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Biomedical subjects

J H Turner

Publications and source records attributed to J H Turner.

At least 37 records · Page 2Linked to original sources
PubMed1991

A phase II study of treatment of painful multifocal skeletal metastases with single and repeated dose samarium-153 ethylenediaminetetramethylene phosphonate.

A phase II study of 153Sm ethylenediaminetetramethylene phosphonate (153Sm-EDTMP) palliative treatment was conducted on 23 patients with painful disseminated skeletal metastases. The administered activity of 153Sm-EDTMP was determined by prospective dosimetry and the radiation absorbed dose to bone marrow was fixed at 2 Gy. Symptomatic relief of bone pain was experienced by 14 of 23 evaluable patients (61%) with a median duration of 8 weeks (range 0-40). Toxicity was limited to myelosuppression with median nadir counts of leucocytes 3.3 x 10(9)/1 (range 1.0-7.5) and platelets 133 x 10(9)/1 (range 24-176) occurring at 2 weeks and 4 weeks, respectively. Retreatment with 153Sm-EDTMP was studied in 15 patients, including in 4 of the 23 patients treated with a single dose. The retreatment median radiation absorbed dose to red marrow was 1.9 Gy given at a median of 9 weeks (range 6-38) after initial treatment. Good control of pain was obtained in 13 of these patients (87%). Both the median duration of pain control (24 weeks) and survival (9 months) in the retreated group were substantially greater than for patients treated with a single dose, where duration was 8 weeks and survival 4 months. Additional toxicity in the retreated patients was confined to anaemia which required blood transfusion in 9 of the 15 patients (60%).

Adult↗
PubMed1989

Samarium-153 EDTMP therapy of disseminated skeletal metastasis.

153Sm-EDTMP (ethylenediaminetetramethylene phosphonate), prepared from a kit, was administered to 28 patients in a clinical trial of therapy for painful skeletal metastases unresponsive to all conventional treatment. The 103 keV gamma emission of 153Sm was utilized for prospective individual estimation of beta radiation absorbed dose to red marrow to minimize myelotoxicity and provide optimum internal radiotherapy to skeletal metastases in each patient. Pain relief occurred within 14 days of administration of 153Sm-EDTMP in 15 of 19 patients (79%) who could be evaluated at 6 weeks, when clinical response was maximal. Duration of response ranged from 4 to 35 weeks. Recurrence of pain responded to retreatment with 153Sm-EDTMP in five of eight cases. No dose-response relationship was apparent for pain relief but reversible myelotoxicity was frequently observed at radiation absorbed doses to bone marrow greater than or equal to 270 cGy. Dosimetry calculation was based on pharmacokinetic studies of a tracer administration of 153Sm-EDTMP in each patient. Assumptions inherent in this prospective method of predicting dose to bone marrow were validated experimentally. Biodistribution studies in rats demonstrated rapid skeletal uptake and long term retention of 153Sm-EDTMP in bone over 5 days. Urinary clearance accounted for 40% of injected dose, and less than 1.0% of administered activity was retained in non osseous tissue. Microdensitometry of autoradiographs of sheep vertebra and femur confirmed surface uptake of 153Sm-EDTMP in cortical bone and demonstrated relatively high trabecular bone activity which is the major component of radiation absorbed dose to bone marrow. Haematological studies in rabbits showed 153Sm-EDTMP-induced myelotoxicity to be transient and no histopathological abnormalities were demonstrable with doses ten times greater than those administered to patients.

Animals↗
PubMed1989

A phase I study of samarium-153 ethylenediaminetetramethylene phosphonate therapy for disseminated skeletal metastases.

Thirty-five patients with disseminated skeletal metastases from a variety of tumor types underwent clinical trial of samarium-153 ethylenediaminetetramethylene phosphonate (153Sm-EDTMP) on a day-patient basis. Individual beta radiation dosimetry was based on pharmacokinetic studies of a 20 mCi tracer dose of 153Sm-EDTMP. The retained skeletal activity varied unpredictably from 40% to 95% of the administered dose, but in all patients greater than 98% of the nonosseous activity was cleared in the urine within 6 hours. Prospective calculation of radiation dosimetry in each patient permitted an accurate dosage schedule based upon total red marrow exposure, starting at 100 cGy and escalating to 280 cGy to define the dose-limiting myelotoxicity. Pain was relieved in 22 of 34 evaluable patients (65%) for periods ranging from 4 to 35 weeks, following a single administration of 153Sm-EDTMP. Recurrence of pain responded to retreatment with 153Sm-EDTMP in five of nine patients. The dose-limiting toxicity was myelosuppression manifested particularly by delayed thrombocytopenia. Platelet counts less than 100 x 10(9)/L occurred in 42% of courses when bone marrow radiation absorbed dose exceeded 200 cGy. Myelosuppression was transient and platelet counts had recovered to pretreatment levels within 10 weeks of treatment. 153Sm-EDTMP is effective for the amelioration of pain due to disseminated skeletal metastases particularly with carcinoma of breast or prostate where 83% of patients experienced pain relief. In 15 of the 34 evaluable patients there was evidence of stabilization or regression of skeletal metastases on radiographs and follow-up technetium-99m methylene diphosphonate (99mTc-MDP) bone scans.

Bone Neoplasms↗
PubMed1989

Labeling of monoclonal antibodies with samarium-153 for combined radioimmunoscintigraphy and radioimmunotherapy.

The labeling of a monoclonal antibody K-1-21 with 153Sm has been investigated using the bifunctional chelate cyclic diethylenetriaminepentaacetic acid (DTPA) anhydride. Labeling efficiencies greater than 60% were obtained using high specific activity [153Sm]chloride and a cDTPAa:MAb conjugation ratio of 20:1. The resultant labeled antibody had a s.a. greater than 150 MBq.mg-1 and a % retained immunoreactivity greater than 90%. Imaging and biodistribution studies in a rat model demonstrated that specific uptake of 153Sm-K-1-21 into s.c. implants of the target antigen could be clearly detected in scintigrams at 6 days p.i. The specific uptake (1.90 +/- 0.45% ID/g, 19.95 +/- 2.20 Implant:Blood ratio) compared favorably to 131I- and 111In-labeled K-1-21 (2.52 +/- 0.20 and 3.33 +/- 0.20% ID/g, 7.69 +/- 0.45 and 10.10 +/- 0.60 I:B, respectively). Labeling of MAbs with 153Sm for combined scintigraphy/therapy is feasible at clinically appropriate specific activities using cDTPAa, with the resultant conjugates retaining immunoreactivity and in vivo antigen localization.

Animals↗
PubMed1987

Samarium-153 chelate localization in malignant melanoma.

153Sm, a radiolanthanide of half life 46.27 h, has a gamma emission of 0.103 MeV which is well suited to imaging, it is also a moderate energy beta emitter and tumour localization of various 153Sm chelates was evaluated in B16 murine melanoma to assess their endoradiotherapeutic potential. 153Sm was prepared from enriched 152Sm in the Australian Nuclear Science and Technology Organization reactor. 153Sm chelates were prepared from 153Sm-chloride and their chromatographic behaviour characterized. Tumour and organ uptake of 153Sm-chloride, 153Sm-citrate and the 153Sm chelates, DTPA, HEDTA, HIDA, BZ, PBH, PIH and NTA were measured at 1, 6, 24 and 48 h after intravenous administration to C57 black mice bearing either melanotic or amelanotic B16 melanoma of mean size 0.75 cm3. Histopathological examination of the tumours at each passaging assured comparability of the degree of melanogenesis and the absence of necrosis. 153Sm-chloride was immobile on chromatography and the rapid hepatic accumulation of both 153Sm-chloride and 153Sm-citrate was attributed to in vivo formation of a colloid. In contrast, 153Sm-DTPA, moving at the solvent front on chromatography, showed no reticuloendothelial accumulation in vivo and was rapidly excreted by the kidneys without tumour uptake. The other 153Sm chelates were of intermediate stability and all localized in both melanotic and amelanotic tumours, although to a significantly lesser degree than 67Ga-citrate. The relatively high 153Sm-HIDA activity in liver and 153Sm-NTA activity in bone impaired tumour definition, but on imaging of all the 153Sm chelates only 153Sm-DTPA failed to demonstrate the B16 melanoma and the best tumour delineation was obtained using 153Sm-HEDTA.

Animals↗
PubMed1985

Post-tubal sterilization syndrome--a misnomer.

Menstrual parameters and gynecologic symptoms of 389 women who underwent laparoscopic tubal banding were studied prospectively and longitudinally. Previous oral contraceptive users exhibited an immediate increase in menstrual flow and dysmenorrhea, which declined slightly with time. No such changes occurred in women who used other methods of temporary contraception. A significant increase in noncyclic pelvic pain, independent of previous contraceptive usage, developed only in women greater than 38 years of age. Menstrual cycles and dyspareunia were not affected. A small control group of women whose husbands underwent vasectomy showed no significant changes in any of these parameters.

Adult↗
PubMed1985

Localization of 11C-radiopharmaceuticals in the Greene melanoma of hamsters.

Seventy Syrian golden hamsters bearing SC transplants of Greene melanoma were used to evaluate the degree of tumour uptake of several 11C-radiopharmaceuticals selected for their potential specificity for melanoma. Tissue distribution studies were performed at 30 and 60 min after IV injection of 11C-compounds and compared with the 24-h uptake of 67Ga-citrate. Gamma camera images were also compared. The highest tumour uptake at 1 h was observed with 11C-methionine (2.42% +/- 0.72%) and although activity in liver, spleen and kidney exceeded that in melanoma the tumour was demonstrated on gamma camera imaging. Melanoma localisation of 11C-chlorpromazine, 11C-flunitrazepam and 11C-ketanserine was comparable at 1% of the dose injected per gram of tumour. High activity in other organs, particularly liver, exceeded uptake in melanoma and attempts at tumour imaging were unsuccessful. Tumour accumulation of 11C-methiodide quinuclidinyl benzylate (MQNB), an 11C-imidazobenzodiazepine (Ro-15-1788) and 14C-pimozide was low and imaging studies were not attempted. None of the 11C-radiopharmaceuticals evaluated for melanoma affinity matched that of 67Ga-citrate. The 24-h tumour uptake of 67Ga-citrate was 4.07% +/- 1.37% dose injected per gram which allowed delineation of the melanoma by gamma camera imaging.

Animals↗
PubMed1985

Predicting in vitro tissue culture growth for cytogenetic evaluation of stillborn fetuses.

A prospective study was undertaken of 131 perinatal deaths to determine whether gestational age, body weight, maceration degree and autopsy interval influenced successful in vitro tissue culture for cytogenetic evaluation. Perinatal populations were categorized as neonatal death (NND), fresh stillbirth (FSB), or graded as macerated stillbirth (MAC-0, MAC-1, MAC-2, MAC-3). Metaphase production by at least 15 cells separated 'growth' from 'no growth' categories after sampling liver, kidney and spleen. Body weight and degree of maceration were predictive of successful 'growth', while gestational age and autopsy interval were not. Body weight was significant in separating 'growth' from 'no growth' in NND (P = 0.05), FSB, MAC-0 and MAC-1 (P = 0.01). Growth probabilities were 0.78 (NND), 0.57 (FSB), 0.49 (MAC-0), 0.38 (MAC-1) and zero for MAC-2 and MAC-3. We conclude that (a) tissues from MAC-2 and MAC-3 fetuses do not grow and thus need not be sampled at autopsy, (b) maceration degree and body weight can be used to predict the growth probability in the other categories, (c) tissue samples can be taken during daylight hours, since autopsy interval does not influence successful growth provided the fetus is refrigerated at 4 degrees C, (d) all of the above conclusions have cost-efficiency implications for cytogenetic laboratories.

Body Weight↗
PubMed1983

Development of a carcinogen-induced rat colon cancer with lymph-node metastases.

The progression from normal colonic mucosa to invasive adenocarcinoma of the colon with lymph-node metastases was documented in Sprague-Dawley rats receiving 30 mg of N-methyl-N-nitrosourea via intrarectal injections. Histologically, these tumors closely resemble human colonic cancer. This model is predictable and reproducible. It offers a genetically nonidentical rat model for the development of cancer biology and therapy models.

Animals↗
PubMed1983

Post-traumatic avascular necrosis of the femoral head predicted by preoperative technetium-99m antimony-colloid scan. An experimental and clinical study.

We used technetium-99m antimony colloid to visualize the bone marrow of the head of the femur within twenty-four hours after interruption of the blood supply by subcapital osteotomy and section of the ligamentum teres in thirteen rabbits and within twenty-four hours after a subcapital fracture in thirty patients. Of the rabbits, all showed loss of marrow radioactivity over the affected femoral head. Bone-imaging with technetium-99m methylene diphosphonate, in contrast, failed to demonstrate any abnormality in the avascular head of the femur for as long as forty-eight hours after osteotomy. This difference between the marrow scan and the bone scan was attributed to earlier loss of function in the marrow cells than in the osteocytes. The thirty patients who had a preoperative scan within twenty-four hours after sustaining a subcapital fracture were treated by internal fixation with a Richards screw and plate and were followed for as long as two years, or until the patient died or radiographs showed evidence of avascular necrosis. The preoperative technetium-99m antimony-colloid activity in the head of the fractured femur was normal in sixteen patients and absent in fourteen; two of the fourteen had no activity in either hip, which precluded assessment of the fractured hip in these patients. In fifteen of the sixteen hips, preservation of the uptake in the marrow of the head of the fractured femur preoperatively predicted normal healing. Late segmental collapse developed in the remaining hip. In eleven of the twelve patients who had loss of marrow activity in the femoral head preoperatively, avascular necrosis developed within two years. One patient was asymptomatic at two years, with no evidence of necrosis. The two patients who had no marrow activity in either hip both had avascular necrosis within one year after surgery.

Aged↗
PubMed1981

Incorporation of bacteriophage DNA into the genome of cultured human lymphocytes.

After exposure of phytohemagglutinin-stimulated human lymphocytes to high doses of tritiated-thymidine labelled phi X-174 or T2 bacteriophage, label from the phage genome became incorporated into lymphocyte DNA. Exposure to bacteriophage DNA, whether biologically active, inactive, or fragmented, had a depressive effect on lymphocyte DNA replication. Incorporation of label from phage DNA into the lymphocyte DNA, however, was maximum for biologically active phage.

Cells, Cultured↗
PubMed1980

Technetium-99m antimony colloid for bone-marrow imaging.

Technetium-99m antimony colloid was prepared in our laboratory for bone-marrow imaging. Optimal production of colloid particles of size range 1-13 nm was achieved by the use of polyvinylpyrrolidone of mol. wt. 44,000. Electron microscopy was used to size the particles. Studies in rabbits showed exclusive concentration in the subendothelial dendritic phagocytes of the bone marrow. Pseudopods from these cells were found to traverse interendothelial junctions and concentrate colloid from the sinusoids. Imaging studies of bone marrow in rabbits showed the superiority of the Tc-99m antimony colloid over the much larger colloidal particles of Tc-99m sulfur colloid. Tissue distribution studies in the rat confirmed that bone-marrow uptake of Tc-99m antimony colloid was greater than that of Tc-99m sulfur colloid, although blood clearance was much slower.

Animals↗
PubMed1979

Legal and social issues in medical genetics.

This paper was written for the purpose of providing the physician with a perspective of the conflicting scientific, individual, and societal interests which have been evoked by increasing medical and scientific innovation in the area of human genetic disease. In it the following subjects are considered: (1) obtaining genetic information by amniocentesis, by genetic counseling, and by screening; (2) disclosure of genetic data to the patient; (3) inclusion of genetic data on the medical record; (4) courses of action available to the individual after disclosure of genetic information, i.e., abortion, sterilization, etc.; (5) the state and involuntary sterilization; and (6) prohibitions on marriage.

Abortion, Legal↗