bluuebunny/crossref_metadata_2025 huggingface dataset:
Necrotizing eosinophilic folliculitis as a manifestation of the atopic diathesis
Authors: Magro Cynthia M. , Crowson A. Neil
Published: March 2003

Abstract

Background  Eosinophilic folliculitis (EF) is an idiopathic eruption of sterile pustules and papules involving the trunk, face, and extremities, associated in many cases with human immunodeficiency virus (HIV) infection. The classic histopathology is one of follicular‐based, eosinophilic spongiosis with variable microabscess formation. We describe nine HIV‐negative patients who manifested a novel form of pustular EF in the setting of atopy.

Materials and methods  Paraffin sections of skin biopsies from ten patients, stained with hematoxylin and eosin and special preparations to evaluate for microbial pathogens, were examined. Detailed clinical histories and serologic studies were obtained.

Results  Among the clinical presentations in seven men, two women, and one girl (age range, 11–62 years) were ulcerative and/or nodular plaques mainly on the face and/or extremities, sometimes in an annular configuration. The clinical considerations included deep mycotic infection, ulcerative herpes, systemic vasculitis, Mucha Haberman disease, and pyoderma gangrenosum. All patients had a personal and/or family history of atopy. Co‐existent medical illnesses included psoriasis, lupus erythematosus, and lymphoproliferative disease. One patient was on a calcium channel blocker, one on multiple antidepressants, and two on antihistamines, all of which are associated with immune dysregulation. All skin biopsies showed variable intra‐ follicular eosinophilic microabscesses, follicular necrosis, folliculocentric necrotizing eosinophilic vasculitis, marked degeneration of connective tissue fiber elements, and striking tissue eosinophilia, including flame figure formation and dermal eosinophilic abscesses. Apart from commensals, such as Pityrosporum and Demodex, microbial pathogens were not identified.

Conclusions  The presentations differed from conventional EF by virtue of a strong association with atopy and by the presence of ulceration, nodule formation, follicular and dermal necrosis, and eosinophilic vasculitis. We propose the term ‘‘necrotizing eosinophilic folliculitis,’' and suggest that the basis of this novel form of EF is an unrepressed T‐helper lymphocyte type 2 (Th2)‐dominant response to various epicutaneous stimuli in patients with atopy, the prototypic immune dysregulatory state associated with a Th2‐dominant cytokine milieu.
Neurologic variant of epidermal nevus syndrome with a facial lipoma
Authors: Egan Conleth A. , Meadows Kappa P. , Van Orman Colin B. , Vanderhooft Sheryll L.
Published: March 2003

A 1‐year‐old girl presented for evaluation of a linear plaque on her forehead. She was born at 36 weeks' gestation following an uncomplicated pregnancy and delivery. At birth, she was noted to have an enlarged right cheek. She had no seizure history, but developed grand mal seizures 1 year later.

On examination, she had a yellow plaque on her forehead which extended onto her nose. Under her right jaw, extending onto her anterior neck, there was a café‐au‐lait macule within which there was a yellow plaque which followed the lines of Blaschko. Her right cheek was enlarged and was erythematous (Fig. 1).

Epidermal nevus on the forehead and right hemifacial hypertrophy

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Magnetic resonance imaging (MRI) of her face showed a mass in the right cheek deep to the subcutaneous fat tissue layer. The signal from the mass was identical to that from the fat, indicating that the mass represented a lipoma. This was later excised surgically and was histologically a lipoma. MRI of the brain demonstrated enlargement of the right lateral ventricle in addition to enlargement of the right cerebral hemisphere. There was also evidence of abnormal gyral architecture. Computerized tomography (CT) three‐dimensional reconstruction of the skull demonstrated overgrowth of the right maxilla, right mandible, and right orbit (Fig. 2).

Computerized tomography reconstruction of skull showing overgrowth of the bones on the right side

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Atypical hemorrhagic bullous pyoderma gangrenosum
Authors: Altunay İlknur Kıvanç , Sezgin Saliha Aslan , İleri Ümran , Ekmekçi Tuğba Rezan , Kuran İsmail , Köşlü Adem , Baş Lütfü
Published: March 2003

A 55‐year‐old woman was seen in the Plastic and Reconstructive Surgery Clinic because of a nonhealing wound on her left leg of approximately 2 months' duration. She had an 8‐month history of multiple wounds appearing on her arms and legs. The patient noted that the majority of the wounds had been treated and healed with the use of topical medications. One wound on her left leg had continued to enlarge rapidly despite topical treatments. Therefore, hyperbaric oxygen therapy had been administered for 15 sessions. No additional healing had occurred with this treatment. Skin grafting was performed on the affected area. She developed ulcers and blistering lesions at surgical and nonsurgical sites after skin grafting. The patient was referred to the Dermatology Department.

Dermatologic examination revealed a deep, necrotic ulcer, 30 cm × 10 cm, with surrounding violaceous erythema on the donor area, ulceration (18 cm × 8 cm) on the graft area, a hemorrhagic bullous plaque (5 cm × 15 cm) over the right malleolus, scattered ecchymotic lesions and small hemorrhagic bullae on both legs, and small pustules around the staplers (Fig. 1a,b). Cutaneous biopsy of a new lesion revealed a focal, dense neutrophilic infiltrate, liquefaction degeneration in the center, lymphocytic and mild plasmacytic infiltration around the venules, and fibrinoid deposits in the walls and lumen of the vessels (Fig. 2a). In addition, excessive polymorphonuclear leukocytes and extravasated erythrocytes were present in the papillary and reticular dermis (Fig. 2b). The patient had a 14‐year history of asthma bronchiale. Physical examination did not reveal any abnormality, except for crackling rales at the base of each lung. Laboratory examinations were within normal limits, except for the sedimentation rate (55 mm/h). Protein electrophoresis, peripheral blood smear, abdominal ultrasound, and thorax and abdominopelvic computed tomography scans were all normal. Swab cultures from the ulcers were negative.

(a) Hemorrhagic bullous lesion on the right malleolus. (b) Ulceration on the donor area

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(a) Histopathologic section of a bullous lesion. Mild subepidermal separation, dense polymorphonuclear infiltration, and fibrinoid deposits in the lumen of the vessels (hematoxylin and eosin, × 10). (b) Focal, dense, neutrophilic infiltrate, liquefaction degeneration, and considerable separation

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Bullous pyoderma gangrenosum was diagnosed on clinical and histopathologic grounds. Prednisolone 80 mg/day was started. Rapid epithelialization was observed within 2 months of treatment. The dose of prednisolone was gradually decreased to 20 mg/day, and was used as a maintenance dose for an additional 6 months. Complete improvement was achieved in 8 months. The patient has been followed up for approximately 1 year. There were no side effects observed during the treatment and in addition no new lesions developed at the follow‐up.
X‐Linked ichthyosis associated with congenital dislocation of the hip
Authors: Okano Masaki , Tanaka Harukazu
Published: March 2003

A 59‐year‐old man was referred to us for evaluation of a rough scaly skin and an abnormal gait of undetermined duration. He had been noted at birth to be covered with thick, dark scales over much of his body, and also he had developed displacement of the femoral head out of the right acetabular socket. He had a strong family history of ichthyosis, implying an X‐linked feature. No other members of the family were known to have musculoskeletal abnormalities. Initial examination revealed large, thick, ichthyotic scales over much of the body, including the preauricular areas and flexure surfaces of the extremities, with sparing of the palms and soles. When he stood up straight, he had to bend the left knee joint, because of apparent shortening of the right leg (Fig. 1). A shambling gait was evident. There were no accompanying symptoms, such as anosmia, hypogonadism, mental retardation, or short stature. Histopathology of the skin demonstrated hyperkeratosis and a conspicuous granular layer of the epidermis. Roentgenograms of the hip disclosed a marked lateral and upward displacement of the head of the right femur (Fig. 2). The spine revealed scoliosis. Epiphyseal dysplasia was not found. A commercial assay for steroid sulfatase demonstrated a deficient enzyme activity of lymphocytes. We made a diagnosis of X‐linked ichthyosis associated with congenital dislocation of the hip. The patient has had no operative therapy to date.

Standing pose with the left knee joint bent. Large, thick, ichthyotic scales cover the buttocks and the legs

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X‐ray findings of the hip. A marked displacement of the right femoral head

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Type III Ehlers–Danlos syndrome: correlations among clinical signs, ultrasound, and histologic findings in a study of 35 cases
Authors: Iurassich Stefano , Rocco Daniela , Aurilia Anna
Published: March 2003

Abstract

Background  Patients with type III Ehlers–Danlos syndrome show hypermobile joints, luxation, and minimal atrophic scars. The disease has an incidence of 9–16% and the molecular defect that underlies this subtype is unknown. In order to widen diagnostic investigations in type III Ehlers–Danlos syndrome, skin and articular areas were studied by ultrasound (US) test.

Methods  Thirty‐five patients, 20 women and 15 men, aged from 18 to 25 years, with type III Ehlers–Danlos syndrome were enrolled in this study. Patients showed hypermobile joints (35 cases), minimal atrophic wrinkled scars (35 cases), and a few ice‐pick acne scars. Hypermobility of phalangeal joints was studied by means of the Beighton scoring system and by a US test (performed by Sonora Logic 400 MD unit with 10 MHz probe). The following US parameters were considered: the distance of the intra‐articular space and the thicknesses of the extensor tendon and of the overhanging dermis and subcutis.

Result US reports showed an increase in distance of the intra‐articular space and a reduction in the thickness of the extensor tendon and of the dermis and subcutis covering it. The dermis showed high and homogeneous echogenicity with irregular hyperechogenic lines.

Conclusion The Beighton scoring system, the US findings, and the aspect and diameter of the scars suggested that the disease can be divided into three different stages which allow the correlation, over progressive intervals of values, of the articular hypermobility and atrophic wrinkled scars. Our results showed that US test is able to confirm the clinical diagnosis and to evaluate the seriousness of hypermobile joints.
Mongolian spots with involvement of the temporal area
Authors: Leung Alexander K. C. , Kao C. Pion , Lee Thomas K. M.
Published: March 2003

A Chinese baby girl was born after an uncomplicated pregnancy and a normal spontaneous vaginal delivery to a gravida 2, para 1, 32‐year‐old mother at 37 weeks' gestation. Neither parent had a history of alcohol or drug ingestion. There was no history of consanguinity.

The Apgar scores were 7 at 1 min and 9 at 5 min. Her birth weight was 5 lb 14 oz and her length was 46 cm. At birth, she was noted to have grayish areas on the face and lower back.

The infant was seen at 3 months of age because of persistent regurgitations. On average, she regurgitated 7–8 times a day. Physical examination showed that the infant was not in distress. Her weight was 6 lb 4 oz and length 47 cm. She had a Mongolian spot measuring 0.8 × 1.2 cm in the left temporal area (Fig. 1) and another Mongolian spot measuring 4 cm in diameter in the lumbar area. The Mongolian spots were grayish in color and the pigmentation was uniform in intensity. The rest of the examination was essentially normal. The infant was diagnosed to have Mongolian spots and gastroesophageal reflux. The latter was treated with postural therapy, thickened feedings, and metoclopramide 0.35 mg q.i.d.

Mongolian spot in the left temporal area

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The infant was seen again at 4 months of age for a reassessment. There was no noticeable change in shape, size, or color of the Mongolian spots.
Congenital atrophic dermatofibrosarcoma protuberans
Authors: Marini Mario , Saponaro Alberto , Magariños Gabriel , De Baldrich Alejandra , Lynch Patricia , Remorino Laura
Published: March 2003

A 16‐year‐old girl presented with a congenital atrophic plaque on the anterior aspect of her right leg. The lesion had slowly enlarged until she was 9 years of age; subsequently, several tumors appeared on the surface and later became reddish, hot, and mildly painful. Within a few months, all the tumors flattened and involuted. A previous biopsy showed a congenital fibroma. The patient was in good health; the physical examination, chest X‐ray films, and laboratory studies were normal. No history of personal or familial diseases was recorded.

Initially, the atrophic plaque measured 6 × 8 cm; shortly after, multiple 0.5–2 cm tumors appeared. These tumors alternated with atrophic and ill‐defined livedo‐like areas (Fig. 1). A satellite lesion, measuring 2 cm in diameter, was also observed. A new biopsy revealed dermatofibrosarcoma protuberans.

(A) 6 × 8 cm plaque on the anterior aspect of the right leg. Multiple tumors alternate with atrophic and ill‐defined livedo‐like areas

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Immunohistochemical findings included positive vimentin and CD34, and negative Factor XIIIa, S‐100 protein, and muscle actin (Fig. 2). One month later, several tumors had almost disappeared. The patient was successfully treated with Mohs' micrographic surgery and remained disease free 9 months later.

The cells are characteristically arranged in a ‘‘storiform’' pattern, sometimes centered around small blood vessels. Involvement of the subcutaneous fat is usual

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A clinical study to determine the efficacy and safety of 1% methotrexate/Azone® (MAZ) gel applied topically once daily in patients with psoriasis vulgaris
Authors: Sutton Lynda , Swinehart James M. , Cato Allen , Kaplan Allan S.
Published: March 2003

The efficacy and safety of an Azone‐enhanced topical gel formulation of 1% methotrexate (MAZ), administered once daily for 8 weeks, was compared with that of placebo vehicle for the treatment of severe plaque psoriasis. Fifty‐three patients were involved in this double‐blind, paired‐comparison study. Changes in disease signs and symptoms indicated that both agents have antipsoriatic activity; however, lesions treated with MAZ exhibited significantly greater improvement. At the end of treatment, 27% of MAZ‐treated lesions demonstrated marked improvement, whereas none of the placebo‐treated lesions exhibited this degree of change. MAZ was most effective in reducing lesional scaling and thickness (P < 0.05 vs. placebo). Thirty‐seven patients experienced adverse events. The majority were local in nature and mild to moderate in degree. No clinically significant changes in hematologic or clinical laboratory parameters were observed, and concentrations of methotrexate were demonstrable in only two of 296 plasma samples. The findings suggest that the MAZ formulation provides percutaneous absorption of methotrexate in amounts sufficient for a beneficial effect in psoriasis, but insufficient to exert systemic toxicities.
Subungual epidermoid cysts
Authors: Del Mar Sáez‐de‐Ocariz María , Domínguez‐Cherit Judith , García‐Corona Cristina
Published: March 2003

Case 1 A 50‐year‐old woman presented to our Dermatology Department with a 2‐month history of edema and pain in the third right toe. She had a past history of common warts, chronic venous insufficiency, fibromyalgia, and noninsulin‐dependent diabetes mellitus. No previous trauma to the toe could be recalled.

Physical examination revealed digital clubbing, minimal lateral onycholysis, and subungual keratosis (Fig. 1). Mycologic examinations (KOH and culture) were negative on two separate occasions and the X‐ray revealed only soft tissue augmentation without evidence of bone involvement. A nail biopsy was performed with the clinical diagnosis of glomus tumor vs. neuroma vs. neurilemmoma. Histologic sections showed a dermal unilocular cyst lined by an epidermis‐like epithelium with a granular cell layer, filled with laminated orthokeratin (Fig. 2); a diagnosis of subungual epidermoid cyst was established. The patient experienced recurrent pain 1 month after surgery, and a re‐excision was performed. The second biopsy showed only fibrous collagen bundles consistent with scar tissue. Intralesional steroid was injected to the site of the scar, and the patient is currently free of pain.

Digital clubbing of the third finger. There is also lateral onycholysis and subungual keratosis

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Hyperkeratosis and, in the dermis, a subungual epidermoid cyst. The wall is composed of stratified squamous epithelium, and the cyst is filled with laminated orthokeratin

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Case 2 A 40‐year‐old woman presented to our Dermatology Department with a 5‐year history of throbbing pain in the first right toe. Her medical history was only relevant for syringomas and onychomycosis, and no traumatic event was recalled.

Physical examination revealed a slight increase in volume in the lateral aspect of the toe. There were no changes in the skin. Palpation increased the painful sensation. With the presumptive diagnosis of neuroma, a nail biopsy was performed, showing a subungual epidermoid cyst. The patient is currently free of pain 15 months after surgery.
Cutaneous leishmaniasis in Hormozgan, Iran
Authors: Zare Shahram , Baghestani Shahram
Published: March 2003

Abstract

Background  Epidemiology of Cutaneous Leishmaniasis in Hormozgan province during April 1994 to March 1998 was studied.

Methods  Data were collected from the Health service Centres throughout the province as well as from dermatologists. The patients were diagnosed clinically or paraclinically and all important details were recorded on specially designed forms.

Results  A total of 4094 patients with 7255 lesions were diagnosed. 42.24% of the sufferers were under 20 years and 6.47% were over 40 years old. 52.10% of the patients had one lesion and 33.98% had two lesions. Most of the cases were seen during January to March. The incidence rate per 10000 ranged from 5.90 in 1998 to 16.98 in 1996.

Conclusions  A decreasing trend in the number of cases after 1996 may be due to the awareness of local health authorities, preventative activities and education.
Striated palmoplantar keratoderma of Brunauer‐Fohs–Siemens
Authors: Kotcher Lauren B. , Jih Ming H. , White Katherine L. , Kimyai‐Asadi Arash
Published: March 2003

A 67‐year‐old African American man presented with callosities of his hands (which he had since adolescence) that were exacerbated by manual labor. His father suffered severe callosities of his feet, but no other family member was afflicted. Physical examination revealed symmetrically distributed linear hyperkeratotic plaques on the palms extending onto the full length of the volar aspect of his digits (Fig. 1). There was no personal or family history of hair, nail, or dental abnormalities. Histologic evaluation showed marked acanthosis, hypergranulosis, and hyperkeratosis of the lesions (Fig. 2). There was no evidence of epidermolytic hyperkeratosis.

Linear hyperkeratotic plaques extending the length of the digits and focally present on the palms

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Marked acanthosis, hypergranulosis, and hyperkeratosis of palmoplantar skin (hematoxylin and eosin, × 200)

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Acneiform lesions in Becker's nevus and breast hypoplasia
Authors: Santos‐Juanes Jorge , Galache C. , Curto J. R. , Carrasco M. P. , Ribas A. , Sánchez del Río J.
Published: March 2003

An 18‐year‐old woman was referred for the evaluation of a dull gray macule on the left breast. From the age of 13 years, the patient noted breast asymmetry beginning with the development of the left breast and the presence of a pigmented stain on its border. Physical exploration revealed hypoplasia of the left breast and a homogeneous, light brown macule on the side of the breast (Fig. 1) without infiltration. Papules and pustules were located mainly around the Becker's nevus on the left anterior chest wall. Biopsy specimens with Fontana's stain disclosed a hyperpigmented acanthotic epidermis. A diagnosis of Becker's nevus, acne, and hypoplasia of the breast was made.

Hypoplasia of the left breast and a homogeneous light brown macule with acneiform lesions

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Prayer marks
Authors: Abanmi Abdullah A. , Al Zouman Abdulrahman Y. , Al Hussaini Husa , Al‐Asmari Abdulrahman
Published: March 2003

Background Prayer marks (PMs) are asymptomatic, chronic skin changes that consist mainly of thickening, lichenification, and hyperpigmentation, and develop over a long period of time as a consequence of repeated, extended pressure on bony prominences during prayer.

Methods Three hundred and forty‐nine Muslims and 24 non‐Muslims were examined for the appearance of PMs at different body sites.

Results The prospective study of 349 Muslims (both males and females) with regular praying habits showed the occurrence of PMs on specific locations, such as the forehead, knees, ankles, and dorsa of the feet, leading to dermatologic changes consisting of lichenification and hyperpigmentation. The incidence of PMs was significantly higher in males than in females. Older subjects (over 50 years of age) demonstrated a significantly higher frequency of lichenification and hyperpigmentation, suggesting that repeated pressure and friction for prolonged periods are the causative factors for the development of PMs. Histologic examination of skin biopsies from the affected sites showed compact orthokeratosis, hypergranulosis, dermal papillary fibrosis, and dermal vascularization. PMs were not associated with any risk of secondary complications, such as erythema, bullous formation, and infections.

Conclusions PMs are commonly occurring dermatologic changes in Muslims who pray for prolonged periods.
Squamous cell carcinoma in a patient with Netherton's syndrome
Authors: Saghari Sogol , Woolery‐Lloyd Heather , Nouri Keyvan
Published: March 2003

A 29‐year‐old white woman with a history of Netherton's syndrome presented with two squamous cell carcinomas on the right dorsal hand and the left upper arm. She reported a 2‐year history of these lesions, which were originally treated as warts. She denied excessive sun exposure, immunosuppressive therapy, or a previous history of skin cancer.

Her past medical history included acute renal failure, multiple urinary tract infections, meningitis, and recurrent otitis media as a child. In addition, she had an ovarian abscess at 4 years of age with resulting salpingo‐oophorectomy. She also reported a history of severe myopia, glaucoma, and multiple ocular infections with a resulting corneal scar. In addition to atopic dermatitis, she had a 10‐year history of psoriasis. Her medications included topical steroids and emollients for atopic dermatitis and psoriasis, in addition to Timolol ophthalmic drops for glaucoma. Her family history was significant for a 22‐year‐old sister with Netherton's syndrome (Fig. 1). She denied any history of skin cancer in her sister or other members of her family.

Patient and sibling with Netherton's syndrome. Features of erythroderma, ichthyosis, and hair abnormalities

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On physical examination, she had an exfoliative erythroderma, madarosis, and diffuse patchy alopecia. In the bilateral axilla, she had well‐defined pink scaly plaques which were confirmed as psoriasis by biopsy. On the right dorsal hand, she had a 1.5 × 1.0 cm pink verrucous plaque (Fig. 2). On the left upper arm, she had a 1.5 × 0.8 cm pink scaly plaque. Biopsies of both sites confirmed squamous cell carcinomas. Both lesions were completely excised with 4 mm margins.

Eroded pink papule on the right dorsal hand

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Trichostasis spinulosa: itchy follicular papules in young adults
Authors: Strobos Michiel A. , Jonkman Marcel F.
Published: March 2003

Trichostasis spinulosa is a common inapparent follicular disorder of retained bundles of vellus hairs. There exist two variants: the classical variant presenting with a non‐itching, comedo‐like lesion on the face in the elderly, and the pruritic variant presenting with itching, follicular papules located on the limbs in young adults. Here we present the microscopic study of the pruritic variant of trichostasis spinulosa in two patients and provide a review of the literature.
Multiple synchronous cutaneous melanomas: implications for prevention
Authors: Carli Paolo , De Giorgi Vincenzo , Chiarugi Alessandra , Stante Marcello , Giannotti Benvenuto
Published: March 2003

Background A subset of about 3–5% of melanoma patients present a second primary melanoma.

Observations We describe two cases of primary multiple synchronous melanomas consecutively observed in the last 6 months in our department in two male patients presenting multiple atypical nevi. In both patients, the second melanoma was diagnosed by the clinician who had identified the first one, but at the time of the first follow‐up consultation, 3 months later. The delayed discovery of the second melanoma required another referral for surgery with additional discomfort for the patients. Concern about the first lesion (the thickest in both cases) probably rendered the second one less evident to both patients and clinician, until the first follow‐up examination after excision of the first lesion.

Conclusion We stress the need for careful and thorough examination of the whole body surface at the time of detection of a cutaneous melanoma in subjects with multiple atypical moles because the finding of synchronous multiple melanomas is not uncommon.
Topical prostaglandin analog (PGE2) in vitiligo – a preliminary study
Authors: Parsad Davinder , Pandhi Roma , Dogra Sunil , Kumar Bhushan
Published: March 2003

Background Several therapeutic options are available for the treatment of vitiligo, but none is uniformly effective. Prostaglandin has been shown to play a role in melanocyte proliferation and melanogenesis. Topical application of prostaglandin E2 (PGE2) over mice skin has been shown to increase melanocyte density.

Aim To evaluate the role of topical PGE2 in the treatment of vitiligo.

Methods We enrolled 27 patients with limited vitiligo lesions in this study. Patients were instructed to apply a translucent gel containing 0.5 mg/3 g (166.6 µg/g) PGE2 to depigmented skin.

Results Twenty‐four patients were evaluated at the end of 6 months, as three patients withdrew for reasons unrelated to the study. At the end of treatment, 15 patients showed marked to complete repigmentation and three patients showed moderate repigmentation. The remaining six patients showed none to minimal repigmentation.

Conclusions Marginal repigmentation with hyperpigmented borders was seen in the majority of lesions. Our results are encouraging and offer a new and potentially efficacious treatment for this pigmentation disorder.
Assessment of histologic criteria in the diagnosis of mycosis fungoides
Authors: Naraghi Zahra Safee , Seirafi Hassan , Valikhani Mahin , Farnaghi Forshad , Kavusi Susan , Dowlati Yahya
Published: March 2003

Background The histologic diagnosis of early mycosis fungoides (MF) can be difficult to establish in many instances because the subtle changes observed in patches of MF are also present in many inflammatory dermatoses.

Methods To assess the frequency and significance of many of these histologic parameters, we retrospectively reviewed 50 slides from patients with documented MF in patch, plaque, and tumor stages. The diagnosis of MF was unequivocally established either by the progression of patients to advanced stages of the disease or by indubitable histologic findings. In the second phase of the study, we compared the histologic parameters observed in 24 patch stage MF patients with those in 24 non‐MF patients. The non‐MF group were patients whose pathologic pattern was suspicious for MF, but who definitely did not have MF on clinical grounds. The two groups were matched by histologic pattern. Two different observers evaluated the slides and the intensities of 32 histologic parameters were graded on a four‐point scale to minimize the subjective variability in the histologic reports.

Results On univariate analysis, the following parameters achieved significance in distinguishing MF from non‐MF: Pautrier's microabscesses, haloed lymphocytes, disproportionate epidermotropism, epidermal lymphocytes larger than dermal lymphocytes, hyperconvoluted lymphocytes in the epidermis and dermis, absence of dyskeratosis, and papillary dermal fibrosis. None of these features proved to have additional discriminating power on multivariate analysis.

Conclusions The efficacy of single histologic features in the diagnosis of early MF is generally poor and, to discriminate MF from its inflammatory simulators, a combination of cytologic and architectural features must be used.
Facile synthesis of orthogonally protected amino acid building blocks for combinatorial N‐backbone cyclic peptide chemistry
Authors: Gellerman G. , Elgavi A. , Salitra Y. , Kramer M.
Published: March 2003

Abstract:ProtectedNα‐(aminoallyloxycarbonyl) andNα‐(carboxyallyl) derivatives of all natural amino acids (except proline), and their chiral inverters, were synthesized using facile and efficient methods and were then used in the synthesis ofNα‐backbone cyclic peptides. Synthetic pathways for the preparation of the amino acid building units included alkylation, reductive amination and Michael addition using alkylhalides, aldehydes and α,β‐unsaturated carbonyl compounds, and the corresponding amino acids. The resulting amino acid prounits were then subjected to Fmoc protection affording optically pure amino acid building units. The appropriate synthetic pathway for each amino acid was chosen according to the nature of the side‐chain, resulting in fully orthogonal trifunctional building units for the solid‐phase peptide synthesis of small cyclic analogs of peptide loops (SCAPLs™).Nα‐amino groups of building units were protected by Fmoc, functional side‐chains were protected byt‐Bu/Boc/Trt andN‐alkylamino orN‐alkylcarboxyl were protected by Alloc or Allyl, respectively. This facile method allows easy production of a large variety of amino acid building units in a short time, and is successfully employed in combinatorial chemistry as well as in large‐scale solid‐phase peptide synthesis. These building units have significant advantage in the synthesis of peptido‐related drugs.
Genetic structure of natural populations of Castanea sativa in Turkey: evidence of a hybrid zone
Authors: Villani  , Sansotta  , Cherubini  , Cesaroni  , Sbordoni
Published: March 2003

This study points out the evidence of a hybrid zone between two groups of genetically differentiated populations of chestnut (Castanea sativa Mill.) in Turkey. Genetic structure, gene flow and introgression levels, based on 16 allozyme loci, were investigated on 34 population samples spanning the entire C. sativa distribution area in this country. The occurrence of the hybrid zone, located in the Bithynian region, was inferred in a group of populations showing the following genetic characteristics: (i) enhanced genetic variability and intermediate allelic frequencies between those of the Western and Eastern groups of populations; (ii) sharp and concordant changes in allele frequencies; (iii) decreased gene flow with the Western and Eastern populations. Starting from the cline width estimated to be 324 km, strength of selection was evaluated from the gene flow distance, as indicated from the degree of genetic structuring outside the hybrid zone. Evolutionary processes shaping the observed genetic differentiation and introgression are discussed on the basis of palynological data, palaeoclimatic events and evidence of hybridization found in other plant and animal species in the same region.
Phylogenetic relationships within the corbiculate Apinae (Hymenoptera) and the evolution of eusociality
Authors: Koulianos  , Schmid-Hempel  , Roubik  , Schmid-Hempel
Published: March 2003

We provide a comparison of 520 base pairs of the mitochondrial cytochrome b gene from exemplars of the Meliponini, the Apini, the Bombini and the Euglossini to determine the phylogenetic relationships within the corbiculate Apinae. Our results strongly suggest (91–97% according to bootstrap resampling) that the Meliponini and the Bombini are sister groups. This finding agrees with those of other molecular studies, but is discordant with previous hypotheses based on morphology and the combination of molecular and morphological data. If the Bombini and Meliponini are sister groups and reversal of advanced eusociality is unlikely, then advanced eusociality arose twice within this clade. However, if reversion of eusociality occurred, then it is not possible to discriminate between single or dual origins of advanced eusociality within this group.
Mechanisms of incomplete prezygotic reproductive isolation in an intertidal snail: testing behavioural models in wild populations
Authors: Rolán-Alvarez E. , Erlandsson J. , Johannesson K. , Cruz R.
Published: March 2003

Two morphs (ecotypes) of the marine snail Littorina saxatilis coexist along Galician exposed rocky shores. They hybridize, but gene flow is impeded by a partial prezygotic reproductive barrier, and we have earlier suggested that this is a case of incipient sympatric speciation. To assess the mechanisms of prezygotic reproductive isolation, we estimated deviations from random mating (sexual selection and sexual isolation) of sympatric snails in 13 localities on the shore, and performed mate choice experiments in the laboratory. We also investigated the microdistribution of both morphs over patches of barnacles and blue mussels in the hybridization zone. We used computer simulations to separate the mechanisms contributing to reproductive isolation.

On the shores sampled, male–female pairs were strongly assortative both with respect to morphs (mean Yule's V = 0.77) and size (mean Pearson's r = 0.47). In the laboratory, males of both morphs mounted other snails and mated other males and juveniles at random. However, mature females of equal sizes mated assortatively with respect to morph. The two morphs were nonrandomly distributed over barnacle and mussel patches in the hybridization zone. Monte Carlo simulations showed that this microdistribution could explain about half the morph and size relationships in male–female pairs, while a simple rejection mechanism, rejecting the first 1–3 mates if they were of contrasting morphs, accounted for the remaining part of the reproductive isolation, and for parts of the size relationships found between mates. A size discriminant mate choice mechanism may also, to a lesser extent, contribute to the sexual isolation. Sexual selection was observed for female size (larger ones being favoured) and among certain morphs, but distinct biological mechanisms may cause these processes.
Parasite local maladaptation in the Canarian lizard Gallotia galloti (Reptilia: Lacertidae) parasitized by haemogregarian blood parasite
Authors: Oppliger A. , Vernet R. , Baez M.
Published: March 2003

Biologists commonly assume that parasites are locally adapted since they have shorter generation times and higher fecundity than their hosts, and therefore evolve faster in the arms race against the host's defences. As a result, parasites should be better able to infect hosts within their local population than hosts from other allopatric populations. However, recent mathematical modelling has demonstrated that when hosts have higher migration rates than parasites, hosts may diversify their genes faster than parasites and thus parasites may become locally maladapted. This new model was tested on the Canarian endemic lizard and its blood parasite (haemogregarine genus). In this host–parasite system, hosts migrate more than parasites since lizard offspring typically disperse from their natal site soon after hatching and without any contact with their parents who are potential carriers of the intermediate vector of the blood parasite (a mite). Results of cross-infection among three lizard populations showed that parasites were better at infecting individuals from allopatric populations than individuals from their sympatric population. This suggests that, in this host–parasite system, the parasites are locally maladapted to their host.
Genetic and environmental components of growth in nestling blue tits (Parus caeruleus)
Authors: Kunz  , Ekman
Published: March 2003

We investigated the effect of brood-size mediated food availability on the genetic and environmental components of nestling growth in the blue tit (Parus caeruleus), using a cross-fostering technique.

We found genetic variation for body size at most nestling ages, and for duration of mass increase, but not of tarsus growth. Hence, nestling growth in our study population seems to have the potential to evolve further. Furthermore, significant genotype–environment interactions indicated heritable variation in reaction norms of growth rates and growth periods, i.e. that our study population had a heritable plasticity in the growth response to environmental conditions.

The decreasing phenotypic variance with nestling age indicated compensatory growth in all body traits. Furthermore, the period of weight increase was longer for nestlings growing up in enlarged broods, while there was no difference to reduced broods in the period of tarsus growth. At fledging, birds in enlarged broods had shorter tarsi and lower weights than birds in reduced broods, but there was no difference in wing length or body condition between the two experimental groups. The observed flexibility in nestling growth suggests that growing nestlings are able to respond adaptively to food constraint by protecting the growth of ecologically important traits.
A bird’s eye view of the peppered moth
Authors: Majerus  , Brunton  , Stalker
Published: March 2003

Industrial melanism in Biston betularia is one of the best known examples of the role of natural selection in evolution and has received considerable scrutiny for many years. The rise in frequency of the dark form of the moth (carbonaria) and a decrease in the pale form (typica) was the result of differential predation by birds, the melanic form being more cyptic than typica in industrial areas where the tree bark was darkened by air pollution. One important aspect of early work evaluating the relative crypsis of the forms of B. betularia on tree trunks with different lichen flora was the reliance on human observers. Humans, however, do not have the same visual capabilities as birds. Birds have well-developed ultraviolet (UV) vision, an important component of their colour processing system that affects many aspects of behaviour, including prey detection. We examined the UV characteristics of the two forms of B. betularia and a number of foliose and crustose lichens. In human visible light the speckled form typica appeared cyptic when seen against a background of foliose lichen, whereas the dark form carbonaria was conspicuous. Under UV light the situation was reversed. The foliose lichens absorbed UV and appeared dark as did carbonaria. Typica, however, reflected UV and was conspicuous. Against crustose lichens, typica was less visible than carbonaria in both visible and UV light. These findings are considered in relation to the distribution and recolonization of trees by lichens and the resting behaviour of B. betularia.
Introgressive hybridization between two species of waterstriders (Hemiptera: Gerridae: Limnoporus): geographical structure and temporal change of a hybrid zone
Authors: Klingenberg  , Spence  , Mirth
Published: March 2003

Where the distribution ranges of the waterstriders Limnoporus notabilis and L. dissortis meet in western Canada, extensive hybridization and introgression occurs. Multivariate ordination analyses of genetic and morphometric data by principal component analysis revealed that a single axis separating the two parent species could account for nearly all the variation in both data sets. Maps of principal component scores for both data sets revealed geographical patterns of variation reflecting specific topographic features in the region. Comparisons of morphometric data from some of the samples collected in the 1980s and from the same sites revisited in the 1990s revealed substantial changes. An ‘island’ of dissortis-like populations inside the range of L. notabilis in interior British Columbia expanded, and a marked local protrusion of notabilis-like phenotypes into the range of L. dissortis on the east slope of the Rocky Mountains diminished during the decade between collections. We conclude that introgressive hybridization between these two species of waterstriders is a spatially complex and highly dynamic process.
Phylogenetic evidence for a single, ancestral origin of a ‘true’ worker caste in termites
Authors: Thompson G. J. , Kitade O. , Lo N. , Crozier R. H.
Published: March 2003

Phylogenetic analysis based on sequence variation in mitochondrial large-subunit rRNA and cytochrome oxidase II genes was used to investigate the evolutionary relationships among termite families. Maximum likelihood and parsimony analyses of a combined nucleotide data set yield a single well-supported topology, which is: (((((Termitidae, Rhinotermitidae), Serritermitidae), Kalotermitidae), (Hodotermitidae, Termopsidae)), Mastotermitidae). Although some aspects of this topology are consistent with previous schemes, overall it differs from any published. Optimization of ‘true’ workers onto the tree suggests that this caste originated once, early in the history of the lineage and has been lost secondarily twice. This scenario differs from the more widely accepted notion that workers are derived and of polyphyletic origin and that extant pseudergates, or ‘false’ workers, are their developmentally unspecialized ancestor caste. Worker gains and losses covary directly in number and direction with shifts in ‘ecological life type’. A test for correlated evolution which takes phylogenetic structure into account indicates that this pattern is of biological significance and suggests that the variable occurrence of a worker caste in termites has ecological determinants, apparently linked to differences in feeding and nesting habits.
Ploidy evolution in the yeast Saccharomyces cerevisiae: a test of the nutrient limitation hypothesis
Authors: Mable B. K.
Published: March 2003

The nutrient limitation hypothesis provides a nongenetic explanation for the evolution of life cycles that retain both haploid and diploid phases: differences in nutrient requirements and uptake allow haploids to override the potential genetic advantages provided by diploidy under certain nutrient limiting conditions. The relative fitness of an isogenic series of haploid, diploid and tetraploid yeast cells (Saccharomyces cerevisiae), which were also equivalent at the mating type locus, was measured. Fitness was measured both by growth rate against a common competitor and by intrinsic growth rate in isolated cultures, under four environmental conditions: (1) rich medium (YPD) at the preferred growth temperature (30 °C); (2) nutrient poor medium (MM) at 30 °C; (3) YPD at a nonpreferred temperature (37 °C); and (4) MM at 37 °C. In contrast to the predictions of the nutrient limitation hypothesis, haploids grew significantly faster than diploids under nutrient rich conditions, but there were no apparent differences between them when fitness was determined by relative competitive ability. In addition, temperature affected the relative growth of haploids and diploids, with haploids growing proportionately faster at higher temperatures. Tetraploids performed very poorly under all conditions compared. Cell geometric parameters were not consistent predictors of fitness under the conditions measured.
On the assignment of fitness to parents and offspring: whose fitness is it and when does it matter?
Authors: Wolf J. B. , Wade M. J.
Published: March 2003

There has been a long-standing conceptual debate over the legitimacy of assigning components of offspring fitness to parents for purposes of evolutionary analysis. The benefits and risks inherent in assigning fitness of offspring to parents have been given primarily as verbal arguments and no explicit theoretical analyses have examined quantitatively how the assignment of fitness can affect evolutionary inferences. Using a simple quantitative genetic model, we contrast the conclusions drawn about how selection acts on a maternal character when components of offspring fitness (such as early survival) are assigned to parents vs. when they are assigned directly to the individual offspring. We find that there are potential shortcomings of both possible assignments of fitness. In general, whenever there is a genetic correlation between the parental and direct effects on offspring fitness, assigning components of offspring fitness to parents yields incorrect dynamical equations and may even lead to incorrect conclusions about the direction of evolution. Assignment of offspring fitness to parents may also produce incorrect estimates of selection whenever environmental variation contributes to variance of the maternal trait. Whereas assignment of offspring fitness to the offspring avoids these potential problems, it introduces the possible problem of missing components of kin selection provided by the mother, which may not be detected in selection analyses. There are also certain conditions where either model can be appropriate because assignment of offspring fitness to parents may yield the same dynamical equations as assigning offspring fitness directly to offspring. We discuss these implications of the alternative assignments of fitness for modelling, selection analysis and experimentation in evolutionary biology.
Wolbachia in leafcutter ants: a widespread symbiont that may induce male killing or incompatible matings
Authors: Van Borm S. , Wenseleers T. , Billen J. , Boomsma J. J.
Published: March 2003

Wolbachia is a maternally inherited bacterium that manipulates host reproduction by inducing cytoplasmic incompatibility (CI), parthenogenesis or male killing (MK). Here, we report on a screening of seven leafcutter ant species of the genera Atta and Acromyrmex. Using Wolbachia-specific polymerase chain reaction (PCR) primers we show that all species are infected, usually by double A + B strain infections. For Acromyrmex echinatior and A. octospinosus, a screening across all castes shows that gynes (prospective queens) have higher infection rates than workers and males. The low infection rate of workers suggests that workers lose their infection during development. This we interpret as adaptive, because a heritable symbiont does not benefit from being present in sterile workers. Both CI and MK could potentially account for the low infection rate of males. Formal theoretical models show greater support for the MK scenario in the free living species A. echinatior and A. octospinosus but indicate that Wolbachia in the social parasite A. insinuator may cause CI, supporting a scenario of sympatric speciation of the social parasite. We conclude that Wolbachia represents a previously unrecognized source of reproductive conflict in leafcutter ant colonies.