A measurement of the atomic hydrogen Lamb shift and the proton charge radius.

The surprising discrepancy between results from different methods for measuring the proton charge radius is referred to as the proton radius puzzle. In particular, measurements using electrons seem to lead to a different radius compared with those using muons. Here, a direct measurement of the n = 2 Lamb shift of atomic hydrogen is presented. Our measurement determines the proton radius to be r p = 0.833 femtometers, with an uncertainty of ±0.010 femtometers. This electron-based measurement of r p agrees with that obtained from the analogous muon-based Lamb shift measurement but is not consistent with the larger radius that was obtained from the averaging of previous electron-based measurements.

Chikungunya infection in the general population and in patients with rheumatoid arthritis on biological therapy.

Chikungunya infection is a febrile illness, which currently is afflicting the Caribbean islands including the Dominican Republic. We would like to report our experience with Chikungunya-related musculoskeletal manifestations in our arthritis clinics in the Dominican Republic. A total of 514 patients presented for the first time to our arthritis clinic exhibiting musculoskeletal manifestations, 473/514 (92%) exhibiting symmetric polyarthralgias, 344/514 (67%) arthritis, and 385 (75%) skin rash. The great majority 457.46 (89%) exhibited very good clinical response to nonsteroidal anti-inflammatory drugs (NSAIDs), 370 (72%) require low-dose steroids, and only 5 patients (0.97%) required methotrexate therapy. In addition, of a total of 328 patients with rheumatoid arthritis on biological treatment, 53 exhibited Chikungunya-related musculoskeletal manifestations; 51/53 (96.2%) exhibited symmetric polyarthralgias, 25/53 (47.1%) arthritis, and 13/53 (24.5%) tendinopathy. Of most patients, 51/53 responded to NSAIDs, of which, 23 patients only responded partially, and in total 25 (47.1%) required low-dose steroids. Disease-modifying antirheumatic drug (DMARD) therapy including biologics remained unchanged in this population.

Phase I study investigating the safety and feasibility of combining imatinib mesylate (Gleevec) with sorafenib in patients with refractory castration-resistant prostate cancer.

BACKGROUND: Determining the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT) of sorafenib (S) plus imatinib (IM) in castration-resistant prostate cancer (CRPC) patients. METHODS: Refractory CRPC patients were enrolled onto this 3+3 dose escalation designed study. Imatinib pharmacokinetics (PK) were determined on day 15, 4 h post dose with a validated LC-MS assay. RESULTS: Seventeen patients were enrolled; 10 evaluable (6 at 400 mg S qd with 300 mg IM qd (DL0) and 4 at 400 mg S bid with 300 mg IM qd (DL1)); inevaluable patients received <1 cycle. The median age was 73 (57-89); median prostatic serum antigen was 284 ng ml(-1) (11.7-9027). Median number of prior non-hormonal therapies was 3 (1-12). Dose-limiting toxicities were diarrhoea and hand-foot syndrome. Maximum tolerated dose was 400 mg S and 300 mg IM both daily. No biochemical responses were observed. Two patients had stable disease by RECIST. Median time to progression was 2 months (1-5). Median OS was 6 months (1-30+) with 3/17 patients (17%) alive at 21 months median follow-up. Ten patients had PK data suggesting that S reduced IM clearance by 55%, resulting in 77% increased exposure (P=0.005; compared with historical data). CONCLUSION: This is the first report showing that S+IM can be administered in CRPC at a dose of 400 mg S and 300 mg IM, daily.

Delayed diagnosis of abdominal mass due to morbid obesity.

Obesity has become an increasing problem in developed countries. Obesity is associated with many of the most common causes of morbidity and mortality, including diabetes mellitus, coronary artery diseases, sleep apnoea, and many types of cancers. Not only is morbid obesity associated to a greater extent to the many medical problems related to obesity, but the body habitus of a morbidly obese patient causes limitation to physical examination, radiologic evaluations, and therapeutic interventions that can delay diagnosis and treatment of the patient. We present a case of a morbidly obese patient whose diagnosis of liposarcoma was delayed for over a year as his obesity hindered proper diagnosis and medical treatment.

Pulsed-dye laser and retinoic acid delay progression of oral squamous cell carcinoma: a murine model.

OBJECTIVES/HYPOTHESIS: This study examined the role of the pulsed-dye laser (PDL) at 585 nm coupled with retinoic acid at therapeutic (5.0 mg/kg) and nontherapeutic (0.5 mg/kg) doses to delay the progression of cancer with a two-hit approach. The existing vasculature is selectively targeted by the laser, whereas retinoic acid inhibits future angiogenesis. STUDY DESIGN: Randomized, prospective study in a murine model. METHODS: Twenty-five athymic nude mice were inoculated with oral squamous cell cancers on six flank sites and randomly divided into five groups: 1) control subjects, 2) treatment with 0.5 mg/kg retinoic acid (RA 0.5), 3) treatment with 5.0 mg/kg retinoic acid (RA 5.0), 4) treatment with RA 0.5 + PDL, and 5) treatment with RA 5.0 + PDL. The PDL groups received irradiation after inoculation. The retinoic acid was administered daily. The tumors were counted and measured for 14 days. RESULTS: The control group developed visible tumors in 50% of the inoculation sites at 3 days compared with 3 days (RA 0.5) and 4 days (RA 5.0) for the retinoic acid groups and 9 days (RA 0.5 + PDL) and 10 days (RA 5.0 + PDL) for the laser treatment groups. There was no tumor growth until day 7 in the RA 5.0 + PDL group. The tumor volume was statistically different between the treatment groups. CONCLUSION: This study demonstrated the superiority of a single treatment with the PDL coupled with retinoic acid to delay the progression of cancer when compared with treatment with retinoic acid alone, thus introducing a novel strategy in cancer control.

Anterior window laryngoplasty: a new anatomic approach for posterior glottic and subglottic stensosis.

This study explores the feasibility of an anterior thyroid window as a new approach for posterior glottic stenosis. An anterior window was made on the thyroid cartilage of human cadaver larynges, with its superior edge below the level of the vocal cords and an inferior pedicle composed of the inferior border of the thyroid cartilage attached to the cricothyroid membrane, which was left intact. By obtaining direct exposure of the posterior glottis and cricoarytenoid joints, mucosal graft suturing and exploration of the joints were easily achieved with an operating microscope. This study demonstrates the anatomic feasibility of an anterior window laryngoplasty as an alternative approach to treating posterior glottic stenosis while preserving the cartilage framework and avoiding the anterior commissure. This technique may improve endolaryngeal manipulation by providing a closer and more direct exposure than do endoscopic techniques, and by having fewer possible complications than traditional open techniques.

A new laser treatment for vocal cord papilloma--585-nm pulsed dye.

OBJECTIVES: Microvascular targeting with the 585- nm pulsed dye laser (PDL) may provide a new form of therapy to control symptoms caused by recurrent respiratory papillomatosis (RRP). METHODS: Ten patients with RRP underwent 13 procedures under general anesthesia with the 585-nm PDL. A micromanipulator (11 procedures) and a flexible nasolaryngoscope (2 procedures) were used to deliver the laser pulses. Patients were followed postoperatively according to protocol. RESULTS: Clinical examination revealed regression of papillomas in all patients. Seven patients had complete regression after PDL surgery, and 2 patients had partial response to treatment. One patient was lost to follow-up. No complications were present during this prospective nonrandomized pilot study. CONCLUSION: Patients treated with PDL experienced regression of their papillomas. PDL may provide patients with RRP with an alternative treatment without the risks associated with CO(2) laser surgery. This procedure also has potential to be delivered on an outpatient basis with flexible fiberoptic laryngoscopes.

Bronchoscopic management of benign stenosis.

In summary, the use of laser technology in the airway for the treatment of benign lesions has become a standard therapeutic modality for the airway endoscopist. It is extremely important that endoscopists be well acquainted with the laser soft tissue interactions of the laser being used and the safety precautions associated with each individual wavelength. They should be conversant with the indications and contraindications and have the ability to use adjuvant therapeutic modalities, such as stents and medications. As usual, patient selection is one of the key factors related to successful management.

Preliminary results of intraoperative mitomycin-C in the treatment and prevention of glottic and subglottic stenosis.

Mitomycin-C is an antineoplastic antibiotic that acts as an alkylating agent by inhibiting DNA and protein synthesis. It can inhibit cell division, protein synthesis, and fibroblast proliferation. The purpose of this pilot study is to investigate intraoperative applications of topical mitomycin-C in treatment and prevention of glottic and subglottic stenosis. Eight patients with posterior glottic and/or subglottic stenosis were treated with endoscopic CO2 laser excision followed by topical application of 0.5 cc of 0.4 mg mitomycin-C per milliliter of saline for 4 minutes at the surgical site. After mean follow-up of 15 months (10-20) all patients had clinical improvement of their airway and resolution of their preoperative symptoms. No complications were noted in this study. Although a longer follow-up and further controlled studies are needed, the use of topical mitomycin-C may prove useful in the treatment and prevention of subsequent restenosis and scar formation in the larynx and trachea.

Primary hypertrophic osteoarthropathy.

We describe seven patients with primary HOA and review 125 cases reported in the English, French, and German literature. The salient clinical features of primary HOA are: a bimodal distribution of disease onset with one peak during the first year of life and the other at age 15, a male predominance (nine to one), uncommon benign joint effusion, and a variety of skin abnormalities resulting from cutaneous hypertrophy or glandular dysfunction. We concluded that HOA is not a synovial disease. It is suggested that synovial effusions, when present, are perhaps a sympathetic reaction to the neighboring periostitis. Proposed diagnostic criteria for HOA, including digital clubbing and radiographic periostitis, appear 86% sensitive. The clinical features, age of onset, and sex distribution suggest that a genetically controlled growth promoting factor, different from growth hormone, plays a role in the pathogenesis of this syndrome.