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Biomedical subjects

C Costello

Publications and source records attributed to C Costello.

17 recordsLinked to original sources
PubMed1992

Chemical contrast in X-ray microscopy and spatially resolved XANES spectroscopy of organic specimens.

The scanning transmission x-ray microscope at the National Synchrotron Light Source has been used to record x-ray absorption near-edge structure (XANES) spectra from 0.01-square-micrometer regions of organic specimens. The spectral features observed reflect the molecular structure of the dominant absorbing atoms and provide the contrast mechanism for high-resolution imaging with chemical sensitivity. This technique was used with x-ray energies near the carbon K absorption edge to identify and map separate phases in various polymer blends and to map the DNA distribution in chromosomes with a spatial resolution of 55 nanometers.

Acrylic Resins↗
PubMed1992

Rectal cancer risk in patients treated for familial adenomatous polyposis. The Leeds Castle Polyposis Group.

Total colectomy with ileorectal anastomosis (IRA) in familial adenomatous polyposis (FAP) leaves patients at risk for rectal cancer. To assess this risk, the rectal cancer incidence in 297 patients with FAP undergoing IRA since 1951 was determined in the population-based registers of Denmark, Finland and Sweden. At the same time, detailed data on 50 patients with FAP and invasive rectal cancer were obtained from 11 international polyposis registries. The cumulative incidence of rectal cancer was 13.1 per cent at 25 years. The 5-year survival rate of patients with FAP developing rectal cancer was 71 per cent. Combining both studies, the risk of dying from rectal cancer after IRA was 2.0 per cent at 15 years of follow-up. These results justify IRA as primary treatment for most patients; restorative proctocolectomy is preferred for some subgroups. The high all-cause mortality rate observed in this relatively young population necessitates lifelong surveillance of patients with FAP.

Adenomatous Polyposis Coli↗
PubMed1992

Massive abdominal lymphadenopathy in hairy cell leukaemia: a report of 12 cases.

Lymphadenopathy is an uncommon finding in hairy cell leukaemia (HCL). We report 12 HCL patients in whom relapse was associated with massive abdominal lymphadenopathy. All but one had long-standing HCL (range 3-25 years; median 10 years); in one it was discovered at presentation. Nine patients had been splenectomized and seven had previously been treated with 2'deoxycoformycin (DCF) and/or alpha-interferon (alpha IFN): three had achieved complete remission and four a partial response. The computerized tomography (CT) scan appearances were similar in all cases with a primary lymph node mass centred around the coeliac axis and involving upper para-aortic and retropancreatic regions. Histology and/or cytology confirmed nodal involvement by HCL in six patients. Large immature hairy cells were seen in both lymph nodes and bone marrow, suggesting a degree of transformation. Nine patients were treated with DCF: one had complete resolution, six responded with 50-90% reduction of the lymphadenopathy, one did not respond and one is still on treatment; alpha-IFN was used concomitantly or sequentially in two of the responders. One responding patient died of sepsis after four injections of DCF. Three patients received either alpha- or beta-IFN alone with no response. One elderly patient was not treated. Abdominal lymphadenopathy could be part of the natural history of HCL and/or may represent a transformation analogous to that seen in other low-grade lymphoproliferative disorders. Routine abdominal CT scanning should be part of the work up of all patients with HCL.

Adult↗
PubMed1979

Cytochemistry of normal and leukaemic lymphocytes: a review.

Findings with six cytochemical reactions demonstrable in normal and leukaemic lymphocytes were reviewed. The two methods which are presently of greater diagnostic value are the acid phosphatase (AP) and alpha-naphthyl acetate esterase (ANAE) reactions. AP has a definitive role in the diagnosis of acute and chronic T-cell leukaemias, where a strong positive reaction helps to distinguish them from most B-cell lymphoproliferative disorders. New findings concerning the ultrastructural localization of this enzyme are presented. ANAE is of value in distinguishing T-lymphocytes (positive localized reaction) from B lymphocytes (negative reaction) and the T micron from the T gamma subpopulation of T-lymphocytes, a positive reaction demonstrable only in the T micron cells. Other reactions reviewed were PAS, beta-glucoronidase, hexosaminidase and alkaline phosphatase.

Acid Phosphatase↗
PubMed1979

Analysis and quantitation of free ceramide containing nonhydroxy and 2-hydroxy fatty acids, and phytosphingosine by high-performance liquid chromatography.

Reaction of ceramides containing nonhydroxy fatty acids with benzoyl chloride in pyridine at 70 degrees C for 1 hr resulted in N-benzoylation to form N,N-acyl,benzoyl derivatives; O-benzoylation also occurred. However with ceramides containing 2-hydroxy fatty acids and phytosphingosine only O-benzoylation occurred even on prolonged treatment. Only O-benzoylation occurred on reaction with benzoic an hydride. However, the benzoylation of ceramides with phytosphingosine could not be achieved with benzoic anhydride and this benzoylation was performed by reaction with benzoyl chloride at 70 degrees C for 4 hr. Because N,N-acyl,benzoyl derivatives of ceramides containing nonhydroxy fatty acids produced by treatment with benzoyl chloride overlap methyl benzoate on high-performance liquid chromatography, benzoic anhydride was preferable for benzoylation of ceramides with nonhydroxy and 2-hydroxy fatty acids. On the other hand, the reaction with benzoyl chloride at 70 degrees C for 4 hr was used for quantitation of benzoylated ceramides containing 2-hydroxy fatty acids and phytosphingosine. 3-(p-Phenylbenzoyl)estrone was used as an internal standard for both reactions and values for ceramides containing 2-hydroxy fatty acids obtained by the two reactions were in good agreement. This procedure was applied to measurement of the ceramide levels in the brain, liver, and kidney of rats during development. The levels of ceramides containing nonhydroxy and 2-hydroxy fatty acids in the brain, liver, and kidney increased to the adult levels and then remained unchanged. Ceramide with phytosphingosine was detected in the liver and kidney, where its concentration gradually increased with age, but it was not found in the brain. The composition of nonhydroxy fatty acids were also analyzed.

Aging↗
PubMed1978

Total synthesis of stereospecific sphingosine and ceramide.

A small-scale synthesis of the four sphingosine stereoisomers (d-erythro, l-erythro, d-threo, and l-threo) and lignoceroyl d- and l-erythro-sphingosines, which is suitable for synthesis of tritium-labeled compounds, is described. Ethyl dl-erythro-2-acetamino-3-hydroxy-4t-octadecenoate was esterified with l(+)-acetylmandeloyl chloride and the two diastereomers obtained were separated from each other by thin-layer or column chromatography. Each diastereomer was subjected to ethanolysis to obtain ethyl d- or l-erythro-2-amino-3-hydroxy-4t-octadecenoate which was then reduced with LiAlH(4) or NaBH(4) to yield d- or l-erythro-sphingosine. d-erythro-[1-(3)H]Sphingosine with high specific activity was prepared by using LiAl(3)H(4) in the last step. d- and l-threo-sphingosines were synthesized from ethyl dl-threo-2-acetamino-3-hydroxy-4t-octadecenoate by using a similar procedure. Ceramide (lignoceroyl sphingosine) was prepared either by acylating sphingosine or by the following new method. Ethyl dl-erythro-2-amino-3-hydroxy-4t-octadecenoate was converted to the N-lignoceroyl derivative and esterified with l(+)-acetylmandeloyl chloride. The two diastereomers obtained were separated and each isomer was treated with a catalytic amount of sodium ethoxide. One of the products, ethyl d-erythro-2-lignoceroylamino-3-hydroxy-4t- octadecenoate, was reduced with NaBH(4) to yield ceramide. N-palmitoyl dl-erythro-sphingosine was also prepared using an identical procedure. N-lignoceroyl d-erythro-[1-(3)H]sphingosine was prepared by NaB(3)H(4) reduction of the corresponding amide ester. A doubly labeled ceramide, [1-(14)C]lignoceroyl [1-(3)H]sphingosine, containing high specific activity, was prepared by mixing the above N-lignoceroyl d-erythro-[1-(3)H]sphingosine and N-[1-(14)C]lignoceroyl d-erythro-sphingosine. The conversion of the doubly labeled ceramide to 3-keto derivative is also described.

Carbon Radioisotopes↗
PubMed1977

Prolonged remission maintenance in acute myeloid leukaemia.

Twenty-five patients with acute myeloid leukaemia were treated with three quadruple drug combinations in predetermined rotation: TRAP (thioguanine, daunorubicin, cytarabine, prednisolone); COAP (cyclophosphamide, vincristine, cytarabine, prednisolone); and POMP (prednisolone, vincristine, methotrexate, mercaptopurine). Fifteen patients (60%) achieved complete remission and five (20%) partial remission. For maintenance, five-day courses of drugs were administered every 14 to 21 days and doses were increased to tolerance. The median length of complete remission was 66 weeks. In eight patients remission maintenance treatment was discontinued and some remained in complete remission for over two years. In this series the remission induction rate was comparable with that reported for other regimens and complete remission lasted longer with this intensive maintenance regimen than with others. Nevertheless, the TRAP programme must still be regarded as only palliative treatment for acute myeloid leukaemia.

Adolescent↗
PubMed1977

Multiple-drug chemotherapy for acute leukemia The TRAMPCOL regimen: results in 86 patients.

A combination of eight cytotoxic drugs, administered simultaneously, has been used in 86 cases of acute leukemia. The regimen, designated TRAMPCOL, incorporated thioguanine, rubidomycin, (daunorubicin), cytosine arabinoside, methotrexate, prednisolone, cyclophosphamide, vincristine, and usually L-asparaginase. Treatment was administered in five-day pulses with treatment-free intervals varying from nine to 23 days. Subjective and objective toxic effects were not more severe than those seen with two- and four-drug regimens previously employed. Substantial clinical and hematologic improvement occurred in 8/19 patients with chronic granulocytic leukemia (CGL) in acute transformation. Complete clinical and hematologic remission (CR) was achieved in 3/7 patients with untreated acute myeloid leukemia (AML), 5/19 patients with AML who had failed to achieve CR with other therapy, and 4/18 patients with AML in relapse after CR obtained with regimens other than TRAMPCOL. CR occurred in 15/17 patients with acute lymphocytic leukemia (ALL), most of whom had had multiple previous relapses. CR was not achieved in four patients with AML superimposed on pre-existing myeloproliferative disorders. The TRAMPCOL regimen merits further evaluation in CGL after acute transformation, as a primary treatment for AML, and as therapy for ALL 1) in relapse, 2) in adults, 3) in children with adverse prognostic features, and 4) in T-cell ALL.

Adolescent↗
PubMed1977

Pyloric origin of gastric and duodenal ulcers: surgical connotations.

A new theory on cause and treatment of peptic diseases proposes that these disorders result from dysfunction of the pyloric muscle causing delay in gastric emptying of solids. It emphasizes the separate function of the duodenal sphincter and the gastric sphincter components of this muscle. Dysfunction of either results in delayed gastric emptying of solids. Peritoneal patch pyloroplasty (PPP) has been devised to correct delayed gastric emptying. Testing of gastric emptying by the barium burger meal is essential to proper diagnosis. One hundred consecutive patients who required surgery for peptic diseases during the past five years have undergone PPP, the first 20 with, and the next 80 without, vagotomy. Results included two deaths and 94 favorable results. Follow-up studies in these patients continue.

Adult↗
PubMed1976

The effect of transfer factor on neutrophil function in chronic mucocutaneous candidiasis.

Chronic mucocutaneous candidiasis with hypoparathyroidism in a 6-year-old-boy is described. In addition to defects of in vivo and in vitro correlates of delayed-type hypersensitivity to Candida albicans the child also had abnormalities of neutrophil function in terms of their capacity to respond by chemotaxis to a known attractant and to kill suspensions of C. albicans. Dialysable transfer factor was given on six occasions at intervals of between 26 and 45 days. Neutrophil chemotaxis (optimal conditions) was restored following each of the six injections, neutrophil chemotaxis (sub-optimal conditions) following five of the six injections and candidicidal capacity following four of the six injections. The effects of transfer factor were transient requiring repeated injections. The Candida delayed-type hypersensitivity skin test was restored to normal but lymphocyte transformation to Candida extract was not consistently positive following treatment. There was a slight clinical improvement following therapy. These abnormalities of neutrophil and lymphocyte function point to the complexity of chronic mucocutaneous candidiasis. The improvement in neutrophil chemotaxis and candidicidal capacity following treatment suggests that transfer factor may be a heterogeneous group of molecules, some of which affect granulocytes and restore defects in their function.

B-Lymphocytes↗
PubMed1976

White cell function in Down's syndrome.

Neutrophil function was studied in 25 patients with Down's syndrome at a mental subnormality hospital and compared with 26 normal controls. In vitro killing of Candida albicans was significantly lower in the Down's group, but there was no difference in the percentage of cells actively involved in phagocytosis or in the phagocytic index. The spontaneous nitroblue tetrazolium reduction was increased in 10 patients, but no abnormality of peroxidase activity or leucocyte alkaline phosphatase activity was found.

Adolescent↗
PubMed1975

Carcinoid tumor metastases. Prospective study of twenty-two patients.

Twenty-two patients with advanced metastatic carcinoid disease, most of whom were moribund were subjected to oral administration of 200 mg of 5-fluorotryptophan three times daily. Seven patients died from complications of the tumor before completing the course of one year's treatment. Of the fifteen patients who survived long enough to complete the year of therapy, the average additional survival time was 2.3 years, varying from one to over nine years. The average survival time after the diagnosis of advanced metastatic carcinoid disease was made and prior to the initiation of treatment with 5-fluorotryptophan in these patients was 5.5 years, varying from one to eight years. Side effects of the analog were limited to gastric upset in one patient only. The control of serotonin production and its associated symptoms was considered excellent. Slowly progressive tumor growth led ultimately to death in thirteen of the fifteen patients which was considered due to mechanical factors and not to hormone abnormalities. Two patients continue to survive with good quality of life nine and six years, respectively, after analog therapy. Life in patients with advanced metastatic carcinoid disease has been extended with good to excellent quality by the simple oral administration of the tryptophan analog, 5-fluorotryptophan. Tumor growth does not seem to have been affected by the analog.

Adult↗