Ethical problems with bioidentical hormone therapy.

The term 'bioidentical' hormone replacement therapy (BHRT) is widely misunderstood by the patient population and misrepresented in patient literature. Within the clinical community, BHRT is currently being prescribed by some as an 'innovative therapy' with no published evidence in peer-reviewed journals that it is better than the current standard of care; in at least one case, BHRT is being used as a study agent in unregulated and unethical research involving very high doses of estrogen and progesterone. Additionally, professional ethics problems abound within the prescribing population, since those claiming expertise and training in BHRT vary widely in competencies, may cross practice boundaries, and may have overt conflicts of interest if they are selling or promoting their own for-profit recipes of BHRT on commercial forums. Ultimately, BHRT presents clinical, research and professional ethics problems that are discussed in depth.

Making sense of medical marijuana.

The case for marijuana's medical use is primarily from anecdotal clinical reports, human studies of delta-9-tetrahydrocannabinol, and animal studies on constituent compounds. The authors believe that while a key policy issue is to keep marijuana out of the hands of children, its use for medicinal purposes should be resolved by scientific research and Food and Drug Administration (FDA) review. Weighed against possible benefits are increased risks such as cancer, pulmonary problems, damage to the immune system, and unacceptable psychological effects. More study is needed to determine the efficacy of marijuana as an antiemetic for cancer patients, as an appetite stimulant for AIDS and cancer patients, as a treatment for neuropathic pain, and as an antispasmodic for multiple sclerosis patients. If this new research shows marijuana to have important medical uses, FDA approval could be sought. However, the better response is accelerated development of delivery systems other than smoking for key ingredients, as well as the identification of targeted molecules that deliver beneficial effects without intoxicating effects. If the National Institutes of Health conducts research on marijuana, we would propose parallel trials on those indications under careful controls making marijuana available to appropriate patients who fail to benefit from standard existing treatments. This effort would begin after efficacy trials and sunset no later than 5 years. If this open-trial mechanism is adopted, the compassion that Americans feel for seriously ill individuals would have an appropriate medical/scientific outlet and not need to rely on referenda that can confuse adolescents by disseminating misleading information about marijuana effects.

Prediction of treatment outcome in cocaine dependent males using quantitative EEG.

This study investigates the existence of outcome related neurophysiological subtypes within a population of abstinent cocaine dependent adults. We have previously reported and replicated the existence of a distinctive quantitative EEG (QEEG) profile in such a population, and demonstrated the persistence of this pattern at one and six month follow-up evaluations. This profile is characterized by significant deficits of absolute and relative delta and theta power, and excess of relative alpha power, as compared with age expected normal values. Abnormalities were greater in anterior than posterior regions, and disturbances in interhemispheric relationships were also observed. In the current study, 35 adult males with DSM-III-R cocaine dependence, were evaluated while residents of a drug-free residential therapeutic community, 5-15 days after last use of crack cocaine. Using multivariate cluster analysis, two neurophysiological subtypes were identified from the baseline QEEGs; Cluster 1 characterized by significant deficits of delta and theta activity, significant excess of alpha activity and more normal amounts of beta activity (alpha CLUS) and Cluster 2 characterized by deficits of delta, more normal amounts of theta and anterior excess of alpha and beta activity beta CLUS). No significant relationships were found between QEEG subtype membership and length of exposure to cocaine, time since last use of cocaine or any demographic characteristics. Further, no significant relationships were found between the commonly reported comorbid clinical features of depression and anxiety and subtype membership. However, a significant relationship was found between QEEG subtype membership and length of stay in treatment, with members of the alpha CLUS retained in treatment significantly longer than members of the beta CLUS.

Persistent QEEG abnormality in crack cocaine users at 6 months of drug abstinence.

The major objective of this study was to examine the persistence of abnormal quantitative EEG (qEEG) measures over a six month time interval in subjects in strictly supervised drug free residential treatment for crack cocaine dependence. Seventeen subjects were assessed with qEEG at five to 10 days, one month and six months following their last use of cocaine. No significant changes were noted over time in abnormal qEEG measures, which included deficits of absolute and relative power in the delta band and increased relative alpha power. The persistence of qEEG abnormality in crack cocaine withdrawal suggests a persistent neurobiologic alteration resulting from chronic cocaine exposure. The specificity of the qEEG findings is discussed, and an interpretation is suggested with reference to the hypothesis of neural sensitization in cocaine dependence.

Quantitative electroencephalographic characteristics of crack cocaine dependence.

This study replicates preliminary findings reporting a quantitative electroencephalographic (QEEG) profile of crack cocaine dependence in abstinence. All subjects (n = 52) met criteria for DMS-III-R cocaine dependence (in the form of crack), and were residing in a drug-free therapeutic community. Baseline QEEG evaluations were conducted at intake (5-10 days after last use of crack, and at follow-up (1 month after last reported use). Previous findings of significant excess of relative alpha power and deficit of absolute and relative delta and theta power were replicated in this expanded group. Abnormalities were greater in anterior than posterior regions, and disturbances in interhemispheric relationships were also observed. Further, QEEG showed little change in the interval between the first and second evaluations. This QEEG profile may reflect persistent alterations in neurotransmission as a possible consequence of chronic cocaine exposure.

Quantitative SPECT imaging: a review and recommendations by the Focus Committee of the Society of Nuclear Medicine Computer and Instrumentation Council.

This article is a review of the physics principles, instrumentation and reconstruction methods behind SPECT imaging. Particular attention is paid to the mechanisms that can significantly affect the accuracy of a SPECT image. We describe instrumentation advances and reconstruction methods used to correct images to improve image quality and produce quantitative images. The clinical importance of improved image quality and quantitation are also reviewed.

HIV antibody testing and client retention in the therapeutic community. A preliminary report of Phoenix House.

This report describes the current approach to testing for the human immunodeficiency virus (HIV) antibody at Phoenix House, a large therapeutic community (TC) in the northeastern United States, and presents findings on retention of clients who have been tested for HIV antibodies and notified of their HIV serostatus. A total of 240 clients were tested while in treatment at Phoenix House between April 1988 and July 1992. Of these, 51 tested HIV positive. An additional 76 clients had tested positive for HIV antibodies prior to entering treatment. The difference in length of treatment stay between those who tested negative while in treatment and those who tested positive while at Phoenix House was not significant (t = 0.41, df = 238, p > .683). Although clients who tested seronegative during treatment were found to remain in treatment a significantly longer amount of time than the total population of seropositive clients (t = 4.54, df = 314, p < .001), those who learned of their seropositive status while in treatment remained in the program longer than clients who entered treatment aware of their seropositivity (t = 4.08, df = 125, p < .001). These findings suggest that acute reactions to the knowledge of seropositivity did not determine most premature terminations. The use of a small group, a core technical element of the TC, may have provided a favorable context for the task of HIV counseling and testing.

The effects of a 3-day increase of ambient temperature on body temperature and REM sleep in an animal model of depression.

This study examined the effects of elevated ambient temperature (Ta) on body temperature (Tb) and rapid eye movement (REM) sleep in depressed and control rats. Previous studies have shown that elevations of Ta to the rat's thermoneutral zone of 29 degrees C produced an increase of REM sleep in control rats. In this study, 15 male Sprague-Dawley rats, seven saline control rats (SAL) and eight rats that were classified as depressed according to the chlorimipramine model of depression (CLI rats), were implanted for continuous Tb and polysomnographic recording and were exposed to two Ta's, 22 degrees C and 29 degrees C. CLI and SAL rats had significantly more REM sleep and a lower body temperature at 29 degrees C than at 22 degrees C. At 22 degrees C, CLI rats had significantly more REM sleep during the light period and a higher Tb in the light and dark periods than SAL control rats. At 29 degrees C, there were no significant differences in REM sleep or in Tb between CLI and SAL rats. Because human endogenous depression is associated with abnormal REM sleep and an elevated nocturnal Tb, these results give further support for the validity of the CLI model of depression and provide insight into the relationships among Tb, Ta, REM sleep and depression.

Sequential viewing of abdominal CT images at varying rates.

PURPOSE: To evaluate radiologists' ability to detect abdominal masses during sequential viewing of series of computed tomographic (CT) scans at varying rates. MATERIALS AND METHODS: Receiver operating characteristic (ROC) analysis was used to assess the ability of five experienced radiologists to determine the presence or absence of subtle abdominal masses in 29 cases (15 positive, 14 negative) while viewing CT scans sequentially at different rates (0.5, 1, 2, 4, 7, and 21 images per second) and also at reader-selectable rates. RESULTS: Even at extremely fast viewing rates (21 images per second), radiologists performed significantly better (P < .05) than would be expected by chance alone (average area Az under the ROC curve = 0.73 vs 0.5). As the viewing rate decreased, their performance increased. The reader-selectable mode was better than any fixed-rate cine mode (average Az = 0.93). CONCLUSION: Fixed-rate sequential viewing of CT images for the primary diagnosis of subtle abdominal masses should be restricted to no more than one or two images per second, but the reader-selectable viewing mode is preferable to any fixed-rate cine mode.

The effect of a 3-day increase of ambient temperature toward the thermoneutral zone on rapid eye movement sleep in the rat.

This study examined the effect of a 3-day increase of ambient temperature (Ta) from the usual room temperature of 22 degrees C to the rat's thermoneutral zone (TNZ) of 29 degrees C on rapid eye movement (REM) sleep. Other laboratories have reported that brief increases of Ta to the TNZ increased REM sleep and that long-term increases of Ta produced long-term increases of REM sleep. However, these studies were limited by the lack of controls for order effects or by restricted recording times. In the present study, which controlled for order effects, polysomnographic recordings for 12 male Sprague-Dawley rats were obtained 24 hours a day for 3 days at an ambient temperature of 22 degrees C and for 3 days at the TNZ of 29 degrees C. In all rats, REM sleep minutes and REM sleep percentage of total sleep time were significantly greater at the higher temperature than at the lower temperature. The increase in REM sleep at 29 degrees C was stable over the 3-day recording period. Prolonged increase of ambient temperature towards the TNZ is a simple, nonpharmacological method of producing a sustained, significant increase of REM sleep in the rat.

Scintigraphy versus pH probe for quantification of pediatric gastroesophageal reflux: a study using concurrent multiplexed data and acid feedings.

We performed 12 simultaneous scintigraphic and pH probe studies in children being evaluated for reflux to determine the ability of scintigraphic images in comparison to pH probe data to quantify gastroesophageal reflux in children and to identify an optimal scintigraphic framing interval. We used a multiplexor to synchronize exactly the scintigraphy and pH probe and an acid meal to avoid missing postprandial episodes with the pH probe. We reformatted the studies in both 60-sec and 10-sec images to compare the two framing intervals. The 60-sec images produced better agreement between pH probe and scintigraphy than the 10-sec images for both the number of reflux episodes and the duration of reflux. Of the 64 reflux episodes detected by either method at this coarser framing interval, scintigraphy detected 80%, the pH probe detected 63% and both methods concurrently detected 42%. Of the 681 60-sec images aggregated across patients, scintigraphy detected 55% of those with intraesophageal refluxate, the pH probe detected 96% and both tests concurrently detected 51%. Within patients, the number of positive scintigraphic images in the postprandial hour correlated with the number of images with pH < 4 during the same hour (p = 0.008, and p < 0.0001 if two patients with very rapid gastric emptying are excluded), but not with the results of the 24-hr pH probe study. A 1-hr scintigraphic study formatted in 60-sec frames provides a quantitative representation of postprandial gastroesophageal reflux for children, particularly if they do not have rapid gastric emptying.

A model system and technique to study the effects of ultrasound irradiation on embryonic development.

To study the effects of ultrasound on development it is important to have a system which provides reliable results. We have designed a system which allows for reproducible irradiations of chick embryos in ovo. The irradiation system includes a heated sonation tank with ultrasound absorbers and a PC/AT computer-based data acquisition system for on-line monitoring of irradiations. The ultrasound detection microprobe and irradiation transducers were calibrated against an NBS traceable balance meter. An acoustic spacer was utilized to provide a more uniform profile of the irradiation beam. At the position of the embryo the ultrasound field geometry was determined. To maintain the chick embryo in its natural physiological state while minimizing ultrasonic reflections and standing-wave generation, two diametrically opposed windows were made in the eggshell along the ultrasound pathway and covered with polyethylene membranes. Using this irradiation system at intensity levels as high as 1.1 W/cm2 (spatial average, temporal average) for 10 min, the temperature rise is minimal.

Primary CT diagnosis of abdominal masses in a PACS environment.

Whether the display medium--film versus cathode ray tube (CRT)--affects observer performance during interpretation of computed tomographic (CT) images is an important research issue in these times of implementation and growth of picture archiving and communications systems in radiology. The authors performed a multiobserver receiver operating characteristic (ROC) study to determine the performance of radiologists who read abdominal CT studies displayed on film, as well as on a high-resolution workstation (video monitor) that made use of three different display modes. A total of 166 examinations were evaluated by eight radiologists, who recorded their ordinal confidence ratings of the demonstration of presence or absence of abdominal masses. ROC analysis showed small differences in the confidence ratings assigned by individual readers for the detection and interpretation tasks. Results for the group as a whole showed no significant reduction or improvement in observer performance when ratings for any one of the workstation display modes were analyzed. The results of this study demonstrate that current CRT display technology is adequate for enabling the primary detection of abdominal masses with CT examinations.

Revascularization of an ischemic limb by use of a muscle pedicle flap: a rabbit model.

A rabbit model of hind limb ischemia was designed to demonstrate that new, hemodynamically significant arterial connections will develop between ischemic skeletal muscle and an independently perfused muscle pedicle flap. The right common iliac artery was divided in 15 rabbits. In eight rabbits a muscle flap based on the left deep inferior epigastric artery was transposed to the right thigh (flap group). In seven rabbits a sham operation was performed where the flap was sutured to the abdominal wall (sham group). After 7 days angiography demonstrated arterial connections between the flap and the native limb circulation in all of the flap group animals. The flap increased muscle perfusion in the ischemic limb (2.99 ml/100 gm muscle/minute in the flap group, vs 2.06 ml/100 gm muscle/minute in the sham group, p less than 0.005). Hemodynamically significant vascular connections will develop between a well-perfused muscle flap and an ischemic limb. The augmentation in perfusion provided by these connections can be quantified.

Effect of ultrasound on axonal outgrowth in the sympathetic nervous system of the chick.

The effects of ultrasound exposure on the rate and specificity of sympathetic preganglionic axonal outgrowth were examined in the chick embryo. Using a technique which allows for exact quantitation of exposure for exact quantiation of exposure conditions, embryos were irradiated in ovo for 5 min daily on 3 consecutive days at an intensity of 1 W/cm2 Spatial Average, Temporal Average (SATA), with a frequency of 1.1 MHz pulsed at 1 kHz and a pulse width of 75 microsecond(s). Our results show no significant difference between irradiated and sham-irradiated embryos. In addition, we have examined the distributions of several major extracellular matrix molecules (fibronectin, laminin and collagen IV) in irradiated and sham-irradiated embryos using immunofluorescent staining. No difference in the staining pattern was found. Finally, we found no increase in the incidence of gross abnormalities and no evidence of lesions and malformations in irradiated embryos.

Ultrasound effects on cell proliferation and migration of chick motoneurons.

The effect of ultrasound exposure on proliferation and migration of motoneurons was examined in chick embryos. Using an egg preparation which minimizes ultrasonic reflections and standing wave generation, chick embryos were exposed to ultrasound in ovo for 10 min at an intensity of 2 W/cm2 Spatial Average, Temporal Average (SATA) with a frequency of 1.1 MHz pulsed at 2 kHz, and a pulse width of 75 microseconds. For cell proliferation studies, embryos were irradiated at the developmental stage of the most active lateral motoneuron proliferation. For cell migration studies, embryos were irradiated at the developmental stage just prior to lateral motoneuron migration. Our results show that the birthdates, migration and proliferation of lateral motoneurons are unaffected by the ultrasound exposure parameters used in this study.