Crack users: the new AIDS risk group?

Crack cocaine, a smokable form of cocaine hydrochloride, is now widely available in American inner cities. Reports of high rates of unprotected sexual activity among crack users, coupled with reports of high rates of sexually transmitted diseases (STDs), have raised fears that this population of drug users may soon be contracting and disseminating sexually transmitted HIV. In a study of 205 black adolescent crack users conducted in Oakland and San Francisco, California, 101 respondents (49% of the sample) who reported using crack in combination with sexual activity were examined. Those respondents who reported having a history of one or more STD were compared using discriminant analysis (DA). A successful discrimination (canonical correlation = 0.61, p = 0.000) identified five variables that distinguished those with a STD history from those with no STD history: gender (being female) (p = 0.000), frequency of marijuana use (p = 0.005), response to the question; "Do you plan for sex or does it just happen?" (p = 0.002), response to the statement, "I use drugs to get away from my problems" (0.029), and response to the question, "Do you agree that sex doesn't feel as good when you use a condom?" (p = 0.006). The selection of these variables was thought to represent an underlying passivity in the way that crack users who combine crack use with sex approach sexual activity.     

Females' perception of date rape: an examination of two contextual variables

This study examined the role of perceived token resistance and previous sexual contact on women's ability to discriminate when a female wants her partner to stop his sexual advances. Participants included 101 White female undergraduate students and were randomly assigned to one of the four conditions: 1) perceived resistance with genital contact; 2) no resistance with genital contact; 3) perceived resistance with no genital contact; and 4) no resistance without genital contact. Subjects listened to an audiotaped date rape after being informed of the couple's sexual history based on the condition assigned to them. They were also informed that the couple had been on five previous dates, in which the man had manipulated the woman's breasts or genitals. In addition, the woman did not object to this contact, or the woman initially objected to the contact but subsequently stopped resisting contact. Participants in the perceived token resistance conditions took significantly longer to determine when the man should refrain from attempting further sexual contact. The findings of this study could be used to increase information on date rape, to educate individuals about the responses associated with date rape, and to reinforce rules concerning appropriate sexual behavior.     

Legg-Calve-Perthes Disease: Imaging Evaluation and Management

Legg-Calve-Perthes disease reflects avascular necrosis of the proximal femoral epiphysis and growth plate in children age 4 to 8 years typically. The most likely etiology is vascular deficiency to the epiphysis and growth plate. The pathologic stages consist of necrosis, resorption, reossification, and remodeling. Radiologic findings reflect the pathologic stages. Containment of the femoral head with the acetabulum is the most important component of treatment, with preservation of range of motion also indicated in most patients. Surgical options for treatment include varus or valgus femoral osteotomy, innominate osteotomy, and shelf arthroplasty.     

Child Abuse: Imaging Findings Pertaining to the Musculoskeletal System

Both underrecognized and underreported, child abuse has a spectrum of findings on imaging of the musculoskeletal structures that may permit the radiologist to first suggest the occurrence of child abuse or to help support clinical concern for a diagnosis of child abuse. This article will discuss the approach to imaging of the musculoskeletal system in suspected child abuse, illustrate many of the more common imaging findings, and present imaging pitfalls and alternative diagnostic considerations. Injuries to the brain, spinal cord, gastrointestinal and genitourinary systems, and cardiopulmonary structures are outside the scope of this article.     

Complement depletion does not reduce brain injury in a rabbit model of thromboembolic stroke

The contribution of the complement system to cerebral ischemic and ischemia/reperfusion injury was examined in a rabbit model of thromboembolic stroke by delivery of an autologous clot embolus to the intracranial circulation via the internal carotid artery. A two-by-two factorial design was employed to study the impact of complement depletion via pretreatment with cobra venom factor (CVF, 100 U/kg i.v.) in the setting of permanent (without tissue plasminogen activator; t-PA) and transient (with t-PA) cerebral ischemia. Thirty-two New Zealand white rabbits were assigned to one of four groups (n=8, each group): control without t-PA, control with t-PA, CVF without t-PA and CVF with t-PA. In the complement intact animals, t-PA administration resulted in an approximate 30% reduction in infarct size when compared to the group not receiving t-PA (20.4+/-6.6% of hemisphere area vs. 30.1+/-7.2%; mean+/-SEM). However, infarct sizes in the complement depleted rabbits, with (30.7+/-8.2%) or without (30.2+/-7.9%) t-PA, were no different from the control group receiving no therapy. Similarly, no difference in regional cerebral blood flow or final intracranial pressure values was noted between any of the four groups. Complement activation does not appear to be a primary contributor to brain injury in acute thromboembolic stroke.     

Hypoxia induces differential changes of dopamine metabolism in mature and immature mesencephalic and diencephalic cell cultures

Summary. Perinatal hypoxia is known as a high risk factor for the development of long-lasting abnormalities in dopaminergic system. The early developmental alterations of dopamine (DA) metabolism induced by hypoxia could contribute to these abnormalities. To understand the hypoxia-induced changes of intra- and extracellular dopamine levels and its main metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in immature dopaminergic neurons, we compared these changes in rat mesencephalic and diencephalic cell cultures on day in vitro (DIV) 2 (immature cells), DIV 8 and DIV 13 (mature cells). Cell cultures were exposed to an oxygen-free gas mixture in a Billups chamber for 2–4 hours. Mature cell cultures responded to hypoxia with an increase of DA levels in the cells and in the medium during the first 45 min (by an average of 57 and 114% respectively). Thereafter, DA levels decreased, and returned to the baseline within the next 30 min. The cellular DA levels continued to decrease up to 15% of the baseline during 255 min hypoxia whereas the extracellular DA content stabilized at the prehypoxic levels. Immature cell cultures (DIV 2) in contrast to mature ones, were unable to maintain normal extracellular DA levels during hypoxia and showed a decrease of the cellular and extracellular levels to 50% of the prehypoxic levels. DOPAC and HVA changes mimick, however, at a lower level, the pattern of DA changes during the exposure to hypoxia. In principle, in the diencephalic cell culture similar effects of hypoxia exposure on the investigated parameters were found (studied during 0–120 min). The present study demonstrates that mature and immature dopaminergic cells differ in the regulation of the extra- and intracellular DA levels during hypoxia. In immature cells the low synthetic capacity of tyrosine hydroxylase and the deficient capacities of the transport and storage processes result in decreased extracellular DA levels. This could be an important factor for the long-term modulation of the expression of tyrosine hydroxylase and subsequent long-term behavioral and/or neurological abnormalities induced by perinatal hypoxia. Received June 8, 1998; accepted July 21, 1998     

The dorzolamide/timolol combination versus timolol plus pilocarpine: patient preference and impact on daily life. United States Patient Preference Study Group. International Patient Preference Study Group.

PURPOSE: To compare the 2.0% dorzolamide/0.5% timolol fixed combination (COSOPT; Merck & Co., Whitehouse Station, NJ) to 0.5% timolol plus 2.0% pilocarpine given concomitantly, and to determine patient preference, tolerability, and impact on daily life in patients with elevated intraocular pressure (IOP). METHODS: Two multi-center, randomized, cross-over, observer masked studies were conducted, one in the United States (97 patients) and one in Europe (93 patients). The Comparison of Ophthalmic Medications for Tolerability questionnaire was used to assess patient preference and perception of side effects and activity limitations resulting from study medications. Intraocular pressure was measured before and 2 hours after the morning dose of study medication (hour 0 and hour 2). RESULTS: In both studies, among patients with a preference, the combination was preterred to timolol plus pilocarpine by a ratio of 4 to 1. The most commonly cited reason for this preference was side effects. Patients in both studies also reported that the combination interfered significantly less with daily life in terms of side effects and activity limitations. They also reported missing significantly fewer doses of study medication while taking the combination and being significantly more satisfied with it. The efficacy of these two treatments was not significantly different, based on IOP measurements at hour 0 and 2 hours after administration. Patients reported significantly more adverse events while receiving timolol plus pilocarpine in both studies, and in the U.S. study, significantly more patients discontinued therapy while receiving timolol plus pilocarpine than while receiving the combination. CONCLUSION: Compared with timolol plus pilocarpine, patients preferred the combination of 2% dorzolamide/0.5% timolol, and reported less interference in daily activities, better tolerability, and better compliance with therapy.     

Stoichiometry of potassium channel opener action

Potassium channel openers (KCOs; e.g., P1075, pinacidil) exert their effects on excitable cells by opening ATP-sensitive potassium channels. These channels are heteromultimers composed with a 4:4 stoichiometry of an inwardly rectifying K(+) channel subunit plus a regulatory subunit comprising the receptor sites for hypoglycemic sulfonylureas and KCOs (a sulfonylurea receptor). To elucidate stoichiometry of KCO action, we analyzed P1075 sensitivity of channels coassembled from sulfonylurea receptor isoforms with high or low P1075 affinity. Concentration activation curves for cDNA ratios of 1:1 or 1:10 resembled those for channel opening resulting from interaction with a single site, whereas models for activation requiring occupation of two, three, or four sites were incongruous. We conclude KCO-induced channel activation to be mediated by interaction with a single binding site per tetradimeric complex.     

Metabolic and neuroanatomical correlates of barrel-rolling and oculoclonic convulsions induced by intraventricular endothelin-1: a novel peptidergic signaling mechanism in visuovestibular and oculomotor regulation?

The neuroactive peptide endothelin-1 has receptors distributed abundantly among subdivisions and nuclei of the visuovestibular and oculomotor systems. In previous work, we and others described the convulsive manifestations resulting from central injection of this neuropeptide, including nystagmus, oculoclonus, exophthalmos, tonic hindlimb extension, and a generalized repetitive motor disturbance called barrel-rolling. We applied the quantitative, autoradiographic [¹⁴C]deoxy-glucose method to examine the hypothesis that visuovestibular and oculomotor structures would become metabolically stimulated when endothelin was introduced into the brain via the ventricular system in conscious rats. Since previous work had demonstrated that hypermetabolic responses to endothelin in other neural systems were inhibited by an antagonist of neuronal calcium L-type channels, nimodipine, we further tested whether the increased function of vestibulooculomotor nuclei whose metabolic activity was sensitive to endothelin could be altered following nimodipine pretreatment via the ventricle. A single unilateral injection of endothelin (9 pmol in 3 l saline) into a lateral ventricle provoked significantly increased rates of glucose metabolism in 22 of 39 individual anatomical structures of the visuovestibular and oculomotor systems. Among those affected were the superficial stratum of the caudal superior colliculus (+25%), the optic tract bilaterally (+ 35 to 43%), the oculomotor cranial nerve nuclei (III, IV, VI; range of +21 to 47%), and the medial terminal nucleus of the accessory optic tract which harbors dense fields of endothelin binding sites (bilateral increase of +70 to 96%). Several other nuclei involved in the proprioceptive and visuovestibular disturbance caused by endothelin displayed increased metabolic activity, including the cuneate, gracile, sensory trigeminal, and prepositus hypoglossal nuclei, the vestibular subnuclear system, and the cerebellar flocculus. Identification of hypermetabolic responsivity to endothelin in these structures provides further information on the anatomical substrates mediating the behavioral phenomenology of endothelin-induced motor convulsions which involve the paroxysmal participation of the extraocular muscles and motor control systems producing barrel-rolling convulsions. Nimodipine pretreatment inhibited both the convulsive activity and the cerebral hypermetabolic responses to intraventricular endothelin. The results indicate that the neural systems sensitive to intraventricular endothelin become functionally active via a calcium-mediated process that may involve the neuropeptide as an intrinsic signaling molecule.