Infantile cortical hyperostosis of the ribs (Caffey's disease) without mandibular involvement

Infantile cortical hyperostosis (ICH), or Caffey's disease, first reported by Caffey and Silverman in 1945, is a benign condition characterized radiographically by corticoperiosteal thickening of bone with subperiosteal new bone formation. Sites of occurrence vary, with the mandible being involved in 75%–80% of cases. The following is a case report of ICH limited to four contiguous ribs with no evidence of mandibular involvement.     

Nicotine patches improve mood and response speed in a lexical decision task

The effects of smoking a cigarette or wearing a transdermal nicotine patch on mood and lexical decision-making were tested in eight smokers. Each participant was tested after 4 hours of smoking abstinence, under 4 conditions: placebo (very low nicotine) cigarette, nicotine cigarette, placebo patch, and nicotine patch. Relative to placebo, wearing the nicotine patch reduced Profile of Mood States (POMS) Total Mood Disturbance and Fatigue/Inertia scores, while increasing the speed of some types of lexical decisions. Smoking a nicotine cigarette did not affect reaction times, but unexpectedly decreased the accuracy of Word/ Nonword lexical decisions. Thus, transdermal nicotine may improve mood and facilitate longterm memory search and/or attentional processes in nicotine-deprived smokers.     

Modifications of blood volume alter the disposition of markers of blood volume, extracellular fluid, and total body water

Recirculatory pharmacokinetic models for indocyanine green (ICG), inulin, and antipyrine describe intravascular mixing and tissue distribution after i.v. administration. These models characterized physiologic marker disposition in four awake, splenectomized dogs while they were normovolemic, volume loaded (15% of estimated blood volume added as a starch solution), and mildly and moderately hypovolemic (15 and 30% of estimated blood volume removed). ICG-determined blood volumes increased 20% during volume loading and decreased 9 and 22% during mild and moderate hypovolemia. Dye (ICG) dilution cardiac output (CO) increased 31% during volume loading and decreased 27 and 38% during mild and moderate hypovolemia. ICG-defined central and fast peripheral intravascular circuits accommodated blood volume alterations and the fast peripheral circuit accommodated blood flow changes. Inulin-defined extracellular fluid volume contracted 14 and 21% during hypovolemia. Early inulin disposition changes reflected those of ICG. The ICG and inulin elimination clearances were unaffected by altered blood volume. Neither antipyrine-defined total body water volume nor antipyrine elimination clearance changed with altered blood volume. The fraction of CO not involved in drug distribution had a significant effect on the area under the antipyrine concentration-versus-time relationships (AUC) in the first minutes after drug administration. Hypovolemia increased the fraction of CO represented by nondistributive blood flow and increased the antipyrine AUC up to 60% because nondistributive blood flow did not change, despite decreased CO. Volume loading resulted in a smaller (less than 20%) antipyrine AUC decrease despite increased fast tissue distributive flow because nondistributive flow also increased with increased CO.     

Suppression of testosterone and estradiol-17beta-induced dysplasia in the dorsolateral prostate of Noble rats by bromocriptine

We, and others, have previously described the histological changes that occur in the prostate gland of intact Noble (NBL) rats following prolonged hormonal treatment. Dysplasia, a pre-neoplastic lesion, develops specifically in the dorsolateral prostates (DLPs) of NBL rats treated for 16 weeks with a combined regimen of testosterone (T) and estradiol-17beta (E2) (T + E2-treated rats). Concurrent with DLP dysplasia induction, the dual hormone regimen also elicits hyperprolactinemia, in addition to an elevation of nuclear type II estrogen binding sites (type II EBS), no alteration in estrogen receptors (ER), and marked epithelial cell proliferation in the dysplastic foci. The aim of this study was to investigate whether the dual hormone action is mediated via E2-induced hyperprolactinemia. Bromocriptine (Br), at a dose of 4 mg/kg body wt per day, was used to suppress pituitary prolactin (PRL) release. Serum PRL levels were lowered from values of 341 +/- 50 ng/ml in T + E2-treated rats to 32 +/- 10 ng/ml in Br co-treated animals. The latter values were comparable to those in untreated control rats. In addition, Br co-treatment effectively inhibited the evolution of dysplasia (six out of eight rats) and the often associated inflammation (five out of eight rats) in most animals. In contrast, Br co-treatment did not suppress the T + E2- induced type II EBS elevation nor alter ER levels in the DLPs of these rats, when compared with T + E2-treated rats. These data extend the many previous studies that have detailed marked influences of PRL on rat prostatic functions. However, the current study is the first to implicate PRL in prostatic dysplasia induction in vivo.      

Cefamandole prophylaxis for cardiovascular surgery: a dosage comparison

For more than a decade, studies have indicated that antibiotic dosing immediately before and for a short time after surgery is effective in reducing the incidence of infectious complications of open-heart operations. At our institution we have used cefamandole, because of its broad spectrum of activity against bacteria common to the skin and respiratory system and its low toxicity. However, in response to more recent studies that threw doubt on the ability of the recommended dosing regimen (1.0 g given intravenously every six hours for three days) to maintain adequate intraoperative levels of cefamandole in heart tissue, we undertook an evaluation of a dosage of 2.0 g given intravenously every 6 hours for two days. This was a randomized study of 211 successive, evaluable, open-heart surgery patients who had no concurrent infections or cephalosporin allergy. Postoperatively, there were eight surgery-related infections (3.9%) and eight nosocomial infections in the 2.0-g dose group, compared with seven surgery-related infections (3.5%) and seven nosocomial infections in the 1.0-g dose group. These differences were not statistically significant. Tissue levels and cardiopulmonary bypass pump time were not risk factors for infection. We conclude that the 2.0-g doses over two days are no more effective than the 1.0-g doses over three days. However, when administration fees are considered, in a cost comparison, the 2.0-g dosing regimen is more economical than the 1.0-g regimen.     

Suprasellar arachnoid cysts: 1. CT recognition

Suprasellar arachnoid cysts are basal midline masses that represent a rare but surgically remediable cause of hydrocephalus and neurologic deficits. These cysts represent a diagnostic challenge and often go unrecognized for many years. The authors review the computed tomographic (CT) findings in seven patients with documented suprasellar arachnoid cysts and define previously undescribed diagnostic criteria. These cysts usually can be differentiated from cystic midline neoplasms by their CT density, homogeneity, and location as well as by their lack of fat, lack of calcification, and absence of contrast enhancement. Accurate distinction from marked third-ventricular enlargement secondary to obstructive hydrocephalus and from third-ventricular ependymal cysts can be made on the basis of basal cisternal expansion, distinctive mass effect and displacement, the characteristic shape and contour of the apparent "third ventricle," and the appearance of structures at the foramen of Monro. Although metrizamide CT ventriculography and cisternography allow confirmation of the diagnosis and evaluation of cerebrospinal fluid dynamics, these definitive studies will not be obtained unless the cysts are first suspected by their conventional CT appearance.     

Building clinical trial capacity to develop a new treatment for multidrug-resistant tuberculosis

Problem

New drugs for infectious diseases often need to be evaluated in low-resource settings. While people working in such settings often provide high-quality care and perform operational research activities, they generally have less experience in conducting clinical trials designed for drug approval by stringent regulatory authorities.

Approach

We carried out a capacity-building programme during a multi-centre randomized controlled trial of delamanid, a new drug for the treatment of multidrug-resistant tuberculosis. The programme included: (i) site identification and needs assessment; (ii) achieving International Conference on Harmonization – Good Clinical Practice (ICH-GCP) standards; (iii) establishing trial management; and (iv) increasing knowledge of global and local regulatory issues.

Local setting

Trials were conducted at 17 sites in nine countries (China, Egypt, Estonia, Japan, Latvia, Peru, the Philippines, the Republic of Korea and the United States of America). Eight of the 10 sites in low-resource settings had no experience in conducting the requisite clinical trials.

Relevant changes

Extensive capacity-building was done in all 10 sites. The programme resulted in improved local capacity in key areas such as trial design, data safety and monitoring, trial conduct and laboratory services.

Lessons learnt

Clinical trials designed to generate data for regulatory approval require additional efforts beyond traditional research-capacity strengthening. Such capacity-building approaches provide an opportunity for product development partnerships to improve health systems beyond the direct conduct of the specific trial.     

Management of osteomyelitis

Early diagnosis and aggressive treatment, which includes thorough debridement and culture-directed antibiotic therapy, are essential for effective management of patients with osteomyelitis. Definitive diagnosis of osteomyelitis usually requires microbial culture of bone specimens obtained either by surgery or by percutaneous needle biopsy. The most common pathogen involved in osteomyelitis is Staphylococcus aureus; however, other organisms, including gram-negative pathogens and coagulase-negative staphylococci, may be found. Often, bone infections may be polymicrobial. Antimicrobial therapy, ideally initiated after complete surgical debridement and microbial confirmation of the diagnosis, is usually maintained for at least 6 weeks. Although therapy has traditionally been administered parenterally during an extended hospital stay, oral antibiotic therapy (often following initial parenteral therapy) and parenteral therapy on an outpatient basis are gaining acceptance for use in patients with osteomyelitis.