Discrimination of butorphanol and nalbuphine in opioid-dependent humans.

The purpose of the study was to evaluate the agonist and antagonist stimulus properties of the mixed opioid agonist antagonists butorphanol and nalbuphine in opioid-dependent subjects. Opioid-dependent volunteers (methadone 30 mg/day, PO) were trained in a three-choice drug discrimination procedure to discriminate between the effects of saline (2 ml), hydromorphone (10 mg/70 kg) and naloxone (0.15 mg/70 kg) administered IM. Subjects earned monetary reinforcement for correctly identifying the training drugs by letter code. Other subjective, behavioral and physiological measures were also collected. Hydromorphone and naloxone increased drug-appropriate responses and other characteristic subjective effects measures. Butorphanol and nalbuphine produced increases in naloxone-appropriate discrimination responding and in those subjective effect measures increased by naloxone. Butorphanol produced greater than 80% naloxone-appropriate responding at 1.05 mg/70 kg; nalbuphine produced 100% naloxone-appropriate responding at 2.1 mg/70 kg. Neither butorphanol nor nalbuphine showed opioid agonist-like effects in these subjects maintained at moderate levels of physical dependence. In opioid-dependent subjects, the stimulus effects of butorphanol and nalbuphine are antagonist-like.     

Distraction vs remodeling surgery for craniosynostosis

Objects We designed several distraction devices and applied these instruments in 14 patients with varying types of craniosynostosis. The aim of this report is to clarify the advantages and disadvantages of these surgical methods and to discuss current concepts for the surgical strategy in the treatment of craniosynostosis. Methods From January 2000 to July 2005, 28 patients with craniosynostosis were retrospectively analyzed. Surgical treatment was performed on 14 patients using the distraction method with internal distraction devices that we designed, in which 5 patients had plagiocephaly, 3 brachycephaly, and 6 scaphocephaly. All patients underwent preoperative and postoperative evaluations, which included the patient’s neurological state, and three-dimensional CT. Results With distraction devices, the time required for the surgery could be shortened almost 3 1/3 h; the bleeding during the surgery was decreased with reduced requirement of more than 200 ml of blood transfusion as compared with remodeling surgery. Postoperatively achieved distraction distances varied from 30.0 to 47.5 mm (mean, 42.99 mm). The average increased volume percent of cranium in distraction surgery group was 20.9% (range, −11.5 to 58.9%) after full distraction. Conclusion With distraction surgery, satisfactory cranial volume expansion and aesthetically pleasing morphological states were achieved in all cases, and the efficacy was statistically significantly high as compared with remodeling method.     

Delineating the sites and progression of in vivo atrophy in multiple system atrophy using fluid-registered MRI.

We describe the pattern and progression of atrophy delineated using fluid registration of serial magnetic resonance imaging scans in a case of multiple system atrophy (MSA). The in vivo findings were consistent with those found at postmortem, including significant supratentorial atrophy concurrent with an unusual degree of cognitive impairment for MSA.     

A group intervention to reduce smoking in individuals with psychiatric disorder: brief report of a pilot study

Objectives: To evaluate a group intervention to help individuals with psychiatric disorder stop smoking.
Method: A waitlist-treatment crossover design. Outcome measures included smoking cessation, motivation to stop, the Fagerstrom Test for Nicotine Dependence (FTND), urinary cotinine and psychiatric symptoms on the General Health Questionnaire.
Results: 38 subjects participated, of whom 19 completed the waitlist and intervention phases. There were no significant differences between subjects and dropouts. During the waitlist period there were no significant changes in tobacco use. At the end of the intervention, almost a quarter had stopped smoking, ( z = -2.24, p =0.02). Subjects also showed significant improvements on state of change, FTND score and urinary cotinine levels. These improvements were maintained at three-month follow-up (n=10). Psychiatric morbidity showed no change.
Conclusions: It is possible to reduce smoking in individuals with psychiatric disorder.
Implications: Larger randomised controlled trials are indicated to determine the relative contributions of nicotine replacement, bupropion and group interventions to smoking cessation in this population.     

Minimally invasive spinal surgery

Minimally invasive surgery offers quicker recovery and less morbidity for our patients through smaller surgical wounds and less tissue trauma. Although minimally invasive surgery has progressed in other fields of surgery for many years, spine surgeons have not previously embraced this philosophy for the various reasons discussed. However, minimally invasive spinal surgery has gained much interest in recent years. With the advent of new instrumentation, technology, and techniques, the promise of minimally invasive surgery in the spinal arena has become a reality. With the use of the microscope, navigational tools, newly developed canula for retraction, and image-guided percutenous pedicle screw systems, we can accomplish the same surgical procedures as currently used through smaller wounds and with greater precision. Nevertheless, all new technology does offer us an initial challenge of steep learning curves. Minimally invasive should not equate to minimal and inadequate treatment for our patients. Furthermore, careful analysis of this new technique is underway to assess its true advantages as compared with our current and proven techniques.     

Expression of pS2, c-erbB-2, and cathepsin D during the menstrual cycle in human breast cancers

Background: Many studies have addressed the effect of the timing of surgery for breast cancer relative to menstrual cycle phase, with conflicting results. Explanations for the possibility that survival could be altered by the appropriate timing of breast cancer surgery in humans remain speculative. Methods: We examined the expression of three estrogen related proteins (c-erbB-2, cathepsin D, pS2) in the breast tumors from 69 premenopausal women sampled in different phases of the menstrual cycle. Data on S-phase fraction and hormone receptor expression were also analyzed. Immunohistochemical assays were used to measure the proteins of interest. S-phase fraction was determined by flow cytometry. Analyses were performed based on fraction of cells staining positive for the protein, density of stain, and a histoscore that combined both fraction of positive cells and density. Results: We found no differences in c-erbB-2, cathepsin D, hormone receptor, or S-phase levels in tumors sampled in the follicular versus luteal phase, or perimenstrual versus periovulatory phase. The exception was pS2, which was expressed at greater levels during the luteal than during the follicular phase of the cycle (p<0.01); but there was no difference in pS2 expression when the patients were classified as periovulatory versus perimenstrual. Conclusions: Our findings do not support a variation in c-erbB-2, cathepsin D, S-phase fraction, or receptor expression as an explanation for the differences in breast cancer prognosis when surgery is timed by menstrual cycle phase. The finding that pS2 (an indicator of hormone sensitivity, and possibly better prognosis) is expressed at higher levels in tumor samples during the luteal phase suggests that the biologic profile of breast tumors may vary with the menstrual cycle and that these variations deserve further study.     

Effects of cocaine alone and in combination with bromocriptine in human cocaine abusers.

This study was conducted to determine whether the acute administration of bromocriptine, a dopamine agonist, modulates the acute pharmacologic effects of i.v. cocaine in humans. Eight current users of i.v. cocaine who were not seeking treatment for their cocaine abuse completed the study while they were inpatients on a research unit. Twelve drug conditions were tested in all subjects in randomized order under double-blind, double-dummy conditions and included cocaine (0, 12.5, 25 and 50 mg, i.v.) in combination with bromocriptine (0, 1.2 and 2.5 mg given orally 2 hr before the cocaine injection). Physiologic and subject- and observer-rated responses were measured. Cocaine alone significantly increased pupil diameter, heart rate and blood pressure, and ratings of drug effect, good effects, liking and rush. Bromocriptine alone significantly increased pupil diameter and heart rate, decreased blood pressure and had only minor effects on subjective measures. There were significant cocaine/bromocriptine interactions on diastolic and mean arterial blood pressure, with combinations producing significantly smaller increases compared to cocaine alone, and on heart rate, with combinations producing significantly larger increases compared to cocaine alone. The physiologic and subjective effects of cocaine were not modified by pretreatment with bromocriptine in any other way that might indicate either a therapeutic benefit or a safety concern. However, bromocriptine alone produced undesirable effects (fainting) that should be considered before administration to outpatient cocaine abusers. Any possible therapeutic benefits of acute administration of bromocriptine in cocaine abuse are not likely to be due directly to modulation of the acute effects of cocaine.     

Who will conceive with IVF?

When considering the chances of establishing a healthy ongoing pregnancy after in vitro fertilization (IVF), the cause of infertility plays a relatively minor role. In recent years, there has been a shift from determining the diagnosis to the individual prognosis for a given patient. A number of prognostic factors were identified, which enabled clinicians to appropriately counsel patients. Patient-determined factors are of crucial importance and some are amenable to intervention such as lifestyle and nutritional advice. However, the attention of clinicians remains on seeking adjuvant therapeutic interventions designed to improve the outcomes of IVF treatment. In this article, the patient-determined factors underlying the individual chance of conceiving and the more commonly prescribed empirical medical therapies prescribed to enhance outcomes are reviewed. It is concluded that greater attention to optimizing the health of the couple before starting IVF treatment may be more beneficial than adjuvant medical therapies during treatment.