Effects of miRNA-143 and the non-coding RNA MALAT1 on the pathogenesis and metastasis of HeLa cells.

Cervical cancer is a common female malignancy of global dimensions. MicroRNAs (miRNAs) play crucial roles in the development, differentiation, proliferation, and apoptosis of tumors. The non-coding RNA MALAT1 participates in various physiological processes that are important for proper functioning of the body. Here, we analyzed the expression of miRNA-143 and MALAT1 in HeLa cells to evaluate their roles in the occurrence and metastasis of cervical cancer. HeLa cells were divided into five groups depending on the treatment conditions, namely, transfected with miRNA-143, MALAT1, miRNA-143 inhibitor and the MALAT1 inhibitor, and the untreated control. Reverse transcription-polymerase chain reaction was used to analyze the expression of miRNA-143 and MALAT1, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to assess proliferation, the trans-well assay to study cell invasion and migration, and western blot to analyze the levels of E-cadherin and vimentin. The proliferation of HeLa cells increased upon treatment with the miRNA-143 inhibitor and decreased when treated with the MALAT1 inhibitor, compared to the proliferation of the groups that were transfected with miRNA-143 and MALAT1, respectively (P < 0.05). Thus, miRNA-143 decreased cell invasion and migration potency, downregulated vimentin and upregulated E-cadherin expression, while MALAT1 had the opposite effects. In conclusion, the low expression of miRNA-143 and high expression of MALAT1 in cervical cancer cells could possibly potentiate cell invasion/migration and alter the levels of vimentin and E-cadherin.

A phase I study of two dosing schedules of volasertib (BI 6727), an intravenous polo-like kinase inhibitor, in patients with advanced solid malignancies.

BACKGROUND: Polo-like kinase 1 (Plk1) has an important role in mitosis. Volasertib (BI 6727), a potent and selective cell cycle kinase inhibitor, induces mitotic arrest and apoptosis by targeting Plk; this phase I study sought to determine its maximum tolerated dose (MTD) in Asian patients with advanced solid tumours. METHODS: Patients were enrolled simultaneously into two 3-week schedules of volasertib: a 2-h infusion on day 1 (schedule A) or days 1 and 8 (schedule B). Dose escalation followed a 3+3 design. The MTD was determined based on dose-limiting toxicities (DLT) in the first treatment course. RESULTS: Among 59 treated patients, the most common first course DLTs were reversible thrombocytopenia, neutropenia and febrile neutropenia; MTDs were 300 mg for schedule A and 150 mg for schedule B. Volasertib exhibited multi-exponential pharmacokinetics (PK), a long terminal half-life of ∼135 h, a large volume of distribution (>3000 l), and a moderate clearance. Partial responses were observed in two pre-treated patients (ureteral cancer; melanoma). Volasertib was generally well tolerated, with an adverse event profile consistent with its antimitotic mode of action and a favourable PK profile. CONCLUSIONS: These data support further development of volasertib and a harmonised dosing for Asian and Caucasian patients.

Noninvasive assessment of liver fibrosis via spleen stiffness measurement using acoustic radiation force impulse sonoelastography in patients with chronic hepatitis B or C.

Portal hypertension and splenomegaly are common in patients with cirrhosis. However, there is limited previous in vivo research on the correlation between spleen stiffness and stages of liver fibrosis. This study aimed to evaluate the diagnostic value of spleen stiffness measurement (SSM), using acoustic radiation force impulse (ARFI) technology, for liver fibrosis assessment. Eligible patients with chronic hepatitis B or C (n = 163) underwent concurrent liver stiffness measurement (LSM), SSM and percutaneous liver biopsy. Receiver operating characteristic curves estimated the diagnostic performance of SSM, with multiple linear regression models for LSM and SSM determining the significance of explanatory factors. Results indicated significant correlation between LSM and SSM (R(2) = 0.574, P < 0.0001). Using SSM to classify METAVIR fibrosis (METAVIR F) scores, the areas under curves were 0.839 (95% CI: 0.780-0.898) for METAVIR F1 vs F2-4, 0.936 (95% CI: 0.898-0.975) for F1-2 vs F3-4 and 0.932 (95% CI: 0.893-0.971) for F1-3 vs F4, all P < 0.001. Multiple linear regression models identified BMI, spleen stiffness, METAVIR F3 and F4, serum alanine aminotransferase, international normalized ratio of prothrombin time, sodium and platelet count as significant independent explanatory factors for liver stiffness (adjusted R(2) = 0.724, P < 0.001). Male gender, liver stiffness, METAVIR F2, F3 and F4 also significantly and independently explained spleen stiffness (adjusted R(2) = 0.647, P < 0.001). ARFI SSM is potentially useful as a single or adjunct predictor of stages of liver fibrosis.

Malignant pleural effusion cells show aberrant glucose metabolism gene expression.

Malignant pleural effusion (MPE) accompanying lung adenocarcinoma indicates poor prognosis and early metastasis. This study aimed to identify genes related to MPE formation. Three tissue sample cohorts, seven from healthy lungs, 18 from stage I-III lung adenocarcinoma with adjacent healthy lung tissue and 13 from lung adenocarcinomas with MPE, were analysed by oligonucleotide microarray. The identified genes were verified by quantitative real-time PCR (qRT-PCR), immunohistochemical staining, and immunofluorescence confocal microscopy. 20 up- or down-regulated genes with a two-fold change in MPE cancer cells compared to healthy tissues were differentially expressed from early- to late-stage lung cancer. Of 13 genes related to cellular metabolism, aldolase A (ALDOA), sorbitol dehydrogenase (SORD), transketolase (TKT), and tuberous sclerosis 1 (TSC1) were related to glucose metabolism. qRT-PCR validated their mRNA expressions in pleural metastatic samples. Immunohistochemical staining confirmed aberrant TKT, ALDOA, and TSC1 expressions in tumour cells. Immunofluorescence confirmed TKT co-localisation and co-distribution of ALDOA with thyroid transcription factor 1-positive cancer cells. TKT regulated the proliferation, vascular endothelial growth factor secretion in vitro and in vivo vascular permeability of cancer cell. Glucose metabolic reprogramming by ALDOA, SORD, TKT and TSC1 is important in MPE pathogenesis.

A phase II study of weekly docetaxel and cisplatin plus oral tegafur/uracil and leucovorin as first-line chemotherapy in patients with locally advanced or metastatic gastric cancer.

BACKGROUND: Docetaxel plus cisplatin and 5-fluorouracil has become a new standard for treating advanced gastric cancer. However, high rates of severe neutropenia limit its application. Modification of the regimen could be the solution to get similar activity but less myelosuppression. METHODS: Patients with histologically confirmed, locally advanced, or recurrent/metastatic gastric adenocarcinoma without previous chemotherapy were enrolled. This regimen consisted of docetaxel (Tyxan, TTY, Taipei, Taiwan) 30-min infusion at a dose of 36 mg m(-2), followed by cisplatin 30 mg m(-2) infusion over 1 h on days 1 and 8, and oral tegafur/uracil 300 mg m(-2) per day plus leucovorin 90 mg per day on days 1-14, every 3 weeks. Tumour response was evaluated after every 2 cycles of treatment. RESULTS: From August 2007 to March 2009, 45 patients were enrolled. The median age was 56 years (range: 22-75). Among the 40 patients evaluable for tumour response, one achieved a complete response, 22 had partial responses and 11 had stable disease. The overall response rates of the evaluable and intent-to-treat (ITT) populations were 58% (95% CI: 41-74%) and 53% (95% CI: 38-68%), respectively. The disease control rates in these populations were 85% (95% CI: 70-94%) and 82% (95% CI: 68-92%), respectively. In the ITT analysis, the median time to progression and overall survival were 6.8 and 13.9 months, respectively. Major grade 3-4 toxicities were neutropenia (51%), anaemia (22%), diarrhoea (16%), and infections (20%). No patient died of treatment-related toxicities. CONCLUSION: Concurrent weekly docetaxel and cisplatin plus oral tegafur/uracil and leucovorin are effective and well tolerated in the treatment of advanced gastric cancer.

Effects of diets with different energy and bile acids levels on growth performance and lipid metabolism in broilers.

This experiment was conducted to evaluate the effects of bile acids (BAs) on the growth performance and lipid metabolism of broilers fed with different energy level diets. 480 one-day-old Arbor Acres broilers (45.01 ± 0.26 g) were allotted to a 2 × 2 factorial design with 2 levels of energy (basal or high-energy level) and 2 levels of BAs (with or without BAs supplementation), resulting in 4 groups of 8 replicates; the experiment lasted 42 d. High-energy diets decreased the feed/gain ratio (F/G) from 1 to 21 d (P < 0.05), and increased the liver index and abdominal fat percentage at 42 d (P < 0.05). The serum total triglyceride (TG) and high-density lipoprotein cholesterol at 42 d were increased by high-energy diets (P < 0.05), while the hepatic lipoprotein lipase (LPL) activity at 21 and 42 d was decreased (P < 0.05). BAs supplementation increased the body weight at 21 d and decreased the F/G during entire period (P < 0.05), as well as improved the carcass quality reflected by decreased abdominal fat percentage at 42 d and increased breast muscle percentage at 21 and 42 d (P < 0.05). The serum TG at 21 and 42 d were decreased by BAs (P < 0.05), and the hepatic LPL activity at 42 d was increased (P < 0.05). In addition, high-energy diets increased the expression of sterol regulatory element binding transcription factor 1, acetyl-CoA carboxylase, and fatty acid synthase (P < 0.05), while BAs diets decreased these genes expression (P < 0.05). Moreover, BAs supplementation also increased the expression of carnitine palmitoyltransferase 1 (P < 0.05), which was increased in high-energy groups (P < 0.05). In conclusion, BAs supplementation could increase growth performance, elevate carcass quality, and improve lipid metabolism in broilers.

Curcumin attenuates heat-stress-induced oxidant damage by simultaneous activation of GSH-related antioxidant enzymes and Nrf2-mediated phase II detoxifying enzyme systems in broiler chickens.

The object of this study was to investigate the effect of curcumin on modulating the glutathione (GSH)-related antioxidant enzymes and antioxidant responses via NF-E2-related factor 2 (Nrf2) signaling pathway in heat-stressed broiler chickens. A total of 400 one-day-old male Arbor Acres broiler chicks was reared in an environmentally controlled room. At 21 d, broiler chicks were divided into 5 treatment groups and were fed one of 4 diets under 2 temperature conditions: 22°C + a basal diet (CON treatment); 34°C for 8 h (0900-1700) + a basal diet supplemented with 0, 50, 100, or 200 mg/kg curcumin (HS, CMN1, CMN2, and CMN3 treatments, respectively). The heat treatment lasted for 20 consecutive days. The results showed that heat stress significantly increased (P < 0.05) the weekly rectal temperature and average head and feet temperature. Compared to the HS treatment, feed conversion was significantly decreased (P < 0.05) in CMN1 and CMN2 treatments. CMN1 administration significantly improved (P < 0.05) the pH24 of muscle. The abnormal changes of serum malonaldehyde and corticosterone concentrations were prevented (P < 0.05) by curcumin. Mitochondrial GSH concentration in the liver was significantly increased (P < 0.05) in CMN1 and CMN2 treatments compared with the HS treatment. The CMN1, CMN2, and CMN3 supplementations significantly increased (P < 0.05) γ-GCL, GSH-Px, and GST activities. Curcumin significantly increased (P < 0.05) the expression of Nrf2, HO-1, and γ-GCLc in the liver as compared to the CON diet. The expression of Cu/ZnSOD and CAT were increased (P < 0.05) by feeding CMN2, respectively, as compared to the HS treatment. It was concluded that curcumin supplementation enhanced the resistance of broilers to heat stress, as evidenced by reversing the FC, increasing the GSH content and GSH-related enzyme activities, and inducing the expression of Nrf2 and Nrf2-mediated phase II detoxifying enzyme genes.

Skin ulcers misdiagnosed as pyoderma gangrenosum.

BACKGROUND: Pyoderma gangrenosum is a diagnosis of exclusion, and the misdiagnosis of pyoderma gangrenosum can result in substantial complications in patients who have other causes of severe cutaneous ulceration. METHODS: We reviewed the charts of 240 patients with a diagnosis of pyoderma gangrenosum who were evaluated at our institution from 1975 through 2000, including 157 consecutive patients treated for presumed pyoderma gangrenosum from 1984 through 1992. We also reviewed the English-language literature. RESULTS: Ninety-five patients (49 from our institution and 46 described in the literature) had skin ulcers with a clinical resemblance to pyoderma gangrenosum. The final diagnoses were vascular occlusive or venous disease, vasculitis, cancer, primary infection, drug-induced or exogenous tissue injury, and other inflammatory disorders. Of the 95 patients studied, 64 had been treated for pyoderma gangrenosum for a median of 10 months (range, 3 to 180). These 64 included 15 of the 157 consecutive patients treated for pyoderma gangrenosum at our institution (10 percent). Of the ulcers in the 64 patients treated for pyoderma gangrenosum, it was clear that those in 23 patients (36 percent) did not respond to treatment directed at pyoderma gangrenosum, those in 8 (12 percent) were exacerbated by such treatment, and those in 15 (23 percent) improved with such treatment. CONCLUSIONS: The misdiagnosis of pyoderma gangrenosum is not uncommon and exposes patients to risks associated with its treatment. A thorough evaluation is required in all patients suspected of having pyoderma gangrenosum in order to rule out alternative diagnoses.

Effects of dietary l-methionine supplementation on the growth performance, carcass characteristics, meat quality, and muscular antioxidant capacity and myogenic gene expression in low birth weight pigs.

The aim of the present study was to investigate the effects of dietary Met supplementation on the growth performance, carcass characteristics, meat quality, and muscular antioxidant capacity and myogenic gene expression in low birth weight (LBW) pigs. Thirty normal birth weight (NBW) and 60 LBW female piglets were selected at birth. In each litter, after weaning, 1 of the LBW piglets (LBW-CON group) and 1 of the NBW piglets (NBW-CON group) were fed the basal diets and 1 LBW littermate was fed the basal diet supplemented with Met (LBW-MET group). Thus, all pigs were distributed into groups of 3 treatments × 6 replicates (pens) × 5 piglets per replicate up to 180 d of age. Compared with NBW-CON pigs, LBW-CON pigs had decreased ADG ( = 0.004) and ADFI ( < 0.001) during the postweaning period and greater backfat thickness ( = 0.015) at slaughter. In addition, LBW-CON pigs exhibited compromised meat quality, as evidenced by a greater drip loss at 24 h postmortem( = 0.037) and a lower pH at 45 min postmortem ntents of malondialdehyde (MDA; = 0.046) and protein carbonyl ( = 0.028) in the LM. The LBW pigs fed the Met-supplemented diets had a greater amount of reduced glutathione (GSH; = 0.009) but a lower level of MDA ( = 0.015) in the LM compared with the LBW-CON pigs. Methionine supplementation increased the pH at 24 h postmortem (pH) value ( = 0.004) but reduced the drip loss at both 24 ( = 0.016) and 48 h ( = 0.005) postmortem of LBW-MET pigs in comparison with the LBW-CON pigs. The Met-supplemented diets increased the -adenosyl-methionine content ( = 0.006), DNA methyltransferase activity ( = 0.007), and CpG methylation levels of the sites +27 ( = 0.008) and +160 ( = 0.009) of myostatin (MSTN) exon 1 but decreased the mRNA expression of MSTN ( = 0.011) in the LM of the LBW-MET group compared with the LM of the LBW-CON group. Additionally, when compared with the LBW-CON group, the area of LM ( = 0.037) was significantly increased in the LBW-MET group, in parallel with the upregulated mRNA abundance of myogenin ( = 0.025), myocyte enhancer factor 2A ( = 0.036), and myocyte enhancer factor 2D ( = 0.015). In conclusion, Met supplementation increases pH and decreases drip loss in the LM of LBW-MET pigs, along with a greater GSH content but a lower MDA accumulation. Also, the LBW-MET pigs showed a greater LM area, which may be associated with the improved expression of myogenic genes.

Alpha-1-antitrypsin deficiency and panniculitis. Perspectives on disease relationship and replacement therapy.

A distinctive form of ulcerative panniculitis develops in a subset of persons with alpha-1-antitrypsin deficiency. This association may be more widely recognized if routine determinations of alpha-1-antitrypsin are performed on patients in whom neutrophilic, ulcerative panniculitis develops without specific, defined underlying causes. Therapies that appear to be of the greatest potential benefit include treatment with dapsone and alpha-1-proteinase inhibitor replacement. Astute recognition of alpha-1-antitrypsin-deficient panniculitis and assessment of response to these and other therapies will ultimately lead to a more complete understanding of the cause of this distinctive and uniquely associated disease.

Primary cutaneous large cell lymphomas. Morphologic, immunophenotypic, and clinical features of 20 cases.

The morphologic, immunophenotypic, and clinical characteristics of 20 cases of primary cutaneous large cell lymphoma were analyzed. Immunoperoxidase stains in paraffin sections indicated B-cell phenotype in 14 cases and T-cell phenotype in six cases. By the Kiel classification, the B-cell lymphomas were classified into the following categories: follicular centroblastic (three patients), centroblastic/centrocytic with a predominance of large centrocytes (two patients), centroblastic (seven patients), and immunoblastic (two patients). The T-cell lymphomas (six cases) were all categorized as pleomorphic medium and large cell type. Three of these had an angiocentric growth pattern. The lymphocyte activation marker CD30 was expressed in three of the 20 cases. Among these 20 patients, the clinical course was remarkably variable. The only clinical or pathologic feature with prognostic significance was multicentricity of the skin lesions. All five patients with multifocal or disseminated skin lesions died within 13 months of their initial presentation; the median survival was 7 months. Most of the patients with localized skin lesions had an indolent clinical course with a median survival of 107 months. These results suggest that multicentricity of the skin lesions and necrosis are closely linked and are important prognostic features in cutaneous large cell lymphoma.

Hypertrophic obstructive cardiomyopathy and lentiginosis: a little known neural ectodermal syndrome.

Eleven patients, 10 male, with classic hypertrophic obstructive cardiomyopathy and lentiginosis are described. Physical examination showed differences from the few previously reported cases in that (1) this condition was not confined to children; (2) mental retardation, sensorineural deafness and gonadal and somatic infantilism were either rare or absent; and (3) detailed family studies provided no evidence that this condition was inherited. Nine patients underwent cardiac catheterization and left ventricular angiography; all had left ventricular outflow obstruction and three had concomitant right ventricular outflow obstruction with a pressure gradient in excess of 100 mm Hg. Ten of the 11 patients were severely symptomatic, and 7, each with a left ventricular pressure gradient of more than 70 mm Hg, underwent successful septal myotomy/myectomy that resulted in marked symptomatic improvement that was maintained after long-term follow-up.

Malignant melanoma: basic approach to clinicopathologic correlation.

To provide an overview of the clinicopathologic correlation of the various types of malignant melanoma, we describe and illustrate the four major types of these tumors and discuss the concept of microstaging for the prognostic evaluation of melanoma. The four major types of malignant melanoma are lentigo maligna melanoma, acral lentiginous melanoma, superficial spreading melanoma, and nodular melanoma. Lentigo maligna melanoma has irregular margins and usually occurs on sunlight-exposed skin in elderly patients. Acral lentiginous melanoma occurs on the hands and feet; it often demonstrates massive invasion when the vertical growth phase occurs. Among Caucasians, superficial spreading melanoma, which affects the trunk and extremities, is the most common malignant melanoma. These lesions are often variegated in color. Nodular melanomas are deeply pigmented and enlarge rapidly. For microstaging of malignant melanoma, determining Clark's level of tumor invasion or Breslow's thickness (from the top of the granular cell layer of the epidermis to the deepest extension of the tumor) is useful for assessment of prognosis. Establishing a definite diagnosis of malignant melanoma is feasible through clinicopathologic correlation. Microscopic measurement of the deepest levels of melanoma involvement in the skin provides a useful indication of the associated prognosis.

Dermatologic manifestations of human immunodeficiency virus infection.

Human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS) have become major health problems in the United States, and patients with manifestations of these diseases are seen by physicians in all areas of medicine. Cutaneous manifestations develop in as many as 92% of HIV-positive persons. Familiarity with these manifestations facilitates early diagnosis and enhances the care of HIV-infected patients. The spectrum of mucocutaneous disorders in these patients includes an acute exanthem, multiple infections, neoplastic processes, and miscellaneous disorders. Herein we review the most common and the most specific dermatologic manifestations associated with HIV infection, which often are atypical, more severe, or less responsive to treatment than the corresponding diseases encountered in non-HIV-infected persons.

Classification of morphea (localized scleroderma)

OBJECTIVE: To classify and describe morphea (localized scleroderma). DESIGN: A review of morphea and its subtypes is presented. RESULTS: The current classification of morphea is incomplete and confusing. As knowledge of the spectrum of disease continues to evolve, the controversy and confusing nature of its multiple subtypes present a challenge for the physician who encounters a patient with this condition. Thus, we propose that morphea be classified into the following five groups: plaque, generalized, bullous, linear, and deep. This classification, based on clinical morphologic findings, will simplify the diagnostic and therapeutic approach. CONCLUSION: Morphea represents a wide variety of clinical entities that seen to be on the opposite end of the scleroderma spectrum from systemic sclerosis. The cutaneous lesions eventually evolve from a sclerotic stage to a nonindurated stage, and residual hypopigmentation or hyperpigmentation follows. The histologic pattern in patients with morphea is similar to that in patients with progressive systemic sclerosis. Although treatment is nonstandardized, hydroxychloroquine sulfate may be beneficial.

Skin cancers associated with acquired immunodeficiency syndrome.

OBJECTIVE: To describe the types of skin cancer associated with the acquired immunodeficiency syndrome (AIDS). DESIGN: A literature review of AIDS-related mucocutaneous neoplasms, including basal cell carcinoma, squamous cell carcinoma, bowenoid papulosis and Bowen's disease, squamous cell carcinoma, cloacogenic carcinoma, and malignant melanoma, is presented, and the incidence, etiopathogenesis, clinicopathologic features, treatment, and prognosis are discussed. RESULTS: The association between cutaneous neoplasms and AIDS is well known. Neoplasms seem to grow more rapidly and be more invasive in patients with AIDS than in other groups of patients. Several oncogenic factors--for example, sunlight exposure or human papillomavirus infection--have been associated with the development of skin cancer in these patients. The morbidity and mortality rates of skin cancer are higher in patients infected with the human immunodeficiency virus (HIV) than in the general population. Early and complete excision of the neoplasm is especially important. CONCLUSION: A link exists between AIDS and the development of skin cancer. HIV-infected patients should be followed up vigilantly for early diagnosis of skin cancer. Because these patients are less able to suppress common cutaneous malignant disease due to their immunocompromised status, biopsy specimens should be obtained from all suspicious lesions, and histopathologic assessment should be done.

Acquired immunodeficiency syndrome-related Kaposi's sarcoma.

OBJECTIVE: To describe Kaposi's sarcoma (KS) associated with the acquired immunodeficiency syndrome (AIDS). DESIGN: A review of AIDS-related KS (AIDS-KS), with its associated epidemiologic and etiologic characteristics, pathogenesis, clinical manifestations, histopathologic features, prognosis, and treatment, is presented. RESULTS: KS is the most frequent malignant lesion in patients with AIDS. The incidence of AIDS-KS is high in homosexual and bisexual men who have multiple sexual partners and in children and women with the human immunodeficiency virus (HIV) infection. Anal-oral contact is one of the main routes of the sexually transmitted agents of AIDS-KS. The major pathogenic factors that may possibly induce AIDS-KS are HIV itself or other sexually transmitted agents, HIV tat gene, some oncogenes and cytokines such as interleukin 6, basic fibroblast growth factor, transforming growth factor-beta, oncostatin M, and platelet-derived growth factor. Treatment includes local therapy, radiotherapy, systemic chemotherapy, zidovudine, interferon, granulocyte-macrophage colony-stimulating factor, and other agents. CONCLUSION: KS may be an early manifestation of AIDS and the most frequent neoplastic complication of AIDS. Growth factors, cytokines, immunosuppression, and interaction with infectious agents seem to have a role in the development of this enigmatic disorder. Treatment of KS should be individualized. Further investigation of the agents and factors of AIDS-KS may help facilitate the treatment and prevention of this neoplasm.

Sweet's syndrome: systemic signs and symptoms and associated disorders.

OBJECTIVE: To characterize the findings associated with acute febrile neutrophilic dermatosis (Sweet's syndrome [SS]) and the response of SS to treatment. DESIGN: We retrospectively reviewed 48 cases of SS encountered at the Mayo Clinic between 1980 and 1992. MATERIAL AND METHODS: Histopathologic specimens and medical records were studied to determine initial manifestations, patterns of involvement, systemic signs and symptoms (including mucosal, musculoskeletal, hematologic, pulmonary, hepatic, and renal findings), and conditions associated with SS. RESULTS: In patients with SS, the typical manifestations are the acute onset of tender, erythematous or violaceous nodules or plaques in association with fever, leukocytosis, and dermal neutrophilia. In our study group, the cutaneous lesions most frequently involved the arms and legs. Of our 48 patients, 26 (54%) had a hematopoietic, plasma cell, or malignant disorder, and many of these patients had associated anemia, especially the male patients. No single laboratory finding specifically indicated an association with serious systemic disease. Most patients were treated with a tapering dose of prednisone, which yielded a good response. CONCLUSION: Clinical acumen and appropriate laboratory tests are the main requirements for detection of hematologic disorders, internal malignant diseases, or other systemic conditions associated with SS.

Lymphoma associated with human immunodeficiency virus infection.

OBJECTIVE: To describe lymphoma associated with human immunodeficiency virus (HIV) infection. DESIGN: A review of HIV-related lymphoma and its associated epidemiology, etiopathogenesis, and clinicopathologic characteristics is presented. Major studies of therapeutic regimens for HIV-related lymphoma are discussed. Factors that could contribute to a poor prognosis are summarized. RESULTS: Malignant lymphoma that develops in patients with HIV infection fulfills diagnostic criteria for the acquired immunodeficiency syndrome (AIDS). The incidence is increasing and varies by subtype of lymphoma, age, sex, race, and risk factors. B-cell hyperactivation is thought to contribute to the development of lymphoma. The mechanisms that may show transformed cell hyperproliferation and clonal expansion are HIV itself or other viruses (for example, Epstein-Barr virus), growth factors, aberrant oncogene or tumor-suppressor gene expression, and factors that induce genetic instability or DNA damage or alter host or viral genome repair. Treatment of HIV-related lymphoma is associated with toxicity, infectious complications, low rate of complete response, and brief median survival time. CONCLUSION: Persons with HIV-induced immune dysregulation have a high risk for the development of aggressive non-Hodgkin's lymphoma characterized by histologic evidence of a high-grade malignant process, B-cell phenotype, an unusual extranodal involvement, and a poor prognosis. The potential role of specific viruses, antiviral treatments, and other therapeutic strategies are future areas of investigation.