Effects of ECG Signal Processing on the Inverse Problem of Electrocardiography.

The inverse problem of electrocardiography is ill-posed. Errors in the model such as signal noise can impact the accuracy of reconstructed cardiac electrical activity. It is currently not known how sensitive the inverse problem is to signal processing techniques. To evaluate this, experimental data from a Langendorff-perfused pig heart (n=1) suspended in a human-shaped torso-tank was used. Different signal processing methods were applied to torso potentials recorded from 128 electrodes embedded in the tank surface. Processing methods were divided into three categories i) high-frequency noise removal ii) baseline drift removal and iii) signal averaging, culminating in n=72 different signal sets. For each signal set, the inverse problem was solved and reconstructed signals were compared to those directly recorded by the sock around the heart. ECG signal processing methods had a dramatic effect on reconstruction accuracy. In particular, removal of baseline drift significantly impacts the magnitude of reconstructed electrograms, while the presence of high-frequency noise impacts the activation time derived from these signals (p<0.05).

Diagnostic value of microtubule-associated protein-2 in Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous carcinoma with neuroendocrine differentiation and a propensity for early spread to regional lymph nodes. Since surgical resection is the mainstay of treatment of MCC, differentiation of MCC from malignant lymphoma, metastatic small cell carcinoma, basal cell carcinoma, and malignant melanoma is very important and is sometimes challenging with routine histologic examination. Immunohistochemical studies may be required to differentiate MCC from other primary and metastatic skin neoplasms. Previously, the authors reported that microtubule-associated protein-2 (MAP-2) is a sensitive and specific marker for pulmonary neoplasms with neuroendocrine differentiation. Because MCC is also a neuroendocrine carcinoma, the authors hypothesized that MAP-2 may be expressed in MCC and therefore may be a useful marker in establishing an accurate diagnosis. MAP-2 staining was demonstrated in all 14 MCCs with diffuse (10 cases) to focal (4 cases) patterns of immunoreactivity. No MAP-2 immunoreactivity was observed in any lymphoma (14 cases), basal cell carcinoma (20 cases), or squamous cell carcinoma (14 cases). CK20 reactivity was present in 12 of 14 cases with focal (2 cases) to diffuse (10 cases) staining having the characteristic perinuclear dot-like pattern. NSE was positive in 13 of 14 cases, SYN was positive in all 14 cases, CHR was positive in 8 of 14 cases, CK7 was positive in 4 of 14 cases, and CD99 was focally positive in 2 cases and diffusely positive in 3 cases. MAP-2 showed a diffuse or focal staining of MCC with a +1 to +4 intensity in most cases. MAP-2 was positive in two cases of MCC that were negative for CK20 and CHR and negative or only slightly positive for SYN and NSE. Therefore, MAP-2 may be a valuable ancillary study in skin tumors suspicious for neuroendocrine origin with faint or negative staining with the antibodies traditionally used for diagnosing MCC. The authors believe this is the first study to demonstrate the utility of MAP-2 in the immunohistochemical workup of MCC. The authors recommend that MAP-2 be added to immunohistochemical panels to confirm the diagnosis of MCC.

Cytotoxic T cells in basal cell carcinomas of skin.

Previous studies have suggested the importance of CD8+ cytotoxic T-cells of hosts against neoplasms. Earlier studies and our previous investigation showed that a majority of tumor infiltrating T-cells in human basal cell carcinomas (BCCs) belonged to CD4+ T-cells. CD8+ cells were also present in the peritumor areas of human BCCs, but in smaller numbers. Published evidence indicates the importance of cytotoxic T-cells in antitumor immunity. Cytotoxic T-cells have been identified by using monoclonal antibodies against various cytotoxic T-cell components. In this study, we used monoclonal antibodies to perforin to evaluate the role of cytotoxic T-cells in the host response against basal cell carcinomas. Perforin-expressing T-cells could be identified in the infiltrate of BCCs in frozen tissue sections, and also in antigen-retrieved paraffin-embedded sections of BCCs, and the presence of perforin-expressing T-cells correlated with the infiltration of CD8+ T-cells. These results suggest that cytotoxic T-cells play a role in host defense against human BCCs.

Eosinophilic spongiosis: a clinical, histologic, and immunopathologic study.

BACKGROUND: Epidermal spongiosis with exocytosis of eosinophils (ES) has been reported in biopsy specimens from patients with various dermatoses. Its diagnostic value and the patient's outcome remain poorly understood in those cases in which ES is not associated directly with diagnostic features of a bullous dermatosis. OBJECTIVE: We evaluated the clinical, histopathologic, and immunopathologic findings and their clinical correlation in patients who had ES in a biopsy specimen but who had no evidence of a bullous dermatosis. METHODS: A retrospective study of 150 cases with ES was performed. Clinical, histopathologic, direct immunofluorescence, and subsequent follow-up data were collected to assess final diagnosis and outcome. RESULTS: A total of 144 patients had generalized eruptions; of these, 34 (24%) had autoimmune bullous disease. Fourteen (41%) of those patients had neither a bullous nor a vesicular eruption. Other diagnoses included eczematous dermatitis, arthropod bites, scabies, and drug eruption. CONCLUSION: The majority of patients whose biopsy specimen revealed only ES had either dermatitis or autoimmune bullous disease, often in the prodromal phase. Direct immunofluorescence is often necessary to distinguish these diseases, and repeated testing may be needed for final diagnosis.

Linear and punctate porokeratosis associated with end-stage liver disease.

A periodic eruption of porokeratosis developed in a 31-year-old black woman with chronic idiopathic hepatitis requiring liver transplantation. The clinicopathologic features were chiefly those of linear and punctate porokeratosis but overlapped those of porokeratosis plantaris, palmaris et disseminata and hyperkeratotic or verrucous porokeratosis. Typical cornoid lamellae were visible on histologic examination. Outbreaks of the lesions occurred during exacerbations of the liver disease. The skin condition rapidly improved after operation, with concomitant improvement in liver function.

Mucinous syringometaplasia mimicked by a clear cell hidradenoma with mucinous change.

An adnexal tumor with features of both clear cell hidradenoma and mucinous syringometaplasia is reported. The lesion occurred as a solitary, asymptomatic, slow growing nodule of 6-months duration on the anterior neck of a 55-year-old woman. Serous fluid could be expressed from a central skin opening. Histologically, there was a squamous-lined invagination with foci of mucin-laden cells. A ductal component with a variable admixture of mucinous cells merged with a nearby clear cell hidradenoma. Because clinicopathologic similarities exist between mucinous syringometaplasia and clear cell hidradenoma with mucinous change, thorough sectioning of mucinous syringometaplasia-like lesions is necessary to exclude an associated sweat gland neoplasm.

Malignant hair matrix tumor ("malignant trichoepithelioma") arising in the setting of multiple hereditary trichoepithelioma.

An unusual adnexal tumor on the scalp of a 59-year-old woman with hereditary trichoepithelioma is reported. After the initial removal, the tumor recurred twice during a 4-year period. Mohs micrographic surgery resulted in full excision of the lesion. Two years later there was no evidence of recurrence. Histologic examination of the tumor showed it to merge with adjacent areas of classic trichoepithelioma. The tumor showed cytologic atypia, mitotic figures, necrosis, deep infiltration, and features of pilar differentiation including clear cells, reminiscent of cells of the follicular outer root sheath, and focal shadow-cell formation. The differential diagnosis of this malignant follicular neoplasm included pilomatrix carcinoma and basal-cell carcinoma with matrical differentiation. The unique clinicopathologic features, however, raised consideration of a "malignant trichoepithelioma."

Necrolytic migratory erythema: dyskeratotic dermatitis, a clue to early diagnosis.

A 57-year-old woman with a 6-year history of a dermatitis that evolved into typical necrolytic migratory erythema is reported. Four biopsy specimens were obtained in 5 years. The early lesions revealed superficial perivascular inflammation in the dermis, minor epidermal spongiosis, and scattered dyskeratotic cells in the upper epidermis. The differential diagnosis of this pattern of dyskeratotic dermatitis, particularly in a chronic eruption, should include consideration of hyperglucagonemia and the possibility of an associated pancreatic islet cell tumor.

The reliability of frozen sections in the evaluation of surgical margins for melanoma.

As the width of surgical margins declines, histologic evaluation of the margins is needed to assess the completeness of excision of a malignant melanoma. We studied 221 specimens in 59 patients and compared the interpretations of frozen and paraffin sections from the same block. Frozen sections had a sensitivity of 100% in detecting melanoma when present and a specificity of 90%.

Clinical trials with purified platelet releasate.

Clinical trials of PDWHF are ongoing and the final results are not yet available; however early lessons learned have allowed us to modify these trials. It is anticipated that the patient accrual will be completed within the next six months, and the last patient will complete the trial within the next year. At that time, we hope to have new insight into the role of PDWHF in the treatment of lower extremity ulcers. At this time, we are encouraged by the early improvement seen in patients entering the PDWHF versus saline trial. Preliminary results suggest that PDWHF improves the healing of diabetic ulcers of the lower extremity.

Comparison of IgG subclass autoantibodies in patients with systemic lupus erythematosus and subacute cutaneous lupus erythematosus.

Circulating antinuclear antibodies and in vivo bound immunoglobulins at the dermal-epidermal junction are frequently seen in patients with lupus erythematosus. The present study was designed to examine the distribution of the IgG subclasses of in vivo skin bound IgG and circulating antinuclear antibodies (ANA) in patients with systemic lupus erythematosus (SLE) or subacute cutaneous lupus erythematosus (SCLE). Immunofluorescence studies on skin biopsies showed IgG1 to be the predominant IgG subclass in SCLE patients, present in 20 of 21 (95%) of the specimens. IgG2 was present in 4 patients (19%), IgG3 in 1 (5%), and IgG4 in 7 (33%). The frequencies of IgG2, IgG3, and IgG4 skin staining were significantly higher in the seven SLE patients who were studied: IgG1 in 7/7 (100%), IgG2 in 7/7 (100%) and IgG4 in 6/7 (86%). Immunoblot analysis for the IgG subclasses was performed on serum of 29 patients with SCLE who had antibodies to SSA/Ro antigen. Twenty-seven (93%) of these patients were positive for IgG1 anti-SSA/Ro antibody, while the frequencies for IgG2, IgG3, and IgG4 anti-SSA/Ro were very low. These studies indicate that there is a difference in the IgG subclass antibody response in patients with SLE and SCLE. The presence of more than one subclass antibody may be indicative of systemic disease.

Establishment of a human cutaneous T-cell lymphoma in C.B-17 SCID mice.

Investigation into the immunobiology of cutaneous T-cell lymphomas (CTCL) would be facilitated by the development of a suitable experimental system. The recent use of mice with severe combined immune deficiency (SCID) as a vehicle to study the human immune system prompted us to try to establish CTCL in SCID mice. We found that a CD4+ lymphocytic infiltrate characteristic of CTCL was maintained within patient skin grafts in place on natural killer cell depleted SCID mice for the month of observation. CTCL cells were not found outside the human skin graft. This chimeric model using SCID mice and patient lesional skin should provide a useful tool to characterize CTCL/skin microenvironmental interactions and to test new therapeutic approaches.

Solitary spindle cell tumor with myoid differentiation of the lymph node.

Spindle cell tumors arising in the lymph nodes are very rare. We report the light microscopic, histochemical, immunohistochemical, and ultrastructural findings of an unusual solitary spindle cell tumor in a peripheral lymph node of a 45-year-old woman. Microscopically, the tumor was characterized by interlacing fascicles of uniform spindle cells with nuclear palisading and formation of Verocay bodies. Numerous erythrocytes were found interstitially. There were no mitotic figures or significant nuclear atypia. The ultrastructural findings of abundant myofilaments with dense bodies indicated myoid differentiation. The clinical and pathologic findings favored this being a benign tumor and could represent a unique example of "intranodal myofibroblastoma." The differential diagnosis includes neurilemoma, leiomyoma, and, more importantly, leiomyosarcoma, Kaposi's sarcoma, and other metastatic spindle cell tumors.

Comparison of IgG subclasses and complement binding activity of autoantibodies from patients with bullous pemphigoid and pemphigus.

Bullous pemphigoid and pemphigus are autoimmune disorders of skin of unknown etiology and are characterized by the presence of immunoreactants in the skin and circulating autoantibodies to skin components. The distribution of IgG subclass antibodies to intercellular substance (ICS) of pemphigus and basement membrane zone substance (BMZ) of bullous pemphigoid was analyzed by using monoclonal antibodies to human IgG subclasses. IgG4 type anti-BMZ antibody was found in the majority of patients with bullous pemphigoid (88% in skin and 96% in serum). One third to one half of bullous pemphigoid patients had IgG1 and IgG2 anti-BMZ antibodies. The majority of bullous pemphigoid skin (92%) had complement in skin, however only one third of their sera had complement binding activity in vitro. IgG1 anti-ICS antibody was the predominant one in patients with pemphigus (86% in skin and 80% in circulation). IgG4 anti-ICS antibody was seen in two thirds of specimens from pemphigus patients. IgG3 subclass antibody was more frequently seen in pemphigus than in bullous pemphigoid patients. Two-thirds of pemphigus sera were capable of activating complement in vitro. The complement binding activity was directly associated with IgG1 and/or IgG3 subclass antibodies. The possible mechanisms for the restricted IgG4 subclass antibodies in bullous pemphigoid and pemphigus are discussed.

Wound healing of skin incisions produced by ultrasonically vibrating knife, scalpel, electrosurgery, and carbon dioxide laser.

An ultrasonically vibrating knife has been developed for producing surgical incisions with reduced hemorrhage. Tissue injury and wound healing of porcine cutaneous incisions produced by this instrument, conventional scalpel, electrosurgery, and CO2 laser were compared regarding clinical, histopathologic, and tensile strength differences. Scalpel incisions had the least tissue injury and fastest healing, but the ultrasonically vibrating knife produced less tissue injury and faster healing than electrosurgery or CO2 laser.