Comparative potency of formulations of mometasone furoate in terms of inhibition of 'PIRHR' in the forearm skin of normal human subjects measured with laser doppler velocimetry

BACKGROUND AND AIMS: Topical glucocorticoid formulations are widely used for effective treatment and control of a variety of dermatoses. Mometasone furoate is a newer corticoid that has high potency but low systemic toxicity. Pharmaceutical factors are known to significantly influence potency and systemic absorption of topically applied glucocorticoids. We studied the potency of "Elocon", a topical formulation of mometasone furoate, compared with two other branded formulations of the same corticoid. METHODS: Corticoid potency was measured by employing a pharmacodynamic parameter of an inhibitory effect of the corticoid on post-ischemic-reactive-hyperemic-response (PIRHR) in human forearm skin under occlusive dressing. The PIRHR was expressed in terms of % increase in the skin blood flow (SBF) as measured with laser doppler velocimetry (LDV). RESULTS : All three active branded formulations of mometasone furoate produced significant inhibition of PIRHR. The AUC(0-2 min) of PIRHR was ( Mean +/- SEM ), Control = 213.52 +/- 11.80, Placebo = 209.77 +/- 19.31, Formulation A = 119.83 +/- 13.71, Formulation C = 53.67 +/- 4.85 and Formulation D = 111.46 +/- 22.87. Formulation "C" exhibited significantly higher topical anti-inflammatory potency than formulations "A" or "D". CONCLUSIONS: Thus, branded formulations of the same glucocorticoid, mometasone furoate significantly differed in their topical anti-inflammatory potency. "Elocon" was significantly more potent than the two other branded formulations studied.     

Society for Reproductive Biology Founders' Lecture 2003. The making of an embryo: short-term goals and long-term implications

During early development, the eutherian mammalian embryo forms a blastocyst comprising an outer trophectoderm epithelium and enclosed inner cell mass (ICM). The short-term goal of blastocyst morphogenesis, including epithelial differentiation and segregation of the ICM, is mainly regulated autonomously and comprises a combination of temporally controlled gene expression, cell polarisation, differentiative cell divisions and cell-cell interactions. This aspect of blastocyst biogenesis is reviewed, focusing, in particular, on the maturation and role of cell adhesion systems. Early embryos are also sensitive to their environment, which can affect their developmental potential in diverse ways and may lead to long-term consequences relating to fetal or postnatal growth and physiology. Some current concepts of embryo-environment interactions, which may impact on future health, are also reviewed.     

Primary pancreatic lymphomas: a cytopathologic analysis of a rare malignancy

BACKGROUND: Primary pancreatic lymphomas (PPL) are extremely rare. Clinically, PPL usually present with symptoms of carcinoma of the pancreatic head. An accurate cytopathologic diagnosis by fine-needle aspiration (FNA) is imperative because the primary treatment is nonsurgical, based on a combination of chemotherapy and radiation therapy. METHODS: Eight cases of PPL were identified from the pathology files of The Johns Hopkins Hospital over a 14-year period (1989-2003). All cases were diagnosed on FNA performed under radiologic guidance. Needle rinses were used to perform flow cytometric (FC) analysis. No tissue studies were performed after the FNA diagnosis was made. RESULTS: A strong male predominance (male-to-female ratio of 7:1) was noted. The patients ranged in age from 35-75 years (mean age, 55 years). The tumors varied in size from 2-14 cm, as evaluated on the radiologic scans (mean dimension of 8.0 cm). Abdominal pain was the most common presenting symptom (six patients) followed by jaundice, acute pancreatitis, small bowel obstruction, and diarrhea. The cytomorphologic features included hypercellularity with discohesive cells with round nuclei, often prominent nucleoli, mitoses, and karyorrhexis. By FC analysis, all eight cases demonstrated a monoclonal pattern of immunoglobulin light chain expression. The patients were treated with either chemotherapy alone or in conjunction with radiation therapy or stem cell transplantation. CONCLUSIONS: PPL is an extremely rare pathologic entity. FNA coupled with FC analysis appears to be highly accurate in the diagnosis of PPL and is the sole diagnostic modality used clinically. Based on cytomorphology, the main differential diagnoses of PPL involve secondary lymphoma, pancreatic endocrine neoplasm, and florid chronic pancreatitis. An accurate FNA diagnosis of PPL is critical for timely, nonsurgical management and obviates the need for an exploratory laparotomy.     

Novel treatment of chronic severe hand dermatitis with bexarotene gel

BACKGROUND: Hand dermatitis is an eczematous inflammation of the hands that is related to occupation or to routine activities. It often becomes chronic, and in some patients may become severe and disabling. Topical corticosteroids are effective treatment, particularly for milder forms, but they often lose effectiveness with time and can produce skin atrophy. OBJECTIVES: To evaluate bexarotene gel topical therapy for safety, tolerability and efficacy in patients with chronic hand dermatitis. METHODS: A phase I-II open-label randomized clinical study of bexarotene gel, alone and in combination with a low- and a mid-potency steroid, was conducted in 55 patients with chronic severe hand dermatitis at two academic clinics. RESULTS: Patients using bexarotene gel monotherapy reached a 79% response rate for > or = 50% clinical improvement and a 39% response rate for > or = 90% clearance of hands. Adverse events possibly related to treatment in all patients were stinging or burning (15%), flare of dermatitis (16%) and irritation (29%). Thirteen patients (24%) withdrew early, including two for related adverse events and five for inadequate response. CONCLUSIONS: Bexarotene gel appears to be safe, tolerated by most patients, with useful therapeutic activity in chronic severe hand dermatitis.     

Activities of daily living in patients with dementia: clinical relevance, methods of assessment and effects of treatment

Disability, characterised by the loss of ability to perform activities of daily living (ADL), is a defining feature of dementia that results in growing caregiver burden and the eventual need for alternative care or nursing home placement. Functional decline in patients with dementia can also result from causes other than dementia, such as comorbid medical and psychiatric illnesses and sensory impairment. ADL consists of instrumental ADL (IADL) [complex higher order skills, such as managing finances] and basic ADL (BADL) [self-maintenance skills, such as bathing]. Assessment of IADL and BADL is recommended to establish a diagnosis of dementia. Functional assessment also helps the healthcare provider to offer appropriate counselling regarding safety concerns and need for custodial care. Functional capacity measures have been used increasingly in pharmacological trials of patients with Alzheimer's disease (AD) and related dementias, although at the present time these measures are generally not primary outcome measures. Functional impairment is not a uniform construct; rather, it is multifaceted and can be measured with various clinical instruments. Many scales have been validated for use in patients with AD for characterising functional impairment and evaluating the efficacy of treatment. Research to date indicates that cholinesterase inhibitors have the potential for modest but meaningful beneficial effects on ADL in patients with mild-to-moderate AD. Memantine also has promising beneficial effects on functional abilities in persons with moderate-to-severe AD. Assessment of ADL as a primary efficacy measure using a validated scale that is non-gender biased and cross-nationally relevant is recommended in new treatment trials of patients with AD and related dementias.     

Laparoscopic tubal sterilization after two or more cesarean sections

STUDY OBJECTIVE: To determine the safety of laparoscopic tubal sterilization in women who have had two or more cesarean sections. DESIGN: Retrospective study (Canadian Task Force classification III). SETTING: Private clinic and hospitals. PATIENTS: Two hundred ten consecutive women. INTERVENTION: Laparoscopic tubal sterilization. MEASUREMENTS AND MAIN RESULTS: The procedures were done with no difficulty in all but two women. In addition to the two failures, one woman experienced bladder trauma. CONCLUSION: Laparoscopic sterilization after several cesarean sections is possible and is associated with low morbidity. Scarring from cesarean sections should not be a contraindication if extra care is taken.