Biomedical subjects
Publications and source records attributed to S Keating.
Although ultrasound is used extensively in medical therapies and diagnostics, it has been recognized only recently as a method for external controlled diversity of drugs. In this paper, firstly, a literature review on drug delivery and the combination with ultrasound is given. Then an experiment is described on measuring the release of a model drug (hexabrix) under ultrasound irradiation, from a polymer carrier.
To determine whether patients with a HLA-identical sibling donor have a better outcome than patients without a donor, an analysis on the basis of intention-to-treat principles was performed within the framework of the EORTC-GIMEMA randomized phase III AML 8A trial. Patients in complete remission (CR) received one intensive consolidation course. Patients with a histocompatible sibling donor were then allocated allogeneic bone marrow transplantation (alloBMT), the patients without a donor were randomized between autologous BMT (ABMT) and a second intensive consolidation (IC2). 831 patients <46 years old and alive >8 weeks from diagnosis were included. HLA typing was performed in 672 patients. AlloBMT was performed during CR1 in 180 (61%) out of 295 patients with a donor. Another 38 patients were allografted: five in resistant disease, 14 during relapse and 19 in CR2. ABMT was performed in 130 (34%) out of 377 patients without a donor in CR1, in six (2%) patients during relapse and in 38 (10%) patients during CR2. The disease-free survival (DFS) from CR for patients with a donor was significantly longer than for patients without a donor (46% v 33% at 6 years; P=0.01, RR 0.78, 95% confidence interval 0.63-0.96). The overall survival from diagnosis for patients with a donor was longer, but not statistically significant, than for patients without a donor (48% v 40% at 6 years; logrank P=0.24). When patients were stratified according to prognostic risk groups, the same trend in favour of patients with a donor was seen for survival duration and the DFS remained significantly longer for this group of patients.
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The increased incidence of cerebral toxoplasmosis in AIDS has led to a resurgence in the use of sulphadiazine. One complication of this is acute renal failure secondary to sulphadiazine-induced crystalluria. Three cases are described which demonstrate a spectrum of ultrasound findings ranging from echogenic foci in the renal parenchyma to echogenic material in both dilated and non-dilated collecting systems. In patients with AIDS having sulphadiazine treatment, these ultrasonic findings suggest that sulphadiazine is the cause of the renal failure.
The Leukemia Cooperative Groups of the EORTC and the GIMEMA conducted a prospective randomized phase III trial, in order to assess the value of autologous BMT (ABMT) vs a second intensive consolidation course (IC2), following a common intensive consolidation course (IC1) for patients with AML. Patients with an HLA-identical sibling donor were not randomized, but were included in an allogeneic BMT (alloBMT) program. This is an analysis of prognostic factors which influence the outcome of treatment after alloBMT in first complete remission (CR). The study included 730 patients < 46 years of age in CR, 270 having a histocompatible sibling donor. In 169 of these patients alloBMT was performed in first CR. Early remitters (122 patients achieving CR with one course of treatment) had a DFS at 3 years of 67%, significantly longer than that of 44% for late remitters (47 patients achieving CR after more than one course of treatment) (P = 0.006). The relapse risk for early vs late remitters was 16 and 40% at 3 years (P = 0.001) and the treatment-related mortality (TRM) at 2 years was 21 vs 27%. Age appeared to be a prognostic factor for TRM, WBC for DFS, whereas the FAB classification was not of prognostic importance. Patients with poor risk cytogenetic abnormalities showed a trend towards a higher relapse risk. Patients transplanted shortly after achieving CR appeared to have a worse prognosis than those transplanted further into remission. Overall, the number of courses of induction therapy needed to achieve CR was the most important prognostic factor for outcome after allogeneic BMT.
Especially in California, there is a growing need to match the ethnic and cultural profiles of nurses and patients. Two Bay Area healthcare programs pooled financial and human resources to develop long-range strategies aimed at increasing the number of minority graduate nurses. Included were a work-study program, a Russian immigrant nurse training program and a scholarship program for minority students. A Cultural Diversity Enhancement Committee is very active and various educational offerings have emerged from the Nursing Education and Research Department.
For a statistical lattice, or Ising network, composed of N identical units existing in two possible states, 0 and 1, and interacting according to a given geometry, a set of values can be found for the mean free energy of the 0-->1 transition of a single unit. Each value defines a transition mode in an ensemble of nu N = 3N - 2N possible values and reflects the role played by intermediate states in shaping the energetics of the system as a whole. The distribution of transition modes has a number of intriguing properties. Some of them apply quite generally to any Ising network, regardless of its dimension, while others are specific for each interaction geometry and dimensional embedding and bear on fundamental aspects of analytical number theory. The landscape of transition modes encapsulates all of the important thermodynamic properties of the network. The free energy terms defining the partition function of the system can be derived from the modes by simple transformations. Classical mean-field expressions can be obtained from consideration of the properties of transition modes in a rather straightforward way. The results obtained in the analysis of the transition mode distributions have been used to develop an approximate treatment of the problem of macromolecular recognition. This phenomenon is modeled as a cooperative process that involves a number of recognition subsites across an interface generated by the binding of two macromolecular components. The distribution of allowed binding free energies for the system is shown to be a superposition of Gaussian terms with mean and variance determined a priori by the theory. Application to the analysis of the biologically interaction of thrombin with hirudin has provided some useful information on basic aspects of the interaction, such as the number of recognition subsites involved and the energy balance for binding and cooperative coupling among them. Our results agree quite well with information derived independently from analysis of the crystal structure of the thrombin-hirudin complex.
A 2.5 year old dysmorphic child with severe gastro-oesophageal reflux was admitted for elective fundoplication. Three days postoperatively, she developed progressive signs of intestinal obstruction. The diagnosis of caecal volvulus was suggested on the plain radiographic appearance, confirmed at laparotomy and treated by right hemicolectomy. The predisposing factors, diagnosis and approach to surgical management are discussed.
One case of malignant peripheral neuroectodermal tumour successfully diagnosed by cytology is presented. Although a Papanicolaou stained smear could not lead to a diagnosis more specific than a malignant small cell tumour, ancillary analytic methods performed on the cytologic material including immunocytochemistry and electron microscopy yielded the correct diagnosis of peripheral neuroectodermal tumour. This case demonstrates that a precise categorization of small round cell tumours may be achieved by cytology as long as some material is kept for immunocytochemical and ultrastructural studies.
The articular cartilage of four fresh osteochondral allografts was biopsied after transplantation, and its viability was studied by autoradiography. The biopsy specimens were labeled with both 3H-cytidine, for newly synthesized ribonucleic acid, and 35S-sulphate, for newly synthesized proteoglycans. The cartilage of a lateral humeral condylar graft at twelve months had 96 to 99 per cent labeled chondrocytes, the articular cartilage of a medial femoral condylar graft at twenty-four months showed 69 to 78 per cent labeled chondrocytes, and the cartilage of a medial tibial-plateau graft at forty-one months had 90 per cent labeled cells. At six years, a lateral tibial-plateau graft had 37 per cent labeled chondrocytes.
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Pigs were treated with N2O which is known to impair vitamin B12 function in vivo. Such pigs demonstrated an inability to gain weight, progressive ataxia, and spinal neuropathy. The ataxia was totally and the neuropathy partially preventable by dietary methionine supplementation. Methionine synthase activity was inhibited in both the liver and brain. There was a marked elevation of S-adenosylhomocysteine in the neural tissues and a concomitant failure of S-adenosylmethionine to rise and thus maintain the methylation ratio, except when supplementary dietary methionine was added. In contrast, the methylation ratio in the rat was affected to a lesser extent. The neuropathy, it is suggested, is caused by raised S-adenosylhomocysteine levels in neural tissue; as a result, the methylation ratio is inverted and S-adenosylmethionine-dependent methylation reactions are inhibited.
Solitary fibrous tumour of the pleura is a benign neoplasm differing from diffuse pleural mesothelioma. It was originally thought to be a variant of mesothelioma because it consists of a spindle cell stroma associated with branching tubular structures lined by cuboidal cells. In this study of two cases the tubular structures were lined with ciliated and non-ciliated cuboidal cells. Ultrastructurally most of the non-ciliated cells had the features of type II pneumocytes, while the stromal cells had all the characteristics of fibroblasts. Immunohistochemical staining showed the epithelial cells to be positive for both keratin and carcinoembryonic antigen, whereas the stromal cells were negative. The findings support the theory that these tumours are fibroblastic in origin, and that the biphasic pattern is due to entrapment of non-neoplastic bronchiolar and alveolar epithelial cells.
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The clinical and pathological features of an apparently unique case of an adenomyotic cyst of the uterus are reported. The cyst was located within the subserosal myometrium of a 39-year-old woman. Prior to hysterectomy, it had ruptured with bleeding into the peritoneal cavity. The differential diagnosis of myometrial cysts is briefly discussed.
Two undifferentiated (embryonal) sarcomas of liver were studied ultrastructurally and immunohistochemically. Electron microscopic examination of the pleomorphic tumor cells revealed fibroblastic and histiocytic characteristics. There were no specific findings to support rhabdomyoblastic, leiomyoblastic, or epithelial differentiation. Cytoplasmic peroxidase-antiperoxidase (PAP) immunohistochemical staining for vimentin, alpha1-antitrypsin, and alpha1-antichymotrypsin was found. No staining for epidermal or internal organ cytokeratins, desmin, myoglobin, or alpha-fetoprotein was observed. The ultrastructural correlates of the cytoplasmic periodic acid-Schiff-positive, diastase-resistant hyaline globules were large, membrane-bound, heterogenous electron-dense inclusions, probably lysosomal in origin. These inclusions did not react on either alpha1-antitrypsin or alpha1-antichymotrypsin PAP staining. Tumor specimens from two metastatic sites were also examined. Neither contained the ducts or cysts that characterized the primary tumor. These studies confirm the mesenchymal nature of this uncommon childhood neoplasm and support the suggestion that the cytoplasmic hyaline globules represent a degenerative phenomenon. There are ultrastructural and immunohistochemical similarities with malignant fibrous histiocytoma.
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