Comparative inhibition of prostate cell invasion by conformationally flexible and constrained bis(2,6-dioxopiperazine)s

Inhibition of the migration of human prostate cancer PC-3 cells by a series of 18 conformationally flexible and constrained bis(2,6-dioxopiperazine)s including selected bis(morpholinomethyl) derivatives was investigated in vitro using the Matrigel invasion assay. The anti-invasion effects were compared to the cytotoxic effects of these experimental drugs. The parent conformationally mobile ICRF-159 (razoxane) and its dextrorotatory isomer ICRF-187 (dexrazoxane) inhibited invasion at concentrations that were at least 19-fold lower than their cytotoxic concentrations. This indicates that the anti-invasion effect was achieved independent of cytotoxicity. Seven conformationally constrained compounds were found to have no appreciable anti-invasive activity. Generally, the morpholinomethyl pro-drug derivatives of seven of the dioxopiperazines, exhibited either anti-invasive or cytotoxic activities that were reduced or unchanged relative to the parent molecules. In summary, certain bis(2,6-dioxopiperazine)s exhibit a promising and selective anti-invasion effect in human prostate cells. This activity seems to require a flexible linker allowing for multiple conformational possibilities of the dioxopiperazine rings.     

The consequences of disclosure: one hospital's response to the presence of an HIV-positive physician

Health care administrators are having to confront the many and complex problems associated with patient fears about the transmissibility of the HIV virus. Particularly acute are concerns that are raised when the physicians are HIV-positive or have AIDS. This article presents a case history of how one hospital handled the problems created by the announcement by one of its emergency room physicians that he was HIV-positive. The hospital's response--which included disclosure to the community, the full cooperation of the physician, provision of free counseling, and HIV testing--and the aftermath of this AIDS-related event are described. This case is discussed in relationship to the ongoing debate about the ethics and consequences of disclosure of the HIV status of health care workers.     

Cervical secretory immunoglobulin A in adolescent girls.

PURPOSE: To determine whether there are differences in levels of cervical secretory immunoglobulin A (sIgA) between adolescent girls in the secretory and proliferative phases of their menstrual cycle. METHODS: Sexually active adolescent girls (n = 117) at health maintenance organization (HMO) based adolescent medical clinic were recruited into the study. In addition to demographic and clinical data, cervical specimens were collected for sIgA measurement and gonorrhea culture, urine for chlamydia ligase chain reaction, and blood for progesterone levels. Subjects were classified as being in the proliferative phase or secretory phase of the menstrual cycle on the basis of their progesterone levels. RESULTS: The mean age of the subjects was 17.2 years old. There was no difference in the sIgA levels between those in the proliferative phase of their cycle (n = 45; mean sIgA level, 0.0055 mg/mL) and those in the secretory phase (n = 40; mean sIgA level, 0.0032 mg/mL) (p > .10). CONCLUSIONS: The secretory phase of the menstrual cycle does not appear to be associated with higher levels of sIgA in adolescent girls. These results suggest that adolescents with anovulatory cycles, i.e., those who lack a secretory phase, may not be at increased risk for genital tract infections such as chlamydia or gonorrhea.     

Assessing the laryngeal cough reflex and the risk of developing pneumonia after stroke

OBJECTIVE: To determine the effectiveness of a new reflex cough test, using nebulized tartaric acid, in the evaluation of the laryngeal cough reflex and the development of aspiration pneumonia. STUDY DESIGN: In this two-phase study, the cough test assessed the cough reflex in 161 stroke subjects. Phase 1 was a double-blinded prospective study of 40 subjects scheduled to have both modified barium swallow and the reflex cough test. Phase 1 subjects with an abnormal cough test showed an increased pneumonia incidence, and therefore, phase 2 was not blinded. In phase 2, 121 subjects were evaluated using the cough test; 38 received a modified barium swallow. Test results were compared using the Fisher exact test. RESULTS: A total of 131 subjects from both phases had a normal reflex cough test; none developed pneumonia (p < .01). Thirty subjects from both phases had abnormal reflex cough test results; 5 developed pneumonia. Modified barium swallow findings did not reliably indicate the risk for developing pneumonia. Specificity of a normal reflex cough test was 100%. CONCLUSION: The reflex cough test reliably evaluated the laryngeal cough reflex and the associated risk of developing aspiration pneumonia in stroke patients. Testing the laryngeal cough reflex may significantly reduce morbidity, mortality, and costs in stroke patients.     

Anesthesia for the superior laryngeal nerves and tartaric acid-induced cough

OBJECTIVE: The internal branch of the superior laryngeal nerve (ibSLN) conveys impulses for the laryngeal cough reflex, which protects the laryngeal aditus and prevents the development of aspiration pneumonia. The purpose of this study was to determine the effect of bilateral anesthesia of the ibSLN on the cough reflex after inhalation of a nebulized chemoirritant solution of tartaric acid. DESIGN: Prospective, clinical investigation. SETTING: Outpatient. PARTICIPANTS: Nine healthy volunteers. INTERVENTIONS: Bilateral injections of 2% lidocaine solution without epinephrine into the paraglottic space containing the ibSLN. MAIN OUTCOME MEASURES: The tidal volume after inhalation of a nebulized 20% tartaric acid solution and forced vital capacity (FVC) were measured before and after injection. Data were analyzed using the Wilcoxon signed ranks, Mann-Whitney, and sign tests. RESULTS: Complete anesthesia of the ibSLN abolished the laryngeal cough reflex. Postinjection tidal volumes were significantly lower than preinjection volumes (p<.01). The decrease in tidal volumes for six subjects with complete bilateral anesthesia was significantly larger than the decrease in tidal volumes for three subjects with partial anesthesia (p<.05). FVC in both the six subjects with complete bilateral anesthesia and the three subjects with partial anesthesia did not significantly change from preinjection to postinjection. None of the subjects in this study had complications or adverse respiratory sequelae. CONCLUSION: Tartaric acid-induced cough may be useful in assessing the integrity of the laryngeal cough reflex after anesthesia or in patients with neurologic injury who are at risk of developing aspiration pneumonia. It may also be useful in making the decision whether to resume oral feeding.     

Techniques to comfort children during stressful procedures

Medical procedures can be unpleasant experiences for children, their parents, and health care providers. We present this model of working with children having invasive procedures with the aim of helping to increase the comfort of infants and children and also parents and medical staff. The model has five parts: (1) Preparing the child and parent for the procedure and for their role during the procedure; (2) inviting the parent/caregiver to be present; (3) utilizing the treatment room for stressful procedures; (4) positioning the child in a comforting manner; and (5) maintaining a calm, positive atmosphere.     

Subtalar repositional arthrodesis for adult acquired flatfoot

Arthrodesis of the subtalar joint is well recognized treatment option for moderate or severe flatfoot associated with adult acquired flatfoot secondary to posterior tibial tendon dysfunction. The success of the subtalar arthrodesis is dependent on restoration of normal bony relationships in the hindfoot and midfoot. For this reason, a distinction is made between a repositional arthrodesis and the traditional in situ type of arthrodesis. An in vitro study of the adult acquired flatfoot identifies an anteroposterior subluxation of the subtalar articulation that can be corrected durably and reliably through a repositional talocalcaneal arthrodesis. Intraoperative reduction techniques are useful in obtaining reduction of the peritalar subluxation. There are certain clinical features that help identify patients with flatfoot deformities who are good candidates for subtalar fusion. As the pathoanatomy of the flatfoot deformity is better elucidated, treatment techniques are modified to better address the key elements of the deformity. A repositional subtalar arthrodesis was shown to produce excellent correction in a moderate to severe in vitro flatfoot example in the authors' clinical series.     

Intra-arterial induction chemotherapy

When effective anti-cancer drugs first became available to clinicians they were commonly used by surgeons by intra-arterial infusion to treat difficult regional cancer problems. Because they were most often used to treat poorly vascularised recurrent cancers results were, in general, unsatisfactory. The intra-arterial approach fell into disrepute and continued use of these techniques has often been criticised and results achieved treated with scepticism. Reasons for the original poor results are now well understood and techniques for effective and safe regional chemotherapy have been developed. These techniques of regional chemotherapy, when appropriately used especially as induction treatment, have an important role to play in a comprehensive oncology therapeutic service. However the criticisms and reluctance to accept the use of chemotherapy on a regional basis remain widespread. Some of the objections and difficulties expressed are valid but some are quite invalid and indicate reluctance to review the situation in spite of valuable progress and understanding and in spite of important clinical applications. Outlined in this review are valid objections, including increased facilities and skills needed and their cost, as well as invalid objections based on misconceptions, inexperience and reluctance to review or accept need for change of familiar practices.