Michele L. Zimbric

Cerebral amyloid angiopathy and plaques, and visceral amyloidosis in aged macaques.

In the present study, we report our extended data on the incidence of two types of cerebral amyloidosis (plaques and plaques associated with angiopathy) and visceral amyloidosis in late adult and aged captive rhesus monkeys (Macaca mulatta). In a total of 81 brains from animals ranging from 16 to 39 years old, beta-amyloid plaques were found in 38, 10 of which were associated with amyloid angiopathy. Brains from eight adults, 16 to 19 years, had no lesions. In aged groups, the rates were 20.8% in the 20- to 25-year group (24), 60.9% in the 26- to 31-year group (41), and 100% in the 33- to 39-year group (8). Twelve monkeys in these aged groups had an involvement of amyloidosis in either the liver, the adrenal, or the pancreatic islets, and 7 of 12 had amyloid plaques (5) and plaques associated with cerebral angiopathy (2). No neurofibrillary tangles were detected in these brain lesions. Amyloid in both plaques and cerebral angiopathy showed immunocytochemical crossreactivity with human amyloid beta (beta/A4) and precursor proteins (APP-A4), but visceral amyloid was negative. Ultrastructurally, amyloid initially appears as loose filaments in the perivascular or Disse space, and they further aggregate to produce dense interlacing bundles. Cerebral amyloid angiopathy associated with plaque appears to be a subclass of senile plaque lesions in aged monkeys as well as in aged humans, and it appears to have no pathogenetic correlation with visceral amyloidosis.

Effect of latanoprost on hair growth in the bald scalp of the stump-tailed macacque: a pilot study.

Latanoprost, a selective FP prostanoid receptor agonist used in the treatment of glaucoma, has a hypertrichotic side effect. Using the macaque model of androgenetic alopecia, we examined the effect of latanoprost on hair growth. Eight monkeys were divided into 2 groups; one group received a daily topical application of 50 microg/ml of latanoprost for 5 months; a control group had a daily application of vehicle. For an additional 3 months, 2 monkeys from each group were given 500 microg/ml latanoprost, while the remaining monkeys continued with the previous treatment. Hair growth was evaluated by monthly photographs and phototricho-graphic analysis. Fifty microg/ml of latanoprost caused minimal hair growth. Latanoprost at 500 microg/ml induced moderate to marked hair regrowth with 5-10% conversion of vellus hairs to intermediary or terminal hairs. The vehicle group showed no effect. Further evaluation of latanoprost as an agent for treatment of human androgenetic alopecia is indicated.

Toxicity and dose-response studies of 1-α hydroxyvitamin D2 in LH-β-tag transgenic mice

Abstract Purpose To determine the effectiveness of a vitamin D analog, 1α-hydroxyvitamin D 2 (1α-OH-D 2 ), in inhibiting retinoblastoma in a transgenic retinoblastoma model (LHβ-Tag mouse) and to evaluate its toxicity. Design Experimental study using an animal (LHβ-Tag transgenic mouse) randomized (controlled) trial. Participants and controls Two hundred seventeen LHβ-Tag transgene-positive 8- to 10-week-old mice total; 179 drug-treated animals, 38 control animals. Methods Mice were fed a vitamin D- and calcium-restricted diet and were randomized to treatment groups receiving control (vehicle), or 0.1, 0.3, 0.5, or 1.0 μg/day of 1α-OH-D 2 via oral gavage 5 times weekly for 5 weeks. Body weight was measured at the start of treatment and twice weekly during treatment. Animals were euthanized on the last day of treatment. The eyes were enucleated, processed histologically, and serially sectioned. Representative sections from the superior, middle, and inferior regions of each globe were examined microscopically and tumor areas were measured using Optimas software. Serum was collected for serum calcium levels. Kidneys were removed for histologic processing and were analyzed microscopically for kidney calcification. Main outcome measures Mean tumor area was measured to determine drug effectiveness. Toxicity was assessed by survival, weight loss over the treatment period, serum calcium, and kidney calcification. Results The mean tumor size in each 1α-OH-D 2 group was smaller than controls (all P values 2 ; 0.1 μg, 31,545 μm 2 ; 0.3 μg, 16,750 μm 2 ; 0.5 μg, 30,245 μm 2 ; and 1.0 μg, 16,049 μm 2 . No dose-dependent response curve was evident. The survival percentage for each group was as follows: control, 97%; 0.1 μg, 91%; 0.3 μg, 88%; 0.5 μg, 70%; and 1.0 μg, 63%. Mortality was higher in the 0.5-μg and 1.0-μg doses ( P values P values Conclusions In the LHβ-Tag mouse, 1α-OH-D 2 inhibits retinoblastoma with no significant increase in mortality in lower doses (0.1–0.3 μg). 1α-OH-D 2 has approval by the Food and Drug Administration as an investigative drug for cancer treatment, and has shown efficacy with low toxicity in adult cancer trials. 1α-OH-D 2 meets the criteria for human clinical trials.

Absence of type I estrogen receptors in choroidal melanoma: analysis of Collaborative Ocular Melanoma Study (COMS) eyes

PURPOSE To evaluate choroidal melanomas in enucleated eyes for the presence of type I estrogen receptors. METHODS Fourteen consecutive eyes with large choroidal melanomas (defined as >16-mm basal diameter and >8 mm thickness) from 14 patients (eight women and six men with a mean age of 57 years; range, 25--74 years) enucleated in accordance with the Collaborative Ocular Melanoma Study (COMS) protocol were investigated. Immunohistochemical techniques were employed to label the choroidal melanomas for the presence of type I estrogen receptors. Each specimen was then evaluated in a masked fashion by an experienced ophthalmic pathologist for positive nuclear staining. RESULTS No tumors showed immunohistochemical evidence of a type I estrogen receptor. CONCLUSION Type I estrogen receptors are not present in choroidal melanoma. Estrogens are not likely to influence choroidal melanoma growth through traditional receptors.

Implementation in the midst of complexity: Using ethnography to study health care–associated infection prevention and control

HighlightsMoving evidence to practice in complex environments may require methods that highlight context.Ethnography is well‐suited to study health care–associated infections (HAIs).Many HAI studies using ethnography have used video‐reflexive methods.Ethnography can intersect with complexity science and influence real‐time practice change. Background: Contextual factors associated with health care settings make reducing health care–associated infections (HAIs) a complex task. The aim of this article is to highlight how ethnography can assist in understanding contextual factors that support or hinder the implementation of evidence‐based practices for reducing HAIs. Methods: We conducted a review of ethnographic studies specifically related to HAI prevention and control in the last 5 years (2012‐2017). Results: Twelve studies specific to HAIs and ethnographic methods were found. Researchers used various methods with video‐reflexive sessions used in 6 of the 12 studies. Ethnography was used to understand variation in data reporting, identify barriers to adherence, explore patient perceptions of isolation practices and highlight the influence of physical design on infection prevention practices. The term ethnography was used to describe varied research methods. Most studies were conducted outside the United States, and authors indicate insights gained using ethnographic methods (whether observations, interviews, or reflexive video recording) as beneficial to unraveling the complexities of HAI prevention. Conclusions: Ethnography is well‐suited for HAI prevention, especially video‐reflexive ethnography, for activating patients and clinicians in infection control work. In this era of increasing pressure to reduce HAIs within complex work systems, ethnographic methods can promote understanding of contextual factors and may expedite translation evidence to practice.