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Biomedical subjects

N P Smith

Publications and source records attributed to N P Smith.

At least 19 recordsLinked to original sources

Effectiveness of a stand-alone aftercare program for drug-involved offenders.

A study was made of the effectiveness of an aftercare program operating in conjunction with area outpatient drug free treatment programs while organizationally independent of those programs. Parolees and probationers mandated to treatment were assigned to aftercare on the basis of residence in the catchment areas in which aftercare facilities were located (n = 32) and randomly to aftercare (n = 62) and control (n = 51) when not a resident in a catchment area. No outcome differences were found between aftercare groups based on proximity to facility. At 6 months postbaseline the combined aftercare group showed significantly lower levels of criminal activity and frequent drug use as compared to controls. At 12 months postbaseline there was an attenuation of group differences with only tendencies toward significance obtained for lower levels of frequent drug use by the aftercare group. The findings are discussed in terms of the relevance of community variables for programming and for understanding long-term treatment outcomes.

Adult↗

Generation of an anatomically based geometric coronary model.

A discrete anatomically accurate finite element model of the largest six generations of the coronary arterial network is developed. Using a previously developed anatomically accurate model of ventricular geometry the boundaries of the coronary mesh are defined from measured epicardial coronaries. Network topology is then generated stochastically from published anatomical data. Spatial information is added to this topological data using an avoidance algorithm accounting for global network geometry and optimal local branch angle properties. The generated vessel lengths, radii and connectivity are consistent with the published studies and a relativity even spatial distribution of vessels within the ventricular mesh is achieved. The local finite element coordinates of the coronary nodes within the ventricular mesh are calculated such that the coronary geometry can be recalculated within a deformed ventricular mesh.

Biomedical Engineering↗

An outbreak of methicillin-resistant Staphylococcus aureus (MRSA) infection in HIV-seropositive persons.

Staphylococcus aureus is a cause of considerable morbidity and mortality in HIV-seropositive persons. Although methicillin-resistant S. aureus (MRSA) is encountered worldwide and in many areas of medical care, little has been reported on clinical infection with MRSA in patients with HIV. We report on an outbreak of MRSA infection in HIV antibody positive patients, using case reports to describe an outbreak of MRSA infection in HIV-seropositive persons. Six cases of clinical MRSA infection were reported over a 4-week period on patients on an HIV dedicated ward. All cases had previous AIDS diagnoses and low CD4 cell counts (median 8 x 10(6)/l; range 0 to 238). Two cases had infected skin lesions and 2 cases had infected indwelling central venous catheters with septicaemia. Two cases had pneumonia, one with concurrent infection at the entry site of a percutaneous endoscopic gastrostomy (PEG) feeding tube. Isolates of MRSA from the 6 cases were compared by pulsed-field gel electrophoresis of Sma1 chromosomal digests. The resultant banding pattern showed the same strain was responsible for all the infections. A seventh inpatient, the index case, had positive carriage with the same strain of MRSA. To define ongoing MRSA carriage after the outbreak, 29 consecutive ward patients were swabbed for MRSA: all were negative. All patients identified with MRSA infection responded to treatment with intravenous teicoplanin, although carriage was unaltered. Four of the 6 cases died within 7 weeks of diagnosis of MRSA. MRSA can cause severe morbidity in patients with end-stage HIV disease. A small outbreak of MRSA was controlled by simple precautionary measures with no subsequent ongoing transmission of MRSA.

AIDS-Related Opportunistic Infections↗

The a-wave of the human electroretinogram recorded with a minimally invasive technique.

A minimally invasive technique is described for recording the a-wave of the human ERG and extracting the parameters of transduction in the rod and cone photoreceptors. A corneal DTL fibre electrode is used, but the pupil is not dilated and the cornea is not anaesthetized. Although the amplitude of the signal collected by the DTL electrode varies from session to session, this is not a problem, as the photoreceptor fractional circulating current is obtained by normalization of the response family. A method is described for varying the effective flash intensity over a wide range, by controlling the duration of the xenon flash. In order to fit the kinetics of the responses, an analytical equation is derived for the convolution of the previous "delayed gaussian" expression with the cell's capacitive time constant. This equation provides a good description of both the rod and the cone response families. For rods, the capacitive time constant was found to be tau rod approximately 1 msec as reported previously, but for the cones a considerably longer time constant of tau cone approximately 4-5 msec was needed. For rods, the amplification constant (Arod approximately 5 sec-2) was close to previous estimates, but for cones the sensitivity (expressed in terms of corneal illuminance) was higher than in previous work. Calculation of the amplification constant of transduction within the cones requires knowledge of their light collection properties, and the absence of hard information makes this estimate somewhat speculative. However, when account is taken of the larger diameter of the inner segments of cones in the peripheral retina, then our estimated amplification constant for the cones (Acone approximately 3-7 sec-2) is of a similar order of magnitude to that obtained for the rods.

Adult↗

Primary metaplastic carcinoma (carcinosarcoma) of the skin. A clinicopathologic study of four cases and review of the literature.

Metaplastic carcinoma (carcinosarcoma, sarcomatoid carcinoma, malignant mixed tumor) is a biphasic tumor comprising malignant epithelial and heterologous mesenchymal elements. Primary cutaneous cases are rare, with only seven cases documented in the English literature to date. We present four further cases, including three that developed in association with squamous cell carcinoma and one in an eccrine porocarcinoma. Heterologous malignant mesenchymal elements included malignant osteosarcoma, chondrosarcoma, leiomyosarcoma, and rhabdomyosarcomas. In contrast to metaplastic carcinomas arising in visceral sites, those primarily arising in the skin do not appear to behave in a very aggressive manner (Recurrence rate 22%, metastasis rate 22%, overall mortality 11%). However, the numbers involved are small and the follow-up period is short. In view of recent developments and progress in our understanding of the possible histogenesis of such tumors, we suggest that metaplastic carcinoma rather than carcinosarcoma is the most appropriate term with which to describe these very rare cutaneous neoplasms.

Acrospiroma↗

Cutaneous histopathology of Sézary syndrome: a study of 41 cases with a proven circulating T-cell clone.

Sezary syndrome is an uncommon variant of cutaneous T-cell lymphoma (CTCL) characterized by erythroderma, pruritus, adenopathy, and circulating atypical T-lymphocytes with cerebriform nuclei. The definition of Sezary syndrome can be further refined by including only patients with a circulating peripheral blood population of clonal T-cells. We have evaluated 79 skin biopsies from such a group of 41 erythrodermic patients with circulating Sezary cells and a clonal population of T-cells detected by T-cell receptor-beta gene rearrangement on Southern analysis of peripheral blood mononuclear cells. Histopathologic features consistent with chronic dermatitis were observed in 26/79 (33%) skin biopsy specimens, emphasizing that a non-specific histologic appearance is common. Evidence of CTCL was lacking in 11/41 patients on biopsy of their erythrodermic skin. The survival of these patients was not significantly different from 30/41 patients in whom skin biopsies revealed changes diagnostic of CTCL, such as a dermal lymphocytic band with atypical lymphocytes (18/79, 23%) or a mycosis fungoides-like infiltrate (30/79, 38%). This study confirms that non-specific cutaneous histopathologic findings are common in Sezary syndrome, even when a circulating T-cell clone is present. This stresses the need for peripheral blood genetic analysis and for multiple or repeat skin biopsies in erythrodermic patients when there is high clinical suspicion of CTCL.

Aged↗

CD44 variant expression in cutaneous T-cell lymphoma.

Expression of the lymphocyte homing receptor CD44 and its splice variants have been linked to tumour dissemination and poor prognosis in non-Hodgkin's lymphoma. Specifically, the in vitro expression of variant exon V6 confers metastatic potential in rat pancreatic carcinoma cell lines. In this study, we investigated the expression of CD44 splice variants in cutaneous T-cell lymphomas, including patients with mycosis fungoides (MF), Sezary syndrome (SS), large-cell anaplastic lymphoma (LCAL) and HTLV1-associated cutaneous lymphoma. In addition, 4 involved lymph nodes from 2 patients with MF and 1 patient with SS were examined. Inflammatory dermatoses, lichen planus and psoriasis, and normal skin were also studied. Immunohistochemistry was performed using a panel of monoclonal antibodies, including those with specificity for CD44H (standard isoform) and variant exons V3, V6 and V8-9. Normal epidermal keratinocytes were consistently CD44H and CD44 V3, V6 and V8-9 positive. In all the different clinicopathological subtypes and stages of cutaneous T-cell lymphomas, including involved lymph nodes, tumour cells consistently expressed CD44H, but were CD44 V3 and V6 negative. CD44 V8-9 was expressed on a majority of tumour cells in 2/5 LCAL and on occasional tumour cells in 2/5 LCAL. Occasional V8-9 positive tumour cells were also identified in 6/13 MF, 1/4 SS and 3/4 HTLV1. In 2/3 lymph node samples from 2 patients with tumour-stage MF, CD44 V8-9 expression was found on a small percentage of atypical mononuclear cells. Scattered V8-9 positive dermal mononuclear cells were present in sections of lichen planus and psoriasis. We have found no evidence to suggest that the metastasis-associated CD44 variant exon (V6) is expressed in cutaneous T-cell lymphoma, or that CD44H expression is associated with an adverse prognostic group. It is not clear whether the strong expression of CD44 V8-9 in 2 patients with CD30 positive LCAL reflects activation status or metastatic potential.

Alternative Splicing↗

The evaluation of diagnostic and prognostic criteria and the terminology of thin cutaneous malignant melanoma by the CRC Melanoma Pathology Panel.

Sections from 95 skin lesions excised at pigmented lesion clinics in England and Scotland were studied by eight histopathologists in order to evaluate consistency in the use of histopathological terms for features of diagnostic and prognostic importance for cutaneous malignant melanoma. The level of agreement (kappa) amongst the panel improved after discussion and re-definement of criteria for several features. These included, architectural and nuclear atypia, pagetoid infiltration and radial and vertical growth phases. A high level of agreement was achieved for an overall benign or malignant diagnosis (kappa = 0.77) but use of more specific terms such as benign naevi with atypia and melanoma < or = 0.76 mm thickness, was associated with only an intermediate level of agreement. Of the original diagnosis of melanoma, 17% were re-classified by the panel as benign with atypia and 2% reported to be benign were judged to be melanoma. This reflected the high proportion of borderline lesions in the study. The use of standardized diagnostic criteria with precise definitions has been shown to improve consistency in diagnosis and it is recommended for general application. From this should emanate more reliable incidence figures for thin melanoma, and improved understanding of the nature of these early lesions, to the benefit of patient and clinician alike. The poor concordance in distinguishing severe dysplasia in the junctional component of melanocyte proliferations from melanoma in situ and superficial dermal invasion improved only modestly despite intensive efforts. Since melanoma in situ and severe dysplasia cannot be distinguished by objective measurements and since their clinical management is the same, the panel suggests that attempts to separate them in diagnostic reports should be discontinued and they could both be referred to as melanocytic intraepidermal neoplasia (MIN). If it becomes accepted that dermal invasion without a vertical growth component can also be managed identically to MIN, then this invasive radial phase may be appropriately referred to as microinvasion and linked to MIN for the purposes of clinical management.

Biopsy↗

Mesenteric vasculitis associated with Sézary syndrome.

A 71 year old lady with Sézary syndrome presented with chronic diarrhoea and cramping abdominal pains. A small bowel meal x ray examination showed two mid-ileal strictures. At laparotomy the small intestine was found to be sub-acutely obstructed and resection of a 15 cm ileal stricture and stricturoplasty of a second, 10 cm stricture were performed. Histological examination of the stricture revealed a mesenteric vasculitis with secondary ischaemic changes in the small bowel wall. Mesenteric vasculitis causing small bowel stricture may be associated with Sézary syndrome.

Aged↗

Differential expression of desmosomal glycoproteins in keratoacanthoma and squamous cell carcinoma of the skin: an immunohistochemical aid to diagnosis.

The distinction between keratoacanthoma and squamous cell carcinoma is a common dermatopathological dilemma. Although the mainstay of the diagnosis is still clinico-pathological correlation, many dermatopathologists now include keratoacanthomas in the spectrum of squamous cell carcinomas. Recent reports, however, have pointed out that keratoacanthoma is "deficient squamous cell carcinoma" since it loses the expression of bcl-2 antigen, consistent with initiation of apoptosis, i.e. its involution. Electron microscope studies performed in keratoacanthomas and squamous cell carcinomas also revealed significantly reduced desmosomes in squamous cell carcinoma, but not in keratoacanthoma. A series of 38 keratoacanthomas and 62 squamous cell carcinomas of the skin (28 well-differentiated, 21 moderately differentiated and 13 poorly differentiated) were stained immunohistochemically with the monoclonal antibody 32-2B to desmosomal glycoproteins desmoglein 1 and desmoglein 3. Thirty-five keratoacanthomas showed extensive pericellular desmoglein expression. Three keratoacanthomas and 20 squamous cell carcinomas (19 well-differentiated, 1 moderately differentiated) showed focal staining, and in 11 squamous cell carcinomas (2 moderately differentiated, 9 poorly differentiated) the staining was negative. The remaining 31 squamous cell carcinomas (9 well differentiated, 18 moderately differentiated, 4 poorly differentiated) showed juxtanuclear staining. None of the squamous cell carcinomas exhibited the extensive pericellular pattern found in keratoacanthomas. Assessment of staining intensity, by 3 independent examiners, revealed a strong negative correlation between desmoglein expression and degree of dysplasia in the squamous cell carcinomas (p < 0.01). This antibody therefore clearly distinguishes these tumours and may be of value in the differential diagnosis of keratoacanthoma and squamous cell carcinomas in routine histopathology.

Autoantigens↗

Malignant melanoma in childhood.

Malignant melanoma (MM) is rare in childhood. We report 24 cases of MM in children 16 years old or less, whose histopathological specimens were referred to our department from 1981 to 1993. In only three cases was the diagnosis of MM made clinically. In some cases histological distinction from benign Spitz naevi was difficult, but other cases were referred because of a reluctance to diagnose MM in a child. One child died of disseminated disease, two developed nodal metastases and two developed local recurrence. Of all the lesions, the one which was considered to show the least difference from a benign naevus histologically occurred in the child who died. Awareness that MM, although rare, does occur in childhood, is vital. However, diagnosis is difficult, both clinically and histopathologically.

Adolescent↗

Phenytoin-induced toxic epidermal necrolysis: a case report.

We present a case of phenytoin-induced toxic epidermal necrolysis resulting in 60-70% skin involvement. Systemic corticosteroids and prophylactic antibiotics used initially were discontinued, and subsequent management concentrated on intensive supportive treatment. The patient survived, but is left with disabling ocular complications.

Adult↗

Computed tomography in the evaluation of cutaneous T-cell lymphoma.

The computed tomography (CT) scans performed in 28 patients with cutaneous T-cell lymphoma (CTCL) were reviewed. Fifteen patients had clinically advanced cutaneous mycosis fungoides, six patients Sézary syndrome and seven variant CTCL. Of the 40 scans available 12 were normal, 15 indeterminate and 13 abnormal. Indeterminate and abnormal nodes showed a predilection for inguinal and axillary sites with a relative sparing of deep nodal regions. Visceral involvement was infrequent. In six patients CT detected abnormalities not obvious clinically and upstaged the disease. CT should be performed as part of the initial staging and as a baseline for follow-up in patients with advanced mycosis fungoides, Sézary syndrome and variant CTCL.

Adult↗

Symptomatic intracranial involvement by mycosis fungoides.

Involvement of the central and peripheral nervous system by mycosis fungoides is rare and usually occurs in the presence of widespread cutaneous and visceral disease. We describe a patient with mycosis fungoides, previously confined to the skin, who developed intracranial parenchymal disease with no evidence of systemic involvement.

Central Nervous System Diseases↗

p53 immunoreactivity is uncommon in primary cutaneous lymphoma.

p53 gene mutation appears to play an important role in the development of systemic lymphoma, and may be associated with tumour progression. Its role in cutaneous lymphoma is currently unknown. We examined p53 expression in 55 biopsies of cutaneous lymphoma, including patch-, plaque- and tumour-stage mycosis fungoides (MF), T- and B-cell lymphoma and lymphomatoid papulosis. Strong, homogeneous p53 expression, thought to correlate most closely with p53 gene mutation, was seen in only three cases; in a plaque and tumour from a patient with tumour-stage MF, in plaque-stage MF in a patient without tumours, and in one case of CD30+ large-cell anaplastic lymphoma. These data suggest that p53 gene mutation is not a critical step in the development of the majority of primary cutaneous lymphomas.

Humans↗

The first report of familial adult T-cell leukaemia lymphoma in the United Kingdom.

We describe two siblings who developed adult T-cell leukaemia lymphoma (ATLL) within 4 years. Both were black of Afro-Caribbean extraction, but one had been born in the United Kingdom and had visited the Caribbean only once. Both patients were HTLV-1 seropositive, as was their mother; their father and brother were negative. The older sibling had the lymphoma form of ATLL, whilst the younger had chronic ATLL. The former was unresponsive to chemotherapy and died of progressive disease; the latter experienced transient responses to various treatments and is alive 5 years after presentation. Immunophenotyping showed a CD4+, CD25+ phenotype; Southern blot demonstrated a monoclonal integration of HTLV-I in the tissues involved. This report, of the first familial ATLL in the U.K., supports the suggestion of transmission of HTLV-I from mother to child and documents the development of ATLL in second-generation Caribbean immigrants.

Adult↗