Quantifying age and model uncertainties in palaeoclimate data and dynamical climate models with a joint inferential analysis.

The study of palaeoclimates relies on information sampled in natural archives such as deep sea cores. Scientific investigations often use such information in multi-stage analyses, typically with an age model being fitted to a core to convert depths into ages at stage one. These age estimates are then used as inputs to develop, calibrate or select climate models in a second stage of analysis. Here, we show that such multi-stage approaches can lead to misleading conclusions, and develop a joint inferential approach for climate reconstruction, model calibration and age estimation. As an illustration, we investigate the glacial-interglacial cycle, fitting both an age model and dynamical climate model to two benthic sediment cores spanning the past 780 kyr. To show the danger of a multi-stage analysis, we sample ages from the posterior distribution, then perform model selection conditional on the sampled age estimates, mimicking standard practice. Doing so repeatedly for different samples leads to model selection conclusions that are substantially different from each other, and from the joint inferential analysis. We conclude that multi-stage analyses are insufficient when dealing with uncertainty, and that to draw sound conclusions the full joint inferential analysis should be performed.

Hereditary neurocutaneous angiomatosis. Report of four cases.

The authors report the coexistence of vascular nevi (hemangiomas and arteriovenous malformations (AVMs) of the skin) with AVMs and venous malformations of the brain in male siblings from two related but nonconsanguineous families of three generations. The proband, his siblings, parents, aunts, uncles, and cousins were examined, underwent magnetic resonance (MR) imaging and MR angiography, and when appropriate, cerebral angiography. A father had vascular nevi and a mother, his sister, had an azygos anterior cerebral artery. No other cutaneous or cerebrovascular malformations were present in the parents. Each of the two families had two boys and one girl, 9 to 18 years of age. All the children had vascular nevi and all of the boys had coexisting cerebrovascular malformations: AVMs in three, and a venous malformation in another. One boy had three cerebral AVMs. Two boys had a cerebral hemorrhage, and one also had focal motor seizures. The skin lesions were not those of the Sturge-Weber-Dimitri, Rendu-Osler-Weber, or Wybum-Mason syndromes. The association of cutaneous and cerebrovascular malformations was seen only in males in these families. but females have also been reported in the literature. The results obtained in these families and three other families reported from Western and Central Europe indicate that the association of cerebral and cutaneous vascular hamartomas constitutes a distinct, hereditary clinicopathological entity with autosomal dominant inheritance and variable penetrance. The clinical manifestations of this syndrome are visible, painful vascular nevi, epilepsy, cerebral hemorrhage, and focal neurological deficits. The preponderance of male patients with the full expression of the syndrome suggests a possible hormonal influence on the expression of the gene.

Characterization of a monoclonal antibody against a mucin-type glycoprotein in human sweat.

We report the preparation and characterization of an IgG2 monoclonal antibody (MAb), HSMA, prepared against a human pooled sweat extract (HPSE). The major component of HPSE was a mucin-type molecule, as revealed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) stained with periodic acid-Schiff (PAS) reagent. By immunoblotting, HSMA revealed a smear in the high molecular weight range, typical of mucins. In enzyme-linked immunosorbent assay (ELISA), HSMA failed to react with HPSE fractions isolated after anionic exchange gel chromatography. Similarly, radio-immunobinding assays demonstrated no reactivity between HSMA and A, B, H, and Lewis blood group-related structures. The immunohistological labeling on normal skin showed that HSMA reacted with the cells of eccrine sweat glands, and to a lesser extent, with sebaceous glands and epidermal cells. Periodate treatment in situ abolished these reactions, thus suggesting the carbohydrate structure of the HSMA-epitope. In indirect immunofluorescence (IF) studies, HSMA also reacted with other exocrine glands, e.g. mammary glands, sublingual glands, mixed sero-mucous glands of the trachea, and in the pancreas. Sparse positive cells were also observed in the testis, kidney, thyroid and digestive tract.

Therapeutic response to a dermatologic patch and betamethasone valerate 0.1 percent cream in the management of chronic plaques in psoriasis.

The efficacy of a hydrocolloid dermatologic patch (Actiderm) in conjunction with topical beta-methasone valerate 0.1 percent cream was studied in outpatients with chronic plaque-type psoriasis treated for three weeks, and observed for an additional two weeks after therapy. A significant degree (p less than 0.05) of lesion resolution occurred at the site treated with the dermatologic patch plus steroid cream, whereas sites treated with either agent alone showed mild but insignificant change. It was concluded that the patch was a highly effective adjunct in the treatment of chronic plaques of psoriasis.

Expression of c-myc protein in skin and synovium in psoriasis and psoriatic arthritis.

Monoclonal antibody against c-myc protein was used in the avidin-biotin-peroxidase complex procedure to examine frozen sections of psoriatic and normal skin and psoriatic synovium for the presence of c-myc protein. A significantly greater percentage (88%) of epithelial cells from psoriatic skin lesions stained for c-myc than uninvolved skin (62%) from both psoriatics and normals (p less than 0.001). The intensity of the stain appeared weaker in normal skin specimens. Greater than 95% of psoriatic hyperplastic synovial lining cells stained strongly for c-myc. In all cases, the c-myc staining was confined to the nuclei with no evidence of cytoplasmic staining.

Systemic mastocytosis: management of an unusual case with histamine (H1 and H2) antagonists and cyclooxygenase inhibition.

A patient with urticaria pigmentosa and systemic mastocytosis developed hypotension following indomethacin administration. He then developed further episodes not related to indomethacin. Based upon the experience of others with the management of patients with systemic mastocytosis who showed exceptional reaction to cyclooxygenase inhibition, it was decided to treat him with H1 and H2 blockade followed by aspirin, another cyclooxygenase inhibitor. The procedure was carried out under careful observation with cardiac monitoring. After 160 mg of aspirin, he developed hypotension, tachycardia, and flushing accompanied by difficulty of breathing and headache. A vasoconstrictor drug (levarterenol) was administered. The patient's symptoms subsided, and after 1 hour aspirin was again administered, this time with no side effects. The dosage was increased to 975 mg every 6 hours, and he has had no further hypotensive episodes on this regime for 2 years. Cyclooxygenase inhibition, combined with H1 and H2 blockade, is an effective treatment for this condition, but for these patients initiation of aspirin therapy should be carried out with extreme care.

Anaphylaxis following the use of bacitracin ointment. Report of a case and review of the literature.

A 52-year-old woman suffered an acute anaphylactic reaction to topically applied bacitracin. An investigation disclosed the presence of concurrent type I and IV hypersensitivity to bacitracin. We review five other cases of anaphylactic reactions to topical medications and describe the clinical characteristics common to all six cases.

Leprosy downgrading reaction associated with griseofulvin.

A dramatic alteration from clinically subpolar tuberculoid leprosy toward subpolar lepromatous leprosy was observed during griseofulvin therapy in a 29-year-old man, despite apparently normal cell-mediated immunity. To our knowledge, this is the first reported case of a downgrading reaction associated with griseofulvin. It is possible that this reaction was due to inhibition of polymorphonuclear leukocyte chemotaxis by griseofulvin.

Cryotherapy for precancerous melanosis (atypical melanocytic hyperplasia) of the conjunctiva.

Two patients with progressive, diffuse precancerous melanosis (intraepithelial atypical melanocytic hyperplasia or melanocytic dysplasia) of the conjunctiva were treated with cryotherapy. In one patient, the contiguous cutaneous portions of both eyelids were involved and received the same therapy; the extensive disease of the patient was managed by two cryotherapy sessions during a period of 21/2 months. The melanocytic process in both patients showed a good response to this therapy, which resulted in a slough of the superficial conjunctiva with reepithelialization from adjacent areas. Neither patients has shown recurrent disease in more than seven months of follow-up, although one patient had incomplete regression of the melanocytic condition in the perilimbal region, which was subsequently treated by an excisional biopsy. Serious complications occurred in one patient who had corneal and lenticular opacities; this patient had severe extensive disease for which exenteration was considered the only feasible alternative therapy to control the melanocytic proliferation disorder adequately. Less severe complications also developed, including trichiasis, ptosis, transient hypotony, and macular edema. In this article, we discuss the clinical and histologic features of acquired pigmentations of the conjunctiva, the criteria for their management, and the approaches to minimize the complications that we have encountered with cryotherapy.

Combined surgery and cryotherapy for diffuse malignant melanoma of the conjunctiva.

Two patients who had refused exenteration for widespread conjunctival melanoma were treated by a combination of cryotherapy and surgical excisions. Cryotherapy was delivered only to the extensive areas of flat intraepithelial melanocytic proliferation (precancerous melanosis), while the surgical excisions were performed on the focal nodules, representing localized invasive melanoma. In our two patients, the invasive nodules measured, respectively, 1.2 and 1.5 mm in greatest thickness, placing them in a low to borderline risk group for metastasis. Repeated cryoapplicatons were required to control the widespread flat intraepithelial disease. The conjunctiva tolerated these procedures well because the substantia propria is not sacrificed as it must be in surgical conjunctivectomy, allowing comparatively normal reepithelialization to occur from adjacent zones, after the treated epithelium containing the melanocytes sloughs. No evidence of invasive melanoma (cancerous melanosis) has developed in any of the cryotreated areas of intraepithelial disease (precancerous melanosis); sequential biopsies have established that the atypical melanocytes have disappeared from the epithelium.

Therapy of infected dermatitis: comparative response to two corticosteroid antimicrobial creams.

In a double-blind, parallel trial which lasted 1 week and comprised eighty-eight patients, a study of the response to topical therapy of the infected component of four common eczematous processes showed that the treatment outcome with corticosteroid antimicrobial creams was not influenced by the type of dermatitis. The cream with fluocinonide 0.05% was significantly better than the cream with triamcinolone 0.1%. Both creams were clinically superior to a cream containing only the antimicrobial agents but exerted a similar antimicrobial activity.