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Biomedical subjects

J Callaghan

Publications and source records attributed to J Callaghan.

At least 19 recordsLinked to original sources
PubMed1996

Inhibition of dihydropyrimidine dehydrogenase by 5-propynyluracil, a metabolite of the anti-varicella zoster virus agent netivudine.

OBJECTIVE: To study the effects of the anti-herpetic drug netivudine on dihydropyrimidine dehydrogenase activity in elderly volunteers and to relate them to concentrations of netivudine and its metabolite 5-propynyluracil. METHODS: Three groups of eight elderly volunteers received 400 or 800 mg netivudine or placebo once daily for 8 days. Plasma netivudine, 5-propynyluracil, and uracil, an indirect measure of dihydropyrimidine dehydrogenase activity, were assayed before the first dose and on days 2, 3, 5, 7 and 8. Full plasma profiles of netivudine and 5-propynyluracil were determined after the last dose. RESULTS: Plasma uracil was unquantifiable in all subjects before the first dose and at all time points in the placebo group. In recipients of netivudine it reached a plateau between days 3 and 5, with mean values of 23.2 and 23.5 mumol/L on day 8 in the subjects who received 400 and 800 mg. Plasma netivudine concentrations were approximately dose proportional, but 5-propynyluracil concentrations were similar in both groups. The half-maximal rise in plasma uracil occurred after a cumulative 5-propynyluracil exposure of 120 mumol/L.hr; such exposures will be achieved even after doses as low as 50 to 100 mg daily. CONCLUSIONS: Netivudine dosing produces complete inhibition of plasma dihydropyrimidine dehydrogenase. Coadministration with the antimetabolite 5-fluorouracil will require a substantial reduction in 5-fluorouracil dose to avoid toxicity but may also improve the therapeutic index of 5-fluorouracil.

Aged↗
PubMed1995

Intravenous methylmethacrylate following cemented total hip arthroplasty.

Both cemented and noncemented techniques have been used for total hip arthroplasty (THA). Each technique has advantages and disadvantages. Among the disadvantages of cemented THA are several perioperative complications, such as intraoperative cardiac or respiratory failure and hypotension, called "cement implantation syndrome," and extrusion of cement beyond the confines of the medullary canal. Cement extrusion can be the result of overreaming of the femoral canal and cortical perforation. This is a worrisome finding, as the risk of subsequent femoral fracture at the site of perforation is increased. Extruded cement, however, does not always indicate a problem. Extruded cement located within the femoral venous system, intravenous methylmethacrylate, for example, is not associated with long-term complications. While uncommon, it is important to differentiate this finding from the more serious cortical perforation. We report four examples of intravenous methylmethacrylate following THA and describe the imaging features that allow differentiation of this entity from the more significant finding of cortical perforation.

Aged↗
PubMed1995

Twenty-five years of gallbladder surgery in a small rural hospital.

BACKGROUND: During a 25-year period from 1967 to 1991, 1,058 gallbladder operations were done by one surgeon in solo practice in a rural 50-bed hospital. METHODS: Open cholecystectomy was performed on all but 6 patients who had cholecystostomy. Operative cholangiography was liberally used, and 19% of all patients required common duct exploration. The majority of the patients were older than 65 years of age and 19% were older than 75 years of age. RESULTS: The overall mortality was 0.7%. There were no deaths following cholecystectomy for chronic or acute nongangrenous cholecystitis, and all deaths occurred in patients older than 77 years of age. Most of the deaths occurred prior to 1978 and the last death was recorded in 1984. CONCLUSIONS: Rural America has a comparatively large proportion of the elderly population of our nation. Most of these patients prefer to have their surgery performed locally, provided the results are comparable with those of large neighboring medical centers. The results from this current series from a small rural hospital compare favorably with the published results from large medical and academic centers.

Adult↗
PubMed1994

A twenty-five year survey of a solo practice in rural surgical care.

A large proportion (55 million) of our population lives in rural America, but there is a paucity of published material regarding the surgical care of this large group. This report is based on 13,793 patients treated in a 50-bed rural hospital by one surgeon during a period of 25 years from 1967 to 1991. Gynecologic, obstetric, orthopedic and urologic surgical treatment accounted for 41 percent of extensive operations, but endoscopic procedures have been increasing in recent years. Good surgical results can be obtained in the smaller rural hospital, but more emphasis on broader training for the would-be rural surgeon is necessary for this to continue.

Adolescent↗
PubMed1993

Surgery for Crohn's disease.

In the last 12 years, 72 operations have been performed on 41 patients for Crohn's disease in this hospital. The patients were predominantly young (mean age 32 yrs) and there were more females than males. 28 had ileocolic disease, three small intestinal, two pan-enteric and eight colonic. Pain (in 76%), diarrhoea (56%) and weight loss (66%) were the main presenting symptoms. Diarrhoea occurred in all those with colonic disease, but in only 43% of those with ileocolic disease. A right hemicolectomy (28 patients), colonic resection (12) and small intestinal resection (9) were the commonest operations. There were no deaths. 22 patients had a total of 26 complications after surgery, eight necessitating further surgery. The mean post-operative stay was 15 days, being lowest in those with ileocolic disease. 19 patients have required only one operation, with a mean follow-up of 5.3 years. These patients also had significantly less complications (p < 0.05). Half of the patients requiring surgery for Crohn's disease have done very well. The other half require many operations and have a substantial morbidity.

Adolescent↗
PubMed1992

A preliminary report on the usefulness of monoclonal antibodies to CA 15-3 and MCA in the detection of micrometastases in axillary lymph nodes draining primary breast carcinoma.

The most critical factor affecting survival in patients with breast carcinoma is axillary nodal involvement. Monoclonal antibodies raised against specific human mammary tumour associated antigens may increase detection of micrometastases. This preliminary report examines two of these antigens; CA15-3 antigen and mucin-like carcinoma associated antigen (MCA) in the detection of such deposits. Specimens from 39 stage 1 (node negative) breast carcinoma patients were assessed. Two further 'negative' sections were stained with antisera to CA15-3 and MCA antigens. Micrometastases were detected in 5 patients and in each, MCA and CA15-3 identified the same micrometastases. 3 of these patients had disease progression compared with 3/34 of the remaining patients. The use of monoclonal antibodies to CA15-3 and MCA significantly (P less than 0.05) increases detection rates of micrometastases and this is associated with significantly worse disease-free survival rates (P less than 0.001).

Adult↗
PubMed1992

An evaluation of the usefulness of primary tumour expression of MCA and CA15-3 as prognostic indicators in breast carcinoma.

CA15-3 antigen and mucin-like carcinoma associated antigen (MCA) show potential as clinically useful serum markers of breast carcinoma. Recently, immunohistochemical versions of these monoclonal antibodies have become available but few data are available as to their clinical usefulness. The aims of this study were (i) to assess CA15-3 and MCA expression by primary breast tumours and to correlate tumour immunoreactivity with tumour behaviour, and (ii) to investigate the relationship between immunohistological staining and oestrogen receptor (ER) status. Pathological material from 39 stage 1 (node free) breast carcinoma patients was assessed. The mean age was 51.3 (range 34-70) years, 19 were premenopausal and the mean duration of follow-up was 3.6 years (range 0.8-14 years). In each case two further sections were stained with antisera to the CA15-3 and MCA antigens. Staining of primary tumour was achieved in 38 cases. Low (less than 30% tumour cell staining) and intermediate (30-60% of cells staining) grade immunoreactivity with both monoclonals correlated with significantly shorter disease free intervals (P less than 0.05). Neither monoclonal can predict ER status. We conclude that the use of monoclonal antibodies to CA15-3 and MCA in staining primary breast carcinoma tumours and their axillary nodes may be a significant (P less than 0.05) prognostic indicator of future tumour behaviour and that this requires further evaluation.

Adult↗
PubMed1991

Purification and partial amino acid sequence of human aconitase.

Aconitase has been purified from membranes prepared from both the human gastric carcinoma cell line Okajima and from porcine gastric mucosa by chromatography on concanavalin A-Sepharose and carboxymethyl-Sepharose, and preparative polyacrylamide gel electrophoresis. Automated Edman degradation of the intact proteins yielded no N-terminal amino acid sequence due, presumably, to N-terminal blockage. Sequence analysis of tryptic peptides derived from S-carboxymethyl porcine and human aconitases established the positions of 95 and 64 amino acid residues, respectively. The amino acid sequence data for porcine aconitase was in perfect agreement with the previously reported cDNA-deduced amino acid sequence [Zheng et al. (1990) J Biol Chem 265:2814-2821]. Comparison of the human amino acid sequence data with the cDNA-deduced amino acid sequence of porcine aconitase indicated that these two proteins have 95% amino acid sequence identity within the sequenced region.

Aconitate Hydratase↗
PubMed1990

Colorectal cancer in a small rural hospital.

Over a 20-year period, 168 cases of colorectal cancer were treated in a 50-bed rural hospital by 1 surgeon. The majority of the patients were older than 70 years of age. The stage of disease was comparatively advanced, with 71% of the patients having nodal or distant metastases, 19% with bowel obstruction, and 8% with perforation. The operability and resectability rates were 100% and 96%, respectively. The crude 5-year survival was 50% for the entire series. The 5-year survival after curative operations in which there was no gross residual tumor at the end of the operation was 63%, and the 5-year survival for resection of localized node-negative disease was 81%. The wound infection rate was 2%, and the operative mortality rate was 1% for combined elective and emergency operations. The results of treatment of colorectal cancer in small rural hospitals are infrequently reported, and this series may be compared with the published results from large teaching institutions.

Adult↗
PubMed1989

Production of parathyroid hormone-related protein by a rat parathyroid cell line.

Parathyroid hormone-related protein (PTHrP), the peptide associated with humoral hypercalcemia of malignancy, has been identified in fetal and adult parathyroid glands. We here report a sub-clone of a rat parathyroid cell line which secretes a single peptide species corresponding in size to PTHrP(1-84). Biological activity of the secretion product was blocked by a specific antiserum against PTHrP, but not by parathyroid hormone (PTH) antiserum. Secretion of PTHrP by these cells was regulated by extracellular calcium in the physiological range. A single messenger RNA species for PTHrP was identified, though PTH mRNA could not be shown in these cells. Hybrid CAT genes containing 700-1000 bp of 5'-flanking DNA from the human PTH or PTHrP genes were transfected into these cells, and the PTHrP gene was expressed at 10-fold higher levels than the PTH gene. These cells thus provide a valuable model system for investigation expression of PTHrP in a non-transformed cell line.

Adenylyl Cyclases↗
PubMed1989

Primary gastric lymphoma: incidence and role of surgery.

The histological subgroups of primary gastric tumours presenting to one surgical unit over two successive six year periods were analysed and the therapeutic value of gastric resection assessed. An increased incidence of gastric lymphoma (13% relative to 5%) occurred in the second six year period. This increase could not be attributed to improved morphological or histochemical techniques. The diagnosis of lymphoma was confirmed preoperatively in 13 (94%) of the 14 patients by a combination of multiple endoscopic biopsies and brush cytology. Five of the six patients who underwent a potentially curative resection are tumour free at a mean follow-up of four years. Histological grading, whether high or low, had no bearing on survival. Gastric lymphoma is increasing in incidence and should be considered in the evaluation of gastric tumours as surgical resection at present offers the best prospect of long term survival.

Adenocarcinoma↗
PubMed1988

Six years clinical experience with the Omniscience cardiac valve.

Clinical data on the Omniscience valve prosthesis were obtained from 194 patients (92 mitral valve replacements, 65 aortic valve replacements, 11 tricuspid valve replacements and 26 multiple valve replacements). Follow-up was 98% complete for a total of 443 patient-years with a mean of 2.6 years and maximum of six years. The mean age of patients was 50.3 +/- 14.5 years, with a range of two months to 75 years. Seventy-five percent of patients were in NYHA functional class III-IV preoperatively; postoperatively, over 93% of patients were in class I-II. Hospital mortality was 12.4% and late mortality was 3.2% per patient-year. The linearized rates for complications were as follows (per patient-year): thromboembolism 2.9%; valve thrombosis 0.7%; anticoagulant bleeding 2.7%; endocarditis 0.9%; pannus formation 0.2%; periprosthetic leak 0.5%. All significant valve related complications occurred at a rate of 5.9% per patient-year. The complications were fatal at a rate of 1.1% per patient-year and the risk of reoperation on the valve site was 1.1% per patient-year. Actuarial survival at six years was 84.8% +/- 5% for the whole group (88.6 +/- 5.7% for aortic, 84.3 +/- 9.4% for mitral valve replacement, 86.0 +/- 5.5% for single valve replacement and 77.1 +/- 10.2% for multiple valve replacements). Based on the duration of the study and absence of restrictive selection criteria, these clinical data demonstrated a reliable degree of safety and performance for this prosthesis.

Adolescent↗
PubMed1987

A six-year study of the Omniscience valve in four Canadian centers.

Stimulated by the recent controversy over the Omniscience valve, we conducted a follow-up study on 413 hospital survivors in whom this prosthesis was implanted at four Canadian centers from 1979 to 1985. One hundred forty-seven underwent aortic valve replacement (AVR), 203 had mitral valve replacement (MVR), 10 had tricuspid valve replacement (TVR) and 53 underwent multiple valve replacement (45 AVR + MVR, 5 MVR + TVR, and 3 AVR + MVR + TVR). The mean age was 50.8 +/- 13 years (range, 2 months to 75 years). Follow-up of 96% was achieved for a mean of 2.6 years and a maximum of 6 years with a total of 1,076 patient-years. Complications were defined and graded according to severity. Analyses were performed to yield linearized and actuarial rates for complications. There were 30 late deaths (2.8% per patient-year). At 5 years, the actuarial survival was 89 +/- 3% (AVR, 89 +/- 3% and MVR, 91 +/- 3%). Percentages for freedom from each complication are as follows: endocarditis, 96 +/- 1% (AVR, 96 +/- 2% and MVR, 98 +/- 1%); periprosthetic leak, 99 +/- 0.6% (AVR, 98 +/- 1% and MVR, 99 +/- 0.6%); thrombotic complications, 87 +/- 3% (AVR, 84 +/- 6% and MVR, 90 +/- 3%); valve thrombosis 99.4% (AVR and MVR, 100%); anti-coagulant-related hemorrhage, 94 +/- 2% (AVR, 97 +/- 2% and MVR, 94 +/- 2%); and all valve-related complications, 77 +/- 3% (AVR, 77 +/- 6% and MVR, 79 +/- 4%). Reoperation was required at the rate of 1.2% per patient-year.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Valve↗
PubMed1987

Long-term renal risk factors in children with meningomyelocele.

We studied renal function and structure in 42 patients with meningomyelocele, 28 treated with intermittent catheterization and 14 with ileal loop diversion. Patients were observed for a minimum of 60 months. Nine of the 28 patients who underwent intermittent catheterization had evidence of unilateral or bilateral reflux, and all patients with ileal loop diversion had free ureteral reflux. Bacteriuria was present in 38% +/- 5% of cultures obtained from patients with catheterization and in 70% +/- 7% of cultures from those with diversion (P less than 0.001). Four (14%) of 28 patients with catheterization had worsening renal function or anatomic appearance by intravenous pyelogram, and required a diversion. Three (28%) of 14 patients with diversion had changes in renal structure or function. Eight of 31 patients from both groups studied with voiding cystourethrography before the onset of therapy had small, noncompliant, trabeculated bladders; all seven patients who had worsening in function or anatomic appearance were from this subset (P less than 0.01). None of the patients with flaccid or distensible bladders demonstrated these changes. Renal disease was unrelated to the level of neurologic function. A small, noncompliant, trabeculated bladder is a risk factor associated with loss of renal function in patients with meningomyelocele.

Adult↗
PubMed1986

Karyotype abnormalities in non-Hodgkin lymphomas.

Karyotype anomalies were found in 9 of 13 non-Hodgkin lymphomas. The observed non-random involvement of chromosomes was non-specific and was associated with chromosome breakpoints rather than recurrent markers. The recurrent markers which were found were similar to those of previously published studies. An attempt to correlate histological classification and chromosome anomalies in published series indicated that there were limited histological associations, the frequency of abnormalities of chromosomes 14 and 18 showing the largest disparity between disease types. Among the breakpoints and translocations found are those known to be associated with oncogene location, and the possibility is raised of an oncogene on 18.

Chromosome Aberrations↗
PubMed1985

Amiodarone and its desethyl metabolite: tissue distribution and morphologic changes during long-term therapy.

The pharmacokinetic characteristics of amiodarone suggest extensive tissue deposition. We confirmed this by measuring tissue concentrations of the drug and of its major metabolite, desethylamiodarone, in human tissues. These were obtained at autopsy (n = 9), surgery (n = 7), or biopsy (n = 2) from 18 patients who had been treated with amiodarone for varying periods of time. High concentrations of amiodarone were found in fat (316 mg/kg wet weight in autopsy specimens, 344 mg/kg wet weight in biopsy specimens). Amiodarone and desethylamiodarone concentrations (mg/kg wet weight, autopsy samples) were also high in liver (391 and 2354), lung (198 and 952), adrenal gland (137 and 437), testis (89 and 470), and lymph node (83 and 316). We also found high concentrations of amiodarone (306 mg/kg wet weight) and desethylamiodarone (943 mg/kg wet weight) in abnormally pigmented ("blue") skin from patients with amiodarone-induced skin pigmentation. These values were 10-fold higher than those in unpigmented skin from the same patients. These high concentrations were associated with lysosomal inclusion bodies in dermal macrophages in the pigmented skin. The inclusion bodies were intrinsically electron dense and were shown to contain iodine by energy dispersive x-ray microanalysis. Lysosomal inclusion bodies shown by electron microscopy to be multilamellar were seen in other tissues. These tissues included terminal nerve fibers in pigmented skin, pulmonary macrophages, blood neutrophils, and hepatocytes and Kupffer cells. These characteristic ultrastructural findings occur in both genetic lipidoses and lipidoses induced by other drugs, e.g., perhexiline. We conclude that during therapy with amiodarone, widespread deposition of amiodarone and desethylamiodarone occurs. This leads to ultrastructural changes typical of a lipidosis. These changes are seen clearly in tissues associated with the unwanted effects of amiodarone, e.g., skin, liver and lung.

Adolescent↗
PubMed1984

Exacerbation of bronchial asthma following treatment with amiodarone. Demonstration of an antiadrenergic effect in vitro.

We describe a patient with bronchial asthma whose respiratory symptoms worsened during treatment and rechallenge with amiodarone. Laboratory studies on cultured pulmonary cells demonstrated an anti-beta-adrenergic effect of amiodarone not due to inhibition of beta-adrenergic receptor binding. Amiodarone should be used with caution in patients with obstructive pulmonary disease.

Amiodarone↗