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Biomedical subjects

A E Jones

Publications and source records attributed to A E Jones.

At least 73 records · Page 4Linked to original sources
PubMed1984

Growth hormone releasing factor: comparison of two analogues and demonstration of hypothalamic defect in growth hormone release after radiotherapy.

Human pancreatic growth hormone releasing factor (hpGHRF(1-40] stimulates the release of growth hormone in normal subjects and some patients with growth hormone deficiency. A study comparing the shorter chain amidated analogue hpGHRF(1-29) with an equivalent dose of hpGHRF(1-40) in seven normal subjects showed no significant difference in growth hormone response between the two preparations. Six patients with prolactinomas were also tested; these patients had received megavoltage radiotherapy previously but had developed growth hormone deficiency as shown by insulin induced hypoglycaemia. In all six patients 200 micrograms hpGHRF(1-40) or hpGHRF(1-29)NH2 produced an increase in the serum growth hormone concentration. These data suggest that hpGHRF(1-29)NH2 may be useful for testing the readily releasable pool of growth hormone in the pituitary and that cases of hypothalamo-pituitary irradiation resulting in growth hormone deficiency may be due to failure of synthesis or delivery of endogenous GHRF from the hypothalamus to pituitary cells.

Adult↗
PubMed1984

Treatment of prolactinomas with megavoltage radiotherapy.

The outcome of treatment of 36 women with prolactinomas using megavoltage radiotherapy combined with interim dopamine agonists (bromocriptine, lysuride, pergolide) was reviewed; 16 of the women showed radiological evidence of a macroadenoma. The most common presenting symptom was secondary amenorrhoea; 26 of the patients had galactorrhoea. In 29 patients who wished to conceive the ovulation rate (as indicated by circulating progesterone concentrations) was 97% and the successful fertility rate 86%. No patient had enlargement of the tumour during pregnancy and there were no complications of radiotherapy. No further tumour enlargement was detected in serial skull radiographs, and an improvement in size of the fossa was noted in 45% of those assessed. When medical treatment was withdrawn a mean of 4.2 years (range 1-11) after radiotherapy in the 27 patients who had completed their families the serum prolactin concentration had fallen appreciably in 26 of them and later became normal in eight. The incidence of growth hormone deficiency rose from 24% of the whole group before radiotherapy to 79% afterwards. Only one patient required thyroxine, and one was receiving gonadotrophin. No patient became deficient in adrenocorticotrophic hormone. A regimen of megavoltage radiotherapy and interim bromocriptine allows women with prolactinomas safely to undergo pregnancy and results in the long term prospect of tumour shrinkage and control of hyperprolactinaemia.

Adenoma↗
PubMed1984

A new 111In-bleomycin complex for tumor imaging: preparation, stability, and distribution in glioma-bearing mice.

A new 111In-bleomycin complex (111In-BLMC) is here reported. Its radiochemical purity was 99% by thin-layer chromatography (TLC) (Rf 0.65) and in 5% agarose gel electrophoresis in 0.02 M NaHCO3 it migrated toward the anode. Autoradiographs of TLC and gel electrophoresis plates showed no change on storage for 3 weeks. Urine and plasma from untreated or glioma-bearing mice after injection of 111In-BLMC were analyzed by TLC and gel electrophoresis. Results indicated stability in vivo, nonbinding to transferrin, affinity to viable tumor, and excretion faster than 111In-BLM-B2, 111In-BLM, or 57Co-BLM. Tissue distributions 24 hr after injection of radiopharmaceutical showed activity ratios of tumor to blood, muscle, and brain of 13.1, 12.4, and 81.6, respectively, which were significantly higher than those for previously prepared 111In-BLM-B2 or 111In-BLM (except for brain, 0.05 less than P less than 0.1). The new 111In-BLM complex may be useful in clinical imaging and for combining radionuclide radiotherapy and chemotherapy.

Animals↗
PubMed1984

A new tumor imaging agent--111In-bleomycin complex. Comparison with 67Ga-citrate and 57Co-bleomycin in tumor-bearing animals.

We have found a new 111In-bleomycin complex (BLMC), which has high affinity to tumor, does not bind to transferrin and is stable in vivo. Distribution in animals bearing glioma, hepatoma, or mammary adenocarcinoma at 48 hours showed: the ratios of tumor to blood, brain, heart, lung, liver, pancreas, stomach, and femur were 1.4-22.4 times as high for 111In-BLMC as for 67Ga-citrate. In mammary adenocarcinoma, 111In-BLMC bound more to viable and 57Co-Bleomycin (BLM) more to necrotic tumor. In viable tumor, the concentration of 111In-BLMC was similar to that of 57Co-BLM. The ratios of tumor to stomach and pancreas were higher, to blood, brain, muscle, heart, and femur were lower for 111In-BLMC than those for 57Co-BLM. The ratios of tumor to lung, liver, spleen, skin, and kidney were similar for the two compounds. Tumors were imaged more distinctly with the new 111In-BLMC and 57Co-BLM than with 67Ga-citrate. 111In-BLMC is promising for tumor imaging.

Animals↗
PubMed1984

Prospective studies of laboratory and radiologic tests in the management of colon and rectal cancer patients: I. Selection of useful preoperative tests through an analysis of surgically occult metastases.

The laboratory and radiologic tests that give useful information in colon and rectal cancer patients over and above that obtained by routine work-up and surgical exploration of the abdomen have not been defined previously. An analysis of surgically occult metastases was used to discover which test would assist in the management of these patients. Occult metastases for radiologic tests were those occurring within one year after resection of the primary tumor; for CEA they were metastases occurring at any time following surgery. Full lung tomography, liver/spleen scan, computerized tomogram of the abdomen, intravenous pyelogram, bone scan, and postoperative baseline CEA greater than 2.5 ng/ml were analyzed. The postoperative baseline CEA was the most sensitive test detecting occult metastases in 57 per cent (12 out of 21) of a high risk patient population. Both postoperative baseline CEA and computerized tomograms of the abdomen had high positive predictive values of 71 and 67 per cent. The negative predictive percentage of computerized tomograms of the abdomen (18 per cent) was lower than that of CEA (21 per cent). In comparing these tests in individual patients with occult recurrence, postoperative CEA and computerized tomograms of the abdomen were seen to be complementary in that approximately 90 per cent of occult metastases were detected when both examinations were used. Computerized tomogram of the abdomen and postoperative baseline CEA are useful in patients with primary colorectal cancer as part of their routine work-up.

Carcinoembryonic Antigen↗
PubMed1983

Assessment of regional left ventricular function by sector analysis: a method for objective evaluation of radionuclide blood pool studies.

Regional wall motion abnormalities are most often detected visually, and hence subjectively, in gated blood pool studies of the heart. Therefore, an automated method was developed to objectively assess regional left ventricular (LV) function. The method was tested in 26 normal volunteers and 29 patients with angiographically proved coronary artery disease. Fifteen patients with coronary artery disease had a normal LV ejection fraction (EF) at rest, and all had an abnormal EF response with exercise; 23 had visual regional wall motion abnormalities with rest or exercise. The left ventricle was divided into 28 sectors that radiated from the LV center of gravity, with 1 region at the LV center. A time-activity curve was generated for each sector and the EF and Fourier phase were computed from each curve. Rest and exercise sector EF versus sector number plots were superimposed and the area difference between these 2 curves was taken as an index of regional contraction. Similarly, an estimator of sector phase differences, obtained from the plot of phase versus sector number, was taken as an index of wall motion asynchrony. Analysis of the reliability of these 2 indexes suggests that this automated technique has at least the same efficiency as subjective evaluation of gated blood pool studies, but possesses the advantage of objectivity. The technique may also be useful in localizing regional defects and, perhaps, in detecting mild abnormalities not readily perceived visually.

Coronary Disease↗
PubMed1983

Control of the carcinogenic potential of 99mTechnetium by the immunologic hormone lymphotoxin.

Immunologic prevention of the carcinogenicity of the diagnostic gamma-emitting radionuclide 99mTechnetium (99mTc) by lymphotoxin was evaluated using an in vivo-in vitro assay of carcinogenesis. Pregnant Syrian golden hamsters received 125-2,300 microCi 99mTc/kg body weight by injection, and 7 days later colonies of morphologically transformed cells were quantitated in vitro. The transformation frequency increased directly with the radionuclide concentration, and cells derived from transformed colonies produced tumors in athymic nude mice. The total absorbed 99mTc dose was 0.20 rad following injection of 250 microCi 99mTc/kg hamster body weight; this compares with an exposure of 0.13 rad following injection of 143 microCi 99mTc/kg body weight in humans. Intravenous injection of purified hamster lymphotoxin immediately after 99mTc caused a dose-dependent reduction in the transformation frequency. Transformation was essentially completely prevented (97%) by injection of 8,000 U of lymphotoxin. Thus, the immune system, through the action of lymphotoxin, has the potential to prevent carcinogenesis induced by gamma-radiation from 99mTc. This emphasizes the importance of considering the recipient's immune and other homeostatic mechanisms as part of a complete diagnostic or therapeutic gamma-radiation regimen.

Animals↗
PubMed1983

The treatment of stage IIIA Hodgkin's disease.

Sixty consecutive previously untreated adults with surgically confirmed stage IIIA Hodgkin's disease (39 stage IIIA1, 21 stage IIIA2) began therapy at St. Bartholomew's Hospital between 1969 and 1981. Prior to 1973, treatment consisted of total nodal irradiation (TNI). From 1973 until 1978 patients were randomly allocated to receive either TNI or cyclic combination chemotherapy of mustine, vinblastine, prednisolone, and procarbazine (MVPP) as part of a Medical Research Council Trial. Since 1978 treatment has been allocated according to substage, those with stage IIIA1 receiving TNI and those with stage IIIA2 receiving MVPP. Seven patients received "non protocol" therapy (extended mantle radiotherapy in three patients, mantle and MVPP in four patients), and have been excluded from the study. Complete remission was achieved in 48 of 53 patients regardless of substage or therapy. Seven have relapsed, one after MVPP and six after TNI. The predicted freedom-from-relapse after MVPP was 96% compared with 60% after TNI, both at 10 years (p less than 0.01). The relapse pattern was the same for both substages in the group receiving TNI. Although overall survival of patients receiving TNI was identical to that of those receiving MVPP, TNI must be considered inappropriate therapy for stage IIIA Hodgkin's disease if permanent freedom-from-recurrence is the goal.

Adolescent↗
PubMed1982

A prospective analysis of laboratory tests and imaging studies to detect hepatic lesions.

A prospective study of the ability of laboratory tests and liver imaging tests to detect hepatic metastases was performed. Eighty patients at risk for hepatic metastases but without clinical evidence of disease were tested with 13 laboratory tests and three liver imaging tests. No single laboratory test had greater than 65% accuracy in the detection of hepatic lesions. No combination of the laboratory tests increased this accuracy. If the laboratory tests were used with one of the liver imaging tests, the accuracy was improved in some combinations to 76%. The CEA assay when analyzed in patients with colorectal primaries had an accuracy of 79%. The results show that the laboratory tests alone are not sufficiently accurate to detect liver metastases. Additional accuracy can be obtained by the combined use of a single liver imaging test and selected laboratory tests. Use of all the liver imaging tests and laboratory tests lowers the accuracy and increases the expense and thus is unnecessary.

Carcinoembryonic Antigen↗
PubMed1982

A prospective study of hepatic imaging in the detection of metastatic disease.

This prospective study of 80 patients compared the results of liver scintiscan, ultrasound, and CT scan to the objective findings recorded at laparotomy. Analysis of these data revealed no significant differences in sensitivity, specificity, or accuracy among these three imaging procedures, although a trend toward increased accuracy of the CT scan was noted. In a composite analysis, the accuracy was not improved by combining two or all three of these examinations. A lesion by lesion analysis revealed the inability of any of the three currently used techniques to accurately detect lesions less than 3 cm in diameter.

Biopsy↗
PubMed1982

hCG beta producing pineal choriocarcinoma.

A patient is described with tumours in the region of the pineal gland and anterior hypothalamus associated with high levels of hCG beta in the serum and cerebrospinal fluid (CSF). He presented aged 19, with hypopituitarism, but persistent secondary sexual characteristics. LH immunoreactivity in serum was due to the hCG beta which probably caused the elevated level of testosterone. Following cranial irradiation the tumour became undetectable and hCG beta was eradicated from the serum and CSF. The patient later died because of an intramedullary metastasis of choriocarcinoma in the cervical spinal cord. The endocrine details of six previously reported intracranial neoplasms which have been shown to secrete hCG beta are reviewed. Only two of these involved the pineal region. Chorionic gonadotrophin production by this tumour enabled early detection of its recurrence. It is unclear how often precocious puberty is caused by tumours producing hCG beta, but patients presenting either with that problem or a pineal tumour should have circulating hCG beta measured.

Adult↗
PubMed1982

Use of functional maps in renal scintigraphy to detect segmental arterial lesions.

Renography using a gamma camera, a minicomputer, [123I]orthoiodohippurate ([123I]OIH), and a canine model was employed to evaluate computer-generated maps of regional renal function. Renograms were obtained before and after ligations of the right renal arterial branch in four dogs, with subsequent angiographic and histologic confirmation of the lesions. Postoperative time-activity curves were normal. Washout and persistence index in three of four right kidneys showed regional abnormality. Functional renal mapping may provide a clinical technique for evaluating human renal vascular hypertension.

Animals↗
PubMed1982

Posttreatment laparotomy as a guide to management in patients with Hodgkin's disease.

Staging laparotomy and splenectomy were performed on 46 adult patients after combination chemotherapy for advanced Hodgkin's disease (HD). There was no preoperative evidence of intra-abdominal disease in 32 patients, 27 of whom were in complete clinical remission, while five had only residual mediastinal abnormalities. In the remaining 14 patients, there was clinical suspicion of active HD. Histologically abnormal tissue was obtained from 19 of 46 (41%) operations. Active abdominal HD was detected in six of 46 patients (13%) or in six of 19 patients having previous evidence of intra-abdominal disease (31%). The spleen was involved in all patients, and in two of these patients there was evidence of both active and ablated disease. Pathologic evidence of ablated HD was detected in 13 patients. The prediction of active intra-abdominal HD, by lymphography or by computerized tomographic scanning, following mustine, vinblastine, procarbazine, and prednisolone therapy, was frequently inaccurate. There was no operative mortality. Morbidity was similar to that of pretreatment laparotomy. At a median followup of 26.5 months (range 5-59), 39 of 40 patients with no evidence of active abdominal HD remain in continuous remission. The contribution of posttreatment laparotomy toward the management of patients with HD is discussed.

Adolescent↗
PubMed1981

A microsomal fraction of Cryptococcus neoformans induces lymphocyte blastogenesis in infected guinea pigs.

Differential centrifugation of a homogenate from a mechanically disrupted, acapsular isolate of Cryptococcus neoformans resulted in a 105,000 x g supernatant (105 K) and a microsomal fraction (MS), both of which were capable of eliciting specific delayed cutaneous hypersensitivity and in vitro blastogenesis in infected guinea pigs. Polyacrylamide gel electrophoresis revealed two major proteins in the MS and seven proteins in the 105 K fractions. Electron microscopy of the MS showed both membranes and ribosomes. In vitro lymphocyte blastogenesis elicited by 1 to 10 micrograms/ml of antigens was maximal after 4 days of incubation; the reacting populations were peripheral blood leukocytes (PBL) and peritoneal exudate cells (PEC). Spleen cells of infected animals were unresponsive to in vitro antigenic stimulation. A simplified schedule of priming animals was infection with a single dose of virulent cryptococci. Under these conditions 3 of 6 animals' PBL responded with stimulation ratios of 6.55, 21.1, 35.42 to the MS and 1.41, 9.33, 17.39 to the 105 K antigens at 1 microgram/ml. Four of six animals' PEC response were positive with stimulation ratios of 2.62, 2.72, 4.02 and 7.20 towards MS, and 2.62, 5.13, 5.71, 10.01 to the 105 K antigens at 1 microgram/ml. When small capsule and large capsule isolates were used for infection, the small capsule form was not isolated from the brain, in contrast to its isolation from 2 of 3 animals receiving large capsule forms. Two of three animals in each group responded with blastogenic indices more vigorous in the PBL, and the most potent antigen was MS. There was no obvious difference in lymphocyte reactivity between the two groups.

Animals↗
PubMed1981

Gallium-67 scanning to stage the alveolitis of sarcoidosis: correlation with clinical studies, pulmonary function studies, and bronchoalveolar lavage.

Current concepts of the pathogenesis of sarcoidosis suggest that the alveolitis of this disorder is related to increased numbers of mononuclear phagocytes and activated T-lymphocytes within the lung. To determine if 67Ga scanning, a procedure commonly used in the evaluation of inflammation, would be useful in staging the alveolitis of sarcoidosis, we studied 41 patients with this disorder and correlated estimates of pulmonary 67Ga accumulation with clinical, roentgenographic, physiologic, and bronchoalveolar lavage studies in these patients. Although 65% of patients with sarcoidosis showed increased amounts of 67Ga accumulation in the lung compared with control subjects, only weak correlations (r less than +/- 0.42, all comparisons) were found between the degree of gallium uptake and the clinical, roentgenographic, or physiologic data. In contrast, there was a strong correlation of 67Ga uptake and the number of lymphocytes and T-lymphocytes recovered from the lungs of these patients by bronchoalveolar lavage (p less than 0.0001, r greater than or equal to 0.67, both comparisons). This data suggested that gallium uptake reflects the intensity of the T-lymphocytes mediated component of the alveolitis in sarcoidosis. Because 67Ga scans are noninvasive, simple to perform, and widely available, they should prove useful to stage the activity of sarcoidosis and to make decisions regarding therapy directed against the alveolitis of the disease.

Adult↗
PubMed1981

Parathyroid imaging after intraarterial injections of [75Se]selenomethionine.

Thirteen patients with persistent hyperparathyroidism after unsuccessful neck surgery were given up to 250 microCi [75Se]selenomethionine intraarterially during parathyroid arteriography, gamma-Camera images of the neck and mediastinum localized abnormal parathyroids in four of five patients receiving complete injections, despite very small glands or unsuccessful arteriograms in some of the patients. Correctly localizing images were obtained in three patients receiving incomplete injections. However, images in five of eight of the remaining patients receiving incomplete injections showed areas of false positive uptake, and there was no way preoperatively to distinguish these from the true positive studies. We conclude that intraarterial injection of radioselenomethionine is a simple supplementary procedure in patients undergoing arteriography that may, with proper technique, be useful in identifying small foci of abnormal parathyroid tissue.

Humans↗
PubMed1980

Diphtheria carriers in Manchester: simultaneous infection with toxigenic and non-toxigenic mitis strains.

A toxigenic strain of Corynebacterium diphtheriae mitis was isolated from a 10-week-old baby with membranous tonsillitis, and over the next 6 months thirty-nine symptom-free carriers of nitrate-positive mitis strains were found. All carriers were cleared by 14 days' treatment with erythromycin, though several relapsed after a 5-day course. Four contacts carried both toxigenic and non-toxigenic mitis strains; epidemiological evidence and phage studies suggest that these had a common origin. These findings have implications for the epidemiology of diphtheria and for the routine testing of isolates for toxigenicity.

Bacterial Toxins↗