A novel method of continuous cage-side monitoring of hyperthyroid cats treated with radio-iodine.

A continuous monitoring system (MGP DM2000X) was assessed for monitoring γ radiation emissions and determining appropriate isolation times for hyperthyroid cats treated with radioactive iodine (I(131)). Daily radiation emitted by 12 cats who had received a range of doses of I(131) (80-200 MBq) was measured and average background radiation readings deducted. The effective half-lives of the I(131) in the cats were found to have a median of 2.54 days (range 1.40-3.24 days). Cats treated with 200 MBq emitted 5 µGy/day more exposure than cats treated with lower doses throughout the study period (P=0.032). All cats were found to emit a total radiation dose exposure less than 100 µGy (range 0-43 µGy) during days 18-21 of isolation. The potential additional dose exposure to owners was calculated at various days that might be considered for the cats to be returned to their owners. Using this provisional data, maximum isolation periods at this institution could be safely reduced to 17 days as long as certain precautions are followed. This preliminary study demonstrated that this novel cage-side monitoring system can be used to calculate the effective half-life of I(131) and to measure γ radiation exposure from treated cats, which may assist other institutions in determining appropriate isolation times for individual cats.

Incidence and correlates of radiation dermatitis in children and adolescents receiving radiation therapy for the treatment of paediatric sarcomas.

AIMS: To investigate the relationship between the maximum grade of skin toxicity, radiation dose and clinical variables in children receiving treatment for sarcomas involving the bone and soft tissue. MATERIALS AND METHODS: Between January 2003 and July 2006, 82 patients with musculoskeletal tumours on an Institutional Review Board (IRB)-approved prospective study at St. Jude Children's Research Hospital received three-dimensional conformal or intensity-modulated radiation therapy for local tumour control. Radiation dermatitis was graded according to the National Cancer Institute's Common Toxicity Criteria version 2.0 during and after radiation therapy. The dose to the skin was calculated for each patient from the radiation treatment plan. RESULTS: The radiation doses delivered to the primary tumour ranged from 4140 to 7020cGy, with a mean dose of 5040cGy. The maximum recorded grade of skin toxicity was: grade 0: seven patients (8.6%); grade 1: 26 patients (31.7%); grade 2: 37 patients (45.1%); grade 3: 10 patients (12.2%); grade 4: two patients (2.4%). A significant association for increased grade of skin toxicity was observed between dose (P<0.01), volume of skin treated above 4000cGy (P=0.03), use of a bolus (P<0.01), Caucasian race (P<0.01) and related pain (P<0.01). CONCLUSIONS: These findings suggest that the delivered dose, use of a bolus, the volume treated, and race may be used in the clinical setting to predict patients at risk for skin toxicity. Alterations in treatment technique and early therapeutic intervention may help to reduce or eliminate radiation-induced skin side-effects and associated pain.

Management of the giant-cell tumours of the distal radius.

BACKGROUND: Giant-cell tumour of the distal radius is a rare neoplasm that affects the peri-articular metaphysial region of the bone. Curettage alone or with bone grafting has been reported to be associated with high incidence of local recurrence in these tumours. In the present series, we report the results of curettage only as the treatment for primary giant-cell tumour of the distal radius carried out at a single centre. PATIENTS AND RESULTS: A total of 287 patients with giant-cell tumour have been referred to us for treatment over the last 28 years; 24 of these were found to have lesion in the distal radius. One patient underwent endoprosthetic replacement of the distal radius. The remaining 23 patients underwent curettage of the primary neoplasm. Four out of the 23 (17%) patients developed local recurrence of disease, The mean time to local recurrence was 17 months (range, 9-27 months). Complications such as collapse of the articular cartilage are more common in patients with an extensive soft tissue component of the tumour. CONCLUSIONS: Curettage alone is adequate treatment for the majority of patients with giant-cell tumours of the distal radius but some form of stabilisation may be required in the presence of extensive bone destruction.

Effects of tamoxifen, fluphenazine and estradiol on ATP levels in preoptic area and hypothalamic slices from ovariectomized rats.

Tamoxifen, the major adjuvant drug treatment for estrogen-dependent breast cancer, has been shown previously to affect both estrogen-dependent and calcium/calmodulin-dependent pathways. In the current study, we developed an in vitro slice system to study the effects of tamoxifen on ATP levels in hypothalamic (HTH) and preoptic areas (POA) of the rat brain. Baseline data showed that, following a 2-h incubation, HTH and POA slices had comparable ATP levels to hippocampal slices, a system used extensively by researchers examining the metabolic responsiveness of the hippocampal region (HPC) of the brain. HTH-POA slice ATP levels remained steady for 2, 4 and 6 h, but fell to 11% of initial levels by 12 h. Neurons from HTH-POA slices incubated for 4 h appeared healthy and demonstrated robust protein synthesis as measured autoradiographically by incorporation of [3H]leucine. We explored the effects of tamoxifen (TAM), fluphenazine (FLU) and estradiol (E2) on ATP levels in HTH and POA slices. The effects of TAM were complex: a 4-h incubation with 10-6 M TAM led to decreased ATP levels in HTH (but not POA), and a 4-h incubation with 10-8 M led to increased ATP levels in POA (but not HTH); a 15-min exposure to 10-6 M TAM decreased ATP levels in POA (but not HTH) slices, while the exposure of slices to the lower concentration of TAM was without effect in either area. As with higher concentrations of TAM, 4-h incubation with 10-6 M FLU decreased ATP levels in HTH (but not POA), while incubation with E2 did not affect slice ATP levels. These data are consistent with the hypothesis that both TAM and FLU alter ATP levels in HTH slices via calmodulin- or calcium-mediated processes.

Characterization of hemolytic and cytotoxic Gallysins: a relationship with arylphorins.

Gallysin-1, an inducible effector protein in the protective response of Galleria mellonella larvae is a 75 kDa component of hemolytically active material (HAM) isolated from immune cell-free hemolymph. The sequence of the first 20 N-terminal amino acids of the antibacterial protein Gallysin-1 is identical to the predicted sequence of the first 20 amino acids of the Galleria arylphorin Lhp76 (larval hemolymph protein 76). A murine monoclonal antibody to the 20 amino acid N-terminal peptide of Gallysin-1 (GYPQYHYDVETRKLDPSLVN) provides additional evidence for a link between Gallysin-1 and Lhp76, and is used to characterize HAM further. HAM, initially characterized as a mixture of two proteins, Gallysin-1 and a 69 kDa component is now identified as a 450-500 kDa heteromultimer, designated Gallysin. In vivo levels of Gallysin rise during the effector phase of an induced immune response. The monoclonal antibody inhibits the hemolytic activity of Gallysin. In addition to a hemolytic activity for mammalian erythrocytes, Gallysin possesses a cytotoxic activity for the human tumor cell line, K562. Lipopolysaccharides (LPS) and a Pseudomonas aeruginosa vaccine induce a cytotoxic activity which reaches its maximum levels in the hemolymph early (2 hours post-vaccination) in the protective response. The partially purified cytotoxic material (Cyt-M) obtained from cell-free hemolymph collected 2 hours after vaccination has hemolytic activity and shows structural similarities to Gallysin and Lhp76. The previously established role of Gallysin-1 as an effector protein in the protective response of Galleria mellonella indicates that arylphorins may play a role in insect immune responses.

ICI 182,780: a pure antiestrogen that affects behaviors and energy balance in rats without acting in the brain.

ICI 182,780 is one of a new class of steroidal antiestrogens that differs from nonsteroidal antiestrogens, such as tamoxifen, in a number of respects. 1) It is bound by estrogen receptors with a high affinity, similar to that for estradiol. 2) It is a "pure" antiestrogen in that it does not mimic any of the effects of estradiol. 3) This class of antiestrogens does not seem to be bound by antiestrogen binding sites. 4) ICI 182,780 may not be active in the brain after peripheral administration. Indeed, ICI 182,780 blocked in vivo cell nuclear binding of [3H]estradiol in uterus, pituitary, and adipose tissue but not in hypothalamus-preoptic area. In vitro, ICI 182,780 competed for binding by neural estrogen receptors with an affinity comparable with that for estradiol. When given to ovariectomized rats, ICI 182,780 did not mimic any of the actions of estradiol. Instead, ICI 182,780 treatment completely blocked the uterotrophic effects of estradiol and attenuated the actions of estradiol on linear growth, carcass fat content, fat pad weight, and sexual receptivity. Treatment with ICI 182,780 also attenuated the estrogenic effects of tamoxifen on food intake, body weight and composition, linear growth, and uterine weight. These findings support the concept that, in addition to its actions in the brain, estradiol can act peripherally to modulate regulatory behaviors, energy balance, and estrous behavior. They are also consistent with the hypothesis that nonsteroidal antiestrogens, such as tamoxifen, affect energy balance via estrogen receptors, rather than antiestrogen binding sites.

Estrogens and antiestrogens: actions and interactions with fluphenazine on food intake and body weight in rats.

Treatment of ovariectomized rats for 3 days with 2 micrograms estradiol benzoate (E2B), 6 micrograms ethinyl estradiol, or 1-2 mg of either of the antiestrogens nafoxidine or tamoxifen led to similar decreases in food intake, body weight gain, adipose tissue lipoprotein lipase activity, and hepatic fatty acid synthetase activity, despite their different effects on uterine growth and induction of progestin receptors in pituitary and adipose tissue. Longer-term (2 wk) treatment with tamoxifen resulted in similar transient changes in food intake and body weight gain, as did treatment with E2B. Daily administration of 50 micrograms fluphenazine (FLU) led to significant decreases in body weight, although there was no change in food intake. Concurrent administration of FLU with either E2B or tamoxifen led to additive effects on body weight and food intake change. None of the treatments had any effect on in vitro binding of [3H]tamoxifen to antiestrogen binding sites in pooled hypothalamic-preoptic area samples.

Complex balance reactions in different sensory conditions: adolescents with and without idiopathic scoliosis.

We measured simple and complex balance responses with a force plate stabiliometer in 70 adolescents: 50 with idiopathic scoliosis (IS) and 20 controls. In stable static balance positions, the two groups performed similarly, but when the visual and somatosensory systems were challenged simultaneously, the IS group had a significantly higher mean body sway than the controls. Within the IS group, children with mild, nonprogressive curves that had not been operated on were significantly more likely to maintain their balance when the visual and somatosensory systems were challenged simultaneously than those with curves > or = 40 degrees, who had had surgery, and who had more rapid progression of the curve. These findings suggest that adolescents with IS have normal balance in static, stable positions but are not able to perform as well as normal adolescents in sensory-challenged positions, particularly if they have a severe, progressive curve. Longitudinal studies are needed to determine whether balance dysfunction can be used to predict progression of the curve.

Antiestrogen binding sites in brain and pituitary of ovariectomized rats.

In addition to interacting with estrogen binding sites in a number of tissues, antiestrogens have recently been shown to interact with a separate, estrogen-non-compatible, antiestrogen-specific binding site (AEBS). In order to better understand possible mechanisms by which the antiestrogens may effect behavioral and physiological changes, we have examined AEBS in several areas of the brain and pituitary in adult, ovariectomized rats. Single point binding assays with 2 nM [3H]tamoxifen (TAM) in the presence of saturating amounts (1 microM) E and +/- 1 microM TAM indicated the existence of specific binding to AEBS throughout the brain and pituitary. In most areas of the brain (cortex, cerebellum, amygdala, area postrema/nucleus of the solitary tract region) as well as pituitary. Scatchard analyses revealed the presence of a single AEBS with a dissociation constant (Kd = 1-4 x 10(-9) M) similar to that previously reported for other tissues. However, in both hypothalamus and preoptic area, an additional, higher affinity site (Kd = 6-9 x 10(-11) M) was found. Competitive inhibition studies revealed that there was little competition by the potent estrogen agonist, diethylstilbesterol, for AEBS binding. Antiestrogens competed in the following order: tamoxifen greater than or equal to nafoxidine much greater than keoxifene. Additional competitive inhibition studies were run using neurotransmitter antagonists. The phenothiazines, chlorpromazine and fluphenazine, bind to both D1 and D2 dopamine receptors and effectively compete with [3H]TAM for binding at the AEBS. Other pharmacological substances, including specific antagonists of the D2 sites, as well as antagonists of the norepinephrine, opiate, histamine, GABA and acetylcholine systems, were ineffective competitors for [3H]TAM binding.

Flexible cystoscopy as an adjunct to extracorporeal shockwave lithotripsy.

Ancillary procedures associated with extracorporeal shockwave lithotripsy (ESWL) include placement and subsequent removal of double pigtail ureteric stents. A simple new technique has been developed for the insertion of these stents. Using the flexible cystoscope, the procedure is performed on an out-patient basis under local anaesthesia. Placement of the stents was successful in 30/34 patients and removal was successful in 14/14 patients.

Percutaneous ablation of canine prostate using transrectal ultrasound guidance. Absolute ethanol and Nd:YAG laser.

Percutaneous absolute ethanol injections and Nd:YAG laser ablations were performed bilaterally in canine prostates (N = 13) using transrectal ultrasound guidance. Seventy-one percent (10/14) of the ethanol injections produced an intraglandular focus of hemorrhagic necrosis. Associated morbidity of ethanol injections included necrosis of the external prostatic sphincter and mucosa of the urethra and bladder. Ninety-two percent (11/12) of the laser ablations produced intraglandular foci of thermal tissue damage, which had distinct margins of transition between necrotic and viable cells. The areas of ablation were well visualized by ultrasound and had minimal associated morbidity. The results of this study demonstrate the technical feasibility and low potential morbidity of transrectal ultrasound guided Nd:YAG laser ablations in the canine prostate.

Prostate cancer: comparison of transrectal US and digital rectal examination for screening.

The authors examined 784 self-referred men over age 60 years to compare clinical usefulness of transrectal ultrasound (US) and digital rectal examination in a screening program for prostate cancer. Biopsy was performed in 77 cases, 83% (64 of 77) for abnormalities detected with transrectal US and 38% (29 of 77) because of findings at digital examination. Twenty-two cancers were detected, 20 with transrectal US and ten at digital examination. Overall detection rate for prostate cancer with transrectal US was two times higher than that with digital examination (2.6% vs 1.3%). Sensitivity, specificity, and negative predictive value for transrectal US and digital examination were calculated for a range of prevalences (0.028-0.1543). Sensitivity was two times higher for transrectal US than for digital examination. Transrectal US demonstrated 100% (17 of 17) of tumors with the most favorable prognosis (less than or equal to 1.5 cm in diameter) compared with 41% (seven of 17) for digital examination. The authors conclude that transrectal US is more sensitive than digital examination in the detection of prostate cancer, and they advocate broader implementation and evaluation of transrectal US as a tool for early detection.

Factors associated with sexual dysfunction following transurethral resection of the prostate.

A retrospective analysis of 62 consecutive potent patients undergoing transurethral resection of the prostate is described. Each patient was interviewed a minimum of six months following surgery. Potency was retained in 89% of patients but 57% of these experienced a decrease from their preoperative level of function. Three factors were found to be significantly associated with a reduction in postoperative potency. These were systemic disease (p less than 0.001), small prostatic resections (p less than 0.001) and a reduced level of potency preoperatively (p less than 0.01). Of those men retaining a degree of potency, 90% achieved their first erection within two months of the procedure. The full extent of sexual dysfunction following transurethral resection of the prostate has not previously been appreciated, nor have the factors associated with this dysfunction.

Strontium kinetics in metastasized prostatic carcinoma: a comparison with the predictions of impulse response function analysis.

Amongst patients referred for 89Sr palliation of disseminated prostatic carcinoma, we have found wide variations in extent of skeletal metastatic disease and in strontium renal plasma clearance. A numerical technique using impulse response function analysis is reviewed which enables the effect of such variations on the total body, plasma and metastatic strontium retention functions to be calculated. The prediction of the model are compared with kinetic data from patients presenting for radiostrontium therapy, and correlations that have important implications for 89Sr dosimetric studies are confirmed. The simplest kinetic data required to allow for these effects in studies of dose-response and haematological toxicity following radio-strontium treatment are discussed and attention is drawn to a small group of patients who may form a significant exception to the general model.

Human immunodeficiency virus and drug misuse: the Edinburgh experience.

During 1985 many drug abusers who lived in Edinburgh were found to be infected with the human immunodeficiency virus (HIV). As a result an alternative counselling and screening clinic for testing for antibodies to HIV was established for use by drug abusers. Four hundred and forty one patients were counselled in the first year, and over 60% were either drug abusers or their sexual contacts. One hundred and fourteen (26%) patients were positive for HIV antibody, and 100 (88%) of these were current or former drug abusers. The HIV seropositivity rate in drug abusers was 52% but was only 7% in their sexual contacts. Services were provided for these people as well as counselling before and after the test. The cost of this counselling service for the first year was 27,000 pounds or 61.22 pounds per patient. The unexpected mobility of 23% of the Edinburgh drug abusers, particularly to other areas of Britain, suggests that similar services need to be set up elsewhere.

Strontium-89 radionuclide therapy: a dosimetric study using impulse response function analysis.

In a series of patients receiving 89Sr palliation for metastasised prostatic carcinoma, strontium renal plasma clearance was found to vary from 0.14 to 11.81 day-1, and the extent of skeletal metastatic disease seen on 99Tcm-MDP images varied from a few small metastases to a superscan. Using a numerical technique based on impulse response function (IRF) analysis, we have investigated the effect of such variation between patients on 89Sr dosimetry. The whole-body IRF, HWB(t), is defined by the deconvolution of the whole-body strontium retention function, RWB(t), with the plasma retention function, P(t). For patients with minimal metastatic bone disease we assumed HWB(t) = HO(t), where HO is the IRF derived from the International Commission on Radiological Protection model for normal strontium metabolism. The strontium plasma clearance, k, was allowed to vary, and the resulting variation of RWB(t), P(t) and absorbed dose to bone marrow calculated. By convoluting P(t,k) with the IRF measured for a discrete metastasis, the effect of varying k on tumour dose was investigated. Tumour and bone marrow dose were shown to change by a factor of three as k varied over the range observed in patients. For patients with extensive metastatic bone disease we assumed HWB(t) = (1-beta)HO(t) + beta HS(t), where HS was the IRF measured for a superscan patient and beta was a parameter reflecting the extent of skeletal metastatic disease. The effect of varying beta on tumour and bone marrow dose was investigated, and dose shown to decrease by a factor of five as beta increased from zero to unity. Impulse response function analysis was found to be a powerful and useful aid in clarifying the relationship between strontium kinetics and 89Sr dosimetry.

Psychomotor impairment and anticonvulsant therapy in adult epileptic patients.

Using a battery of simple tests, psychomotor performance was assessed in 11 healthy subjects, 14 untreated epileptic patients and 66 epileptics on chronic anticonvulsant medication. Significant differences were found between controls and untreated patients for choice reaction time, card sorting and Simple Simon memory game. Treated patients performed less well than both untreated epileptics and controls in choice reaction time (p less than 0.05; p less than 0.001), card sorting (p less than 0.01; p less than 0.001), Simple Simon (p less than 0.05; p less than 0.001) and finger tapping (p less than 0.05; p less than 0.001). Patients with centrencephalic epilepsy were slower than those with discrete focal EEG abnormalities in reaction time and card sorting. Patients receiving treatment with carbamazepine, phenytoin or sodium valproate alone all performed similarly to each other and to those patients taking anticonvulsant polypharmacy. Monotherapy patients with potentially "toxic" plasma anticonvulsant concentrations did no worse than those within or below the "therapeutic" range. Both the disease and its treatment reduce psychomotor performance. All major anticonvulsants appear to cause a similar degree of impairment across a wide range of concentrations. The effect of chronic anticonvulsant medication on "quality of life" should not be neglected in the pursuit of perfect seizure control.

Diabetes mellitus and primary hepatocellular carcinoma.

In view of the increasing incidence of primary hepatocellular carcinoma in western Europe and concern that this may in part be related to long-term use of drugs which cause hepatic microsomal enzyme induction, we undertook a comparison of long-term drug use in 105 patients with hepatocellular carcinoma and equal numbers of age and sex-matched patients with colorectal tumours and with fractures of femur. We found no patients with hepatocellular carcinoma who were long-term anticonvulsant users and only one who used oral contraceptives. However, we observed a four-fold excess of diabetic patients among the group with hepatocellular carcinoma. This association did not appear to be due to pre-existing haemochromatosis, alcoholic cirrhosis or viral hepatitis. The association was strongest in patients receiving drug treatment for diabetes, but the data, although suggestive, were insufficient to determine whether any specific anti-diabetic agent could be responsible. Further studies are required to elucidate the nature of this unexpected association. An association of this magnitude with diabetes mellitus could account at least in part for the increasing incidence of hepatocellular carcinoma in western Europe.