Tricholemmal carcinoma:

Tricholemmal carcinoma (TLC) is a cutaneous adnexal tumor with presumed external hair sheath differentiation. In order to better understand the salient features of this neoplasm, we analyzed the histologic and clinical findings in 10 cases of TLC. Eight patients were males, and two were female; they ranged in age from 55-88 years. Each tumor occurred in hair bearing, sun-exposed skin, and involved the scalp, face, trunk, or upper extremities. The lesions were usually slightly raised, pale tan or reddish, and keratotic; were usually present for less than 1 year; and measured 0.4-2.0 cm. All of them were treated by wide local excision; neither recurrence nor metastasis was reported after 11 to 92 months of clinical followup. Histologically, each TLC was composed of a lobular proliferation centered on the pilar apparatus. Cells with glycogen-rich, mucin-negative, clear or pale eosinophilic cytoplasm predominated. Brisk mitotic activity (4-39 mitoses per 10 high power fields) was typical. Involvement of the interfollicular epidermis was invariably noted, with superficial ulceration in seven tumors. Transitional zones between TLC and the adjacent epidermis were not seen, although pagetoid spread occurred in two examples. Invasion of reticular dermis was present in eight cases, with infiltration to mid-dermis in five TLC. All tumors exhibited areas of tricholemmal type keratinization; dyskeratotic cells were noted in six examples. Hyperkeratosis and parakeratosis were variably present as well. Actinic damage was a constant feature. Despite local invasion at diagnosis, the clinical course of TLC was indolent in all cases.     

Effect of FK-506 on xenografted human Graves' thyroid tissue in severe combined immunodeficient mice

OBJECTIVE We studied the macrolide antibiotic FK-506, an immunosuppressive agent, in an attempt to ameliorate the lesion of autoimmune thyroid disease in human thyroid tissue xenografted into severe combined immunodeficient (SCID) mice. It was not felt appropriate to employ this agent directly in patients with autoimmune thyroid disease because adequate therapeutic modalities are available and the introduction of new, experimental agents could not be justified. Moreover, the study of the tissue before and after treatment could not have been undertaken directly in patients. DESIGN Human thyroid xenografts from four patients with Graves' disease and two normal persons were xenografted into SCID mice. Two weeks after xenograft-ing, human immunoglobulin G (IgG) was detectable in all SCID mice xenografted with Graves' thyroid tissue. Mice were divided into two groups with human IgG levels similar to each other. Mice in the first group were treated with FK-506 daily for 6 weeks; mice in the second (similar) group were given phosphate-buffered saline (PBS) only (control group). MEASUREMENTS Blood samples were taken every 2 weeks from the tail veins for human IgG, thyroid stimulating antibody, thyroperoxidase antibodies, thyroglobulin antibodies, and interferon-gamma (IFN-7). After 8 weeks treatment, animals were sacrificed; thyroid tissue was examined histologically and for thyrocyte HLA-DR expression. FK-506 was also added to thyrocytes in in-vitro tissue culture conditions. RESULTS After 4–6 weeks of FK-506 therapy, human IgG, all thyroid antibodies and IFN-7 were suppressed, while the levels remained elevated in the control group. Lymphocytic infiltration virtually disappeared in the human thyroid tissue of the FK-506-treated mice and thyrocyte HLA-DR expression markedly declined; in the control mice, lymphocytic infiltration remained heavy and HLA-DR expression remained high. On the other hand, FK-506 added directly to thyrocytes in vitro (without lymphocytes) did not reduce thyrocyte HLA-DR expression. CONCLUSIONS FK-506 appears to suppress the activation of intrathyroidal lymphocytes, but not thyrocytes. From these observations, it is concluded that this agent, by its action on intrathyroidal lymphocytes, is able to ameliorate the immunologically mediated histological and serological disturbance in human autoimmune thyroid disease, at least under these circumstances.     

Detection of liver fibrosis with magnetic cross-relaxation

The utility of MRI using magnetization transfer (MT) enhanced pulse sequences to diagnose hepatic cirrhosis in a rat model was investigated. Hepatic T₁ was measured with and without MT off-resonance RF pulses in 17 treated and six control rats. The livers were evaluated histologically, and the hydroxyproline content quantitatively measured. We did not find a statistically significant linear correlation between the MR relaxation times and the degree of tissue injury. However, the MR measurements performed with MT were superior to those without differentiating the treated and control groups. Specifically, the T₁ times were 695 ±76 ms for the treated group, versus 748 ± 61 ms in the controls; P= 0.095. The T_1sat times were also lower in the treated group, with statistical significance: 367 ± 51 ms versus 421 ± 38 ms, P = 0.016. Finally, the change in the relaxation rates (the inverse of the relaxation times) with and without saturation were 1.31 ± 0.22 s^?1 (treated group) versus 1.05 ± 0.12 s^?1 (controls), which differed significantly, P= 0.001.     

Short communication: treatment of relapsing-remitting multiple sclerosis 96 patients with IFN-beta1b: results of a 6-year follow-up.

The first pharmacon with proved efficacy for the treatment of patients with the relapsing-remitting or relapsing-progressive form of multiple sclerosis (MS) was interferon-beta1b (IFN-beta1b). In 1996, we started treating 34 relapsing-remitting (RRMS) and 2 relapsing-progressive MS (RPMS) patients with IFN-beta1b. Of these 36 patients, 28 received continuous medication for 6 years. The primary end point of the study was the effect of 6 years of continuous IFN-beta1b treatment on the annual relapse rate, the secondary end point was the change in the progression index during the 6 years, and the tertiary end point was the alteration in the expanded disability status scale (EDSS) score of the patients. Finally, we give the reasons for the dropouts. The relapse rate decreased by 80.62% (p < 0.001), the mean EDSS score increased significantly, by approximately 0.5 points, to 2.21 +/- 1.48 (p = 0.016), and the reduction in the mean progression index was 67.19% (p < 0.001). This increase of < 0.5 point in the EDSS score is appreciably different from the 3-point deterioration expected after 6 years for the natural course of the disease. The significant improvement in the progression index clearly demonstrates that 6 years of IFN-beta1b therapy slowed the progression of the disease, thereby improving the quality of life of these MS patients.     

Colonization with methicillin-resistant Staphylococcus aureus after liver transplantation.

Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent cause of infection after orthotopic liver transplantation (OLT). Colonization with MRSA is associated with a higher risk of infection. Previous studies have shown a high prevalence of MRSA colonization among OLT candidates. However, the risk of colonization with MRSA after OLT is still unclear. The objective of this study was to estimate the incidence and the factors associated with colonization with MRSA after OLT. This was a prospective cohort study including patients submitted to OLT between the years 2000 and 2002. Surveillance cultures of nasal swab specimens were performed within the 1st 72 hours of hospital admission and, subsequently, on weeks 2, 6, 13, and 26. Patients whose baseline cultures revealed nasal carriage of MRSA were excluded. A total of 60 patients were included in the study. The median follow-up was 72 days. A total of 9 patients (15%) became colonized. In multiple logistic regression analyses, the use of a urinary catheter for > or =5 days (P = .006), postoperative bleeding at the surgical site (P = .009), and preoperative use of fluoroquinolones (P = .08) were associated with a higher risk of colonization. Patients without any of these risk factors did not become colonized. In conclusion, nasal carriage of MRSA is frequently acquired after OLT. Periodic postoperative screening for MRSA carriage should be an integral component in programs designed to reduce nosocomial MRSA transmission in these patients. Further studies are needed to set up and validate a predictive model that could allow targeting postoperative screening to high-risk OLT recipients.     

Renal cell carcinoma. A clinicopathologic and DNA flow cytometric analysis of 103 cases

Renal cell carcinoma is unpredictable in outcome, although the best predictor is tumor stage, followed by histologic grade. The authors retrospectively assessed the clinicopathologic features and DNA ploidy of 103 cases of renal cell carcinoma, the latter determined by flow cytometry of formalin-fixed, paraffin-embedded tissue. The study group comprised 63 men and 40 women (age, 28-80 years; mean, 57 years). Robson stage at diagnosis was Stage I in 52 patients, Stage II in 21, and Stage III in 30. Statistically significant variables in predicting outcome were Robson stage (P less than 0.0001), DNA ploidy (P = 0.0008), mitotic rate (MR, P less than 0.0001), worst nuclear grade (WNG, P = 0.00009), predominant nuclear grade (P = 0.019), and sex (P = 0.044). Tumor size, cell type, and architectural pattern were also assessed but did not prove to be significant. Statistically significant associations occurred between DNA ploidy and WNG (P less than 0.0001), stage (P = 0.0037), and MR (P = 0.015); between WNG and MR (P less than 0.0001) and stage (P = 0.0007); and between stage and MR (P = 0.002). Cox proportional hazards regression analysis of all significant variables showed Robson stage, tumor ploidy, and MR to be independent, significant predictors of outcome. If ploidy data had not been available, WNG would have been independently significant. The authors conclude that DNA ploidy analysis provides significant predictive information on renal cell carcinoma.     

Scale-up of Adhesive Transdermal Drug Delivery Systems

Pharmaceutical Research -     

Metastatic tumor formation: processes within the visual system

Metastatic cancer is the most common form of neoplasm affecting the eyes and orbit. Six cases of metastatic cancers with origination or dissemination within the visual system are presented. Typical and atypical characteristics of metastatic cancer of the visual system are discussed.     

The asymptomatic patient with suspected myocardial contusion

Diagnostic criteria and guidelines for hospital admission for suspected myocardial contusion (MCC) remain unclear. This study defines and examines the clinical sequelae of patients admitted with a suspicion of MCC. Criteria for observation following isolated, minor blunt chest trauma are suggested. Hospital and trauma registry records of patients admitted over a 33-month period with suspected MCC were reviewed. Conventional evaluation criteria, cardiac-related complications, and associated injuries were analyzed for 524 patients. Twenty-eight cardiac-related complications occurred in 27 of 524 patients (5%). These complications included 23 dysrhythmias, 3 infarctions, and 2 pericardial effusions. There were 23 patients with abnormal admission electrocardiograms and 4 with normal ones. Of the latter, one patient developed dysrhythmia 4 hours after admission, and three had other major multi-system injuries requiring admission to the intensive care unit. The overall incidence of cardiac-related complications in minimally injured patients was 0.1%. There were no complications in patients with isolated chest wall contusions, a normal admission electrocardiogram, and a normal rhythm at 4 hours. There was no significant association between creatine phosphokinase isoenzymes or echocardiogram and cardiac-related complications. The complete absence of significant cardiac sequelae in patients with isolated chest wall contusion, normal admission and 4-hour electrocardiograms, and no other associated major injuries suggests that these patients need not be admitted.