Transmission ionization chambers for measurements of air collision kerma integrated over beam area. Factors limiting the accuracy of calibration

Kerma-area product meters (KAP meters) are frequently used in diagnostic radiology to measure the integral of air-collision kerma over an area A (integral of A Kc,air dA) perpendicular to the x-ray beam. In this work, a precise method for calibrating a KAP meter to measure integral of A Kc,air dA is described and calibration factors determined for a broad range of tube potentials (40-200 kV). The integral is determined using a large number of TL dosimeters spread over and outside the nominal field area defined as the area within 50% of maximum Kc,air. The method is compared to a simplified calibration method which approximates the integral by multiplying the kerma in the centre of the field by the nominal field area Anom. While the calibration factor using the precise method is independent of field area and distance from the source, that using the simplified method depends on both. This can be accounted for by field inhomogeneities caused by the heel effect, extrafocal radiation and scattered radiation from the KAP meter. The deviations between the calibration factors were as large as +/- 15% for collimator apertures of 5-100 cm2 and distances from the source of 50-160 cm. The uncertainty in the calibration factor using the precise method was carefully evaluated and the expanded relative uncertainty estimated to be +/- 3% with a confidence level of 95%.     

Isolation of novel and known genes from a human fetal cochlear cDNA library using subtractive hybridization and differential screening

V79 (Chinese hamster lung fibroblast) cell lines expressing a functional recombinant phenobarbital-inducible rat liver UDP-glucuronosyltransferase (UGT), i.e., UGT2B1, were established. Western blot analysis of positive colonies, using anti-rat liver UGT antibodies, revealed the presence of an immunoreactive polypeptide of the expected molecular mass of 52 kDa. The substrate specificity of the recombinant enzyme toward > 100 compounds was determined. Phenolic and alcoholic substrates included 4-methylumbelliferone, 4-hydroxybiphenyl, chloramphenicol, and testosterone, but a range of carboxylic acids of both endogenous (medium-chain saturated fatty acids, long-chain polyunsaturated fatty acids, and bile acids) and exogenous (profen nonsteroidal anti-inflammatory drugs, fibrate hypolipidemic agents, and sodium valproate) origin were also accepted, indicating that the enzyme was capable of forming both ether- and ester-type glucuronides from various structurally unrelated compounds. Determination of apparent kinetic constants for the glucuronidation by UGT2B1 of selected aglycones revealed a high maximal velocity toward the 3-position of morphine (49.3 +/- 2.2 nmol/min/mg of protein), compared with other known substrates such as 4-methylumbelliferone (2.67 +/- 0.11 nmol/min/mg of protein) or clofibric acid (0.06 +/- 0.02 nmol/min/mg of protein). To gain a better insight into the mechanisms underlying the apparently wide substrate specificity of UGT2B1, series of structurally related compounds were tested as potential substrates. The rate of glucuronidation of unbranched saturated fatty acids and omega,omega,omega-triphenylalkanoic acids increased progressively with increasing alkyl chain length and then declined, with the best substrates in these two homologous series being decanoic acid and 4,4,4-triphenylbutanoic acid, respectively. Glucuronidation of para-substituted phenols always proceeded at a higher rate than that of the corresponding para-substituted benzoic acids. This could mean that the aglycon hydroxyl group was better positioned in the enzyme active site in the case of phenols. Alternatively, if the initial interaction with the enzyme required the aglycon to be in the protonated uncharged form, then the observation could be explained by the difference in ionization between phenols and benzoic acids at the incubation pH used. The introduction of a bulky alkyl group into the para-position led to increases of up to 300-fold in the rate of glucuronidation, probably as a result of the increased aglycon lipophilicity. Finally, the enzyme showed a degree of stereo- and regiospecificity, preferring (S)-ibuprofen to the R-enantiomer (Vmax/Km, 3.06 and 1.10 microliters/min/mg of protein, respectively) and glucuronidating lithocholic acid but not hyodeoxycholic acid, which differs by only a single hydroxyl group.(ABSTRACT TRUNCATED AT 400 WORDS)     

Use by visitors of the services of the Queen Elizabeth Hospital, Barbados, W.I

The successful excision of genitourinary malignancies extending to the inferior vena cava relies heavily on accurate preoperative imaging. For the majority of these patients magnetic resonance imaging, inferior venacavography, abdominal ultrasound or abdominal computerized tomography will reliably predict the extent of inferior vena caval involvement by tumor. However, occasionally the results of these studies will conflict or be called into question intraoperatively. We report on 8 patients considered to be at risk for inferior vena caval involvement by tumor and for whom intraoperative ultrasound was obtained to clarify the presence or extent of thrombus. Five patients had renal cell carcinoma and 3 had adrenal carcinoma. In all patients concern as to the extent or presence of tumor was based on either inconclusive preoperative studies or unexpected intraoperative findings. In each case intraoperative ultrasound clearly visualized the inferior vena cava and established the presence or extent of tumor invasion. In 4 patients venacavotomy was avoided as a consequence of these findings. Intraoperative ultrasound is a useful tool that can accurately assess the inferior vena cava for possible tumor invasion, especially when the presence or extent of tumor involvement is not definitively established preoperatively.     

Effect of ageing on androgen levels in elderly males

The past four decades have brought with it modern medical technology accompanied by better quality and longer life resulting in the increase in number of aged males in this locality. It has now been well established by various investigators that there is a statistically significant decline of the biologically available level of serum testosterone with ageing. This decline in androgen levels is more manifest in the free testosterone levels compared to the total serum testosterone levels which are routinely measured in the laboratory. Not withstanding this statistical decline the serum testosterone levels in the majority of aged men often fall within the normal range (300-1000 ng/dl) of eugonadal young males. This age related decline is usually associated with decline in sexual function in ageing men manifesting as erectile dysfunction. However, it has now been established beyond doubt that age itself rather than the androgen decline is the most influential variable of sexual activity in old men.     

Selective serotonin reuptake inhibitors dissociate fenfluramine's anorectic and neurotoxic effects: importance of dose, species and drug

Fenfluramine, a clinically prescribed appetite suppressant, has been found to damage brain serotonin (5-HT) neurons in every animal species tested to date. Recent findings indicate that fluoxetine, a selective 5-HT reuptake inhibitor (SSRI), can prevent fenfluramine-induced 5-HT neurotoxicity without blocking fenfluramine-induced appetite suppression. The purpose of our studies was several-fold: 1) To determine whether the ability for fluoxetine to dissociate fenfluramine-induced anorexia and neurotoxicity is dose-related; 2) to ascertain whether other SSRIs also prevent fenfluramine-induced neurotoxicity without altering its anorectic effect; 3) to determine whether similar fluoxetine/fenfluramine interactions are seen in another animal species (i.e., mice) and 4) to determine whether decreases in food intake seen after the fluoxetine/fenfluramine combination can be attributed to nonspecific behavioral suppression. Results from our studies indicate that fluoxetine's effects are, indeed, dose-related, because higher doses of fluoxetine are required to protect against the 5-HT neurotoxic effects of higher doses of fenfluramine. Further, our results indicate that fluoxetine's effects generalize to all other SSRIs tested (citalopram, paroxetine and sertraline), as well as to other species (mice). Finally, our results demonstrate that anorexia in animals receiving the fenfluramine/fluoxetine combination is not secondary to nonspecific behavioral suppression, because water intake is increased although food intake is decreased in the same animals. Together, these data suggest that the anorectic and 5-HT neurotoxic effects of fenfluramine may involve different mechanisms, and that by combining fenfluramine with SSRIs, it may be possible to exploit fenfluramine's clinically useful properties (e.g., anorexia) without risking brain 5-HT neural injury.     

Calretinin expression as a critical component in the control of dentate gyrus long-term potentiation induction in mice

We have recently reported that mice homozygous (Cr-/-) for a null mutation in the calretinin gene have impaired long-term potentiation (LTP) induction in the dentate gyrus (S. Schurmans et al. (1997) Proc. Natl. Acad. Sci. USA, 94, 10415 ). Here, we investigated dentate LTP induction in mice heterozygous (Cr+/-) for the same mutation. Despite the presence of calretinin in neurons of these mice, although at reduced levels as compared with normal mice, LTP induction in dentate gyrus was totally impaired. Spatial memory and learning were found unaffected in Cr+/- mice, such as in Cr-/- mice. Altogether, our results suggest that calretinin is a critical component in the control of dentate synaptic plasticity in mice, and that levels of calretinin higher than those observed in Cr+/- mice are required to induce LTP in this area. The possible mechanisms leading to the absence of correlation between gene dosage and biological effects are discussed.     

Palliative treatment of wrist joint metastasis of primary bronchial carcinoma with a dynamic compression plate

The authors describe a patient with a wrist metastasis of a primary pulmonary carcinoma. Palliative radiotherapy in combination with splinting failed to release the pain. He was then successfully treated by radiocarpal bridging with a dynamic condylar plate.     

Adrenal androgen excess in the polycystic ovary syndrome: sensitivity and responsivity of the hypothalamic-pituitary-adrenal axis

Over 50% of patients with the polycystic ovary syndrome (PCOS) demonstrate excess levels of adrenal androgens (AAs), particularly dehydroepiandrosterone sulfate (DHS). Nonetheless, the mechanism for the AA excess remains unclear. It has been noted that in PCOS the pituitary and ovarian responses to their respective trophic factors (i.e. GnRH and LH, respectively) are exaggerated. Similarly, we have postulated that excess AAs in PCOS arises from dysfunction of the hypothalamic-pituitary-adrenal axis, due to 1) exaggerated pituitary secretion of ACTH in response to hypothalamic CRH, 2) excess sensitivity/responsivity of AAs to ACTH stimulation, or 3) both. To test this hypothesis we studied 12 PCOS patients with AA excess (HI-DHS; DHS, > 8.1 mumol/L or 3000 ng/mL), 12 PCOS patients without AA excess (LO-DHS; DHS, < 7.5 mumol/L or 2750 ng/mL), and 11 controls (normal subjects). Each subject underwent an acute 90-min ovine CRH stimulation test (1 microgram/kg) and an 8-h incremental i.v. stimulation with ACTH-(1-24) at doses ranging from 20-2880 ng/1.5 m2.h) with a final bolus of 0.25 mg. All patient groups had similar mean body mass indexes and ages, and both tests were performed in the morning during the follicular phase (days 3-10) of the same menstrual cycle, separated by 48-96 h. During the acute ovine CRH stimulation test, no significant differences in the net maximal response (i.e. change from baseline to peak level) for ACTH, dehydroepiandrosterone (DHA), androstenedione (A4), or cortisol (F) or for the DHA/ACTH, A4/ACTH, or F/ACTH ratios was observed. Nonetheless, the net response of DHA/F and the areas under the curve (AUCs) for DHA and DHA/F indicated a greater response for HI-DHS vs. LO-DHS or normal subjects. The AUC for A4 and A4/F and the delta A4/delta F ratio (delta = net maximum change) indicated that HI-DHS and LO-DHS had similar responses, which were greater than that of the normal subjects, although the difference between LO-DHS patients and normal subjects reached significance only for the AUC of the A4 response. No difference in the sensitivity (i.e. threshold or minimal stimulatory dose) to ACTH was noted between the groups for any of the steroids measured. Nonetheless, the average dose of ACTH-(1-24) required for a threshold response was higher for DHA than for F and A4 in all groups. No difference in mean responsivity (slope of response to incremental ACTH stimulation) was observed for DHA and F between study groups, whereas the responsivity of A4 was higher in HI-DHS patients than in normal or LO-DHS women. The net maximal and the overall (i.e. AUC) responses of DHA were greater for HI-DHS than for normal or LO-DHS women. The response of A4 and the delta A4/delta F ratio were greater for HI-DHS patients than for LO-DHS patients or normal subjects. Alternatively, HI-DHS and LO-DHS patients had similar overall responses (i.e. AUC) for A4 or A4/F, although both were greater than those of normal subjects. The relative differences in response to incremental ACTH stimulation between steroids was consistent for all subject groups studied, i.e. A4 > F or DHA. In conclusion, our data suggest that AA excess in PCOS patients is related to an exaggerated secretory response of the adrenal cortex for DHA and A4, but not to an altered pituitary responsivity to CRH or to increased sensitivity of these AAs to ACTH stimulation. Whether the increased responsivity to ACTH for these steroids is secondary to increased zonae reticularis mass or to differences in P450c17 alpha activity, particularly of the delta 4 pathway, remains to be determined.     

Thermal tolerance reduces hyperthermia-induced disruption of working memory: a role for endogenous opiates?

Previous reports indicate that microwave-induced hyperthermia can impair learning and memory. Here, we report that preexposure to a single 20-min period of hyperthermia can produce thermal tolerance and, thereby, attenuate future physiological and behavioral reactions to heating. Because endogenous opioids have been implicated in thermoregulation and reactions to microwave exposure, we also determined how opioid receptor antagonism might modulate these effects. In an initial experiment, rats were exposed daily, over 5 successive days, to 600-MHz microwaves (at a whole-body specific absorption rate of 9.3 W/kg) or sham exposed. In animals exposed to microwaves, thermal tolerance was evidenced by declining rectal temperatures over time. Temperature reductions following microwave exposure were prominent after a single previous exposure. Therefore, in a second study, a single hyperthermic episode was used to induce thermal tolerance. On Day 1, rats were either exposed, over a 20-min period, to 600-MHz microwaves (at a whole-body specific absorption rate of 9.3 W/kg) or sham exposed. Just prior to radiation/sham-radiation treatment, rats received either saline or naltrexone (0.1 or 10 mg/kg, intraperitoneally (i.p.)). The following day (Day 2), rats were either microwave or sham exposed and tested on a task which measures the relative time subjects explore a familiar versus a novel stimulus object. Normothermic rats spend significantly more time in contact with new environmental components and less time with familiar objects. Brain (dura) and rectal temperatures were recorded on both days of the study. Microwave exposure produced a reliable hyperthermia which was significantly lower (on Day 2) in rats receiving repeated treatments (tolerant group). On the behavioral test, rats exposed only once to microwave-induced hyperthermia (nontolerant group) exhibited significantly different patterns of object discrimination than did tolerant or sham-exposed animals. Sham-exposed and tolerant animals showed a distinct preference for the new object whereas the nontolerant animals did not. Naltrexone (10 mg/kg) antagonized the hyperthermia-induced disruption of the object discrimination task (in nontolerant rats) and produced patterns of object exploration that were similar to those of sham-irradiated and thermal-tolerant rats, suggesting that endogenous opioids play a role in the organism's response to heating. Taken together, these data are consistent with the conclusions that 1) microwave-induced hyperthermia can cause a dose-dependent disruption of the normal discrimination between new and familiar objects, 2) physiological reactions to a single hyperthermic episode can produce a thermotolerance that expresses itself in both reduced levels of hyperthermia and attenuated behavioral disruptions following microwave exposure, and 3) opioid antagonism can partially reverse some of the behavioral effects of microwave-induced hyperthermia.     

External genital warts: report of the American Medical Association Consensus Conference. AMA Expert Panel on External Genital Warts

A consensus process was undertaken to describe and evaluate current information and practice regarding the diagnosis, treatment, and evaluation of patients with external genital warts (EGWs) and their sex partners. This process developed a number of key statements that were based on strong evidence in the literature or reasonable suppositions and opinions of experts. Key statements included the following. In most cases, EGWs can be diagnosed clinically by visual inspection. No one treatment is ideal for all patients or all warts. Women with EGWs and female sex partners of men with EGWs are at increased risk for human papillomavirus-related cervical disease and, like all women, should be screened for cervical cancer. The diagnosis of EGWs in children requires a sexual abuse evaluation. Clinicians who treat EGWs have a responsibility to counsel patients and to provide information about the infectivity, diagnosis, treatment, and natural history of EGWs and general information about sexual health and other sexually transmitted diseases.