105Changes in Nitric Oxide Levels After Deep Dermal injury in the Female,Red Duroc Pig (FRDP)

Introduction : Hypertrophic scar is a devastating sequel to burns and other tangential skin injuries. It follows deep dermal injuries and does not occur after superficial injuries. Nitric oxide (NO) plays many important roles in wound healing from inflammation to scar remodeling. Studies have shown that expression of nitric oxide synthase and nitric oxide production are decreased in human hypertrophic scar. However little is known about NO involvement in the early stages of hypertrophic scarring, because of the lack of an animal model. It was recently reported that the female red Duroc pig (FRDP) makes thick scar, which is similar to human hypertrophic scar. We hypothesized that NO production in wounds on the female, red Duroc pig is similar to that of human hypertrophic scar and that NO involvement in deep wounds is different from that in superficial wounds. Methods : Superficial (0.015” to 0.030”) and deep (0.045” to 0.060”) wounds were created on the backs of four FRDPs. Biopsies were collected at weeks 1.5, 4, 8 and 21 post wounding including samples of uninjured skin. Nitric oxide levels were measured with the Griess reaction assay and normalized with tissue protein level. Results : Superficial wounds healed with an invisible scar whereas the deep wounds healed with scar resembling mild hypertrophic scar. The thickness of the scars from the deep wounds was significantly greater than uninjured skin and healed superficial wounds (p < 0.01). NO levels were increased at 1.5 weeks in deep wounds compared to superficial wounds and uninjured skin (p < 0.05). At 8 weeks, NO levels in deep wounds had returned to the level of uninjured tissue and superficial wounds. By 21 weeks, NO levels had decreased significantly when compared to superficial wounds (p < 0.01). There were no differences in NO levels between uninjured skin and superficial wounds at any time point (p > 0.05). Conclusions : NO production is similar in late, deep wounds on the female, red Duroc pig to that reported in the literature for human hypertrophic scar further validating this animal model. NO production is quite different after deep wounds as compared to superficial wounds in the FRDP. Early elevation in nitric oxide production might account for excessive inflammation in deep wounds that become thick scars in the FRDP. Nitric oxide regulators and effects at early stages of scar formation should be elucidated further and the FRDP appears to be a useful model.     

TREATMENT OF PALMOPLANTER HYPERHIDROSIS BY IONTOPHORESIS

Twenty-seven patients with idiopathic palmoplanter hyperhidrosis were treated with Iontotherapy over a one year period. In twenty-four cases there was a good response but maintenance therapy was required every 3-4 weeks.KEY WORDS: Iontophoresis, Palmoplanter hyperhidrosis     

Brassiere wearing and breast cancer risk: A systematic review and meta-analysis

AIM: To evaluate existing evidence for the association between different type of brassiere exposures and the risk of breast cancer. METHODS: Ovid Medline, CINAHL, Cochrane Data Base of Systematic Reviews, Pubmed, Scopus, Proquest, Sciencedirect, Wiley Online Library, WanFang Data, Hong Kong Index to Chinese Periodicals, China Journal Net, Chinese Medical Current Contents, Chinese Biomedical Literature Database, China Academic Journals Full-Text database, Taiwan Electronic Periodical Services and HyRead; reference lists of published studies; original research studies published in English or Chinese examining the association between type and duration of brassiere-wearing and breast cancer risk. Data were abstracted by a first reviewer and verified by a second. Study quality was rated according to predefined criteria. “Fair” or “good” quality studies were included. Results were summarised by meta-analysis whenever adequate material was available. RESULTS: Twelve case-control studies were included in the review. Meta-analysis showed brassiere wearing during sleep was associated with a two times of increased odds. CONCLUSION: The present review demonstrates insufficient evidence to establish a positive association between the duration and type of brassiere wearing and breast cancer. Further research is essential; specifically, a large-scale epidemiological study of a better design is needed to examine the association between various forms of brassiere exposure in detail and breast cancer risk, with adequate control of confounding variables.     

B19 parvovirus replicates in circulating cells of acutely infected patients

B19 parvovirus is the etiologic agent of fifth disease and transient aplastic crisis. In natural infections, B19 antigen and DNA have been detected in sera early in the course of aplastic crisis and only rarely in fifth disease. We have found B19 DNA in circulating cells of infected patients by DNA dot blot with a virus-specific probe: in four of four sickle cell patients with aplastic crisis, in one asymptomatic sibling, and in one normal adult with fifth disease. Only two of the sera showed B19 DNA. High-molecular weight intermediate forms were detected by Southern analysis of DNA extracted from cells, thus indicating active replication of virus in cells rather than passive adsorption to their surface membranes. Separation of cells into high- and low-density fractions resulted in a concentration of the virus DNA in the granulocytic fraction.     

Identification of glycoprotein Ib as a target for autoantibody in idiopathic (autoimmune) thrombocytopenic purpura

An antibody (DIL) from a patient with idiopathic thrombocytopenic purpura (ITP) was shown to have autospecificity on the basis of reactions with autologous platelets that were identical to those obtained with platelets from normal subjects. DIL antibody also reacted strongly in an immunofluorescence test with platelets from a patient with Glanzmann's thrombasthenia, but failed to react with platelets from a patient with the Bernard-Soulier syndrome who was known to be deficient in glycoprotein Ib (GPIb). Purified GPIb and control platelets, but not Bernard-Soulier platelets, inhibited the lytic activity of DIL. Using the GPIb-specific monoclonal antibody AP1 and one-dimensional rocket electrophoresis into gels containing rabbit antihuman platelet membrane antibody, it was shown that staphylococcal protein A-Sepharose beads coated with DIL antibody selectively remove GPIb from solubilized platelet preparations. By crossed immunoelectrophoresis it was found that DIL recognizes a determinant on GPIb on the membrane side of the cleavage site of the platelet calcium- activated protease (calpain). These studies provide direct evidence for binding of a platelet autoantibody to a determinant on GPIb relatively close to the site of insertion of this protein into the platelet membrane.     

The effect of thrombopoietin on the proliferation and differentiation of murine hematopoietic stem cells

In this study, we explored whether thrombopoietin (Tpo) has a direct in vitro effect on the proliferation and differentiation of long-term repopulating hematopoietic stem cells (LTR-HSC). We previously reported a cell separation method that uses the fluorescence-activated cell sorter selection of low Hoescht 33342/low Rhodamine 123 (low Ho/low Rh) fluorescence cell fractions that are highly enriched for LTR-HSC and can reconstitute lethally irradiated recipients with fewer than 20 cells. Low Ho/low Rh cells clone with high proliferative potential in vitro in the presence of stem cell factor (SCF) + interleukin-3 (IL-3) + IL-6 (90% to 100% HPP-CFC). Tpo alone did not induce proliferation of these low Ho/low Rh cells. However, in combination with SCF or IL-3, Tpo had several synergistic effects on cell proliferation. When Tpo was added to single growth factors (either SCF or IL-3 or the combination of both), the time required for the first cell division of low Ho/low Rh cells was significantly shortened and their cloning efficiency increased substantially. Moreover, the subsequent clonal expansion at the early time points of culture was significantly augmented by Tpo. Low Ho/low Rh cells, when assayed in agar directly after sorting, did not form megakaryocyte colonies in any growth condition tested. Several days of culture in the presence of multiple cytokines were required to obtain colony-forming units-megakaryocyte (CFU-Mk). In contrast, more differentiated, low Ho/high Rh cells, previously shown to contain short- term repopulating hematopoietic stem cells (STR-HSC), were able to form megakaryocyte colonies in agar when cultured in Tpo alone directly after sorting. These data establish that Tpo acts directly on primitive hematopoietic stem cells selected using the Ho/Rh method, but this effect is dependent on the presence of pluripotent cytokines. These cells subsequently differentiate into CFU-Mk, which are capable of responding to Tpo alone. Together with the results of previous reports of its effects on erythroid progenitors, these results suggest that the effects of Tpo on hematopoiesis are greater than initially anticipated.     

Scalp Metastasis as the First Sign of Small-Cell Lung Cancer: Management and Literature Review

Cutaneous metastasis from primary visceral malignancy is a relatively uncommon clinical entity, with a reported incidence ranging from 0.22% to 10% among various series. However, the presence of cutaneous metastasis as the first sign of a clinically silent visceral cancer is exceedingly rare. We describe here a case of an asymptomatic male patient who presented with a solitary scalp metastasis as the initial manifestation of an underlying small-cell lung cancer. Diagnostic evaluation revealed advanced disease. We conclude that the possibility of metastatic skin disease should always be considered in the differential diagnosis in patients with a history of smoking or lung cancer presenting with cutaneous nodules. Physicians should be aware of this rare clinical entity, and appropriate investigation should be arranged for early diagnosis and initiation of the appropriate treatment. The prognosis for most patients remains poor.Key words: Small cell lung carcinoma, Scalp, MetastasisCutaneous metastasis from a primary visceral malignancy is a relatively uncommon clinical entity, with a reported incidence ranging from 0.22% to 10% among various series.^1–10 In a meta-analysis of 7 studies comprising a total of 20,380 patients, Krathen et al⁵ found that the overall incidence of cutaneous metastasis was 5.3% and that the most common tumor to metastasize to the skin was breast cancer.⁵ Cutaneous involvement may occur due to direct extension of the tumor as a local metastasis or as a distant metastasis,⁹ and it has been associated with advanced disease and poor prognosis.^3,4,11–13 Half of the patients with cutaneous metastases die within the first 6 months after the diagnosis, whereas lung cancer has been associated with the poorest prognosis.¹⁴ Cutaneous metastasis as the first sign of an internal malignancy is an exceedingly rare occurrence. It has been reported to occur in only 0.8% of the cases and has been associated with advanced disease.¹⁵ Skin metastasis from lung cancer is a rare clinical entity that has been reported to occur in 0.22% to 12% of patients with lung cancer.^{1–4,6,10,15–17} In most cases, metastases occur after the initial diagnosis and treatment of the primary lung tumor.¹⁷ Skin metastasis as the initial manifestation of an underlying lung cancer is a very rare occurrence.^4,6,16,17 We describe herein an exceedingly rare case of an asymptomatic male patient who presented with a solitary scalp metastasis as the initial manifestation of an underlying small-cell lung cancer. Diagnostic evaluation and management are discussed along with a review of the literature.

Case Presentation

A 74-year-old man presented with a 2-month history of a slowly growing, painless nodule in his right temporal region. His past medical history was significant for arterial hypertension. He was a heavy smoker but had no history of lung disease. He denied any respiratory symptoms, fever, or weight loss, and his general condition was good.Clinical examination revealed a painless, movable, nonulcerated nodule in the right temporal region measuring approximately 2 cm in diameter. There were no signs of infection and the overlying skin was normal. A chest X-ray showed a large mass occupying the upper lobe of the left lung. Subsequent computed tomography (CT) showed a large mass involving the left upper lobe associated with extensive mediastinal lymphadenopathy. In addition, a head CT revealed 3 metastatic brain lesions.The scalp lesion was easily resected down to the epicranial aponeurosis. Histopathologic examination and detailed immunohistochemical analysis revealed extensive infiltration from small-cell lung carcinoma (Fig. 1). Immunohistochemically, the tumor cells were strongly positive for TTF-1 and cytokeratin 8.18 and focally positive for CD56 and synaptophysin (Fig. 2). A CT-guided biopsy of the lung tumor confirmed the presence of a small-cell lung carcinoma, and the patient was advised to start chemotherapy and radiotherapy. Unfortunately, although he completed the first cycle of chemotherapy, he refused to continue and was subsequently lost to follow-up.Open in a separate windowFig. 1Histopathologic findings. (1A) Typical appearance of small-cell carcinoma. Small hyperchromatic nuclei and squeezing artifact [hematoxylin and eosin (H&E) ×100]. (1B) Whole-mount section showing large metastatic infiltration of dermis leaving surprisingly unaffected the epidermis (H&E ×25). (1C) Note the border between neoplastic cells (left) and the basal layer of epidermis (right; H&E ×200).Open in a separate windowFig. 2Immunohistochemical analysis. (2A) Strong nuclear positivity for TTF-1 (original magnification ×400). (2B) Diffuse cytoplasmic reactivity for cytokeratin 8/18 (original magnification ×400). (2C) Many of the neoplastic cells show membranous-pattern positivity for CD56 (original magnification ×200). (2D) Focal cytoplasmic positivity for synaptophysin (original magnification ×400).