Heparin, lipoproteins, and oxygenated fatty acids in blood: a cautionary note.

We measured 16 nonesterified oxygenated fatty acid derivatives (oxylipids) in plasmas from seven human subjects. Two arterial samples from each subject were analyzed, drawn approximately 2h apart. We observed a marked increase in levels of most oxylipids in the second sample, as high as 470-fold. Between the first and second samples, subjects received approximately 800-1000 IU of heparin to prevent clotting in intravascular catheters. We postulate that heparin activated lipoprotein lipases, which, in turn, released oxylipids from triglycerides and phospholipids in plasma lipoproteins. Some of that lipolysis may have occurred during sample storage. Measurements of nonesterified lipids in human plasma may be distorted if heparin is administered to subjects before blood is drawn and if lipase inhibitors are omitted from stored samples.

Nontraditional aspects of aldosterone physiology.

Aldosterone is the most important circulating mineralocorticoid. It is secreted by the zona glomerulosa of the adrenal gland and plays a major role in sodium and potassium metabolism by binding to epithelial mineralocorticoid receptors (MR) in the renal collecting duct, promoting sodium resorption and potassium excretion. The action of aldosterone on its classic target epithelia has been extensively studied, and many of the signaling events that mediate its effects have been described. Recently, there has been increased interest in aldosterone actions on the cardiovascular system, which are mediated through nonclassical actions. These include local tissue production, nongenomic actions, and effects on nonepithelial targets. In this review article, we focus on the effects of aldosterone in nonepithelial tissues that are mediated through MR, especially cardiovascular effects.

Spironolactone reduces cerebral infarct size and EGF-receptor mRNA in stroke-prone rats.

Remodeling of the cerebral vasculature contributes to the pathogenesis of cerebral ischemia. Remodeling is caused by increased smooth muscle proliferation and may be due to an increase in the responsiveness of vascular cells to epidermal growth factor (EGF). Aldosterone is a risk factor for stroke, and the literature suggests it may play a role in increasing the expression of the receptor for EGF (EGFR). We hypothesized that mRNA for the EGF-stimulated pathway would be elevated in the vasculature of stroke-prone spontaneously hypertensive rats (SHRSP) and that this and experimental ischemic cerebral infract size would be reduced by aldosterone inhibition with spironolactone. We found that spironolactone treatment reduced the size of cerebral infarcts after middle cerebral artery occlusion in SHRSP (51.69 +/- 3.60 vs. 22.00 +/- 6.69% of hemisphere-infarcted SHRSP vs. SHRSP + spironolactone P < 0.05). Expression of EGF and EGFR mRNA was higher in cerebral vessels and aorta from adult SHRSP compared with Wistar-Kyoto rats. Only the expression of EGFR mRNA was elevated in the young SHRSP. Spironolactone reduced the EGFR mRNA expression in the aorta (1.09 +/- 0.25 vs. 0.56 +/- 0.11 phosphorimage units SHRSP vs. SHRSP + spironolactone P < 0.05) but had no effect on EGF mRNA. In vitro incubation of aorta with aldosterone +/- spironolactone produced similar results, suggesting a direct effect of aldosterone. Thus spironolactone may reduce the size of cerebral infarcts via a reduction in the expression of the EGFR mRNA, leading to reduced remodeling.

Electrosurgical facial resurfacing: a prospective multicenter study of efficacy and safety.

BACKGROUND: A novel electrosurgical technology that uses a bipolar electrode-tipped stylet to deliver relatively low-radiofrequency energy through an electrically conductive medium has been developed. OBJECTIVE: To evaluate the efficacy and safety of the radiofrequency resurfacing system for the treatment of facial wrinkles. DESIGN: Multicenter, prospective, noncomparative study with longitudinal follow-up. SETTING: Four US academic dermatologic surgery clinics. PATIENTS: Ninety-five patients with mild to severe photodamage (Fitzpatrick classes I-III) involving periorbital (75 treatment sites) and perioral (50 sites) facial skin. INTERVENTION: Radiofrequency resurfacing with the use of 2 to 3 passes at 125 or 139 V. MAIN OUTCOME MEASURES: Wrinkle and cosmetic improvements evaluated by patients, investigators, and, by means of photographs, an independent panel of 5 evaluators. RESULTS: All evaluators determined a positive mean improvement in wrinkles for both periorbital and perioral anatomic sites, with greater improvement for patients with more severe wrinkles at baseline. An increased number of passes and higher voltage settings had a positive impact on wrinkle improvement. Transient postinflammatory hyperpigmentation occurred in 26% of periorbital and 4% of perioral sites. Hypertrophic scars occurred in 3.8% of treatment sites, with all but 1 scar resolving by 6 months. For the most part, healing was rapid, pain was minimal, and erythema largely resolved within 2 months. Other untoward effects were relatively few and short-lived. CONCLUSIONS: At the study settings used, radiofrequency resurfacing is an effective modality in the treatment of periorbital and perioral wrinkles in patients with Fitzpatrick class I, II, and III photodamage. There is less severe postoperative morbidity than seen with carbon dioxide or coagulating erbium:YAG lasers. The potential risks are similar to those seen with other resurfacing modalities.

Microcystic adnexal carcinoma: forty-eight cases, their treatment, and their outcome.

BACKGROUND: Microcystic adnexal carcinoma, or sclerosing sweat duct carcinoma, is an uncommon cutaneous neoplasm associated with extensive local invasion. The standard of care with regard to the best excisional method in treating microcystic adnexal carcinoma has not been established. OBJECTIVES: To perform a retrospective study comparing patients treated by Mohs micrographic surgery with those treated by wide excision and to elucidate the epidemiological features of microcystic adnexal carcinoma. PATIENTS AND METHODS: A retrospective analysis of a case series involving 48 primary and referral patients diagnosed as having microcystic adnexal carcinoma using standardized criteria. All cases were reviewed by the same dermatopathologists. RESULTS: Microcystic adnexal carcinoma predominantly affects the left side of the face of middle-aged women. Microcystic adnexal carcinoma is misdiagnosed 30% of the time. The recurrence rate is 1.98% per patient-year. Mohs micrographic surgery and simple excision show comparable complication rates. Clear margins were obtained in fewer procedures and, therefore, fewer office visits when the lesions were treated with micrographic surgery. The defect surface area after full extirpation following Mohs micrographic surgery was a mean of 4 times that of the clinically apparent size. The wide range of difference between the pre- and the post-Mohs micrographic surgery surface area noted in our data indicates that a margin cannot be safely predicted. CONCLUSIONS: Microcystic adnexal carcinoma is a predominantly left-sided, locally aggressive facial tumor, which results in significant morbidity. Our data do not support the use of standardized predictable margins. Mohs micrographic surgery is a reasonable initial treatment, as it accomplishes cure in fewer office visits and does not rely on predicted margins.

High-fat diet elevates blood pressure and cerebrovascular muscle Ca(2+) current.

Dietary fat contributes to the elevation of blood pressure and increases the risk of stroke and coronary artery disease. Previous observations have shown that voltage-gated Ca(2+) current density is significantly increased in hypertension and can be affected by free fatty acids (FAs). We hypothesized that a diet of elevated fat level would lead to an increase in blood pressure, an elevation of L-type Ca(2+) current, and an increase in saturated FA content in vascular smooth muscle cell membranes. Male Osborne-Mendel rats were fed normal rat chow or a high-fat diet (Ob/HT group) for 8 weeks. Blood pressures in the Ob/HT group increased moderately from 122.5+/-0.7 to 134.4+/-0.8 mm Hg (P<0.05, n=26). Voltage-clamp examination of cerebral arterial cells revealed significantly elevated L-type Ca(2+) current density in the Ob/HT group. Voltage-dependent inactivation of the Ob/HT L-type channels was significantly delayed. Total serum FA contents were significantly elevated in the Ob/HT group, and HPLC analyses of fractional pools of FAs from segments of abdominal aorta revealed that arachidonic acid levels were elevated in the phospholipid fraction in Ob/HT. No differences in vascular membrane cholesterol contents were noted. Plasma cholesterol was significantly elevated in portal venous and cardiac blood samples from Ob/HT rats. These findings suggest that an elevation of plasma FAs may contribute to the development of hypertension via a process involving the elevation of Ca(2+) current density and an alteration of channel kinetics in the vascular smooth muscle membrane.

Mechanisms in the pressor effects of hepatic portal venous fatty acid infusion.

Portal venous infusion of oleate solution has pressor effects. We have examined efferent mechanisms, measured the response to sustained infusion, and determined the effect of linoleate. Eight conscious animals received concurrent infusions of prazosin or vehicle with portal venous infusion of oleate. Oleate alone increased mean arterial pressure from 109.0 +/- 4.1 to 123.0 +/- 5.8 mmHg (P = 0.02), whereas no increase in blood pressure occurred when oleate was infused with prazosin. In 10 rats, concurrent infusion of losartan had no effect on the pressor activity of portal oleate infusion. Twenty-two animals received portal oleate or vehicle as a continuous infusion for 7 days. Mean arterial pressure (126.1 +/- 2.0 vs. 107.8 +/- 2.6 mmHg, P < 0.001) and heart rate (383 +/- 5 vs. 366 +/- 5, P = 0.0257) were increased in oleate-infused animals. No differences in plasma fatty acids, glucose, insulin, pressor hormones, liver enzymes, or in vitro arterial pressor responsiveness were observed. Portal venous infusion of linoleate increased arterial pressure by 12.2 +/- 3.2 mmHg (P = 0.033). These results indicate that alpha-adrenergic activity is necessary for the acute pressor effects of portal oleate, that sustained portal oleate infusion results in persistent blood pressure elevation, and that other long-chain fatty acids besides oleate have pressor effects.

Efficacy of a 2-mm spot size lens for the treatment of superficial vascular lesions with a flashlamp-pumped dye laser.

BACKGROUND: The flashlamp-pumped dye laser, using either a 3 or 5 mm spot size, is an excellent instrument for the treatment of port-wine stains and other superficial cutaneous vascular lesions. Problems exist with patient acceptance due to prominent and prolonged blue-black discoloration and the pain associated with the treatment. OBJECTIVE: To assess the effectiveness of a flashlamp-pumped dye laser equipped with a 2 mm spot size lens in the treatment of superficial vascular lesions. METHODS: Twenty-one patients with telangiectasias, cherry angiomas, and angiokeratomas were treated at a variety of fluences. RESULTS: Three of 21 patients had complete clearing of their superficial vascular lesions. An improvement of greater than 75% was noted by 11 patients, and six patients noted a 50%-75% improvement. One patient had less than 50% improvement. Less post-treatment discoloration and less pain were noted with the 2 mm spot size lens. CONCLUSIONS: The 2 mm spot size lens, used with the flashlamp-pumped dye laser is an effective instrument for the treatment of superficial cutaneous vascular lesions.

Repair of central upper lip (philtral) surgical defects with island pedicle flaps.

BACKGROUND: Surgical defects of the central upper lip (philtrum) are a particularly difficult area to achieve satisfactory cosmetic and functional repair. Reconstruction of the central upper lip has been accomplished primarily through the use of side-to-side closure, bilateral advancement or rotation flap, and full-thickness graft. Repair may be complicated by distortion of the vermilion border, obliteration of the normal contour of the philtrum, eclabium, and trapdooring of the flap. OBJECTIVE: We review the options for reconstruction of this area and describe our experience using an island pedicle flap to complete reconstruction. METHODS: Four patients presented with basal cell carcinomas of the mid upper lip (philtrum). Tumors were cleared by Mohs micrographic surgery. Reconstruction was achieved by island pedicle flaps utilizing donor tissue from the superior philtrum. RESULTS: The patients had excellent cosmetic results with minimal distortion of the vermilion border or obliteration of the philtrum or philtral ridges. Scars healed in a nearly imperceptible fashion, keeping within one cosmetic unit (the philtrum) without extending along the vermilion border as seen in bilateral advancement or rotation flaps. CONCLUSIONS: Island pedicle flaps may be an effective cosmetic and functional repair of selected surgical defects of the central upper lip involving the philtrum.

Simultaneous scintigraphic depiction of aldosteronoma and adrenal infarction.

Primary aldosteronism is a potentially curable cause of hypertension, especially when caused by an adrenal adenoma. Aldosteronomas because of their small size often elude techniques to locate them. This case illustrates the advantages, disadvantages and complications of noninvasive techniques used for their diagnosis. A patient with hypertension and hypokalemia underwent an adrenal venous effluent sampling for measurement of aldosterone concentrations. This procedure was complicated by an injury to the right adrenal gland. Subsequently, it was difficult to control the patient's hypertension and hypokalemia with medical therapy alone. A re-assessment years after his initial diagnosis included a CT scan, which now visualized a left adrenal tumor. The functional status of this tumor and lack of function of the previously injured right adrenal gland were demonstrated by NP-59 scintigraphy. This information modified the surgical intervention (adenectomy rather than total adrenalectomy) and the residual left sided adrenal tissue prevented adrenocortical insufficiency. A year later the patient remains euadrenal.

Treatment of adenoma sebaceum with the copper vapor laser.

BACKGROUND: Angiofibromas of the central part of the face (adenoma sebaceum) occur pathognomonically in tuberous sclerosis, causing significant cosmetic and hygienic morbidity. Treatment has included excision, dermabrasion, cryosurgery, carbon dioxide laser, and argon laser. Copper vapor lasers emit light at 511 nm (green) ad 578 nm (yellow), useful for treating pigmented and vascular lesions, respectively. OBJECTIVE: Because of the vascular nature and progressive pigmentation of adenoma sebaceum, we examined the utility of the copper vapor laser in treating this disorder. METHODS: Nine patients with adenoma sebaceum were treated with the copper vapor laser. Individual lesions were treated with the yellow light (578 nm) at 0.4 to 0.6 mW. Pigmented lesions or lesions resistant to treatment were treated with the green light (511 nm) at 0.4 to 0.9 mW. Intervals between treatments were at least 6 weeks. RESULTS: Good to excellent cosmetic results were seen in all treated patients. Scarring or hyperpigmentation occurred in none of the patients. Most patients required additional treatments with the copper vapor laser as new lesions developed. CONCLUSION: The copper vapor laser is safe and effective for the treatment of adenoma sebaceum in tuberous slerosis.

Pressor effects of portal venous oleate infusion. A proposed mechanism for obesity hypertension.

Increased visceral fat accumulation is a strong predictor of arterial hypertension. In this study, we explored the hypothesis that increased hepatic portal venous free fatty acid delivery results in increased blood pressure. Such an effect might explain the link between visceral obesity and hypertension. In nine conscious, instrumented rats, we studied the effects of 1-hour infusions of sodium oleate solution into the portal and femoral veins and infusions of sodium caprylate solution into the portal vein on 3 separate days. Basal blood pressure was not significantly different on the 3 study days. Mean arterial pressure increased 29 +/- 4 mm Hg during portal oleate infusion and 13 +/- 2 mm Hg during femoral oleate infusion (both significant increases over basal, P < .001). Mean arterial pressure did not change during portal caprylate infusion. The increase during portal oleate infusion was greater than that during femoral oleate infusion (P = .028). Heart rate rose during all three infusions; the increase was greatest during portal oleate infusion (334 +/- 4 to 412 +/- 2 beats per minute). During portal venous oleate infusion in five rats, plasma norepinephrine rose from 2.17 +/- 0.34 to 3.58 +/- 0.50 nmol/L, epinephrine rose from 0.79 +/- 0.28 to 1.84 +/- 0.44 nmol/L, and corticosterone rose from 147 +/- 55 to 1130 +/- 289 nmol/L. Three rats given portal venous oleate infusions for 1 week had increased blood pressure compared with baseline (mean increase, 16 +/- 4 mm Hg). These studies indicate that increases in portal venous fatty acid concentrations have significant pressor effects, perhaps mediated by increased sympathetic tone.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibiotic prophylaxis in dermatologic surgery.

Antibiotic prophylaxis is generally administered either to prevent wound infection or to hinder the development of endocarditis. Although the use of antibiotics in certain circumstances to prevent wound infection can be straightforward, there are other circumstances in which the decision to use antibiotics is much less clear. Endocarditis prophylaxis has traditionally been based on the American Heart Association's guidelines, which do not cover dermatologic surgery. This article discusses the rationale and controversies surrounding the use of antibiotic prophylaxis for prevention of both wound infection and endocarditis, reviews the few studies that pertain to dermatology, and provides recommendations for antibiotic prophylaxis on a case-by-case basis for those who perform dermatologic surgery.