Characterization of the mononuclear infiltrate involved in regression of halo nevi

Halo nevi are characterized by progressive degeneration of nevus cells surrounded by a mononuclear cell infiltrate. We studied the morphological features of the nevus cells and the composition of the mononuclear cell infiltrate in 15 cases of halo nevi using immunohistochemical techniques and a battery of antibodies to different subsets of lymphocytes and histiocytes. Regression could be divided into four more or less identifiable stages, associated with different subsets of lymphocytes and monocyte-macrophage lineage cells. Stage I (preregression): nests of unremarkable nevus cells were surrounded by a moderate number of T lymphocytes (relatively small percentage of helper/inducer T cells), occasional B cells and macrophages. Stage II (early regression): large number of T lymphocytes and FXIIIa-positive cells were in close contact with nevus cell clusters which showed ragged edges. Lysozymepositive cells and epidermal Langerhans cells were mildly increased. Stage III (late regression): single nevomelanocytes showing mild atypia were present. Numerous T lymphocytes and macrophages positive for lysozyme, KP1 and/or FXIIIa were interspersed between the nevus cells. Increased numbers of epidermal Langerhans cells were present. Stage IV (complete regression): no nevus cells were observed and moderate numbers of T lymphocytes only remained. These results suggest that T cells, especially T-suppressor cells, and different subsets of macrophages participate in the regression of the nevi.     

Models of staff support for mental health/mental retardation community boards

With the advent of the 1975 Amendments to federal mental health legislation which call for community governing bodies to oversee local mental health services, the question of effective board functioning becomes crucial. This paper describes professional staff roles and staff support models that can be used to enable better functioning of community boards. Questions of placement in the hierarchy and selection of the worker are also addressed.Ms. Dreer, is former consultant to the Community Advisory Board of the Thomas Jefferson University Community Mental Health and Mental Retardation Center and is currently in private practice as a management consultant.     

Quantitative GSTP1 methylation and the detection of prostate adenocarcinoma in sextant biopsies

Hypermethylation of the 5' promoter region of the glutathione S-transferase pi gene (GSTP1) occurs at a very high frequency in prostate adenocarcinoma. We compared the results of blinded histologic review of sextant biopsy samples from 72 excised prostates with those obtained using a quantitative methylation-specific polymerase chain reaction assay (QMSP) for GSTP1. Formal surgical pathologic review of the resected prostates was used to determine the number of patients with (n = 61) and without (n = 11) prostate cancer. Histology alone detected prostate carcinoma with 64% sensitivity (95% confidence interval [CI] = 51% to 76%) and 100% specificity (95% CI = 72% to 100%), whereas the combination of histology and GSTP1 QMSP at an assay threshold greater than 10 detected prostate carcinoma with 75% sensitivity (95% CI = 63% to 86%) and 100% specificity (95% CI = 72% to 100%), an 11% improvement (95% CI = 5% to 22%) in sensitivity over histology alone. The combination of histology and GSTP1 QMSP at an assay threshold greater than 5 detected prostate adenocarcinoma with 79% sensitivity (95% CI = 68% to 89%), a 15% improvement (95% CI = 7% to 26%) over histology alone. Thus, GSTP1 QMSP improved the sensitivity of histologic review of random needle biopsies for prostate cancer diagnosis. Further studies should determine whether detection of GSTP1 hypermethylation in a biopsy sample with normal histology indicates the need for an early repeat biopsy at the same site.     

Refractory overactive bladder after urethrolysis for bladder outlet obstruction: management with sacral neuromodulation

Refractory overactive bladder (OAB) after urethrolysis for iatrogenic bladder outlet obstruction (BOO) is a clinical dilemma without established guidelines for management. We sought to evaluate the efficacy of sacral neuromodulation (SNM) in the management of this complex patient population. Retrospective review identified eight patients who underwent SNM secondary to refractory OAB after urethrolysis or sling take-down. SNM was performed with the Interstim® device (Medtronic, Minneapolis) using a two-stage implant technique. SNM outcomes were determined subjectively during follow-up. Validated questionnaires were completed to assess symptom bother, patient satisfaction, and quality of life. Statistical analyses were conducted using Stata® version 9.0. Six patients had a favorable response to SNM during test stimulation and underwent implantation of the implantable pulse generator (IPG). With follow-up of 15.7?±?11.1 months (6–34), all patients significantly improved, with three patients being dry and three patients having one to two urgency incontinence episodes per week. Patient-reported outcomes indicated that patients perceived themselves as very much improved (3) or much improved (3) after SNM, while those failing test stimulation perceived no change. Quality of life and symptom bother were significantly better in SNM responders vs nonresponders. SNM appears to be an effective and viable treatment option in this complex patient population. Further work is needed to determine clinical factors predictive of outcome and durability of response.     

The effect of isosorbide dinitrate on left ventricular size,wall stress and left ventricular function in chronic refractory heart failure: An echocardiographic study

To determine the effect of a long-acting vasodilator isosorbide dinitrate (ID) on ventricular performance, 16 patients with refractory congestive heart failure underwent echocardiographic studies during control and for a period of 2 hours after the administration of 10 mg of sublingual ID. The effects of ID were seen in 5 to 10 minutes, reached maximum at 30 ± 3 minutes lasted for 60 minutes and dissipated thereafter. At the maximal drug effect, a significant decline in mean blood pressure (74 ± 2 versus 81 ± 3 mm Hg, p < 0.001), left ventricular afterload (228 × 10³ ± 9 × 10³ dynes/cm² versus 273 × 10³ ± 12 × 10³ dynes/cm² p < 0.001), end-diastolic dimension (5.90 ± 0.13 versus 6.40 ± 0.15 cm, p < 0.005) and end-systolic dimension (4.8 ± 0.15 versus 5.50 ± 0.17 cm, p < 0.001) occurred. These changes were associated with a significant increase in per cent fractional shortening (19 ± 2 per cent versus 14.5 ± 1.3 per cent, p < 0.001), mean rate of circumferential fiber shortening (VCF) (0.78 ± 0.06 versus 0.61 ± 0.05 circumferences per second (circ/sec) p < 0.001) and normalized mean posterior wall velocity (VPW) (0.65 ± 0.05 versus 0.47 ± 0.03 sec^?1, p < 0.001) when heart rate was not significantly altered. All 16 patients were maintained on long-term ID therapy. Six of 16 patients (38 per cent) died within 17 to 270 days after the acute study. Nine of 16 patients have been followed for a period of three to 24 months and are clinically improved. These findings suggest that (1) ID reduces left ventricular size, preload and afterload, and improves ventricular performance; and (2) the use of ID might be of value as adjunctive therapy in acute/chronic management of refractory heart failure.