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J M Weinberg

Publications and source records attributed to J M Weinberg.

At least 19 recordsLinked to original sources
PubMed2001

Efficiency comparisons of rank and permutation tests based on summary statistics computed from repeated measures data.

A popular method of using repeated measures data to compare treatment groups in a clinical trial is to summarize each individual's outcomes with a scalar summary statistic, and then to perform a two-group comparison of the resulting statistics using a rank or permutation test. Many different types of summary statistics are used in practice, including discrete and continuous functions of the underlying repeated measures data. When the repeated measures processes of the comparison groups differ by a location shift at each time point, the asymptotic relative efficiency of (continuous) summary statistics that are linear functions of the repeated measures has been determined and used to compare tests in this class. However, little is known about the non-null behaviour of discrete summary statistics, about continuous summary statistics when the groups differ in more complex ways than location shifts or where the summary statistics are not linear functions of the repeated measures. Indeed, even simple distributional structures on the repeated measures variables can lead to complex differences between the distribution of common summary statistics of the comparison groups. The presence of left censoring of the repeated measures, which can arise when these are laboratory markers with lower limits of detection, further complicates the distribution of, and hence the ability to compare, summary statistics. This paper uses recent theoretical results for the non-null behaviour of rank and permutation tests to examine the asymptotic relative efficiencies of several popular summary statistics, both discrete and continuous, under a variety of common settings. We assume a flexible linear growth curve model to describe the repeated measures responses and focus on the types of settings that commonly arise in HIV/AIDS and other diseases.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Protection of ATP-depleted cells by impermeant strychnine derivatives: implications for glycine cytoprotection.

Glycine and structurally related amino acids with activities at chloride channel receptors in the central nervous system also have robust protective effects against cell injury by ATP depletion. The glycine receptor antagonist strychnine shares this protective activity. An essential step toward identification of the molecular targets for these compounds is to determine whether they protect cells through interactions with intracellular targets or with molecules on the outer surface of plasma membranes. Here we report cytoprotection by a cell-impermeant derivative of strychnine. A strychnine-fluorescein conjugate (SF) was synthesized, and impermeability of plasma membranes to this compound was verified by fluorescence confocal microscopy. In an injury model of Madin-Darby canine kidney cells, ATP depletion led to lactate dehydrogenase release. SF prevented lactate dehydrogenase leakage without ameliorating ATP depletion. This was accompanied by preservation of cellular ultrastructure and exclusion of vital dyes. SF protection was also shown for ATP-depleted rat hepatocytes. On the other hand, when a key structural motif in the active site of strychnine was chemically blocked, the SF lost its protective effect, establishing strychnine-related specificity for SF protection. Cytoprotective effects of the cell-impermeant strychnine derivative provide compelling evidence suggesting that molecular targets on the outer surface of plasma membranes may mediate cytoprotection by strychnine and glycine.

Adenosine Triphosphate↗
PubMed2001

Energetic determinants of tyrosine phosphorylation of focal adhesion proteins during hypoxia/reoxygenation of kidney proximal tubules.

Anaerobic mitochondrial metabolism of alpha-ketoglutarate and aspartate or alpha-ketoglutarate and malate can prevent and reverse severe mitochondrial dysfunction during reoxygenation after 60 minutes of hypoxia in kidney proximal tubules.(34) The present studies demonstrate that, during hypoxia, paxillin, focal adhesion kinase, and p130(cas) migrated faster by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, their phosphotyrosine (pY) content decreased to approximately 5% of that in oxygenated tubules without changes in total protein, and the normally basal immunostaining of beta1 and alpha6 integrin subunits, pY, and paxillin was lost or markedly decreased. During reoxygenation without supplemental substrates, recovery of pY and basal localization of the focal adhesion proteins was poor. alpha-Ketoglutarate and aspartate, which maintained slightly higher levels of ATP during hypoxia, also maintained 2.5-fold higher levels of pY during this period, and promoted full recovery of pY content and basal localization of focal adhesion proteins during subsequent reoxygenation. Similarly complete recovery was made possible by provision of alpha-ketoglutarate and aspartate or alpha-ketoglutarate and malate only during reoxygenation. These data emphasize the importance of very low energy thresholds for maintaining the integrity of key structural and biochemical components required for cellular survival and reaffirm the value of approaches aimed at conserving or generating energy in cells injured by hypoxia or ischemia.

Adenosine Triphosphate↗
PubMed2001

Morphoea of the breast in a young girl.

Localized morphoea is an uncommon sclerosing skin disorder. Prognosis is usually good but it may lead to contractures, perturbed limb growth, atrophy, pigmentary changes and cosmetic disturbance. We describe a case of morphoea that developed in one breast in a 9-year-old white female. Treatment comprised topical ammonium lactate 12% cream and tretinoin 0.025% cream but no topical corticosteroids were prescribed. One year later she was noted to have bilateral symmetrical breast development and, although signs of morphoea were still present in one breast, the plaque had softened and there was no breast deformity. It is important to remember that most cases of morphoea improve spontaneously, although a number of possible therapeutic options may be indicated in some patients.

Breast↗
PubMed2001

Evaluation of pigmented lesions of the nail unit.

Acquired pigmentary changes of the nail are secondary to a number of etiologies. These include nail matrix nevi; physical induction secondary to trauma; malignant melanoma; nutritional deficiencies; inflammation secondary to lichen planus; endocrine causes such as Addison's disease; or secondary to bacterial, fungal, or viral infections. The most important task faced by clinicians is to distinguish benign from malignant etiologies of nail pigmentation. We will briefly review the various entities that can yield dyspigmentation and their differentiation from melanoma of the nail.

Humans↗
PubMed2001

Erythema elevatum diutinum in a patient with human immunodeficiency virus.

Erythema elevatum diutinum (EED) is a chronic cutaneous leukocytoclastic vasculitis. This rare disease is characterized by red, brownish-purple, and yellow papules, plaques, and nodules distributed symmetrically about the extremities. There have been recent reports of the disease in association with infection with the human immunodeficiency virus (HIV). We describe the case of a 51-year-old man with HIV who presented with EED, which was successfully treated with dapsone.

Anti-Infective Agents↗
PubMed2001

Short-duration oral terbinafine for the treatment of tinea pedis in HIV-positive patients.

Management of tinea pedis in patients who have the human immunodeficiency virus (HIV) is problematic; in those patients, dermatophytoses may be more difficult to treat than in the general population. This prospective, open-label, multicenter, randomized study evaluated the efficacy and safety of a short course of oral terbinafine for tinea pedis in patients who are HIV positive. Twenty-seven patients were randomized to receive oral terbinafine 250 mg once daily for 2 or 4 weeks; 17 patients with positive initial cultures and follow-up cultures were evaluable for efficacy at week 8. Mycological cure (defined as negative potassium hydroxide [KOH] microscopy and culture results) occurred in 47% (8) of patients; and modified mycological cure (defined as negative follow-up cultures) occurred in 65% (11) of patients. All 27 patients were evaluated for safety. Clinical cure (defined as minimal residual signs and symptoms) occurred in 82% (14) of patients. Oral terbinafine was well tolerated, indicating that regimens of 2 or 4 weeks are safe and effective for the treatment of tinea pedis in patients who are HIV positive.

Administration, Oral↗
PubMed2001

The ocular manifestations of rosacea.

The ocular manifestations of rosacea are commonly nonspecific and variable. The etiology of the inflammation is unknown and there is no diagnostic test for the disease. Ocular rosacea is often underdiagnosed, despite the potential for serious sight-threatening sequelae. When evaluating patients with rosacea, dermatologists should obtain a careful history of eye complaints and examine the eyelid margins thoroughly. Treatment is aimed at controlling symptoms and is multifaceted. The foundation of treatment is good lid hygiene and oral tetracyclines. Those patients with moderate-to-severe ocular findings will benefit from a multidisciplinary approach, including evaluation by an ophthalmologist.

Adult↗