Lung clearance index and high-resolution computed tomography scores in primary ciliary dyskinesia.

RATIONALE: Lung clearance index (LCI) is a more sensitive measure of lung function than spirometry in cystic fibrosis (CF) and correlates well with abnormalities in high-resolution computed tomography (HRCT) scanning. We hypothesized LCI would be equally sensitive to lung disease in primary ciliary dyskinesia (PCD). OBJECTIVES: To test the relationships between LCI, spirometry, and HRCT in PCD and to compare them to the established relationships in CF. METHODS: Cross-sectional study of 127 patients with CF and 33 patients with PCD, all of whom had spirometry and LCI, of which a subset of 21 of each had HRCT performed. HRCT was scored for individual features and these features compared with physiological parameters. MEASUREMENTS AND MAIN RESULTS: Unlike in CF, and contrary to our hypothesis, there was no correlation between spirometry and LCI in PCD and no correlation between HRCT features and LCI or spirometry in PCD. CONCLUSIONS: We show for the first time that HRCT, spirometry, and LCI have different relationships in different airway diseases and that LCI does not appear to be a sensitive test of airway disease in advanced PCD. We hypothesize that this results from dissimilarities between the components of large and small airway disease in CF and PCD. These differences may in part lead to the different prognosis in these two neutrophilic airway diseases.

MR imaging evaluation of fibroid clearance following open myomectomy for massive/multiple symptomatic fibroids.

PURPOSE: To evaluate the technical success of total fibroid clearance at open myomectomy for massive and/or multiple symptomatic fibroids using MR imaging (MRI) as the imaging modality. METHODS: The study group comprised 27 women [mean age 37.4 ± 6.9 years (range 27-53)] who underwent open myomectomy for the treatment of massive/multiple symptomatic fibroids at our institution between January 2009 and April 2010. Myomectomy was performed with the intention of achieving complete fibroid clearance. Pre- and postmyomectomy MRI was performed to assess changes in uterine volume and fibroid burden. Periprocedural data (including blood loss and complications) and relief of clinical symptoms at follow-up were also recorded. RESULTS: The mean time to MRI and clinical follow-up was 10 months (range 6-15 months). The mean uterine volume premyomectomy was 795 ± 580 cc and postmyomectomy was 123 ± 70 cc (p < 0.001). The mean percentage reduction in uterine volume was 80.3 % (range 43.0-98.1 %). Of the 10/27 (37.0 %) women with residual fibroids at follow-up: 7 patients had fibroids measuring up to 1 cc in volume, 3 patients had fibroids measuring up to 6 cc. Postoperative adnexal seromas were observed in 6/27 (22.2 %) patients. The clinical success rates of myomectomy amongst the 22/27 (81 %) responders were: 73 % for menorrhagia, 64 % for pain, and 36-64 % for mass-related symptoms. CONCLUSIONS: Using MRI, we have confirmed that open myomectomy can achieve total or near-total fibroid clearance in the majority of patients with massive and/or multiple fibroids.

Image quality of computed tomographic pulmonary angiography for suspected pulmonary embolus in patients with diffuse interstitial lung disease.

PURPOSE: To investigate the effect of diffuse interstitial lung disease (DILD) on the image quality of computed tomographic pulmonary angiography (CTPA). MATERIALS AND METHODS: The study group comprised 130 patients with DILD who underwent CTPA between April 2005 and April 2009. One hundred and thirty patients without significant parenchymal lung disease were used as a control group. Contrast enhancement of pulmonary arteries in the left upper lobe and right lower lobe was evaluated to the sub-subsegmental level both subjectively and objectively. The global and lobar extents of interstitial lung disease were also estimated in the study group. Subjective assessment was performed by 2 observers, initially independently and subsequently by consensus in cases of discordance. RESULTS: At the sub-subsegmental level, the number of patients with adequately opacified arteries was significantly lower in the DILD group (29.2% left upper lobe, 36.2% right lower lobe) compared with the control group (78.5% left upper lobe, 89.2% right lower lobe) (P<0.001). Subjective image quality scores of the sub-subsegmental arteries were strongly correlated with mean vascular attenuation values at this level (P<0.001) but not to the global or lobar extent of lung parenchymal disease. There was no clinically significant difference in image quality (either subjectively or objectively) between the DILD and control groups in the subsegmental and more proximal arterial branches. CONCLUSIONS: In the majority of patients with DILD, CTPA image quality is sufficient only to the subsegmental level. Emboli at the sub-subsegmental level, which may have greater clinical significance in patients with DILD than in those without, are unlikely to be excluded using CTPA.

Use of a TriPollar radio-frequency device for the treatment of acne vulgaris.

INTRODUCTION: Acne vulgaris is a common disease affecting mainly teenagers and young adults. Current treatment modalities include local or systemic medications, which often require a long intake. Light and radio-frequency (RF) devices have recently been used to treat acne in selected patients. OBJECTIVE: To evaluate the safety and efficacy of TriPollar RF technology for non-invasive treatment of acne vulgaris lesions. METHODS: Twenty patients with active acne lesions underwent TriPollar RF treatments once a week for 6 weeks. Results were evaluated using photographs and active lesion counts at baseline, before subsequent treatment sessions and at follow-up visits. Patients also rated their satisfaction on a 5-score rating scale. RESULTS: An average reduction of 42% in active acne lesions was found after six TriPollar sessions, which was sustained at the 4-week follow-up visit. The average improvement rated by patients at the 4-week follow-up visit was 2.5, indicating good to very good satisfaction with the clinical results. No significant adverse events were recorded during the study and follow-up period. CONCLUSION: The findings confirm the safety and efficacy of TriPollar RF for the treatment of acne vulgaris.

Imaging in the assessment and management of Achilles tendinopathy and paratendinitis.

Achilles tendinopathy is a common overuse injury in patients engaged in athletic activities. Tendon degeneration is often accompanied by paratendinitis. Radiologists are frequently asked to use imaging techniques to evaluate patients with problems at or around the Achilles tendon. The main imaging modalities used in the assessment of Achilles tendon disorders are plain radiography, ultrasound, and magnetic resonance imaging. In recent years, ultrasound has also been used to guide minimally invasive local treatments for Achilles tendinopathy, which may prevent the need for surgery if conservative treatments have failed. In this article, we review the imaging features of Achilles tendinopathy and consider the relative strengths and weaknesses of the various imaging techniques. The role of imaging in directing patient management is also discussed, with particular focus on ultrasound-guided treatments.

Ultrasound-guided treatments for chronic Achilles tendinopathy: an update and current status.

Minimally-invasive treatments for chronic Achilles tendinopathy may prevent the need for surgery when conservative methods have failed. Whilst injections have traditionally been used to manage symptoms, recently described therapies may also have disease-modifying potential. Ultrasound provides the ability to guide therapeutic interventions, ensuring that treatment is delivered to the exact site of pathology. Treatments can be broadly categorised according to their intended therapeutic targets, although some may act through several possible mechanisms. In this article, we review the ultrasound-guided techniques currently used to treat chronic Achilles tendinopathy, with reference to the available literature. There is strong pilot-level evidence supporting the use of many of these techniques, although large definitive trials are lacking. An approach towards the management of chronic Achilles tendinopathy is suggested.

X-ray computed tomography of the heart.

INTRODUCTION: Cardiac imaging is an emerging application of multidetector computed tomography (MDCT). This review summarizes the current capabilities, possible applications, limitations and developments of cardiac CT. SOURCES OF DATA: Relevant publications in peer reviewed literature and national and international guidelines are used to discuss important issues in cardiac CT imaging. AREAS OF AGREEMENT AND CONTROVERSY: There is broad consensus that coronary CT angiography is indicated in patients with an intermediate pre-test probability of coronary artery disease (CAD) when other non-invasive tests have been equivocal. In this context, CT can reliably exclude significant CAD. Cardiac CT also has an established role in the evaluation of bypass grafts and suspected coronary anomalies. Radiation exposure from CT procedures remains a concern, although techniques are now available to reduce the X-ray dosage without significantly compromising the image quality. However, with the current level of knowledge, the cardiac CT examinations are not justified to screen for CAD in asymptomatic individuals. Neither is it considered appropriate in patients with a high pre-test probability of CAD, for whom invasive catheter coronary angiography is usually of more benefit. GROWING POINTS AND AREAS TIMELY FOR DEVELOPING RESEARCH: The ability to reconstruct the volumetric cardiac CT data set opens up avenues for advanced physiological analyses of the heart. For example, if CT myocardial perfusion assessment becomes a reality, there is potential to revolutionize the practice of MDCT imaging. Research is also ongoing to investigate whether cardiac CT has a role in the appropriate triage of patients with chest pain in the emergency department.

An interesting cause of recurrent haemoptysis: haemoptysis 7 years after a foreign body penetrated the lung parenchyma and aorta.

A 43-year-old man presented with a 12-month history of recurrent haemoptysis. Postero-anterior chest X-ray of a patient with a history of a penetrating thoracic trauma 8 years previously showed a long wedge-shaped opacity just above the left hemidiaphragm, representing the 'tip of the knife' appearance, and penetrating from the lateral chest wall deep to the thoracic aorta. After consultation with the cardiovascular surgeons, it was decided that the patient should have an operation to remove the foreign body penetrating the aorta. During the operation, a piece of glass was located in the posterior segment of the left lower lobe, and it had also penetrated the aorta through to the posterior wall. The glass had a pointed end, was wedge-shaped and measured 8 cm x 3 cm x 0.5 cm. It was removed, and a 5-cm segment of aorta was replaced with dacron graft. Patients with penetrating chest trauma require routine chest X-rays as many will have a haemothorax, pneumothorax or a penetrating foreign body in the chest in the absence of clinical findings. Postero-anterior chest X-rays as well as lateral X-rays must be carefully and systematically examined for foreign bodies.

Preliminary guidelines for the evaluation and management of dyslipidemia in adults infected with human immunodeficiency virus and receiving antiretroviral therapy: Recommendations of the Adult AIDS Clinical Trial Group Cardiovascular Disease Focus Group.

Dyslipidemia is a prevalent condition that affects patients infected with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy. These preliminary recommendations summarize the current understanding in this area and propose guidelines for management. Existing guidelines for the management of dyslipidemia in the general population formed the general basis for our recommendations. Data on the prevalence and treatment of dyslipidemia of HIV-infected patients, implications of treatment-related dyslipidemia in other chronically ill populations, and pharmacokinetic profiles for the available hypolipidemic agents in non-HIV populations were considered. Although the implications of dyslipidemia in this population are not fully known, the frequency, type, and magnitude of lipid alterations in HIV-infected people are expected to result in increased cardiovascular morbidity. We propose that these patients undergo evaluation and treatment on the basis of existing guidelines for dyslipidemia, with the caveat that avoidance of interactions with antiretroviral agents is paramount.

Clarithromycin or rifabutin alone or in combination for primary prophylaxis of Mycobacterium avium complex disease in patients with AIDS: A randomized, double-blind, placebo-controlled trial. The AIDS Clinical Trials Group 196/Terry Beirn Community Programs for Clinical Research on AIDS 009 Protocol Team.

The efficacy and safety of clarithromycin and rifabutin alone and in combination for prevention of Mycobacterium avium complex (MAC) disease were compared in 1178 patients with AIDS who had < or =100 CD4 T cells/microL in a randomized, double-blind, placebo-controlled trial. MAC disease occurred in 9%, 15%, and 7% of those randomized to clarithromycin or rifabutin alone or in combination, respectively; time-adjusted event rates per 100 patient-years (95% confidence interval [CI]) were 6.3 (4.2-8.3), 10.5 (7.8-13.2), and 4. 7 (2.9-6.5). Risk of MAC disease was reduced by 44% with clarithromycin (risk ratio [RR], 0.56; 95% CI, 0.37-0.84; P=.005) and by 57% with combination therapy (RR, 0.43; 95% CI, 0.27-0.69; P=. 0003), versus rifabutin. Combination therapy was not more effective than clarithromycin (RR, 0.79; 95% CI, 0.48-1.31; P=.36). Of those in whom clarithromycin or combination therapy failed, 29% and 27% of MAC isolates, respectively, were resistant to clarithromycin. There were no survival differences. Clarithromycin and combination therapy were more effective than rifabutin for prevention of MAC disease, but combination therapy was associated with more adverse effects (31%; P<.001).

A pilot study evaluating ceftriaxone and penicillin G as treatment agents for neurosyphilis in human immunodeficiency virus-infected individuals.

To compare intravenous (iv) ceftriaxone and penicillin G as therapy for neurosyphilis, blood and CSF were collected before and 14-26 weeks after therapy from 30 subjects infected with human immunodeficiency virus (HIV)-1 who had (1) rapid plasma reagin (RPR) test titers >/=1&rcolon;16, (2) reactive serum treponemal tests, and (3) either reactive CSF-Venereal Disease Research Laboratory (VDRL) tests or CSF abnormalities: (a) CSF WBC values >/=20/microL or (b) CSF protein values >/=50 mg/dL. At baseline, more ceftriaxone recipients had skin symptoms and signs (6 [43%] of 14 vs. 1 [6%] of 16; P=.03), and more penicillin recipients had a history of neurosyphilis (7 [44%] of 16 vs. 1 [7%] of 14; P=.04). There was no difference in the proportion of subjects in each group whose CSF measures improved. Significantly more ceftriaxone recipients had a decline in serum RPR titers (8 [80%] of 10 vs. 2 [13%] of 15; P=. 003), even after controlling for baseline RPR titer, skin symptoms and signs, or prior neurosyphilis were controlled for. Differences in the 2 groups limit comparisons between them. However, iv ceftriaxone may be an alternative to penicillin for treatment of HIV-infected patients with neurosyphilis and concomitant early syphilis.

Efficacy and safety of delavirdine mesylate with zidovudine and didanosine compared with two-drug combinations of these agents in persons with HIV disease with CD4 counts of 100 to 500 cells/mm3 (ACTG 261). ACTG 261 Team.

To evaluate the antiretroviral activity of delavirdine mesylate, a non-nucleoside reverse transcriptase inhibitor of HIV-1, we performed a phase II, randomized, double-blind, multicenter trial comparing the three-drug combination of delavirdine with zidovudine and didanosine to two-drug combinations of these drugs. Patients with CD4 cell counts between 100 and 500 cells/mm3 without prior or <6 months of monotherapy with zidovudine or didanosine were randomized to one of four arms and observed on a follow-up basis for 48 weeks. In total, 544 patients were evaluated. In those assigned to the three-drug regimen, mean short-term (weeks 4-12) and long-term (weeks 40-48) change in CD4 cells from baseline were 49.3+/-8.1 and 65.4+/-13.4 cells/mm3, respectively; mean short-term and long-term HIV-1 RNA changes from baseline were -1.13 log10+/-0.12 and -0.73+/-0.12 copies/ml, respectively. These responses in CD4 cell counts and HIV-1 RNA levels were better in comparisons with each of the two-drug arms at all study points; however, differences were not consistently significant. Gastrointestinal side effects were experienced by 33% of patients (178 of 544), and 30% (121 of 407) receiving delavirdine experienced rash, only one case of which was severe. In this study, therapy with delavirdine + zidovudine + didanosine was safe and showed modest, but not always significant, antiviral activity and CD4 cell count benefit compared with two-drug regimens with these agents. Key

ACTG 260: a randomized, phase I-II, dose-ranging trial of the anti-human immunodeficiency virus activity of delavirdine monotherapy. The AIDS Clinical Trials Group Protocol 260 Team.

ACTG 260 was an open-label, four-arm trial designed to study the safety and anti-human immunodeficiency virus (anti-HIV) activity of delavirdine monotherapy at three ranges of concentrations in plasma compared to those of control therapy with zidovudine or didanosine. Delavirdine doses were adjusted weekly until subjects were within their target trough concentration range (3 to 10, 11 to 30, or 31 to 50 microM). A total of 113 subjects were analyzed. At week 2, the mean HIV type 1 (HIV-1) RNA level declines among the subjects in the three delavirdine arms were similar (0.87, 1.08, and 1.02 log10 for the low, middle, and high target arms, respectively), but by week 8, the subjects in the pooled delavirdine arms showed only a 0.10 log10 reduction. In the subjects in the nucleoside arm, mean HIV-1 RNA level reductions at weeks 2 and 8 were 0.67 and 0.55 log10, respectively. Because viral suppression by delavirdine was not maintained, the trial was stopped early. Rash, which was usually self-limited, developed in 36% of subjects who received delavirdine. Delavirdine monotherapy has potent anti-HIV activity at 2 weeks, but its activity is time limited due to the rapid emergence of drug resistance.

Phase I study of atevirdine mesylate (U-87201E) monotherapy in HIV-1-infected patients.

The safety, tolerability, and antiviral activity of atevirdine (ATV), a nonnucleoside reverse transcriptase inhibitor, were studied in a phase I/II clinical trial (ACTG 187) of patients with CD4 counts < or =500/mm3. In all, 34 HIV-1-infected patients were randomized to receive ATV for 12 weeks in doses chosen to achieve one of three serum trough levels: 5 to 13 microM, 14 to 22 microM, or 23 to 31 microM. Rash was the most common adverse event, with a grade 3 or 4 rash occurring in 4 patients. No significant change from baseline in HIV-1 plasma RNA mean copy number was detected at week 4 (+0.09 log10 copies/ml; p = .30). However, some evidence indicated moderate antiviral activity at week 4, based on median changes in CD4 count (+23/mm3; p = .05), and viral peripheral blood mononuclear cell (PBMC) titer (-0.68 log10) copies/ml; p = .03). In addition, 2 of 4 patients with detectable baseline serum p24 antigen showed declines of >50%. HIV-1 resistance to ATV was detected in 41% of patients and was most commonly associated with RT mutations K103N and Y181C. In contrast, the Y181C mutation was not detected in ATV-resistant isolates obtained from patients enrolled in ACTG 199, a study of ATV given in combination with zidovudine. Under the conditions of this study, ATV failed to demonstrate significant antiretroviral activity. However, transient in vivo activity might have been obscured by rapid development of resistance coupled with inadequate sampling at early time points following initiation of ATV therapy.

Pilot study of topical trifluridine for the treatment of acyclovir-resistant mucocutaneous herpes simplex disease in patients with AIDS (ACTG 172). AIDS Clinical Trials Group.

SUMMARY: Twenty-six AIDS patients were enrolled in an open label pilot study to evaluate the efficacy and toxicity of topical 1 percent ophthalmic trifluridine solution for the treatment of chronic mucocutaneous herpes simplex virus disease unresponsive to at least 10 days of acyclovir therapy. Susceptibility testing to acyclovir, trifluridine, and foscarnet was determined by plaque reduction assay. Twenty-four patients were evaluable for efficacy and 25 for toxicity analyses. Seven patients (29 percent) had complete healing of lesions. The overall estimated median time to complete healing was 7.1 weeks. An additional seven patients had > or = 50 percent reduction in lesion area. The overall estimated median time to 50 percent healing was 2.4 weeks. Ten (42 percent) patients discontinued treatment for reasons other than primary treatment failure and seven (29 percent) for failure to respond to therapy. Baseline patient characteristics associated with greater reduction in lesion area included higher Karnofsky score (p = 0.05), fewer lesions (p = 0.07), smaller lesion area (p = 0.11), and trifluridine susceptibility (p = 0.07). Eight (33 percent) patients developed new lesions outside of the treatment area while on study, reflecting the local nature of this therapy. No dose-limiting toxicity attributable to trifluridine was reported. Given the limited options for the treatment of acyclovir-resistant herpes simplex disease, topical trifluridine may be a useful alternative in selected patients.

Perinatal immunity to group B beta-hemolytic streptococcus type Ia.

Sera from 14 of 56 adult women protected mice from intraperitoneal challenge with mouse-virulent group B Streptococcus serotype Ia, and sera from seven of 25 nonparturient women in this group were bactericidal for greater than 99% of the organisms in the presence of normal polymorphonuclear leukocytes. There were no discrepancies between the in vivo and in vitro assays. Protective activity was found in the IgG class in seven sera, and in the IgM class in one. Opsonic activity was partially dependent on heat-labile serum factors. Of 31 mother-cord serum pairs studied, seven maternal sera were protective, but four of the corresponding cord sera were not. Pooled human gamma-globulin injected by either the intraperitoneal or the intramuscular route protected mice from bacterial challenge.