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Biomedical subjects

C Costello

Publications and source records attributed to C Costello.

87 records · Page 5Linked to original sources
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↗
PubMed1974

Chronic granulocytic leukaemia: multiple-drug chemotherapy for acute transformation.

The response to 60 trials of therapy in 50 patients with chronic granulocytic leukaemia (C.G.L.) in acute transformation is reported. None of the 13 patients who received single-agent chemotherapy had a satisfactory response. The use of two drugs in combination produced only one satisfactory response in 30 patients. Various types of multiple-drug treatments in eight patients achieved one good response which lasted four months. In contrast when nine patients with rapidly progressive acute transformation of C.G.L. received a regimen-TRAMPCO(L)-incorporating seven or eight drugs (thioguanine, daunorubicin, cytarabine, methotrexate, prednisolone, cyclophosphamide, and vincristine, with or without L-asparaginase colaspase) five improved significantly. Four patients had a good clinical and haematological response with survival for over three, eight, over 12, and 14 and a half months; and one patient had a partial response. Toxicity was not extreme and maintenance therapy with the same regimen was given on an outpatient basis. TRAMPCO(L) seems superior to previously reported regimens and should be considered for rapidly progressive transformation of C.G.L. especially when simpler treatments have failed.

Adolescent↗
PubMedDate not supplied

Predicting conversion of laparoscopic cholecystectomy for acute cholecystitis.

BACKGROUND AND OBJECTIVES: Laparoscopic cholecystectomy can be safely performed in patients with acute cholecystitis. However, the rate of conversion to open cholecystectomy remains higher when compared with patients with chronic cholecystitis. Preoperative clinical or laboratory parameters that could predict the need for conversion may assist the surgeon in preoperative or intraoperative decision making. This could have cost-saving implications. METHODS: A retrospective review of 46 patients undergoing laparoscopic cholecystectomy for acute cholecystitis was performed. Records were assessed for preoperative clinical, laboratory and radiographic parameters on admission. Temperature and laboratory parameters were also recorded prior to surgery after an initial period of hospitalization that included intravenous antibiotics. The effect of admission and preoperative parameters as well as the trend in these parameters prior to surgery upon the rate of conversion to open cholecystectomy was assessed. RESULTS: Ten patients (22%) required conversion to open cholecystectomy. Conversion was required more often in males (43%) when compared with females (4%) (p=0.003). Conversion rate was 30% in patients with increased wall thickness by ultrasound compared with 12% for patients without wall thickening (p=ns). No admission or preoperative laboratory values predicted conversion. The trend in the patient's temperature (p=0.0003) and serum LDH value (p=0.043) predicted the need for conversion to open surgery. CONCLUSIONS: Preoperative prediction of the need for open cholecystectomy remains elusive. Male patients and patients with rising temperature and LDH levels while on intravenous antibiotics require conversion at increased frequency. However, the benefits of laparoscopic cholecystectomy warrant an attempt at laparoscopic removal in most patients with acute cholecystitis.

Acute Disease↗