Aggressive Nodular Malignant Melanoma.

A subtype of malignant melanomas, nodular melanoma often carries a poor prognosis because of local invasion and frequent distant metastasis. Here, we report a case of progressive dyspnea due to one of the largest primary melanomas in the literature to date along with management strategies and elucidate some of the reasons why patients delay seeking care.

Miniaturized electromechanical devices for the characterization of the biomechanics of deep tissue.

Evaluating the biomechanics of soft tissues at depths well below their surface, and at high precision and in real time, would open up diagnostic opportunities. Here, we report the development and application of miniaturized electromagnetic devices, each integrating a vibratory actuator and a soft strain-sensing sheet, for dynamically measuring the Young's modulus of skin and of other soft tissues at depths of approximately 1-8 mm, depending on the particular design of the sensor. We experimentally and computationally established the operational principles of the devices and evaluated their performance with a range of synthetic and biological materials and with human skin in healthy volunteers. Arrays of devices can be used to spatially map elastic moduli and to profile the modulus depth-wise. As an example of practical medical utility, we show that the devices can be used to accurately locate lesions associated with psoriasis. Compact electronic devices for the rapid and precise mechanical characterization of living tissues could be used to monitor and diagnose a range of health disorders.

Ultra-fast absorption of amorphous pure drug aerosols via deep lung inhalation.

A deficiency of most current drug products for treatment of acute conditions is slow onset of action. A promising means of accelerating drug action is through rapid systemic drug administration via deep lung inhalation. The speed of pulmonary drug absorption depends on the site of aerosol deposition within the lung and the dissolution rate and drug content of the deposited particles. Alveolar delivery of fast-dissolving, pure drug particles should in theory enable very rapid absorption. We have previously shown that heating of thin drug films generates vapor-phase drug that subsequently cools and condenses into pure drug particles of optimal size for alveolar delivery. Here we present a hand held, disposable, breath-actuated device incorporating this thermal aerosol technology, and its application to the delivery of alprazolam, an anti-panic agent, and prochlorperazine, an anti-emetic with recently discovered anti-migraine properties. Thermal aerosol particles of these drugs exist in an amorphous state, which results in remarkably rapid drug absorption from the lung into the systemic circulation, with peak left ventricular concentrations achieved within 20 s, even quicker than following rapid (5 s) intravenous infusion. Absorption of the thermal aerosol is nearly complete, with >80% absolute bioavailability found in both dogs and human normal volunteers.

Loss of renal function and microvascular blood flow after suprarenal aortic clamping and reperfusion (SPACR) above the superior mesenteric artery is greatly augmented compared with SPACR above the renal arteries.

OBJECTIVE: Renal insufficiency continues to be a complication that can affect patients after treatment for suprarenal aneurysms and renal artery occlusive disease. To our knowledge, no data are available showing that suprarenal aortic clamping and reperfusion (SRACR) above the renal arteries (renal-SRACR) preserves renal function compared with SRACR above the superior mesenteric artery (SMA-SRACR). This study examined the hypothesis that SMA-SRACR-induced downregulation of renal blood flow and function is more severe than renal-SRACR owing to the addition of systemic oxygen-derived free radical (ODFR) release. METHODS: Male Sprague-Dawley rats (about 350 g) were anesthetized and microdialysis probes or laser Doppler fibers were inserted into the renal cortex (depth of 2 mm) and into the renal medulla (depth of 4 mm). Laser Doppler blood flow was continuously monitored, and the microdialysis probes were connected to a syringe pump and perfused in vivo at 3 microL/min with lactated Ringer's solution. RESULTS: SMA-SRACR and Renal-SRACR decreased medullary and cortical blood flow and nitric oxide (NO) synthesis. SMA-SRACR downregulated cortical inducible NO synthase, whereas renal-SRACR did not. The cortex and medulla responded to the decreased blood flow and NO synthesis by increasing in prostaglandin E2 synthesis, which was due to increased cyclooxygenase-2 content. Superoxide dismutase restored SMA-SRACR (but not renal-SRACR) cortical and medullary NO synthesis, suggesting that ODFRs generated during mesenteric ischemia-reperfusion were one of the systemic mechanisms contributing to decreased renal NO synthesis in the SMA-SRACR model. The 90% decrease in creatinine clearance after SMA-SRACR was greater than the 60% decrease after renal-SRACR. CONCLUSIONS: These data show that NO is important in maintaining renal cortical and medullary blood flow and NO synthesis after renal and SMA-SRACR. These data also suggest that in addition to the renal ischemia-reperfusion caused by both models, SMA SRACR induces mesenteric ischemia-reperfusion, resulting in the generation of ODFRs, which contribute to decreased renal cortical and medullary NO synthesis. Maintaining splanchnic blood flow or attempting to keep SRACR below the SMA level may be helpful in developing strategies to minimize the renal injury after SRACR.

Preliminary results of subintimal angioplasty for limb salvage in lower extremities with severe chronic ischemia and limb-threatening ischemia.

OBJECTIVE: This study examined the hypothesis that superficial femoral artery (SFA) subintimal angioplasty (SI-PTA) can maintain limb salvage with minimal complications in patients with symptomatic occlusive arterial disease. METHODS: From March 1, 2004, until April 28, 2006, 78 patients with rest pain (62.2%), gangrene (25.6%), or severe progressive claudication (12.2%) were treated consecutively with 82 SFA SI-PTAs (4 bilateral). The mean age was 59 +/- 1.2 years, and 21 (27%) of the patients were female. All patients were treated in the operating room under local anesthesia by using fluoroscopic guidance, and the percentage SFA that was occluded was measured during the diagnostic portion of the procedure. Selective stent placement was performed after successful recanalization of the occluded arterial segments. Patients were treated with chronic aspirin and clopidogrel bisulfate for 3 months and followed up at 30 days and then every 3 months with physical examination and arterial duplex scan. RESULTS: Of the 82 SFA SI-PTA attempts, 76 (92%) were initially successful, with an increase in the ankle-brachial index from 0.46 +/- 0.02 to 0.88 +/- 0.01 (P < .001). Five of the six patients with a failed SFA SI-PTA were female, two of the six had had previous bypass attempts, and one of the six had had a previous SFA SI-PTA attempt by another physician. Forty-nine (64%) of the 76 initially successful SFA SI-PTAs required placement of a stent, and 43 (56.5%) of the successful 76 SFA SI-PTAs required additional PTA of 1 or more arterial segments. The group treated with a successful SFA SI-PTA had 42.5% +/- 3.5% SFA occlusion, compared with 82% +/- 10% (P < .05) in the group with a failed attempt at SFA SI-PTA. Two of the six patients with initial SI-PTA failure underwent leg amputation within 30 days, three were treated with successful leg bypass surgery, and one was lost to follow-up. Of the 76 successful SFA SI-PTAs, 5 (6.5%) failed within 90 days, and the patients were treated successfully with leg bypass surgery. Of the 71 limbs with patent SI-PTAs at 90 days, 68 have remained patent with a mean follow-up 10.4 +/- 0.7 months (range, 2-24 months). Three of the 71 SFA SI-PTAs failed between 4 and 7 months (mean, 5 +/- 0.7 months): 1 patient was treated with successful bypass surgery, 1 patient is currently considering further intervention, and 1 patient was treated with amputation. Ten (14%) of the 71 successful SFA SI-PTAs required limited PTA for asymptomatic restenosis, as identified by the arterial duplex scan (7.4 +/- 1.4 months; range, 2-16 months). There were no perioperative deaths, and three patients have died during follow-up with patent SFA SI-PTAs (9.3 +/- 1.4 months). CONCLUSIONS: These data suggest that SFA SI-PTA can be successfully used for limb salvage with minimal morbidity and mortality in a group of patients with severe lower extremity occlusive vascular disease.