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Autologous fat transfer is an increasingly popular surgical procedure with many applications in the cosmetic realm and beyond. It is found to be an efficacious procedure, but there is growing concern over adverse effects.1, 2 Potential risks include common complications such as fat necrosis, seroma formation, and cellulitis.1 More serious complications have also been reported, including life-threatening infections and potentially fatal fat emboli, especially in gluteal fat transfer.1, 3 The American Society of Plastic Surgeons recently issued a warning identifying gluteal fat grafting as the aesthetic procedure with the highest mortality rate (1 in 3000 procedures).4 Historically, use of silicone for gluteal enhancement has resulted in numerous cases of granulomatous foreign body–like reactions.5, 6 Theoretically, the use of autologous tissue would decrease the incidence of these reactions. Here we report the first case, to our knowledge, of a granulomatous reaction to autologous fat transfer in the gluteal region.

Activation of oncogenic Kras in murine lung leads to the development of numerous small adenomas, only some of which progress over time to overt adenocarcinoma. Thus, although Kras is the initiating oncogene, it is likely that secondary genetic events are required for progression from adenoma to adenocarcinoma. Some of these secondary events may also be important in human lung adenocarcinoma. By comparing gene expression profiles with DNA copy number changes, we sought to identify genes that play key roles in tumor progression in this model. Gene expression profiling revealed significant heterogeneity among the tumor samples. In 27% of the tumors analyzed, whole- or subchromosome duplications or deletions in one or more chromosomes were seen. Recurrent duplications were seen on chromosomes 6, 8, 16, and 19, whereas chromosomes 4, 11, and 17 were frequently lost. Notably, focal amplifications or deletions were not seen. Despite the lack of focal amplication, we showed that chromosome duplication has a measurable effect on gene expression that is not uniform across the genome. We identified a group of genes whose gene expression was highly correlated with changes in DNA copy number. These highly correlated genes were enriched for gene ontology categories involved in the DNA damage response and telomere maintenance. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat. © 2005 Wiley-Liss, Inc.

Background: The clinical course of hypopigmented mycosis fungoides has not been well described. Objective And Methods: We sought to review the management and follow-up of patients with hypopigmented mycosis fungoides evaluated between January 1990 and August 1998. Results: There were 7 African American and 2 Asian patients (5 male and 4 female patients); 8 had stage Ia and 1 had stage Ib disease. The mean age at diagnosis was 34.4 years, the mean latent period was 9.2 years, and the mean follow-up period after diagnosis was 6.5 years. Treatment modalities used included psoralen UVA, UVB, and topical mechlorethamine. Eight had complete clinical responses, and another had a partial response. The remission period ranged from 2 months to 3 years. In all but one patient, lesions recurred; all responded rapidly to another course of therapy. Conclusion: Hypopigmented mycosis fungoides is characterized by early onset, occurrence in dark-skinned individuals, and good response to therapy. Recurrences are common. In most, it has a biologically benign course. (J Am Acad Dermatol 2000;42:33-9.)

Adrenomedullin (ADM) is a new 52 amino acid peptide originally isolated from extracts of human pheochromocytoma. ADM's biologic properties are nearly identical to those of atrial natriuretic peptides. Thus, the 4 peptide hormones originating from amino acids 1-30 [long acting natriuretic peptide], 31-67 [vessel dilator], 79-98 [kaliuretic peptide] and 99-126 [atrial natriuretic factor; ANF] of the 126 amino acid ANF prohormone as well as ADM have blood pressure lowering and diuretic properties. The present investigation was designed to determine if one or more of these 4 atrial natriuretic peptides increase adrenomedullin within the circulation of healthy humans. Infusion of 100 ng/kg body weight/minute for 60 minutes of the respective atrial peptides resulted in a 4-fold (P < 0.001) increase in the circulating concentration of adrenomedullin secondary to the ANF infusion but no increase in adrenomedullin with the long acting natriuretic peptide, vessel dilator, or kaliuretic peptide infusions. The four-fold increase of adrenomedullin in the circulation persisted throughout the infusion of ANF, but returned to pre-infusion levels within 30 minutes of stopping the ANF infusion. Infusion of 10 pg/kg body weight/minute for 60 minutes of ANF resulted in a 2 1/2-fold increase (P < 0.05) in the circulating concentration of adrenomedullin. There was a significant (P < 0.01) diuresis and blood pressure lowering effect with each of the atrial natriuretic peptides in the present investigation. This investigation suggests that 1) atrial natriuretic factor increases the release of adrenomedullin and 2) that the diuretic and blood pressure lowering effects previously attributed to atrial natriuretic factor may be partially due to adrenomedullin since both increased during the ANF infusion and both have similar biologic effects. As opposed to atrial natriuretic factor, adrenomedullin was not increased by long acting natriuretic peptide, vessel dilator, or kaliuretic peptide suggesting that their biologic effects do not involve adrenomedullin.

The present investigation was designed to examine the effect of four atrial peptide hormones with vasodilatory properties on the circulating immunoreactive (ir) levels of the vasoconstrictive peptide endothelin (ET) in 36 healthy human subjects. Circulating levels of human ET and cyclic guanosine monophosphate ([cGMP], a potential mediator of the effects of atrial peptides), were measured every 30 minutes during 1-hour preinfusion, 1-hour infusion, and 3-hour postinfusion periods. Atrial natriuretic factor ([ANF] amino acid (aa) 99 to 126 of the 126-aa ANF prohormone) and kaliuretic peptide (aa 79 to 98 of this same prohormone) significantly (P

Atrial natriuretic factor (ANF), consisting of amino acids 99-126 of the 126 amino acid ANF prohormone, increases cyclic guanosine monophosphate (GMP) (thought to be the mediator of its physiologic effects) in plasma and urine of human subjects. Long-acting natriuretic peptide, vessel dilator, and kaliuretic peptide, consisting of amino acid 1-30, 31-67, and 79-98, respectively, of this same prohormone have natriuretic, diuretic, kaliuretic, and blood pressure lowering properties in humans. These three new peptide hormones increase cyclic GMP in vitro but were never investigated to determine whether they also cause extrusion of cyclic GMP from cells, resulting in an increase of cyclic GMP in plasma and/or urine. Infusion of each of these peptide hormones at their 100 ng/kg body weight/min concentrations for 60 minutes into healthy humans resulted in a sevenfold increase in cyclic GMP in plasma and urine secondary to ANF, but no significant increase secondary to the other atrial peptide hormones. Based on the current data, ANF has a unique effect on the metabolism of cyclic GMP, causing it to be extruded from the cell, whereas the other three atrial peptides represent the more classical metabolism of cyclic GMP via cyclic GMP phophodiesterases.

BACKGROUND Three peptides consisting of amino acids 1-30, 31-67, and 79-98 of the 126-amino acid atrial natriuretic factor prohormone (proANF), which have blood pressure-lowering, diuretic, natriuretic, and/or kaliuretic properties in animals, were investigated to determine if they have similar properties in humans. METHODS AND RESULTS Thirty-six healthy, normotensive human volunteers (18 men and 18 women, ages 20 to 58 years) were divided into six similar groups based on age, sex, weight, blood pressure, and heart rate. After a 60-minute baseline period, 100 ng of proANFs 1-30, 31-67, 79-98, or ANF/kg body wt per minute was given intravenously for 60 minutes followed by a 3-hour postinfusion data collection period. Each of the atrial natriuretic peptides decreased systolic and diastolic blood pressures (P < .05), with proANF 31-67 causing the largest decrease. Urine flow increased 4- to 12-fold and was still significantly increased (P < .01) for 2 to 3 hours after stopping the respective infusions of proANFs 1-30, 31-67, and 79-98. Atrial natriuretic factor (ANF) increased urine flow 4- to 11-fold but by 2 hours after infusion was significantly increased in only 1 of 6 subjects. Sodium excretion increased 3- to 8-fold, 3- to 6-fold, 0- to 2-fold (NS), and 3- to 11-fold, respectively, with proANFs 1-30, 31-67, 79-98, and ANF. Natriuretic effects of proANFs 1-30 and 31-67 were significantly prolonged (P < .001) compared with ANF. ProANFs 1-30, 31-67, 79-98, and ANF increased potassium excretion 2- to 3-fold, 0-fold, 3- to 4-fold, and 2-fold, respectively. High-performance gel permeation chromatography followed by the respective radioimmunoassays revealed that proANFs 1-30, 31-67, 79-98, and 68-98, as well as ANF circulate as distinct peptides. CONCLUSIONS ProANFs 1-30, 31-67, and 79-98, as well as ANF have significant blood pressure-lowering and diuretic properties. ProANFs 1-30 and 31-67 also have natriuretic properties in humans that are significantly (P < .001) prolonged compared with ANF. ProANF 79-98, although not possessing any natriuretic property, is the strongest stimulator of potassium excretion of the four atrial natriuretic peptides.

Background:Calciphylaxis is a rare and life-threatening condition occurring in patients with end-stage renal disease on dialysis. The diagnosis is frequently delayed or missed and therapy is often unsuccessful.Objective:The clinical and pathological components of calciphylaxis are emphasized in a patient that may facilitate early diagnosis and initiation of therapy.Results:Early recognition of the clinical signs and symptoms of calciphylaxis is crucial. The tissue diagnosis requires large elliptical biopsies because histological findings are segmental and often missed.Conclusion:Early diagnosis and intervention in calciphylaxis is critical. Parathyroidectomy should be considered in all cases.

Medical researchers are legally required to protect patients' privacy by removing personally identifiable information from medical records before sharing the data with other researchers. We present an evaluation of methods for computer-assisted removal and replacement of protected health information (PHI) from free-text nursing notes collected in the intensive care unit as part of the MIMIC II project. A semiautomated method was developed to allow clinicians to highlight PHI on the screen of a tablet PC and to compare and combine the selections of different experts reading the same notes. An analysis of the performance of three human expert de-identifiers and of an automated system is presented. Expert adjudication demonstrated that inter-human variability was high, with few false positives and many false negatives. The sensitivity of human experts working alone ranged from 0.63 to 0.93, with an average of 0.81, and the average positive predictive value was 0.98. An algorithm generated few false negatives but many false positives. Its sensitivity was 0.85, but its positive predictive value was only 0.37. The de-identified database of nursing notes was re-identified with realistic surrogate (but unprotected) dates, serial numbers, names, and phrases to provide a gold standard database of over 2600 notes (approximately 340,000 words) with over 1700 instances of PHI. This reference gold standard database of nursing notes and the Java source code used to evaluate algorithm performance will be made freely available on Physionet in order to facilitate the development and validation of future de-identification algorithms.

All personally identifiable information must be removed from patient medical records before the data can be shared with other researchers. We present an automated method of removing protected health information (PHI) from free-text nursing notes taken from a U.S. hospital. We have previously shown that one clinician can locate PHI in nursing notes with an average sensitivity of 0.81, and for teams of two clinicians the sensitivity is 0.94. Our method uses lexical look-up tables, regular expressions, and simple heuristics to locate PHI with an overall sensitivity of 0.92 (0.98 for names, 0.96 for dates), which is significantly better than the average sensitivity of a single human. The algorithm has a positive predictive value of only 0.44, so additional software was developed to allow the user to review the terms identified as PHI and manually eliminate false positives. The algorithm is open-source and will be made freely available on PhysioNet together with a re-identified corpus of nursing notes

Syringolymphoid hyperplasia with alopecia is an uncommon, but histopathologically distinct, skin disorder that has been reported to occur with and possibly represent a syringotropic variant of cutaneous T-cell lymphoma. We report 2 patients with syringolymphoid hyperplasia with alopecia. Both had CD4-positive infiltrates; 1 also demonstrated loss of CD7. One patient had evidence of T-cell clonality by gene rearrangement studies, but neither had histologic evidence of cutaneous T-cell lymphoma. Because the natural progression of syringolymphoid hyperplasia with alopecia remains to be fully explained, close follow-up of patients is advised.

The present investigation was designed to determine whether atrial natriuretic peptides consisting of amino acids 1–30 (long acting natriuretic peptide), 31–67 (vessel dilator) and 79–98 (kaliuretic peptide) as well as 99–126 (atrial natriuretic factor (ANF)) of the 126 amino acid ANF prohormone inhibit aldosterone secretion. Thirty healthy human subjects were studied following infusion of 100 ng/kg body weight/min for 60 min of each of the respective peptides. Kaliuretic peptide decreased plasma aldosterone concentration by the greatest amount (6-fold) and plasma aldosterone was still significantly decreased (P Journal of Endocrinology (1995) 146, 373–380

The present investigation was designed to determine whether atrial natriuretic peptides consisting of amino acids 1-30 [i.e. pro-ANF-(1-30)], 31-67 [i.e. pro-ANF(31-67)], 79-98 [i.e. pro-ANF-(79-98)], and 99-126 [i.e. atrial natriuretic factor (ANF)] of 126-amino acid ANF prohormone have a negative feedback on their own and each others' release. Thirty healthy human subjects were studied with infusion of 100 ng/kg BW.min for 60 min of each of the respective peptides. Pro-ANF-(1-30) decreased the circulating concentrations of pro-ANF-(31-67) and ANF 51% and 89%, respectively. Pro-ANF-(31-67) decreased the circulating concentration of ANF by 55% and the peptides immunologically recognized by the pro-ANF-(1-30) RIA by 58% [this assay recognizes pro-ANF-(1-30) (50%) and pro-ANF-(1-98) (50%)]. Pro-ANF-(79-98) decreased the circulating concentration of ANF by 40%, pro-ANF-(31-67) by 31%, and the peptides recognized by the pro-ANF-(1-30) RIA by 46%. ANF decreased the circulating concentration of pro-ANF-(31-67) by 40% and the peptides recognized by pro-ANF-(1-30) RIA by 38%. Infusion of pro-ANF-(1-30), -(31-67), -(79-98), and -(99-126) also decreased the excretion of the other atrial natriuretic peptides measured in the urine by 32-84%. Infusion of vehicle only did not result in any decrease in these atrial natriuretic peptides in either plasma or urine. These data taken together indicate that each of the respective atrial natriuretic peptides inhibits the release, rather than breakdown, of each other, as increased breakdown would have resulted in their urinary concentrations being increased. This study further indicates that because pro-ANF-(1-98) was decreased in the circulation secondary to pro-ANF-(31-67) and pro-ANF-(79-98) infusions, they inhibit their own release, as they are both derived from pro-ANF-(1-98).

We report two unusual cases of cutaneous lupus erythematosus presenting as dramatic eyelid edema and erythema. Neither patient had evidence of systemic or other significant cutaneous involvement. The eyelid edema and erythema were unilateral in one case and bilateral in the other. Both cases responded to therapy with antimalarial drugs.

We have studied human Thy-1 and T-cell receptor (TCR) antigen expression in mycosis fungoides and benign inflammatory dermatoses. The study included 24 biopsy specimens from 21 patients with mycosis fungoides (nine patch stage from eight patients, 13 plaque stage from 11 patients, and two tumor stage from two patients), six specimens from five patients with premycotic parapsoriasis (pre-mycosis fungoides), three specimens from three patients with lichen planus, 11 specimens from 11 patients with lupus erythematosus, 13 specimens from 13 patients with dermatitis, six specimens from six patients with drug eruptions, nine normal skin specimens from nine subjects, and three specimens from three patients with small plaque (benign) parapsoriasis. Immunoperoxidase studies using the avidin-biotin complex technique on serial frozen sections were performed. Primary antibodies were anti-human Thy-1, anti-alpha heterodimer of the TCR, anti-beta heterodimer of the TCR, and anti-delta heterodimer of the TCR. An extensive dendritic network of Thy-1+ cells was seen in all cases of mycosis fungoides. Epidermotropic cells were Thy-1 negative, and Thy-1 was expressed perivascularly in normal individuals and patients as previously reported. Epidermal gamma/delta cells were seen only in mycosis fungoides, where up to 60% of the epidermal lymphocytes expressed this TCR. The increased numbers of Thy-1 and gamma/delta T cells in mycosis fungoides were statistically significant when compared with normal skin or benign inflammatory dermatoses. The role of these dendritic dermal Thy-1+ cells and epidermal gamma/delta T cells in mycosis fungoides is unclear. The significant numbers of these potentially immunomodulating cells that were seen suggest that they are involved in the pathogenesis of mycosis fungoides.

Three young women recently returned to the metropolitan Detroit area with cutaneous larva migrans. All three had vacationed at a popular club resort on the Caribbean island of Martinique. Cutaneous larva migrans is frequently seen in the southern United States, Central and South America, and other subtropical areas but rarely in northern climates. Several organisms can cause cutaneous larva migrans, or creeping eruption. The larvae of the nematode Ancylostoma braziliense are most often the causative organisms. Travel habits of Americans make it necessary for practitioners in northern climates to be familiar with diseases contracted primarily in warmer locations. The life cycle of causative organisms and current therapy are reviewed.

Twenty-two patients with alopecia areata were treated with a combination of topical 0.1% 8-methoxypsoralen and UVA (PUVA). Eight of the twenty-two patients (36.3%) responded with excellent regrowth (terminal hair in at least 75% of the treated scalp), and two patients (9.1%) showed good regrowth (terminal hair in 50% to 75% of the treated scalp). The mean total UVA exposure and the mean total number of treatments for the entire treatment course for these responders was 171.7 joules/cm2 and 47.4 treatments, respectively. Eight of the nine responders available for follow-up experienced some degree of relapse when PUVA treatments were tapered or during a follow-up period (mean, 8.3 months) after treatment was discontinued. Despite the failure of topical PUVA to change the long-term course of alopecia, the combination of PUVA with other therapeutic modalities may result in the prolongation of the beneficial effect in selected patients. The mechanism of action of PUVA in alopecia areata might involve an immunomodulatory effect.

The ubiquitous wart plagues us all-patients, parents, atid physicians. Although some of us probably opt for benign neglect, others believe that a temperate or even aggressive approach to therapy is the most appropriate course of action. In this symposium, several practitioners offer their philosophy of therapy as well as specific favored potions and procedures for tackling this problem in chiWren atid adolescents.

Many cutaneous disorders are associated with acquired immunodeficiency syndrome. We prospectively evaluated eighteen patients with acquired immunodeficiency syndrome and twelve patients with the immunodeficiency syndrome-related complex for dermatologic disorders. A high prevalence of seborrheic dermatitis was found in patients with acquired immunodeficiency syndrome--83%, in comparison with 1% to 3% of historic control subjects. Patients with the related complex also had an increased incidence of 42%. Seborrheic dermatitis in this population was often more explosive, inflammatory, and severe than is usually seen in otherwise healthy patients. Severity of seborrheic dermatitis correlated with a poor overall prognosis in our patients. Additionally, seborrheic dermatitis may be one of the most common cutaneous manifestations of acquired immunodeficiency syndrome.

Relatively little has been reported about the joint effects of magnitude and probability of shock on choice behavior. Cole, Belenky, Boucher, Fernandez, & Myers (1965) have given a brief review of findings where correction procedures were used. Cole et al found increasing overmatching of 11 = .667 with increasing shock intensity, also using a correction procedure. The present study was designed to study the effects of varying both probability and intensity of shock on choice behavior, using a non-correction procedure. It was expected that increasing both shock level and probability in one side would increase the probability of choosing the more frequently shock-free side. A second purpose was to see if a non-correction procedure would yield learning described by an identity operator model for the effect of nonreinforced trials (Weinstock, North, Brody, & LoGuidice, 1965). Method The Ss were 48 male, hooded rats, 90-120 days old. Beginning 10 days before the experiment, Ss were main­ tained on a 1/2 hr. per day feeding schedule, and handled by E for 5 min. each day. The Ss were about 20 hr. food deprived at the beginning of each session. The apparatus was a Y -maze made of galvanized steel. The stem was 6 in. long. The arms were 30 in. long and 3-1/2 in. wide, with floors having a downward angle toward the center with a 2/3 in. separation along their lengths, so that when the floor was charged it was impossible for S to avoid the shock. An Applegate generator supplied the shock. Each arm terminated in a goal box. Guillotine doors between the start box and stem, and between the stem and each arm, prevented retracing. Photocells located 8 in. inside each arm turned on the shock throughout the length of the arm. The only escape from shock was in the goal boxes, which were baited with four 97 mgNoyesfoodpellets on every trial. Since it was possible for S to avoid shock by not running, food deprivation and reward were used to insure running. Each S received 22 pre-experimental trials without shock: six forced-choice trials on days 1 and 2, with

• We report a case of the Peutz-Jeghers syndrome in which the characteristic pigmented macules developed within preexisting psoriatic plaques in sites extremely unusual for the syndrome. To our knowledge, ours is the first report of such a case in the English literature. ( Arch Dermatol 1986;122:679-683)

Syringomas are fairly common, benign, appendageal tumors that are believed to represent tumors of intraepidermal eccrine ducts. 1,2 Multiple lesions on the trunk have been reported as a rare type of syringoma under the name "eruptive hidradenoma." 3 An unusual case of eruptive syringomas occurred on the trunk and extremities, with a preponderantly right-sided distribution. Report of a Case A 7-year-old boy was seen in 1971 with a two-month history of a skin eruption. On examination, there were pinpoint-sized, hypopigmented to flesh-colored, shiny, grouped papules on the inner aspects of the right thigh, right side of the lower part of the abdomen, and the right forearm (Fig 1). The patient did not return until 1978, when, at the age of 14 years, he had multiple new lesions on the right lower extremity. Many additional papules were present on the right thigh, abdomen, and forearm. There were only a few scattered

• Several cases of isolated C2 deficiency in man have been reported In the medical literature. The earliest cases did not seem to be associated with known diseases or syndromes; more recently, reports of C2 deficiency associated with systemic lupus erythematosus; anaphylactoid purpura, recurrent infections, and dermatomyositis have appeared. We report here another case of C2 deficiency. The propositus, a 24-year-old woman, had a lupus erythematosus-like rash and a history of arthralgia, as well as a selective deficiency of C2. Studies of hemolytic C2 of the immediate members of her family indicate an autosomal-recessive mode of inheritance. These findings add to the increasing evidence that a C2 deficiency predisposes some persons to serious vascular diseases. ( Arch Dermatol 112:671-674, 1976)

The Mycosis Fungoides Cooperative Group has been following patients with cutaneous T-cell lymphoma, including mycosis fungoides and the Sézary syndrome variant. Previous analyses identified the extent of skin involvement and the number of sites of clinically enlarged lymph nodes as important prognostic variables. These two variables were used to classify 340 patients into four clinical stages. Repeat analysis based on additional followup data shows the usefulness of this clinical staging system for identifying patients with differing survival experience. An alternative grouping suggested by fitting a survival model to the data also has been studied. Staging systems based only on skin involvement and lymph nodes are recommended for general use because the information needed is readily available, requiring only physical examination.