum lengths of 65-70 nm. Alcianophylic segments are the ultrastructural evidence of structural proteoglycans. These observations suggest that the culture conditions influence the collagen and proteoglycans secretion, so that the final organization of the matrix results quite different.


The topographic organization of the retinal ganglion cell layer of the lizard Ctenophorus nuchalis. The numbers of neurons of the ganglion cell layer (GCL) and their distribution in the retina of an Australian lizard Ctenophorus nuchalis were investigated. Retinal wholemounts and sections were prepared for light microscopic and optic nerves for electron microscopic study. Counts of cell numbers in the GCL from wholemounts varied from 200,000 to 380,000. Neurons in the GCL were non-uniformly distributed, forming a high cell density streak along the naso-temporal axis of the retina. Neurons of the GCL formed 2 to 9 layers in the visual streak and a single layer in the rest of the retina. The number of neurons of the GCL in this area was estimated at about 2,100,000. Although the visual streak represented only 16% of the total retinal surface area, it contained about 90% of all neurons of the GCL. Optic axon counts yielded 147,000 myelinated and 2,643,000 unmyelinated fibres. The estimated optic fibre number of 2,790,000 was 18.2% less than the total number of neurons counted from sections in the GCL of the same eye. The unexpected high number of neurons in the area of the visual streak indicates that cell numbers obtained only from wholemount preparations may vastly underestimate the total neuron numbers in the GCL of the lizard retina.


Morphological modifications during long-term survival of Meckel's cartilage hypertrophic chondrocytes transplanted in the mouse spleen. To examine the ultimate fate of hypertrophic chondrocytes, Meckel's cartilage bars from 18-day-old mouse embryos were transplanted into isogenic mouse spleen for 3, 7, 14 and 21 days and observed at the light and electron microscopic levels. The midportions of these Meckel's cartilage bars were used as explants; they were characterized by many hypertrophic chondrocytes containing euchromatic round nuclei, a large amount of glycogen particles, and some vacuoles. Grafted cartilage adapted well to the splenic tissue, showing intense metachromasia around the territorial matrix. Ultrastructural observations indicated that the number of large vacuoles and glycogen aggregates in the hypertrophic cells became markedly reduced with grafting time, whereas the Golgi apparatus and rough endoplasmic reticulum were well-developed. Needle-like crystals showing initial apatite deposition appeared in association with matrix vesicles; these proliferated as time elapsed after transplantation. On day 14 after transplantation, cells displaying such various structural features as pyknotic nuclei, large vacuoles, and cytoplasmic shrinkage were noted in addition to intact hypertrophic chondrocytes. Following resorption of the calcified cartilage by multinucleated giant cells, many osteoblasts appeared along the border of the calcified matrix. Some remaining hypertrophic cells in the calcified matrix had transformed into osteocyte-like cells. On day 21, the resorbed area of the calcified cartilage was invaded by many blood vessels. Hypertrophic chondrocytes, now exposed from cellular lacunae, and the osteocyte-like cells in the calcified matrix displayed involutional changes. The present study showed that, although the hypertrophic chondrocytes in Meckel's cartilage essentially underwent regressive changes, they retained the ability to stimulate endochondral ossification within the microenvironment of the spleen. In addition, some of these cells were transformed into osteocyte-like cells.


Odontoclastic resorption at the pulpal surface of coronal dentin prior to the shedding of human deciduous teeth. Histological and histochemical observations of more than 150 extracted human deciduous teeth revealed that, prior to shedding, odontoclastic resorption as a rule takes place at the pulpal surface of coronal dentin. We also found that this phenomenon occurs in all kinds of deciduous teeth. The process of this internal resorption of coronal dentin of deciduous teeth clearly showed time-related histological changes. During the time the roots were actively being resorbed, the pulpal tissue retained its normal structure. However, when root resorption neared completion, inflammatory cells started to gradually infiltrate into the pulp, and odontoblasts began to degenerate. After that, multinucleate odontoclasts appeared, and resorption proceeded from the predentin to the dentin. The odontoclastic activity was initially detected only on the pulpal surface at the bottom areas of the crown. It gradually spread towards the pulpal horn regions along the wall of the pulp chamber. However, this internal resorption of coronal dentin did not continue until the teeth were finally shed. After the elimination of resorption, the resorbed dentin surface was repaired by a cementum-like deposition or covered with fibrous connective tissue.


Plasma cells in the spleen of the Aleutian skate, Bathyraja aleutica. Splenic white pulp of the Aleutian skate (Bathyraja aleutica), an elasmobranch, was investigated using light and transmission electron microscopy. The major cellular constituent was plasma cells, of the typical Marshalko type, characterized by well developed rough-endoplasmic reticulum and a Golgi complex. The morphology of the rough-endoplasmic reticulum was variable, being lamellar in some cells and spherical in others. Plasma cells with distended cisternae of rough-endoplasmic reticulum and cells with Russel bodies were often observed. Only a small number of lymphocytes were encountered. These findings indicate that the splenic white pulp is the major site for immunoglobulin production in this fish, thus confirming our previous immunocytochemical observation. Globules presumably containing immunoglobulin were found consistently associated with the Golgi complex. The secretion mechanism of immunoglobulin by plasma cells is discussed in connection with the globules.


Fine structure of the dorsal epithelium of the tongue of the Japanese terrapin, Clemmys japonica (Cheloia, Emydinae). As reptiles are situated phylogenetically between the amphibians and the mammals, they exhibit considerable variation in the structure of their tongues. The present study, one of a series of studies on reptile tongues, aims to demonstrate the three-dimensional structure of the dorsal lingual surface of a turtle, the Japanese terrapin Clemmys japonica, and to clarify the ultrastructural features of the lingual epithelial cells. In the study lingual papillae were observed by scanning electron microscopy to be widely distributed over the dorsal surface of the tongue. Irregularly shaped (conical, columnar or angular) papillae were located in the anterior and central areas, and ridge-like ones, in the latero-posterior area. Histological examination revealed that the connective tissue penetrated into the core of the papillae, and the epithelium was of a stratified squamous and/or cuboidal type. Under the transmission electron microscope, two types of cells were identified in the intermediate layer of the apical epithelium of the lingual papilla: one type was probably an immature mucous cell, whereas the other was elongated in a baso-apical direction, its cytoplasm containing fine granules. In the surface layer of the apical epithelium, typical mucous cells and cells containing numerous, fine, electron-lucent granules were recognized. Both types of cells possessed microvilli on their free-surfaces. In the lateral epithelium of the lingual papillae, the cytological features from the basal layer to the superficial intermediate layer were essentially the same as in the apical epithelium. However, in the surface layer, mucous cells were significantly larger in number than in the apical epithelium.


Reticular endings of Purkinje cell axons in the rat cerebellar nuclei: scanning electron microscopic observation of the pericellular plexus of Cajal. The pericellular plexus of Purkinje cell axons in the cerebellar nuclei was first recorded by Cajal (1911), using the Golgi method. The present study observed the axonal plexus in the rat by scanning electron microscopy after the plexus' detachment from the soma of target neurons by NaOH maceration. The pericellular plexus revealed numerous axons with ellipsoidal and moniliform swellings. They branched and crossed with each other to form, as a whole, a reticulum which enveloped the target neuron instead of multiple isolated boutons. Some axon terminals were separated from each other by thin glial processes, while others lacked such septa, thus being directly juxtaposed. Immunohistochemistry for spot 35 protein, a Purkinje cell-specific protein, detected similar beaded and reticular axons terminating on the neuronal somata, confirming their identification as Purkinje cells. Transmission electron microscopic observation showed that most of the axon terminals in question contained elliptical vesicles, characteristic for Purkinje cells. The vesicles were not accumulated toward small patchy areas of synaptic specialization but disseminated along the entire length of the terminal portion of axons.


Microstructures of the osseous spiral laminae in the bat cochlea: a scanning electron microscopic study. The architecture and surface structures of the primary and secondary osseous spiral laminae in the cochlea of the bat, an animal able to hear high frequency sounds, were examined by scanning electron microscopy to understand the micromechanical adaptations of the bony supportive elements in the inner ear to the specific hearing function. The bat used was Myotis frater kaguyae. The myotis bat cochlea was seen to consist of a hook and a spiral portion with one and three-quarter turns and was characterized by: 1) a distinct ridge-like projection running spirally along the middle line on the vestibular leaf of the primary osseous spiral lamina; 2) a wide secondary osseous spiral lamina; and 3) a narrow spiral fissure between the primary and secondary osseous spiral laminae. The ridge on the primary osseous spiral lamina was 150 microns high in the hook and basal turn, then lowered toward apex, and flattened before the apical end. The surface structures appeared to provide a firm anchorage of the auditory teeth. The secondary osseous spiral lamina, which anchors the fibers of the basilar membrane, was sharply projected and measured 150 microns in width in the hook, and then narrowed gradually toward apex to disappear in the helicotrema. The spiral fissure for the basilar membrane was about 40 microns in width in the hook and about 120 microns in the apical turn. The findings suggest the presence of a narrow and rigid basilar membrane with a high amount of fibers and a strong bony support to the auditory teeth for scaffolding the tectorial membrane during intense vibration in response to high frequency sounds.(ABSTRACT TRUNCATED AT 250 WORDS)


4-hydroxyandrostenedione: a new treatment for postmenopausal patients with breast cancer. We have evaluated 4-hydroxyandrostenedione, a specific inhibitor of aromatase, as treatment for breast cancer in a phase I dose-ranging study and a phase II study of the best-tolerated dose. 168 postmenopausal patients with locally advanced and metastatic breast cancer were treated intramuscularly. 19% of patients attained a complete or partial response but 26% of those who completed at least 4 weeks treatment responded. Side-effects were least in the group receiving 250 mg every 2 weeks. 13% of patients experienced local discomfort due to the injection and 5% had other side-effects. Serum oestradiol fell to 42.4 and 26.5% of baseline at 7 days after the start of treatment with the 250 mg and 500 mg dose, respectively. We conclude that 4-hydroxyandrostenedione at 250 mg every 2 weeks is a safe and effective form of treatment for postmenopausal patients with metastatic breast cancer.


Variations in breast cancer management between a teaching and a non-teaching district. We compared the management and outcome of 999 women with breast cancer presenting between 1982 and 1986 at two centres in a region, one in a teaching district. A comparison was also made with relevant research and The Kings Fund Consensus Statement. The centres frequently differed markedly in the investigations done, diagnostic procedures, histology reporting, axillary sampling, and in the treatment given, also differing from the Consensus with no trend towards it. Survival was better at the teaching centre, both disease-free (N.S.) and overall [odds ratio 1.46 (1.16-1.84) P = 0.0009 unadjusted]. This should be interpreted cautiously as the median follow-up time was relatively short and the study was non-randomised. We conclude that how women with breast cancer are managed is determined as much by where they are referred as by scientific evidence. This indicates the need to introduce standards and protocols into business plans, making audit and service specifications easier.


Serum vanillylmandelic acid/homovanillic acid contributes to prognosis estimation in patients with localised but not with metastatic neuroblastoma. In 211 patients with neuroblastoma, serum vanillylmandelic acid (VMA) and homovanillic acid (HVA) levels were determined and correlated to stage, histological differentiation, ferritin, neuron-specific enolase, lactate dehydrogenase (LDH) and outcome. Elevated serum VMA and/or HVA levels were found 16% less frequently than elevated urine levels. The incidence of the elevated serum levels increased with stage (stages I-III 58%, IV 78%, IVS 100%). Increased VMA/HVA ratios were not associated with a higher grade of tumour differentiation. Serum ferritin and neuron-specific enolase showed no correlation, and LDH a borderline non-random correlation with the serum catecholamine metabolites. Using age-related reference values a quotient of serum VMA/HVA (P = 0.061) < 0.7 indicated a poorer event-free survival (48 +/- 10%) than ratios > or = 0.7 (event-free survival 81 +/- 6%) for children with localised neuroblastoma (P = 0.0004). No correlation with prognosis was detected for patients with stage IV and stage IVS disease. We conclude that serum VMA and HVA determinations may be useful as tumour markers for 71% of neuroblastoma patients, and aid in estimating the prognosis in children with localised disease.


Treatment of poor prognosis Burkitt's lymphoma in adults with the Société Française d'Oncologie Pédiatrique LMB Protocol--a study of the Federation Nationale des Centres de Lutte Contre le Cancer (FNLCC). 14 adult patients between 16 and 50 years old with small non-cleaved cell lymphoma (Burkitt's lymphoma) were prospectively treated from 1982 to 1990 with the LMB protocols of the Société Française d'Oncologie Pédiatrique (SFOP). No HIV-positive patients were included. All patients had extensive disease with bad prognosis factors, i.e. 10 patients had Murphy stage III and 4 had stage IV with bone marrow involvement. The LMB protocols were characterised by high-dose fractionated cyclophosphamide, high-dose methotrexate (HD-MTX), and cytosine arabinoside. No local or central nervous system irradiation was used. Treatment duration ranged from 5 (LMB 84) to 12 (LMB 81) months. There were no therapy-related deaths. All patients achieved complete remission (CR). 6 patients relapsed between 2 and 30 months following CR. 8 of the 14 patients (57%) are still alive and disease-free after treatment by LMB protocol alone. 2 patients were salvaged with bone marrow transplantation after relapse and a total of 10 out of 14 patients (71%) are disease-free at the time of this report. Our results showed the high curability of advanced Burkitt's lymphoma using a paediatric protocol, even in adult patients. The LMB protocol may be applied to adult patients but requires intensive care during the induction period.


Phase II study of tauromustine in malignant glioma. 46 eligible patients with either anaplastic astrocytoma (AA) or glioblastoma (GBM) and clinical and computed-tomography-confirmed relapse following primary surgery and radiotherapy received oral tauromustine 130 mg/m2 every 5 weeks. A prospective design allowed for concurrent assessment of both clinical and radiological responses and drug toxicity. 41% of patients improved clinically whilst 46% improved radiologically with 3 complete, 7 partial and 7 minimal responses (WHO criteria). Toxicity included grade III or IV gastrointestinal side-effects (15%), grade III or IV leukopenia (24%) and grade III and IV thrombocytopenia (44%). In 9 clinically responding patients, haematological toxicity led to discontinuation of treatment. All patients were followed-up until death and second-line chemotherapy was not used. Median post-treatment survival was 26 weeks for patients with GBM and 57 weeks for patients with AA. Overall 2-year survival rate was 69% for AA and 23% for GBM. Tauromustine given at the time of relapse has demonstrable antitumour activity in patients not previously treated with chemotherapy.


Mitozantrone and methotrexate chemotherapy with and without mitomycin C in the treatment of advanced breast cancer: a randomised clinical trial. Patients with advanced breast cancer were randomised to 3M (mitozantrone 6.5 mg/m2q 21 days, methotrexate 30 mg/m2q 21 days, mitomycin C 6.5 mg/m2q 42 days) or 2M (as 3M but without mitomycin C). The objective response rates of 30% in 51 evaluable patients receiving 3M and 26% of 54 patients receiving 2M were not significantly different. 4/16 patients not responding to 2M responded to 3M on crossover. Both regimes were well tolerated but there was significantly less haematological toxicity and fewer dose reductions and delays with 2M. We conclude that patients should initially be treated with 2M and that non-responding patients should be crossed to 3M.


A phase II study of 5-fluorouracil and high-dose folinic acid in combination with cyclophosphamide and mitoxantrone for advanced breast cancer. 38 patients with advanced breast adenocarcinoma were treated in a phase II study with 5-fluorouracil and high-dose folinic acid combined with cyclophosphamide and mitoxantrone. 6 patients had received prior chemotherapy for advanced disease, all with an anthracycline-containing regimen. Treatment was generally well tolerated. The most common side-effect was myelosuppression, with 1 toxic death due to leukopenia-related sepsis. 1 patient developed severe congestive heart failure 12 months from the end of therapy. 36 patients were evaluable for response. The overall response rate was 55%. Median duration of response was 8 months and median survival time was 16 months. This regimen warrants further investigations.


Borderline malignancy of the ovary and controlled hyperstimulation, a report of 2 cases. We report 2 patients who developed a borderline malignancy of the ovary after treatment with follicular stimulants in the context of an in vitro fertilisation (IVF) programme. In both cases, conservative surgery for the borderline malignancy was sufficient treatment. Ultimately, both patients became pregnant, 1 after IVF treatment and 1 without treatment, and both delivered healthy babies. In addition to the presentation of both cases, the literature concerning the possible risks of treating patients with high dosage, exogenously administered hormones is reviewed and the possible association between exogenous hormones and the risk of developing ovarian cancer is discussed.


Unexpected prolonged myelosuppression after mitomycin, mitoxantrone and methotrexate. 28 patients (26 with breast cancer and 2 with colon cancer) received mitomycin, mitoxantrone and methotrexate (MMM). Half the patients had grade III-IV leukopenia and 29% had grade III-IV thrombocytopenia. The median time of recovery to WHO grade 0 was 62 and 128 days, respectively. Thrombocytopenia and leukopenia were more frequent and longer lasting after the three-drug part of the therapy, which suggests a critical role for mitomycin in this toxicity.


Uroepithelial and nephrotubular toxicity in patients receiving ifosfamide/mesna: measurement of urinary N-acetyl-beta-D-glucosaminidase and beta-2-microglobulin. The effect of three ifosfamide/mesna regimens on urinary N-acetyl-beta-D-glucosaminidase (NAG) activity and beta-2-microglobulin (beta 2 M) was studied. All regimens produced significant increases in these urinary proteins, indicating nephrotubular damage. In regimen A (n = 15), plasma nitrobenzylpyridine (NBP) alkylating activity area under the curve (AUC) on day 1 correlated with the percentage increase above baseline of maximum urinary NAG activity (r2 = 0.538, P = 0.0022) and maximum beta 2 M concentration (r2 = 0.413, P = 0.0097). In regimen B (n = 5), plasma NBP alkylating activity AUC correlated with the percentage increase above baseline of maximum NAG activity (r2 = 0.843, P = 0.03) and beta 2 M (r2 = 0.78, P = 0.046). In these two regimens the renal exposure to ifosfamide metabolites correlated with the increases in urinary NAG and beta 2 M. The relation of these urinary protein abnormalities to longer term effects on renal function with different ifosfamide/mesna schedules requires further study.


Tumour burden as the main indicator of prognosis in Hodgkin's disease. A method of estimating the total tumour burden in patients with Hodgkin's disease was devised, combining the number of involved regions with the tumour size in each region. Further, a method of estimating the total tumour cell burden was devised, combining the estimate of the total macroscopic tumour burden with an estimate of the concentration of tumour cells in the tumour tissue. The prognostic significance of the total tumour burden was examined in multivariate studies of 300 patients in pathological stages I and II treated in the Danish National Hodgkin Study and 506 patients in all stages treated at the Finsen Institute, Copenhagen, Denmark, during a 15-year period. The total tumour burden turned out to be the most important prognostic factor in Hodgkin's disease. Most of the hitherto known prognostic factors were shown to be correlated with the total tumour burden and to lack independent prognostic significance.


Evaluation of a breast cancer screening programme--the DOM project. In several studies it has been shown that breast cancer screening by means of mammography reduces breast cancer mortality. To ensure that when organising a service screening programme the aim is reached, it is necessary to control and monitor the process. This is possible by several methods. In this study, disease-free intervals and survival rates were used as monitoring tools. The DOM project, a breast cancer screening programme for women aged 50-64 years old at intake, started at the end of 1974. All breast cancer cases diagnosed between 1973 and 1989 were followed up to 1991. It is clear that disease-free interval and survival rates are proper predictors of the effects of screening on breast cancer mortality.


Constitutive tissue factor expression of human breast cancer cell line MCF-7 is modulated by growth factors. Expression of tissue factor, the initiator of the extrinsic coagulation protease cascade, is a feature of certain malignant tumours. To study the modulation of tissue factor expression we incubated the breast cancer cell line MCF-7 with several growth factors. Epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha) and interleukin-1 (IL-1) rapidly increased tissue factor expression of MCF-7 cells peaking at 6-8 h after starting point of incubation, as determined by clotting test, enzyme linked immunosorbent assay and flow cytometry. The data presented support the hypothesis that modulation of constitutive tissue factor expression in tumour cells by TGF alpha and IL-1 could also occur in vivo possibly resulting from interactions of stromal and cancer cells. The meaning for tumour biology, however, remains unclear.


Modulation of tumour marker CA-125 expression in cultured ovarian carcinoma cells. The aim of this study was to elucidate whether proliferation of ovarian carcinoma cells may affect the biosynthesis and release of CA-125. In a cell culture model the tumour marker CA-125 expression in cytosol, surface membrane, and release into culture medium was studied in six human carcinoma cell lines. Cell cycle analysis of propidium iodide stained nuclei was performed using a fluorescent activated cell sorter. The turnover of CA-125 is very rapid, within 24 h the equivalent amount found in each cell was also released in the supernatant culture medium. A good relation between cytosolic, membrane, and released CA-125 was observed. CA-125 expression was associated predominantly with the G0/G1 phase of the cell cycle and was dependent on cell density. The results presented here demonstrate that factors associated with tumour cell proliferation could influence the CA-125 serum level in ovarian cancer patients.


Biological characterisation of primary and metachronous lesions in breast cancer patients. Proliferative activity, evaluated as [3H]thymidine labelling index ([3H]dT LI), and hormone receptors were determined on 97 primary breast cancers and on metachronous lesions from the same patient. Overall, the [3H]dT LI of metachronous lesions was significantly higher than that of the primary tumour (P = 0.003). Hormone receptor profiles of the two lesions were similar in about 75% of the cases; disagreements were mainly due to a disappearance of hormone receptors in metachronous lesions. In contralateral tumours, [3H]dT LI and hormone receptors were unrelated to those of the relative primary lesion. In this series of relapsing patients, [3H]dT LI was unrelated to hormone receptor status in the primary tumour, but it was higher in the metachronous lesions from patients with hormone receptor-negative primary tumours. For patients given no systemic therapy between surgery and relapse, the time to develop local-regional recurrences or contralateral tumours was inversely related to the [3H]dT LI of the metachronous lesions.


The effect of a low-fat diet on hormone levels in healthy pre- and postmenopausal women: relevance for breast cancer. It has been postulated that differences in the levels of circulating hormones may be the explanation for the epidemiological link between per capita dietary fat intake and the incidence of breast cancer. We have investigated this possible relationship in 19 postmenopausal, and 18 premenopausal women who completed a 4-week period on a diet aiming to reduce fat intake to around 20% of total kilocalories. 7-day dietary records revealed a significant decrease in dietary fat intake in both the pre- and postmenopausal groups (from 37.2% of calories from fat to 23.2% and from 37.9 to 24.3%, respectively). There was a minor increase in the level of sex hormone-binding globulin, and a small decrease in prolactin in the postmenopausal group, which were of borderline significance. There were no significant changes in total oestradiol (E2), or non-protein-bound (free) E2 concentrations. In the premenopausal group there were no significant changes in any of the hormone levels investigated.


Patterns of childhood cancer incidence and mortality in Europe. Histograms including age-standardised (0-14 years, world standard) incidence and mortality rates from selected childhood cancers are presented for 21 European cancer registration areas and 24 countries. The overall range of variation in all childhood cancer incidence rates across various cancer registration areas in Europe was around a factor 1.5, with highest rates in Spain, Italy, Sweden and France, and lowest rates in Poland, Hungary, UK, Germany and Yugoslavia. For most single cancer sites, however, the observed pattern is essentially attributable to random variation alone. A clearer pattern, however, emerged with reference to mortality. The overall range of variation, in fact, was around a factor two in both sexes, with highest rates in Bulgaria, Portugal, Hungary, Czechoslovakia and Poland, and the lowest rates in Austria, UK, Germany, The Netherlands and Finland. Trends in mortality from childhood cancers between 1950 and 1989 were also presented. Recent declines were observed for total childhood cancer mortality, leukaemias, kidney cancer (Wilms' tumours), Hodgkin's disease and other lymphomas in most European countries. These declines, however, were generally earlier and larger in northern as compared with southern and, mostly, with eastern European countries. This pattern of trends likely reflects the different adoption and impact of newer efficacious therapies of childhood cancer, and hence, confirms that there is ample scope for further reduction in childhood cancer mortality in several eastern and some southern European countries.


Risk factors for kidney cancer in New South Wales--I. Cigarette smoking. In a population-based case-control study of kidney cancer in New South Wales, data from structured interviews with 489 cases of renal cell cancer (RCC), 147 cases of renal pelvic cancer (CaRP) diagnosed in 1989 and 1990, and 523 controls from the electoral rolls confirmed an increased risk associated with cigarette smoking in both types of cancer. The risk among current smokers was consistently higher than among ex-smokers, and was nearly twice as great for CaRP than for RCC. Additional information provided by this study includes reduced risks following cessation of smoking within 12 years for CaRP, but only after 25 years for RCC. Starting to smoke before, rather than after, the age of 18 years is linked independently with almost twice the risk for CaRP, but does not affect the risk for RCC. No independent trend was found with number of cigarettes smoked per day.


Graft vs. leukaemia reactions in chronic myeloid leukaemia. A 39-year-old female relapsed 36 months after allogeneic bone marrow transplantation for chronic myeloid leukaemia. Infusion of peripheral blood leucocytes from her bone marrow donor resulted in complete remission, and she remains leukaemia-free 18 months later. This case provides direct evidence for a 'graft vs. leukaemia' (GVL) effect contributing to the eradication of leukaemia after marrow transplantation. Existing evidence for GVL and its possible mechanisms are reviewed.


[Primary gastric lymphomas].

[Primary gastric lymphomas]. A series of 13 patients with primary gastric lymphoma treated between 1981 and 1990 are presented. Primary gastric lymphoma made up 4.8% of all gastric tumors treated during this period of time. Histologically, there were 3 lymphoplasmocytoid and 3 centroblastic forms (according to Kiel's classification) followed by 2 lymphocytic and 2 centrocytic-centroblastic. According to Mushoff's classification. 4 patients belonged to stage I E, 3 to II E1, 3 to II E2, 2 to III E, and one patient to stage IV E. In all cases gastrectomy was performed (9 subtotal and 4 total) although 3 out the former were palliative (23%). The operative morbidity was 30.7% and the mortality 7.7%. Seven patients received additional treatment with chemotherapy. Survival after 2 years was 70%.


[The recurrence of colorectal cancer and blood transfusion]. Report of a retrospective study on 303 patients operated from colorectal carcinoma to whom colonic resection was done in B and C stages of Astler-Coller's classification. The aim was to try to find a relation between blood transfusion and colorectal carcinoma recurrence. The statistical study is made with the program LOGIT, studying the surgical incision, evolutive stage and blood transfusion variables. The significant contribution of each variable in the occurrence of recurrence is studied with the Wald Test. As a result it can be deduced that the prognosis of colorectal cancer is influenced by three factors: the evolutive stage, the surgical incision (1.87 times more frequent for the abdomino-perineal) and the transfusion of more of three units of blood in the perioperative period which multiplies by 2.85 the risk of recurrence of colorectal carcinoma. In our hospital almost exclusively red cell concentrates (including red cells, white cells and minimal fraction of plasma), are transfused; possibly the white cells are responsible for the recurrence.


[The prognosis of colorectal cancer with synchronous liver metastases]. Between January 1985 and December 1989, 583 patients with carcinoma of the colon and rectum have been studied. In 85 with synchronous liver metastases discovered at laparotomy and followed-up, median survival time has been 5.8 months and 1 and 3 year survival 23 and 6 percent respectively. Favorable factors for survival were rectosigmoid location, single metastasis in the right hepatic lobe, normal values of alkaline phosphatase, resection of the tumor as well as stage II of Duke's classification.


[A biliary fistula after T-tube removal in the transplant patient: its diagnosis by Tc-99m-HIDA]. The Tc-99m HIDA scan is a valuable study after liver transplantation, associated with other image techniques. We have used this technique as a reliable and objective diagnostic method for biliary fistula after removal of the T-tube in 5 liver transplantation patients with pain after T-tube removal. All five patients who developed fistula not only were diagnosed immediately but, furthermore, the surgical technique was indicated by the gammagraphic study. After this experience, we propose to remove the T-tube during the Tc-99 HIDA scan.


[Primary gallbladder carcinoma. A review of 41 cases]. We present a retrospective study of primary carcinoma of the gallbladder with a total of 41 cases over a period of 11 years. In the majority of cases the clinical presentation (cholelithiasis, choledocholithiasis); there were only 7 cases of suspected diagnosis, mainly through the use of new diagnostic techniques (echography, computerized tomography). The classification used is that described by Nevin (1976) of affection of gallbladder wall and adjacent tissues. The conclusions of our study are as follows: a) primary neoplasias of the gallbladder are aggressive tumours carrying a poor prognosis aggravated usually late diagnosis due to the scarce symptomatology, b) given the high incidence of cholelithiasis, it is advisable to perform routine cholecystectomy, c) survival is related to the histological grading of the tissues.


[Esophageal involvement in Behçet's disease]. We report the case of a female patient that fulfills major criteria of Behcet's disease. Multiple esophageal aphthous ulcers seen by endoscopy responded to therapy with steroids and colchicine.


[A primary gastric Burkitt's lymphoma in a child]. We report a case of a primary gastric Burkitt's lymphoma in a 8-year-old child, which first symptoms were abdominal pain, dysphagia, melena and a constitutional syndrome. The differential characteristics of this case are its peculiar gastric infiltration and the existence of oesophageal extension, which is very infrequent among this kind of tumors.


[An inflammatory fibroid polyp (eosinophilic granuloma) and Crohn's disease located in the ileum]. Lower gastrointestinal tract bleeding as a manner of presentation of the Crohn's disease is uncommon. In most cases there is an other concomitant pathology responsible for that bleeding. We report a case of lower gastrointestinal tract bleeding to an inflammatory fibroid bowel polyp in a patient with ileal Crohn's disease. A commentary is made about the etiopathogenic factors of the both diseases.


[Hepatic fascioliasis. Resistance to praziquantel treatment and the radiological findings]. We report a case of hepatic fascioliasis. Fever and epigastric pain was the clinical presentation. We describe the features of the ultrasound and computed tomography examination. Symptoms were persistent after praziquantel treatment. Bithionol was effective and cured the patient.


[Cholecystectomy via laparoscopy: one and a half year's experience]. Results of the first 175 laparoscopic cholecystectomies performed at our hospital over the last 18 months were reviewed. In 17 (9.7%) of cases, due to operatory complications, and in some cases due to instrumental deficiencies, we were obliged to perform conventional laparotomy. In 8 patients, we performed simultaneous alternative surgery during laparoscopy. Our results were satisfactory, with no important complications, no re-operations and only 6.2% of minor complications. Hospital stay was low (2.5 days), and after 10 days patients returned to normal life.


[100 cases of laparoscopic cholecystectomy]. The first one-hundred cases of laparoscopic cholecystectomy performed in this department are reviewed. The patients are grouped according to the classification of McSherry: type I: 5%; type II: 50%; type III; 27%; and type IV: 18%. Our technique, which is similar to the one of Troidl, except for entry of the number 4 port, is described. The results are analyzed according the classification of Troidl and 83% of the cases had no complications. There were technical incidents which had no repercussion for the patient in 7% of the cases. In 3% of the patients there were minor complications. There was no mortality.


[Pancreatic function and morphology in chronic alcoholism with and without cirrhosis]. We have made a prospective study in alcoholic patients, with and without hepatic cirrhosis, in order to evaluate the presence of modifications in the composition of pancreatic juice (JPP) and in the pancreatogram that allows us to diagnose the existence of chronic pancreatitis associated with alcoholic cirrhosis (CE). The patients where 23 chronic alcoholics, 13 of them with CE and the other 10 with no hepatic injury (AC). In all, an endoscopic retrograde cholangiopancreatography (CPRE) was made and after having obtained a pancreatogram a intravenous infusion of secretin and cholecystokinin was performed. The total volume, the concentrations and the out-puts of bicarbonate, amylase, lipase and total proteins were measured in the pancreatic juice collected during 12 minutes. The pancreatogram was normal in the 92.3% of CE and in all the AC. Patients with CE had similar values of all the evaluated parameters to AC patients. In conclusion, there seems to be a good correlation between the pancreatogram and the analytic study of JPP, because the JPP has no qualitative and quantitative anomalies when the Wirsung duct is normal. In our opinion the study of JPP is not useful in the diagnostic of chronic pancreatitis associated with alcoholic hepatic cirrhosis.


[The prediction of the severity of acute pancreatitis by C-reactive protein]. Reactive C Protein (RCP) has been determined in fifty-one patients with acute pancreatitis. RCP has been compared with Ranson's criteria which include several clinical and biochemical parameters. The value of 20 mg/dl is the one which discriminates serious acute pancreatitis from the mild forms in a 84.3% of patients. Sensitivity and specificity of RCP and Ranson's criteria are compared, the results obtained are similar (88.9% vs. 81.8% and 94.4% vs. 97%). In summary, the determination of RCP is very useful for its simplicity and accuracy in the prognosis of acute pancreatitis.


[The diagnosis of peptic ulcer penetration into the liver by endoscopic biopsy. A report of 2 cases and a review of the literature]. We report two patients and review six additional published cases with liver penetrating peptic ulcer diagnosed by the finding of hepatic tissue in endoscopic biopsies. Clinical and laboratory data were non-specific. The presence of a large (2 cm) gastric or duodenal ulcer, with malignant appearance, or a protruding mass, with secondary ulceration and located in the gastroduodenal posterior wall or in the lesser curvature of the stomach, may suggest the endoscopic diagnosis of this complication. Definitive diagnosis is established by endoscopic biopsies of the ulcer base and/or of the associated mass.


[Biliary ascaridiasis].

[Biliary ascaridiasis]. A case of biliary ascaridiasis is presented in which biliary obstruction and pancreatitis were diagnosed. Recovery followed surgical removal of the worms. The literature is reviewed.


[The focal brain ischemia with disturbance of venous drainage]. The focal brain ischemia with disturbance of cerebral venous drainage often lead to brain edema and hemorrhagic infarction and make mortality and morbidity worse. So we tried to make sure of this fact using a middle cerebral artery (MCA) occlusion model in adult cat. The MCA was exposed by the transorbital approach and temporally obstructed by Zen's clip. We divided the animals into two groups of eight cats. One group is only MCA occlusion group (sham group) and the other in MCA occlusion with disturbance of venous drainage (VRD group). We ligated bilateral external jugular vein (EJV) and internal jugular vein (IJV) and injected embolic sources from the left EJV to obstruct the venous system of cat brain. The pressure of superior sagittal sinus was increased up to 18.7 +/- 5.3 mmHg by this method. A cranial window was made above the ectosylvian gyrus, which has poor anastomosis. The reactivity of pial arteriole and regional cerebral blood flow (rCBF) were observed through the window. And histological brain examination was also performed. The result was that the reactivity of pial arterioles was severely disturbed in VRD group. The area of cerebral infarction and edema were also significantly expanded in VRD group. Considering from these facts, when the venous drainage was disturbed, cerebral perfusion pressure relatively decrease. Because of the decrease in cerebral perfusion pressure, cerebral infarction and edema probably expand to the area so called penumbra.


[Hyponatremia and cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage]. We studied retrospectively the relationship between hyponatremia and cerebral vasospasm in 121 consecutive patients with aneurysmal subarachnoid hemorrhage. In 19 patients sodium levels fell below 130 mEq/l on at least two consecutive days. Hyponatremia developed at average 8.9 hospital day and lasted for 4.4 days. It was mild (126 to 130 mEq/l) in 15 patients, moderate (121 to 125 mEq/l) in 3 patients, and severe (116 to 120 mEq/l) in 1 patient. Cerebral vasospasm was evaluated by angiography, symptoms and CT finding. Angiographical vasospasm was found in 57 patients, symptomatic vasospasm in 38 patients and low density area on CT in 20 patients. Angiographical vasospasm developed in 15 of the 19 patients (78.9%) with hyponatremia, symptomatic vasospasm in 16 patients (84.2%), low density area on CT in 8 patients (42.1%), the difference being significantly high. (respectively, p < 0.01, p < 0.001 and p < 0.01 by chi-square test) Polyuria of 2500 ml or more immediately before the onset of hyponatremia developed in 14 patients (87.5%). When symptomatic vasospasm and hyponatremia coincided, there were only 4 patients in which symptomatic vasospasm was preceded by hyponatremia. So, it is difficult to predict the development of vasospasm from that of hyponatremia. This study found incidence of cerebral vasospasm after aneurysmal subarachnoid hemorrhage to be significantly higher in patients who developed hyponatremia, which raised suspicion about the presence of dehydration. Hyponatremia with central origin generally remains asymptomatic, but it is important to treat positively when the pathology of cerebral vasospasm is taken into consideration.


[Perinatal neurosurgical care for one fetal hydrocephalus on twin gestation]. Twin gestations are responsible for a disproportionate amount of perinatal mortality and morbidity. Such gestations may impose greater demands on maternal and child physiologic systems than singleton pregnancies. The most common antenatal complications were preterm labor. The clinical record of myelomeningocele infant presenting with overt hydrocephalus in utero at 27 weeks of twin gestation and operated miniature Ommaya's reservoir placement early after birth and intentional delayed back closure for myelomeningocele was reported. Although perinatal neurosurgical care for one fetal hydrocephalus on twin gestation is clearly advantageous, it alone is relatively ineffective in reducing the incidence of the complication, preterm labor.


[Pontine infarction presenting non-paralytic pontine exotropia--evaluation of its clinical course and its MRI findings]. We report two patients with brainstem infarction who presented non-paralytic pontine exotropia (NPPE) in acute phase. Case 1 was a 76-year-old woman. NPPE observed 3 hours after the onset disappeared two days later. Case 2 was a 60-year-old man. Paralytic pontine exotropia was observed 4 hours after the onset of his stroke. NPPE was noted on the next day and left medial longitudinal fasciculus (MLF) syndrome was still present on the third day. Seven days later, the disturbances of ocular movement was disappeared. T2-weighted cranial MRI showed high signal intensity lesions in the paramedian portion of the mid-pontine tegmentum beneath the fourth ventricle in both cases. Although it has been thought that NPPE is a rare clinical symptom, we think that NPPE is by no means a rare symptom in the acute stage of brainstem infarction.


[A case of general paresis with marked improvement of cerebral blood flow after antiluetic therapy--case report]. Although the incidence of neurosyphilis has declined dramatically after the World War II because of the development of antibiotics, it is recently increasing a little bit. There has been few reports on the neuroimaging of general paresis. We studied a fresh case of general paresis by X-ray CT (XCT), MRI and PET scans, and report the changes of neuroimages before and after the therapy. A 38-year-old man was admitted with disorientation, thought disorder and personality change. He also had insomnia and megalomania. There were neither obvious neurological signs nor particular changes of the XCT scan abnormalities on admission. His clinical symptoms were gradually worsened within three months, when the XCT and MRI scans showed moderate brain atrophy especially in the frontal and temporal lobes with mild dilatation of the lateral ventricles. In the PET study, the cerebral blood flow was decreased in the entire brain, especially in the frontal lobes, although the thalamus and the basal ganglia had normal levels. By immunological procedures and the cerebrospinal fluid (CSF) studies, the diagnosis of general paresis was made. He was treated with penicillin G and other antibiotics. In one year after his first therapy, many symptoms vanished. Although the cerebral atrophy was a little advanced, the cerebral blood flow was dramatically increased. As far as we know, this is the first PET study of general paresis before and after penicillin treatments.


[A case of encephalitis with MRI abnormalities localized in the bilateral amygdala and hippocampus]. We report a patient with encephalitis who showed anterograde and retrograde amnesia with MRI abnormalities localized in the bilateral amygdala (AM) and hippocampus (HIPP). A 25-year-old man suddenly experienced a generalized tonic-clonic seizure (GTCS). He was admitted because of increasing lethargy with two further GTCSs during the following 6 days. The patient had high fever, and neurological examination revealed somnolence, disorientation, amnesia, and nuchal stiffness. MRI revealed bilateral symmetrical abnormalities localized in the AM and HIPP, which showed low intensity on T1-weighted images and high intensity on T2-weighted images. Cerebrospinal fluid examination showed a mildly elevated cell count. We suspected herpes simplex virus type I encephalitis and began treatment with acyclovir. After the patient regained a clear consciousness, his antero- and retrograde amnesia continued for several months. The MRI abnormality became less distinct with the improvement of amnesia. We consider that the MRI abnormality was indicative of inflammation and edema, and that the lesion in the AM and HIPP had induced the amnesia.


[A case of Tolosa-Hunt syndrome accompanied by facial and vestibular nerve damage]. A 37-year old man, who had repeatedly suffered from transient ophthalmoplegia in his left eye at the age of 29 and 36, developed left painful ophthalmoplegia accompanied by ipsilateral facial nerve palsy in August, 1991. Neurological examination revealed involvement of the left oculomotor, trochlear, ophthalmic division of the trigeminal, abducens, facial and vestibular nerves. Gadolinium-enhanced MRI which was taken at the acute phase of the illness demonstrated markedly enhanced left cavernous sinus and adjacent thickened dura mater in the middle cranial fossa. At the remission phase after starting corticosteroid therapy, these enhanced lesions were no longer observed even in enhanced MRI studies. We diagnosed him as suffering from Tolosa-Hunt syndrome presently accompanied by facial and vestibular nerve damage because of his history of illness, confined lesion in the left cavernous sinus and steroid-induced remission. We concluded that Tolosa-Hunt syndrome may be accompanied by damage of other cranial nerves in its course and that repeated gadolinium-enhanced MRIs are necessary for diagnosis and observation of the patients.


["Left unilateral agraphia with right hemiparesis" after occlusion of the left middle cerebral artery]. This paper presented a case of a right-handed male who showed a right hemiplegia without aphasia and apraxia. He lost the ability to write with the left hand. A 56-year-old right-handed man, who had a daughter of left-handedness, was sent to our hospital with a homonymous hemianopsia, facial weakness, spastic hemiparesis and sensory disturbance in the right side. CT scan revealed an infarction in the territory of the left middle cerebral artery. On a month after the onset, he was alert and oriented. His speech was normal and verbal comprehension was intact. Although he neglected the right side of the page, he could read and comprehend it correctly. In contrast with his normal abilities to speak, comprehend, and read, difficulties in writing were prominent. Spontaneous writing with the left hand was extremely poor, and he even had difficulty writing his own name. His dictation was also poor, but his writing improved with copying letters. Agraphia had seen even after USN was recovered. Analysis of this case suggested the presence of the dominance for speech, comprehension, and praxis in the intact right hemisphere, and writing center in the damaged left hemisphere.


[Hallucinose pédonculaire with left MLF syndrome caused by midbrain infarction--a case report]. A 65-year-old male suffering from left MLF syndrome accompanied by transient hallucinose pédonculaire caused by the midbrain infarction is reported. In the first night of his admission with MLF syndrome, he complained of sleeplessness followed by transient visual hallucination. The hallucination was vivid and colored scene in which many strangers were seen around the patient, and he was well oriented without dreadfulness at that time. A small infarction in the left tegmentum was revealed by MR imaging, which was supposed to cause the hallucination.


[Kainic acid-induced generalized seizures in cats--microinjection into caudate nucleus]. Electroencephalographic and behavioral changes were observed after 2 micrograms of kainic acid (KA) injection through a chronically implanted cannula into unilateral caudate nucleus (CN) of freely moving and non-anesthetized cats. The control group showed no changes on EEG or behavior during the observation period. In KA group, from 2 to 5 minutes after KA injection, the cats showed contralateral circling. On EEG, focal spikes were elicited at the injected site of the right CN. From 15 to 25 minutes after the injection, secondarily generalized seizures were observed on EEG repeatedly. However, the behavioral change was not remarkable and only the behavioral arrest was observed during the electrographic generalized seizure. From 6 to 8 hours after injection, they showed clonic seizure of the contralateral hindlimb followed by generalized tonic-clonic convulsion. These seizures were frequent during 6 to 16 hours after injection. However, these seizures subsided within 48 hours after the injection and the cats became normal afterward. Histopathological examination revealed focal pyknosis and gliosis only at the injection site of caudate nucleus. The results suggested that an epileptogenic focus of the caudate nucleus demonstrated a rapid evolution from the focal seizure status to the secondarily generalized seizure status. This fact explains that the caudate nucleus may be a possible key structure as a relay nucleus for the secondary generalization of a focal seizure.


[Epidemiological study of motor neuron disease in Hokkaido island--its incidence, prevalence and regional distributions--ALS Study Group]. The incidence, prevalence and regional distributions of sporadic motor neuron disease (MND) from 1980 through 1989 were evaluated in collaboration with multiple neurological institutes in Hokkaido island. Patients with sporadic MND were collected from three sources: 1) neurologist practicing in Hokkaido island, 2) sending inquiries to 620 major hospitals, 3) notification file of MND provided by Japanese Ministry of Welfare and Health. Three hundred and eighty-nine patients with sporadic MND were ascertained for this study. Of 389 patients, 238 patients were men and 151 patients were women, and the ratio of men to women was 1.6:1. The mean age of onset was 58.2 +/- 10.3 years old, 57.7 +/- 10.4 for men and 58.9 +/- 10.0 for women. Their clinical presentations were 303 patients with ALS, 52 patients were PBP and 34 patients were SPMA. The crude incidence rate for both sexes combined for 1980 through 1989 was estimated as 0.69 per 100,000 person-year. The age- and sex-adjusted incidence for men was 0.86 per 100,000 person-year (95% CI, 0.75 to 0.97) and that is higher than 0.53 per 100,000 person-year (95% CI, 0.45 to 0.61) for women. The average, crude prevalence rate from 1985 through 1989 was estimated as 2.25 per 100,000 person-year. There are no overall trends of changing the pattern in incidence and prevalence of MND in Hokkaido island, however the geographic distributions of the incidence of MND according to towns and cities disclosed the presence of some relative clustering areas.(ABSTRACT TRUNCATED AT 250 WORDS)


[Ruptured aneurysm at the peripheral branch of the posterior cerebral artery with systemic lupus erythematosus]. We report a 73-year-old woman with systemic lupus erythematosus (SLE) in whom intracerebral and intraventricular hemorrhage developed secondary to a ruptured aneurysm on the peripheral branch of the posterior cerebral artery. We reviewed data on 22 patients (43 aneurysms) in previous reports of ruptured cerebral aneurysms associated with SLE, including our case. Of these aneurysms, 34 (79.1%) were located on the major artery, and 9 (20.9%) were located on the peripheral small artery. Fusiform aneurysms accounted for 27.9% of the total. The prognosis was poor, and 14 patients (63.6%) died. Direct aneurysmal surgery was performed in 11 patients (50%), but 4 patients died of other diseases associated with SLE.


[Studies on the erythrocyte membrane skeleton in a patient with chorea-acanthocytosis--theoretical speculation on the mechanism of neurological involvement]. Patients with chorea-acanthocytosis exhibit symptoms of self-biting, choreic movement, and acanthocytosis, but not dementia. The mechanism of choreic movements is still unknown. In order to clarify the etiologic mechanism underlying these movements, we evaluated the erythrocyte membrane in one patient with chorea-acanthocytosis. A 35-year-old female was admitted to Saitama Medical School Hospital because of involuntary movements. She was alert, well-oriented, and had no gross memory defects. She had slurred speech, choreic movements and lip biting. Laboratory examination showed acanthocytes in her peripheral red blood cells, normal serum lipid values, and caudate atrophy on her brain CT scan. In analyzing the acanthocytes, we initially evaluated the size of the acanthocyte population by incubating her red blood cells with plasma. The cell population approximately doubled after 2 hours incubation. Next we examined the protein composition of erythrocyte ghost by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). There was no significant difference between the patient's erythrocyte ghosts and those of a control. Then we investigated morphological changes in the patient's erythrocyte by scanning and transmission electron microscopy (SEM and TEM). SEM showed the typical acanthocyte shape. The quick-freeze, freeze-substitution method confirmed that the routine TEM section was not artifactual, and was in fact in accurate reflection of the actual features of acanthocytes. TEM of the sections prepared from erythrocyte ghosts demonstrated that spectrin tended to be accumulated in the thorn region. Furthermore, TEM of quick-freeze, deep-etched replica of the ghost revealed more clearly a spectrin network densely packed on the inner hydrophilic surface.(ABSTRACT TRUNCATED AT 250 WORDS)


[Immunohistochemical and clinicoendocrinological studies of gonadotropin producing pituitary adenomas]. In order to study the secretion of gonadotropins in clinically non-functioning pituitary adenomas, 83 cases were investigated by immunohistochemistry. Expression of one or more of gonadotropin subunits (alpha-subunit, follicle-stimulating hormone (FSH) beta, luteinizing hormone (LH) beta) was found in 38 (45.8%) of all adenomas studied. alpha subunit and FSH beta were positive in 28 (33.7%) and 27 (32.5%) cases respectively, whereas LH beta was detected in seven (8.4%) adenomas. The presence of both alpha subunit and FSH beta was found in 17 cases, while alpha subunit was singly positive in 11 cases and FSH beta, in 10 cases. LH beta was not detected alone, but was always accompanied by alpha subunit or FSH beta. By the double staining method, alpha subunit and FSH beta were not always colocalized in the same cells. Some cells were found to contain both alpha subunit and FSH beta, but others contained either alpha subunit or FSH beta. Clinical characteristics of gonadotropin positive adenomas (38 cases) were studied in comparison with null cell adenomas (37 cases), which were negative for all anterior pituitary hormones. The former (male 27, female 11) ranged in age from 21-74 years old (mean, 46.5 yr.), and the latter (male 16, female 21) from 28-68 yr (mean, 49.5 yr.). Gonadotropin positive adenomas tended to occur in middle-aged men. All 38 adenomas were macroadenomas, and 29 patients complained of visual failure. Clinical symptoms accompanied by hypersecretion of FSH was infrequent. Hypogonadism (amenorrhea, galactorrhea, loss of libido) were observed in 8 (9.6%) cases.(ABSTRACT TRUNCATED AT 250 WORDS)


Pressure ulcers, Part two: Management strategies. The goal of this article is to facilitate the successful resolution of pressure ulcers. The nurse practitioner (NP) is an ideal health care professional to manage pressure ulcer care. This article reviews the basic principles related to wound care. The healing trajectory is discussed to assist an NP to determine appropriate therapy. Current, research-based management strategies are provided.


Stress and tobacco addiction.

Stress and tobacco addiction. Primary care providers are confronted on a daily basis with persons who are addicted to tobacco. Research studies have demonstrated an association between substance use and stress and coping. This paper discusses macro- and micro-level perspectives of stress that need to be considered in the management of tobacco addition. Lazarus's stress and coping paradigm is emphasized as a useful framework for managing addicted clients.


The role of the nurse practitioner in adult day care. During the past 25 years, nurse practitioners (NPs) have become health care providers in a variety of settings. Adult day care is one of the settings in which it is increasingly clear that there is a role for the NP. Nurse practitioners have the potential to provide increased comprehensive primary health care to clients participating in these programs.


A new look at pharmacologic therapy for adult asthma. Antiinflammatory agents in conjunction with beta agonists in the form of inhaler cromolyn or steroids are currently the cornerstone of therapy for recurrent asthma after the patient has failed on beta agonists alone. Early treatment with antiinflammatory agents is strongly recommended, and may prevent irreversible airflow obstruction caused by chronic inflammation, reducing the mortality from this illness.


The number of fibroblastic colonies formed from bone marrow is decreased and the in vitro proliferation rate of trabecular bone cells increased in aged rats. Four- and 21-month old female Sprague-Dawley rats were sacrificed and their tibiae and femurs isolated for histology and initiation of bone marrow and trabecular bone cultures. The bone loss observed in 21-month old rats was associated with a markedly decreased osteoblastic index. The percentages of mineralizing trabecular surfaces were only slightly decreased in aged rats, whereas the percentages of mineralizing endocortical surfaces were strikingly decreased. Diaphyseal femoral marrows from 21-month old rats were less cellular than those from four-month old rats, and developed in culture fewer fibroblast colony forming units (FCFU) and fewer adherent cells with phenotypic characteristics of osteoblast-like cells. Trabecular bone cultures from 21-month old rats produced as many cells as cultures from four-month old rats, whereas the amount of trabeculae put into culture was much less in aged rats. Moreover, the proliferation rate in secondary culture was significantly increased in 21-month old rats. Similar responses to calcitriol were observed in bone marrow and trabecular bone cells from aged and younger mature rats, while cAMP responses to PTH were decreased in cells from aged rats. Our data confirm the age-related decrease in the FCFU efficiency of the bone marrow and show a stimulated proliferation of trabecular bone cultures from 21-month old rats that could be seen either as the result of the inhibition in vivo of the response to a signal to proliferate, or as a rebound response to factors present in the serum-enriched medium and lacking in vivo.


Provision of health care in a frontier setting: an Alaskan perspective. The Community Health Aide Program is the Indian Health Service's answer to to the provision of care to 45,000 Alaska Native people living in remote areas of the state. Community health aides are local people who live and work in their villages. They offer health services from emergency to preventative care with the help of their referral physician, who may be up to 1,300 miles away. Nurse practitioners play an important role in the training and supervision of community health aides. This article gives an overview of the program, its successes and problems, with implications as a health care delivery model for care in other underserved areas of the United States.


The health beliefs and practices of an Old Order Amish family. In caring for people from different cultures, it is important that nurses acknowledge the health beliefs and practices of clients. The purpose of this case study was to describe the health beliefs and practices of one Old Order Amish family. The study was conducted by interviewing a Lancaster County, Pennsylvania, Old Order Amish family. The data focused on five areas of inquiry: (a) care of elderly family members, (b) health practices, (c) home births, (d) death, and (e) health insurance. This study revealed that the Old Order Amish have health beliefs and practices that are unique to their culture.


A quantitative evaluation of osteoblast-osteocyte relationships on growing endosteal surface of rabbit tibiae. Scanning electron microscopy (SEM) was used to quantify the intercellular relationships between osteoblasts and osteocytes on the growing endosteal surfaces of the medullary canal of the tibia in four rabbits of different ages. The area of each osteoblast was measured on the SEM micrographs by means of an Image Analyzer. The number of osteocyte cytoplasmic processes was indirectly evaluated by counting the canalicular openings present on the same microscopic fields after the removal of the osteoblasts. The metabolic activity of the osteoblasts was indirectly evaluated from their shape, and the structure was analyzed by transmission electron microscope (TEM) in sections taken from the samples studied by SEM. In all four animals, the surface area of the osteoblasts (OA) was found to vary a great deal, whereas the density of canalicular openings was fairly uniform. Moreover, although the OA mean value increases significantly with the age of the animals, the density of canalicular openings does not; it would therefore appear that the older the animal and the more flattened the osteoblasts, the greater the number of canaliculi beneath them. Since osteoblast activity has previously been shown to be inversely proportional to the area of the protoplasm in contact with the bone surface, it appears that the less active osteoblasts should contact a greater number of osteocyte cytoplasmic processes. These findings suggest that osteocytes might play an important role in modulating osteoblast activity and in recruiting osteoblasts that differentiate into osteocytes, possibly by means of inhibitory signals transmitted via gap junctions.


Assessment of combined 24,25(OH)2D3 and 1 alpha (OH)D3 therapy for bone disease in dialysis patients. An increasing body of experimental data suggests a role for 24,25(OH)2D3 in bone metabolism. The present study was carried out to assess a possible therapeutic role of this vitamin D metabolite in renal osteodystrophy. Twenty-two chronic dialysis patients, most of whom were previously maintained on 1 alpha (OH)D3 therapy, received additional treatment with 10 micrograms/day 24,25(OH)2D3 and were compared to 19 patients receiving 1 alpha (OH)D3 alone. Analysis of transiliac bone biopsies obtained at study entry and following 10-16 months of treatment revealed that the combined therapy produced a decrease in bone turnover. Specifically, the addition of 24,25(OH)2D3 inhibited an increase in trabecular bone volume (BV/TV) and suppressed osteoclastic parameters. Thus BV/TV increased from 26.2 +/- 8.6 to 32.1 +/- 7.5% (p < 0.01) in the 1 alpha (OH)D3 group, but it remained unchanged in the combined therapy group. In contrast, the eroded surface (ES/BS), the osteoclast surface (Oc.S/BS), and the osteoclast numbers were significantly suppressed in patients receiving both 24,25(OH)2D3 and 1 alpha (OH)D3, as compared with those receiving 1 alpha (OH)D3 alone (p < 0.01, p < 0.01, and p < 0.001, respectively). These improvements were independent of changes in 1 alpha (OH)D3 dosage. The extent of bone aluminium deposits was unrelated to the administration of 24,25(OH)2D3 or to its effect. 24,25(OH)2D3 therapy was not associated with any adverse effects.


Effects of gallium nitrate on calcium transients in UMR-106 rat osteoblastic osteosarcoma cells. Gallium nitrate is an effective antihypercalcemic and antiresorptive agent. Although its effects on osteoclasts are well documented, the mechanism of action of gallium nitrate on osteoblasts is still not established. To determine the effects of gallium nitrate on calcium signalling, we studied its effects on intracellular calcium concentration in UMR-106 rat osteoblastic osteosarcoma cell line. Cells were loaded with a calcium binding fluorescent dye, fluo-3. Changes in fluorescence reflected changes in cytosolic calcium. Gallium nitrate elicited a dose-dependent biphasic calcium transient with an initial decrease followed by an increase, and these changes were seen at high extracellular calcium concentration. Markedly altered signal was seen in nominal calcium-free medium, suggesting that gallium nitrate mobilized calcium only partly from intracellular stores. Gallium nitrate, at concentrations as low as 3 micrograms/ml, inhibited parathyroid hormone-stimulated calcium transients. High doses of parathyroid hormone could overcome this inhibition. This inhibitory effect appears to be selective, since gallium nitrate did not prevent calcium transients elicited by alpha-thrombin or prostaglandin F1 alpha. Failure of gallium nitrate to prevent calcium transients elicited by these agents, even after the inhibition of parathyroid hormone-induced signal, indicates that the inhibition is not a toxic effect. In conclusion, gallium nitrate has a marked effect on calcium signalling in UMR-106 cells that might be of major importance in modifying the effects of calcemic hormones or local factors on osteoblasts.


Osteogenic activity of growth cartilage examined by implanting decalcified or devitalized ribs and costal cartilage zone, and living growth cartilage cells. The formation of cartilage prior to bone in an endochondral bone formation process suggests that some osteogenic factors exist in the cartilage. This osteogenic activity of cartilage or cartilage cells was examined by implanting ribs and costal cartilage zone into a subcutaneous pocket of abdominal wall, or the growth cartilage (GC) cells into a peritoneal cavity. Rib segments of young (four-week-old) rabbits and rats were decalcified (DCed) in 0.6 N HCl for 24 h at 4 degrees C, or devitalized (DVed) by freezing/thawing and submerged in water for 48 h at 4 degrees C. These specimens were implanted into the subcutaneous pocket of abdominal wall of eight-week-old rabbits and rats. Both the DCed ribs and the DVed ones formed bone at costal GC zone after four to six weeks. Costal cartilage zone of young rabbits and rats was DCed or DVed as stated above, and implanted into the subcutaneous pocket of abdominal wall of eight-week-old rabbits and rats. The DVed costal cartilage zone specimens formed bone after three to four weeks, but the DCed ones did not, even after eight weeks. GC cells were dissociated enzymatically from rat costal GC zone, centrifuged to be made into pellets (5 x 10(5) cells/pellet), and implanted into the peritoneal cavity of eight-week-old syngeneic rats. After four weeks, implanted GC cells formed bone. These results suggest that there are some osteogenic factors in the GC zone produced by GC cells, whose activity is lost by decalcification, and which are different from known BMPs.


Reducing children's pain-distress associated with injections using cold: a pilot study. This study used an experimental design to test the question, "Does ice reduce the pain-distress children experience with injections?" One half of the 38 preschool children had ice applied to the preimmunization site for 30 seconds. The remaining children received the injection without the extra intervention. Measures included the Global Mood Scale, pulse rate, Oucher scale, and Faces scale. The results failed to show that ice reduces children's pain-distress with injections. Reasons for the failure are discussed, with comments on the various measures and suggestions for further study in this area of child nursing care.


Regulation of prostaglandin E2 production by vitamin D metabolites in growth zone and resting zone chondrocyte cultures is dependent on cell maturation. The production of PGE2 by chondrocytes and its regulation by vitamin D metabolites was examined in this study as a function of cell maturation. Costochondral chondrocytes, derived from the resting zone and growth zone cartilage, were grown in culture to fourth passage. At confluence, they were exposed to 10(-8)-10(-11)M 1,25-(OH)2D3 or to 10(-7)-10(-10)M 24,25-(OH)2D3 for either five minutes or 3, 6, 12, or 24 hours. Indomethacin (10(-7)M) was added to one-half of the cultures to block the production of PGE2. The amount of PGE2 released into the media was determined by radioimmunoassay. Both growth zone and resting zone cells produced PGE2 in a time-dependent manner; PGE2 concentration was greater in the resting zone cell cultures. 1,25-(OH)2D3 stimulated PGE2 production by growth zone cells in a dose-dependent manner, significant at 10(-8)-10(-10)M. This effect was observed at 3 hours and remained elevated during the 24 hours of culture. 1,25-(OH)2D3 had no effect on PGE2 production by resting zone cells. However, 24,25-(OH)2D3 (10(-7)-10(-8)M) inhibited PGE2 production from 3-24 hours. No effect was noted when 24,25-(OH)2D3 was added to growth zone cells. Indomethacin reduced PGE2 production to baseline values in all groups examined. The results indicate that chondrocytes in culture produce PGE2. Production is regulated by vitamin D3 metabolites and is cell maturation-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)


Trends in the incidence of histologically diagnosed intra-oral squamous cell carcinoma in Northern Ireland, 1975-89. Studies in Britain point to a rise in the incidence of intra-oral cancer in the last 20 years, paralleling trends evident in other European countries. Cases of histologically-diagnosed primary intra-oral squamous cell carcinoma have been ascertained by reviewing the records of pathology departments in Northern Ireland. Trends in the incidence of the disease have been determined for the period 1975-89. There has been a significant increase in the incidence among men, rising from 1.78 to 3.14 per 100,000. In women over the same period the incidence rose from 0.87 to 1.19 per 100,000, but this change was not significant. These trends concur with recent findings from other countries.


The influence of examination frequency and changing dentist on dental treatment provision in an Australian defence force population. During the early 1980s, a number of studies into dental treatment provision in the General Dental Service were conducted in Scotland. These studies indicated that the frequency with which an individual attended the dentist for treatment, or changed their dentist, influenced the amount of dental treatment that they received. The present study was designed to test these findings in an independent population, in this case, 100 members of the Royal Australian Air Force. While the frequency of attending the dentist did not have any significant effect on restoration longevity or the number of restorations a subject received, it did influence the cost of such treatment, indicating that frequent attenders received more expensive treatments rather than more treatment. Changing dentist did not display any significant influence on any of the parameters used in the present study.


Synthesis, NMR spectra and function of peptides with alpha-methylserine attached to the RGD sequence of osteopontin. The three-dimensional structure of the RGD-adhesion sequence has been studied previously by means of linear and cyclic peptides. These peptides show widely differing affinities to integrins, ascribed to a strong dependence on steric factors in the receptor recognition. Insertion of alpha-methylserine next to the RGD sequence in this investigation resulted in lower affinity for both stereoisomers, and several small changes in chemical shifts and coupling constants relative to the parent serine peptide GRGDSL.


Palladium-catalyzed intramolecular cyclization of vinyl and aryl triflates. Associated regioselectivity of the beta-hydride elimination step. The Pd(0)-catalyzed intramolecular olefination of vinyl and aryl triflates has been studied with a view to gaining insight into the question of kinetically preferred reductive elimination when at least two options are available. In either series, a non-activated alkene participant was found to be converted most readily into the non-conjugated cyclization product. This trend is seen despite the more forcing conditions necessary to engage the less reactive aryl triflates in ring closure. On the other hand, when the pendant chain is terminated by an alpha-methyl acrylate unit, the conjugated diene is kinetically preferred. The two reactions appear to be closely balanced energetically since product distributions are not greatly disparate. Nevertheless, their complementarity could be utilized to advantage in the synthesis of polycyclic molecules possessing multiple sterogenic centers.


Pyridine-substituted hydroxythiophenes. I. Preparation of o-(2-, 3- and 4-pyridyl)-3-hydroxythiophenes. 2-(2-, 3- and 4-pyridyl)-3-hydroxythiophenes and 4-(2-, 3- and 4-pyridyl)- 3-hydroxythiophenes have been prepared by hydrogen peroxide oxidation of the corresponding boronic esters. In the former case the boronic esters were obtained in three steps from 2,3-dibromothiophene via the corresponding 3-bromo-2-pyridylthiophenes synthesized by Pd(0)-catalyzed coupling between 3-bromo-2-trimethylstannylthiophene and the corresponding bromopyridines. In the latter case the known isomeric pyridylthiophenes were converted into the corresponding boronic esters in three steps via tribromo- and 3-bromo-4-pyridylthiophenes successively. 4-(3- and 4-pyridyl) thiophen-2(5H)-ones were also obtained in the syntheses of 4-(3- and 4-pyridyl)-3-hydroxythiophene. They are suggested to arise from rearrangement during the halogen-metal exchange. Spectroscopic investigations by 1H NMR and IR show that these hydroxythiophene systems exist exclusively as enol forms.


Metabolic and respiratory changes after cholecystectomy performed via laparotomy or laparoscopy. We have compared metabolic and respiratory changes after laparoscopic cholecystectomy (n = 15) with those after open cholecystectomy (n = 15). The durations of postoperative i.v. therapy, fasting and hospital stay were significantly shorter in the laparoscopy group. During the first and second days after operation, analgesic consumption but not pain scores (visual analogue scale) were significantly smaller after laparoscopy, while vital capacity, forced expiratory volume in 1 s, and PaO2 were significantly greater. The metabolic and acute phase responses (glucose, leucocytosis, C-reactive protein) were less after laparoscopy compared with laparotomy. Although plasma cortisol and catecholamine concentrations were not significantly different between the two groups, after surgery interleukin-6 concentrations were less in the laparoscopy group.


Effect of the laryngeal mask airway on lower oesophageal sphincter pressure in patients during general anaesthesia. We have studied the tone of the lower oesophageal sphincter (LOS) in 40 adults undergoing routine body surface surgery and allocated randomly to receive anaesthesia either by face mask and Guedel airway or by laryngeal mask airway. In the laryngeal mask group there was a mean (SEM) decrease in barrier pressure (LOS minus gastric pressure) of 3.6 (1.4) cm H2O, compared with a mean increase of 2.2 (1.2) cm H2O in the face mask group (P < 0.005).


Anaesthesia for transthoracic endoscopic sympathectomy in the treatment of upper limb hyperhidrosis. Renewed interest has been shown in transthoracic endoscopic sympathectomy (TES) for the treatment of upper limb hyperhidrosis. We review our experience and discuss the anaesthetic technique and perioperative problems encountered in 58 patients undergoing TES for hyperhidrosis. Patients were monitored for arterial pressure, heart rate, ECG, pulse oximetry (SpO2), end-tidal carbon dioxide concentration, peak inspired airway pressure and skin temperature. General anaesthesia, with a double-lumen endobronchial tube, enabled the lungs to be collapsed alternately, thereby ensuring easy and clear access to the sympathetic chain. Controlled ventilation with 100% inspired oxygen was necessary to obviate hypoxaemia. In two patients, severe hypotension and bradycardia occurred during insufflation of carbon dioxide into the chest cavity. Four patients required underwater drainage of the pleural cavity for treatment of pneumothorax or haemothorax. The success and safety of the procedure depends on a scrupulous anaesthetic technique.


Perioperative continuous monitoring of ST-segment changes in patients undergoing elective caesarean section. Using continuous ambulatory electrocardiography, we have investigated the incidence of ST-segment changes occurring in patients undergoing elective Caesarean section under extradural, spinal or general anaesthesia. There was no evidence of significant perioperative ST-segment changes. The findings contrast with the results of other work published recently.


EEG burst suppression with propofol during cardiopulmonary bypass in children: a study of the haemodynamic, metabolic and endocrine effects. We have studied the effects of propofol, given to maintain EEG suppression throughout cardiopulmonary bypass (CPB), in 20 children aged 1-15 yr, in a parallel group comparison. Anaesthesia was produced by fentanyl 50 micrograms kg-1, enflurane or halothane and midazolam 0.1 mg kg-1 at the start of CPB. After randomization, 50% of the children also received propofol during CPB. All children were cooled during CPB (25-28 degrees C) and pump flows (non-pulsatile) were 2.4 litre min-1 m-2, reducing to 1.2-1.6 litre min-1 m-2 during hypothermia. Large rates of infusion of propofol were required to maintain EEG suppression, particularly during rewarming. Compared with control, the propofol group showed significant increases in mixed venous oxygen saturation and significant reductions in systemic oxygen uptake and glucose and cortisol concentrations. There were no differences in triiodothyronine and lactate concentrations, mean arterial pressure during CPB and inotrope requirement after CPB, or in recovery times.


Infusion of propofol to identify smallest effective doses for induction of anaesthesia in young and elderly patients. We studied 110 patients older than 60 yr or aged 18-50 yr as separate groups in two stages to identify the smallest effective doses of propofol for induction of anaesthesia. In the elderly patients, in stage 1, at infusion rates of 25, 50 or 100 mg min-1 the mean (SD) doses administered were propofol 0.82 (0.14) mg kg-1, 1.22 (0.24) mg kg-1 and 1.65 (0.60) mg kg-1 and the induction times 140.1 (21.9) s, 103.2 (23.5) s and 69.4 (10.0) s, respectively. In stage 2, after induction with a fixed dose of 0.82 mg kg-1 as a bolus over 5 s or as an infusion at 25 mg min-1, the times for induction were 38.5 (14.0) s and 144.5 (36.6) s, respectively. In the young patients, at induction rates of 33.3, 50, 100 or 200 mg min-1, the doses administered were propofol 1.36 (0.28) mg kg-1, 1.46 (0.12) mg kg-1, 1.85 (0.43) mg kg-1 and 2.39 (0.50) mg kg-1 and the induction times 145.0 (25.4) s, 120.0 (18.4) s, 80.2 (19.2) s and 54.5 (10.4) s, respectively. In stage 2, a fixed induction dose of 1.46 mg kg-1 resulted in induction times of 35.0 (8.5) s and 134.0 (26.8) s, respectively. In stage 2 of each age group, induction was achieved with smaller doses than those recommended previously and there was no difference in the number of patients in whom induction of anaesthesia was successful or in the measured cardiorespiratory variables between the two induction regimens. This suggests the latter effects are caused by the dose administered and not the rate of administration.


IV bolus administration of subconvulsive doses of lignocaine to conscious sheep: effects on circulatory function. We have studied the effects of subconvulsive doses of lignocaine on circulatory function in five conscious, chronically instrumented sheep. In the absence of overt signs of central nervous system toxicity, 50-, 75- or 100-mg i.v. bolus doses of lignocaine induced reductions in myocardial contractility, as assessed by the maximum rate of increase in left ventricular pressure (LV dP/dtmax), of 17 (SD 4)%, 25 (4)% and 33 (4)%, respectively. The durations of these reductions in myocardial contractility were 2-3.5 min. There were no significant changes in cardiac output, coronary artery blood flow, mean arterial pressure, heart rate or left ventricular systolic and diastolic pressures. It is concluded that the initial toxic effects of lignocaine are on the heart rather than the central nervous system, as is generally believed. This negative inotropic effect of lignocaine in vivo may be more deleterious to myocardial function when the heart is compromised by pre-existing disease, or the co-administration of other myocardial depressive drugs.


Effect of graded infusion rates of propofol on regional and global left ventricular function in the dog. We have studied the effects of graded infusion rates of propofol (0.2-0.5 mg kg-1 min-1) on left ventricular global and regional function, in eight acutely instrumented dogs. Global function was assessed by measurement of aortic and left ventricular pressure, LV dP/dtmax, aortic blood acceleration and stroke volume. Regional function was assessed by measurement of systolic shortening and the end-systolic pressure-length relationship. The response of the coronary circulation to short periods of occlusion was also assessed. Administration of propofol significantly reduced left ventricular preload, as indicated by reductions in end-diastolic pressure and length; contractility was depressed, the depression being greater in the apex than in the base of the left ventricle. High infusion rates impaired relaxation. Regulation of coronary blood flow was not disrupted. Reductions in preload and contractility contributed to the propofol-induced hypotension. After 60 min, recovery from the greatest infusion rate was incomplete.


Porcine model for studying the passage of non-depolarizing neuromuscular blockers through the blood-brain barrier. A method has been developed for blood-brain barrier disruption to provide reproducible access to the cerebrospinal fluid of the cerebello-medullary cistern. The technique was used successfully to investigate transfer of pancuronium to the cerebral CSF compartment in pigs. After osmotic disruption of the blood-brain barrier, pancuronium concentrations increased significantly in the cerebrospinal fluid.


One-compartment kinetics.

One-compartment kinetics. The mathematical development of the equations needed to determine the plasma concentrations of drug in a one-compartment pharmacokinetic model are developed from first principles and are illustrated (with caution) by the use of morphine given by bolus or continuous i.v. injection or by a simulated i.m. injection. The equations allow the calculation of concentrations, given a knowledge of what drug is currently present, what are the sizes of the boluses by either i.m. or i.v. injection and what is the constant infusion rate. What happens when changes occur is also illustrated. The development illustrates the principles needed to apply to more complex models.


A new technique for two-hand bag valve mask ventilation. A method of bag valve mask ventilation (BVM) in which the resuscitator compresses the self-inflating bag between the open palm and body was compared with both standard single resuscitator and two-resuscitator BVM ventilation. Eighteen subjects ventilated a modified recording manikin using each method in random order. The tidal volume (VT) was greater with the open palm (mean 684 (SD 182) ml) than standard single resuscitator ventilation (mean 520 (152) ml). The difference was greater in the nine subjects with small hands (mean 196 (103) ml). VT was less than with two-resuscitator ventilation (mean VT 953 (236) ml).


Topical anaesthesia for extracorporeal shock wave lithotripsy. We have investigated 60 patients in a prospective double-blind, placebo-controlled study to assess the efficacy of EMLA (Eutectic Mixture of Local Anaesthetics) cream to provide analgesia during extracorporeal shock wave lithotripsy (ESWL) with a second generation lithotriptor. Before operation, EMLA or placebo cream was applied to the patient's back at the anticipated shock head-skin interface. During the procedure increments of fentanyl 0.5 micrograms kg-1 were given i.v. on patient demand. There was no significant difference (P = 0.83) in the dose of fentanyl given to each group. We cannot recommend, therefore, the use of EMLA cream as an analgesic during ESWL with a second generation lithotriptor.


Transient bradycardia associated with extradural blood patch after inadvertent dural puncture in parturients. We have studied prospectively 10 ASA I or II postpartum patients after inadvertent dural puncture during labour. An extradural blood patch (autologous blood 15 ml) was performed within 18 h of delivery, with continuous EEG, upper facial EMG (Datex: Anesthesia and Brain Activity Monitor), pulse oximetry and heart rate measurement before, during and for 30 min after extradural injection. Non-invasive arterial pressure measurements (Dinamap) were recorded at 5-min intervals. After extradural blood patch, a statistically significant (Student's t test, P < 0.05) decrease in heart rate, from a mean baseline of 88.6 (SD 7.31) beat min-1 to 51.3 (7.6) beat min-1, occurred within 122.6 (16.9) s from the time of the EBP. Bradycardia was observed for a mean duration of 12.4 (1.1) s. Upper facial EMG, EEG, SpO2 and arterial pressure did not change.


Effects of omeprazole, ranitidine, famotidine and placebo on gastric secretion in patients undergoing elective surgery. We have compared the effects of omeprazole, ranitidine, famotidine and placebo on gastric secretion in a double-blind study in 110 patients undergoing elective surgery. Three hours before operation, the patients received, orally, omeprazole 40 mg, ranitidine 150 mg, famotidine 40 mg or placebo. Gastric volume and pH were measured immediately after induction of anaesthesia. Omeprazole, ranitidine and famotidine produced a significant increase in gastric pH and a significant decrease in gastric volume compared with placebo. When the effects of omeprazole on gastric volume were compared with those of ranitidine and famotidine, no significant difference was found, but omeprazole was significantly less effective in increasing gastric pH. The number of patients having a pH less than 2.5 and a volume greater than 0.4 ml kg-1 were: none in the ranitidine group, one (3%) in the famotidine group, four (15%) in the omeprazole group and six (23%) in the placebo group. We conclude that omeprazole 40 mg given 2-4 h before surgery does not afford adequate prophylaxis for the acid aspiration syndrome.


Surgical face masks are effective in reducing bacterial contamination caused by dispersal from the upper airway. We have studied the effectiveness of surgical face masks in reducing bacterial contamination of a surface, produced by dispersal of organisms from the upper airway. Twenty-five volunteers were asked to speak at blood agar plates positioned in close proximity to the mouth, initially whilst not wearing a face mask and then wearing a surgical face mask over the mouth and nose. A fresh face mask almost completely abolished bacterial contamination of agar plates 30 cm from the mouth. After 15 min there was an increase in the level of contamination which was statistically insignificant.