Michele M. Thompson

Interactions of the Kallikrein-Kinin and Renin-Angiotensin Systems in Experimental Diabetes

The kallikrein-kinin system (KKS) has been postulated to play a role in modulation of hemodynamic function in diabetes and to contribute to the hemodynamic effects of angiotensin-converting enzyme inhibition (CEI). To further explore the KKS and its interactions with the renin-angiotensin system (RAS), studies were conducted in nondiabetic control rats and in moderately hyperglycemic diabetic rats. In protocol 1, control and diabetic rats were studied before and after administration of one of two dissimilar B2 kinin receptor antagonists (BK2As), or vehicle. At a low dose (0.5 μg · kg−1 · min−1), the first generation antagonist D-Arg, [Hyp3,Thi5,8,D-Phe7]-bradykinin significantly reduced the glomerular filtration rate (GFR) and renal plasma flow rate in diabetic rats, despite variable effectiveness in blocking the hypotensive response to injected bradykinin. However, a similar hemodynamic effect occurred in nondiabetic rats, suggesting that the observed effect was not specific to diabetes. Higher doses (20 μg bolus, then 1 μg · kg−1 · min−1 infusion) did not affect hemodynamics in either group, perhaps because of partial agonist effect. The second BK2A tested was the newer compound, icatibant (Hoe 140; D-Arg,[Hyp3,Thi5,D-Tic7,Oic8]-bradykinin). Hoe 140 consistently blocked the vasodepressor action of injected bradykinin, but had no effect on systemic or renal hemodynamics in either control or diabetic rats. In protocol 2, control and diabetic rats were pretreated with the CEI ramipril for 1–2 weeks, after which renal function was studied before and after Hoe 140 (0.1 mg s.c. and i.v.) or vehicle. CEI lowered blood pressure in both groups. Hoe 140 did not affect renal function in control rats, but in diabetic rats pretreated with ramipril, it induced a modest but significant decline in GFR. Ramipril induced the predicted changes in the systemic and intrarenal RAS, while acute BK2A had no consistent effect on RAS parameters. These studies suggest that the endogenous KKS has only a minor role in modulation of renal hemodynamics in the euvolemic diabetic rat, in the absence of KKS stimulation by CEI. However, angiotensin-converting enzyme is also kininase II, which serves to increase endogenous kinin activity. The increased kinin activity resulting from CEI treatment may participate, to a modest degree, in hemodynamic regulation of the diabetic kidney.

Prevalence and morphology of hand eczema in patients with atopic dermatitis.

Background: Patients with hand eczema frequently have a history of atopic dermatitis or atopy. No specific morphologic pattern of hand eczema helps distinguish atopic hand eczema from other etiologies. There are few studies of hand eczema prevalence and morphology in a well‐defined population of patients with atopic dermatitis. Methods: We evaluated 777 consecutive patients with atopic dermatitis (diagnosed by standard criteria) for hand involvement. An additional 100 patients had further evaluations, including evaluation of the historical and morphologic characteristics of their hand eczema. Results: The prevalence of hand involvement in patients with active atopic dermatitis was 58.9% (458 of 777 patients). Nail dystrophy was present in 16% (124 of 777) of patients. There was a significant trend toward an increasing prevalence of hand involvement with increasing age. Hand eczema tended to involve primarily the dorsal hand surfaces and the volar wrist. Conclusions: The hands are frequently involved in patients with active atopic dermatitis and present unique physical, social, and therapeutic challenges for patients. During the evaluation of patients presenting with hand eczema, the involvement of dorsal hand surfaces and the volar wrist may suggest atopic dermatitis as a contributing etiologic factor.

Diagnostic pitfalls in syringocystadenocarcinoma papilliferum: case report and review of the literature.

We report the first case, to our knowledge, of syringocystadenocarcinoma papilliferum with p63-verified squamous differentiation and extensive dermal invasion accompanying in situ components. An 86-year-old woman presented with a neoplasm on the neck, and the intralesional heterogeneity typical of these neoplasms led to an initial diagnosis on needle biopsy favoring squamous cell carcinoma. Excision illustrated diverse morphology, raising a broad differential diagnosis, including more common extracutaneous malignancies, such as breast, gastrointestinal, and ovarian primary tumors. Fortuitous sectioning revealed a focal connection to the skin surface with evidence of apocrine differentiation allowing final diagnosis as syringocystadenocarcinoma papilliferum. Our literature review shows the histologic and immunohistochemical features of syringocystadenocarcinoma papilliferum are not well defined outside of their clear morphologic overlap with syringocystadenoma papilliferum. We describe our findings and diagnostic pitfalls to help pathologists encountering this unusual apocrine neoplasm.

Melanocytes: A possible autoimmune target in alopecia areata

fold decrease; Fig 1, B). Thus, IPL treatment appears to be able to modify UVB-induced activation of AP-1 transcription. We next investigated whether IPL treatment may also alter the expression of MMP-1 in vitro. As shown in Fig 1, C, MMP-1 expression by fibroblasts was increased after UVB treatment (1.56-fold, compared with control), a finding that is in accordance with previous reports, while IPL treatment decreased the MMP-1 expression level by 11.47-fold (vs control), which is conistent with the report by Luo et al. In summary, we have provided limited evidence for the possible molecular mechanisms that govern the photorejuvenation effect of IPL treatment by demonstrating that IPL may downregulate the AP-1 expression enhanced by UVB. More investigation will be necessary to solidify the relevance of IPL’s influence on AP-1 expression to downstream signaling events and its photorejuvenation effects.

Patterns of care and referral in children with atopic dermatitis and concern for food allergy

ABSTRACT:  Although many providers believe that up to 30% of atopic dermatitis (AD) is food induced, food challenge studies show that food‐induced eczematous reactions are rare. When food allergy is suggested to cause AD, it often leads to allergy testing with a high false‐positivity rate, in turn further focusing parents on food allergy. Study subjects were children less than 11 years old with AD and food allergy suspicion. Prior diagnoses, provider, and testing patterns were assessed by questionnaire given to the parents. Thirty‐eight patients with AD were enrolled. Most subjects parents suspected food allergy induced AD. Initial skin diagnoses were made by pediatricians (79%) and family practitioners (18%) as eczema. Allergy was suggested by providers as cause for AD in 63% of the present studys patients. Seventy‐nine percent had allergy testing. Greater than 90% of parents claimed their children had food allergy and food‐induced AD. Sixty‐six percent had positive food allergy tests and 37% had definite history of immediate IgE reactions to food. The majority of this population had allergy suggested as causative for eczema by their primary care provider and were subsequently evaluated by allergist and allergy testing. Consensus about the role of food allergy between the different providers of AD in children would result in more effective, efficient, and less costly health care.

Impaired adaptation to renal mass reduction in the polycystic rat

Autosomal dominant polycystic kidney disease (ADPKD) is a serious cause of renal failure. In many renal-disease models, surgical renal mass reduction accelerates disease progression. We explored whether surgical renal mass reduction and the method of renal mass reduction accelerate the course of ADPKD. Studies were conducted in male heterozygous cystic Han:SPRD rats and unaffected littermate controls. Control and cystic rats were subjected to 50% renal mass reduction by uninephrectomy, 50% renal mass reduction by infarction of half of each kidney, or sham operation. Most groups were followed up to the age of 20 weeks, with serial measurements of blood pressure and proteinuria. At 20 weeks, glomerular filtration rate (GFR) and renal plasma flow (RPF) rate were measured. Similar studies to 12 weeks of age were performed in additional groups of control and cystic rats with either sham operation or 50% renal infarction. In noncystic rats, uninephrectomy led to minimal effects on blood pressure and proteinuria and to substantial compensatory renal hypertrophy, hyperfiltration, and hyperperfusion. Similar renal mass reduction by segmental infarction led to greater values for blood pressure and proteinuria and significant compensatory hyperfiltration. In contrast, the cystic rats showed a significant reduction in baseline renal blood flow, more profound increases in blood pressure and proteinuria, and no compensatory increases in GFR and RPF after reduction of renal mass. These studies suggest that the ability of cystic kidneys to respond to acquired loss of nephrons is impaired and that these kidneys are at greater risk when additional renal injury is superimposed.

A Novel Form of Amyloid Deposited at the Site of Enfuvirtide Injection

Cutaneous amyloidosis represents the extracellular deposition of amphophilic hyaline material, which has characteristic staining properties and a fibrillar ultrastructure. The origins of amyloid are diverse; at least 26 amyloid precursor proteins have been described and six have relevance to the skin. While typically of autologous origin, cutaneous amyloidosis has been rarely associated with deposition of medication within the dermis and subcutis.1 Herein, we present a case of cutaneous amyloidosis at the injection site of the antiretroviral medication, enfuvirtide. A 55 year old female who was seropositive for the human immunodeficiency virus (HIV) presented with large, indurated plaques at the sites of subcutaneous enfuvirtide injections on her arms and abdomen (Figure 1). She reported that the sites became ‘‘hot and red’’ after enfuvirtide injections