Systematic description of an interdisciplinary multimodal pain treatment programme for patients with chronic musculoskeletal pain, using the TIDieR checklist.

OBJECTIVE: To provide a thorough and systematic description of an interdisciplinary multimodal pain treatment programme (IMPT) for patients with chronic musculoskeletal pain (CMP), using the TIDieR checklist as a guide. RESULTS: The main goal of the 'Centre for Integral Rehabilitation (CIR) Excellent' IMPT is to improve daily functioning, participation and quality of life of patients with CMP by helping them to adapt their behaviour so as to better manage their symptoms. A combination of physical and psychosocial treatment methods is employed, including Emotional Awareness and Expression Therapy (EAET), Pain Neuroscience Education (PNE), Acceptance and Commitment Therapy (ACT), graded activity, exposure in vivo, and experiential learning through physical training. The interdisciplinary treatment team comprises physiotherapists, psychologists and a physiatrist. The programme lasts 10 weeks (61 h in total) and consists of three phases: a start (Week 1), education (Weeks 2-3), and skills learning phase (Weeks 4-10). Patients come in twice a week and participate in 2-4 sessions (3-4 h) per treatment day. The programme consists of both individual (physical and mental coaching) and group sessions (education, movement and behaviour outdoors/indoors). Individualisation through personal goal-setting is an important characteristic of the treatment, as well as frequent interdisciplinary consultation between care providers.

Follicular and epidermal alterations in patients treated with ZD1839 (Iressa), an inhibitor of the epidermal growth factor receptor.

We report the cutaneous side-effects of ZD1839 (Iressa), a new anticancer agent that acts by inhibiting epidermal growth factor (EGF) receptor signal transduction. Three patients receiving ZD1839 developed an eruption consisting of follicular papules and pustules in an acneiform distribution as well as diffuse fine scaling of the skin. Additionally, hair growth abnormalities were noted in two patients. Histologically, a superficial purulent folliculitis and disordered differentiation with focal parakeratosis were seen. The follicular eruption appeared to respond favourably to treatment with tretinoin cream and minocycline. The cutaneous adverse effects of ZD1839 are similar to those of other EGF receptor-targeted agents and result from direct interference with the functions of EGF receptor signalling in the skin.

Effect of hypothermia on the hepatic uptake and biliary excretion of vecuronium in the isolated perfused rat liver.

BACKGROUND: Hypothermia prolongs the time course of action of nondepolarizing muscle relaxants. It is not known whether this prolongation is caused by a reduced rate of extrahepatic distribution or elimination, liver uptake, metabolic clearance, or biliary excretion. Therefore, the authors studied the effects of hypothermia on the net hepatic uptake, metabolism, and biliary excretion of vecuronium in isolated perfused rat liver. METHODS: Livers of Wistar rats were perfused with Krebs Ringer solution (1% albumin, 3.3% carbon dioxide in oxygen, pH 7.36-7.42, 38 degrees C). Each perfusion experiment (recirculatory perfusion system) was divided into three phases. In phase 1, a bolus dose of vecuronium (950 microg) was followed by a continuous infusion of vecuronium (63 microg/min) throughout the perfusion experiment. In phase 2, the temperature was reduced to 28 degrees C. In phase 3, temperature was restored. In controls, the temperature was kept constant throughout the perfusion. Concentrations of vecuronium and its metabolites were measured in perfusion medium, bile, and liver homogenate. Parameters of a multicompartmental liver model were fitted to the concentration patterns in perfusion medium and in bile. RESULTS: Hypothermia increased vecuronium concentrations in the perfusion medium from 4.0 microg/ml (range, 2.5-6.6) to 15.6 microg/ml (11.5-18.4 microg/ml; P = 0.018). Hypothermia reduced the biliary excretion rate of 3-desacetyl vecuronium from 18% (range, 6-37%) to 16% (range, 4-19%) of that of vecuronium (P = 0.018). Pharmacokinetic analysis confirmed that hypothermia reduced the rate constants of hepatic uptake and metabolism from 0.219 to 0.053 and from 0.059 to 0.030, respectively. CONCLUSIONS: Hypothermia significantly and reversibly reduced the net hepatic uptake of vecuronium. Hypothermia reduced the metabolism of vecuronium and the biliary excretion rate of 3-desacetyl vecuronium.

Multiple primary melanomas.

BACKGROUND: Patients with clinically diagnosed dysplastic nevi or a family history of melanoma with or without histologically diagnosed dysplastic nevi seem to be at higher risk for the development of multiple melanomas. OBJECTIVE: Our purpose was to determine which factors increased the risk for the development of subsequent melanomas. METHODS: This was a retrospective study in 56 patients with 157 melanomas. RESULTS: Early age at onset (58.9%), clinically diagnosed dysplastic nevi (82.0%), a histologically diagnosed dysplastic nevus (64%), family history of clinically diagnosed dysplastic nevi (70.8%) or melanoma (64.7%) and a histologically diagnosed dysplastic nevus in combination with a family history of melanoma (48%) were found in a high percentage of patients. The mean age at diagnosis was 38.2 years. The mean interval between the first and second melanoma was 34.3 months. Of the second melanomas, 76.8% developed in a different anatomic region from the first melanomas. The mean tumor thickness (Breslow) decreased from 1.11 mm for the first melanomas to 0.90 mm for the second melanomas. CONCLUSION: The results suggest that genetic factors might be involved in a certain subset of patients in whom melanomas develop early and successively.

Clinimetric evaluation of the pain observation scale for young children in children aged between 1 and 4 years after ear, nose, and throat surgery.

This study assessed the reliability, validity, and responsiveness of a new pain measure for children aged 1 to 4 years that was developed from the Children's Hospital of Ontario Pain Scale and its Neonatal Infant Pain Scale. Pain in 311 children, aged 1 to 4 years, was measured by two observers at fixed intervals after adenotonsillectomy (n = 114), adenotomy (n = 109), or insertion of ventilation tubes (grommets) (n = 88) until discharge using a dichotomous pain scale of 9 behavioral and physiological categories. The scale proved to be strongly homogeneous. The interobserver agreement was substantial for 7 items. On these final 7 items, the ability to distinguish between patients with differing degrees of pain and the sensitivity to detect changes over time within each patient were substantial. The resulting Pain Observation Scale for Young Children is reliable and easy to use for assessment of short- and longer-lasting pain after ear, nose, and throat surgery and may be used for assessing pain with other conditions.

Quality assessment by expert opinion in melanoma pathology: experience of the pathology panel of the Dutch Melanoma Working Party.

Some cutaneous melanocytic lesions are notoriously difficult to diagnose by histopathology. For that reason, the Pathology Panel of the Dutch Melanoma Working Party was instituted and is regularly approached to provide an expert opinion on problem cases. In order to identify the most common diagnostic problems, 1069 consecutive referral cases of submitted lesions (1992 to 1994 inclusive) were analysed. About 60 per cent of the requests came from small laboratories, with up to three consultant pathologists. Two-thirds of the lesions reviewed concerned women and nearly 50 per cent of the patients were 30 years of age or younger. In 8 per cent of the cases, the referring pathologists felt unable to make a confident diagnosis; in 14 per cent, melanoma was suspected; and in 12 per cent, a differential diagnosis only had been formulated. The panel felt able to provide an unequivocal diagnosis in 93 per cent of the requests. Of the 158 lesions classified as 'invasive melanoma' by the referring pathologists, 22 were considered to be benign by the panel. Conversely, 108 invasive melanomas (panel diagnosis) had originally been considered as benign lesions, dysplastic naevi or melanoma in situ. These high numbers of discordancies reflect the intrinsic difficulty of the differential diagnoses in this selected material submitted to the panel. Diagnostic difficulties were most often encountered with Spitz naevi and dysplastic naevi. Although the rate of overdiagnosis and underdiagnosis is quite high, in the majority of cases the diagnosis of the referring pathologist matched the diagnosis of the panel. This may reflect a proper awareness of difficult melanocytic lesions in pathology practice. The activities of the Pathology Panel of the Dutch Melanoma Working Party contribute to the improvement of the quality of diagnosis in cutaneous melanocytic lesions, as they increase the number of unequivocal diagnoses and reduce the number of incorrect diagnoses. On the basis of the systematic comparison of the diagnosis by the referring pathologist and the panel, postgraduate teaching and quality control can be more focused on specific diagnostic problems.

Lymph node classification systems in cutaneous T-cell lymphoma. Evidence for the utility of the Working Formulation of Non-Hodgkin's Lymphomas for Clinical Usage.

BACKGROUND: This study was undertaken to compare three classification schemes used to evaluate lymph nodes (LN) obtained from patients with cutaneous T-cell lymphoma (CTCL): a modified Rappaport classification, the National Cancer Institute-Veterans Administration (NCI-VA) classification based on the relative numbers of cerebriform cells in the paracortical areas, and the Dutch classification based on the presence of cerebriform cells with large nuclei in mycosis fungoides (MF) and diffuse infiltration by cerebriform cells in Sézary syndrome. METHODS: A study set of 195 LN obtained from patients with CTCL (MF, Sézary syndrome, and nonepidermotropic T-cell lymphomas) and 14 LN from patients with benign dermatoses was reviewed independently by three groups of pathologists familiar with each classification system. RESULTS: Each classification system provided useful prognostic information. However, contrary to prior reports, no significant difference in survival was apparent in patients with uneffaced LN when classified according to the NCI-VA (LN0-2 versus LN3) or Dutch (Gr0-1 versus Gr2) ratings. In addition, all classification systems demonstrated a poor survival time associated with effaced LN. By combining results from the modified Rappaport and Dutch classifications, three prognostic groups could be identified based on cell morphology: a low-grade category with a small cell histologic subtype (median survival time, 40 months); a high-grade immunoblastic subtype (median survival time, 9 months) composed of cells with an oval nucleus containing a large, usually solitary central nucleolus; and an intermediate-grade category composed of all cases without the distinctive small cell and immunoblastic morphologies (median survival time, 26 months). CONCLUSIONS: The authors propose that clearly involved LN in CTCL can be categorized on the basis of cell morphology into prognostic groups analogous to what has been proposed for the Working Formulation for Non-Hodgkin's Lymphomas for Clinical Usage.

Diagnostic and prognostic significance of clonal T-cell receptor beta gene rearrangements in lymph nodes of patients with mycosis fungoides.

In this study, 25 involved and uninvolved lymph nodes from 22 patients with mycosis fungoides (MF) and seven dermatopathic lymph nodes from patients with benign skin disorders were studied for the presence of clonal T-cell receptor beta (TCR beta) gene rearrangements by Southern blot analysis. These results were correlated with the histological classification, follow-up data, and survival. The results of the histological classification and Southern blot analysis were concordant in 26 of 32 cases. Clonal TCR beta gene rearrangements were found in all six MF lymph nodes showing (partial) effacement of the normal lymph node architecture, but in none of the eight uninvolved dermatopathic MF lymph nodes and in none of the seven dermatopathic control lymph nodes. In addition, in 5 of 11 dermatopathic MF lymph nodes that were considered to have early involvement by MF at histological examination, clonal TCR beta gene rearrangements were detected. In the group of MF patients with dermatopathic lymphadenopathy, patients with detectable clonal T-cell populations had a significantly shorter survival than patients without such a population (P < 0.01). The results of this study indicate that within the group of dermatopathic MF lymph nodes, prognostically different groups can be distinguished and that TCR beta gene rearrangement analysis may be an important adjunct in the early diagnosis of lymph node involvement by MF.

PUVA keratosis. A clinical and histopathologic entity associated with an increased risk of nonmelanoma skin cancer.

BACKGROUND: Various types of hyperkeratotic lesions can be observed in patients with psoriasis treated with PUVA. Clinically it can be difficult to classify them and to differentiate benign from malignant hyperkeratotic lesions. Recently, we introduced the term PUVA keratosis, which we regard as a distinct entity. OBJECTIVE: The purpose of the study was to describe in more detail the clinical and histopathologic features of PUVA keratoses and to investigate a possible relation with nonmelanoma skin cancer. METHODS: A group of 13 psoriasis patients with PUVA keratoses was studied and compared with 247 psoriasis patients without these keratoses, who had also received long-term therapy with PUVA. RESULTS: The presence of PUVA keratoses was associated with an increased risk of nonmelanoma skin cancer. The estimated relative risk for skin cancer in patients with PUVA keratoses, adjusted for age, sex, and UVA dose, as compared with psoriasis patients without these keratoses, who had also received long-term PUVA treatment, was 6.5 (95% confidence interval, 1.3 to 32.1). Squamous cell carcinomas contributed the most to this increased risk. CONCLUSION: PUVA keratoses are associated with an increased risk of nonmelanoma skin cancer. Therefore careful clinical follow-up of psoriasis patients with PUVA keratoses is necessary, and cessation of PUVA treatment should be considered.

Validity of the histopathological criteria used for diagnosing dysplastic naevi. An interobserver study by the pathology subgroup of the EORTC Malignant Melanoma Cooperative Group.

Ten (dermato)pathologists studied 50 cutaneous melanocytic lesions including common naevocellular naevi, dysplastic naevi (DN), melanomas in situ and invasive primary melanomas, with emphasis on the histological criteria of DN. Using a standardised form, 20 defined histopathological features were scored (semi)quantitatively. Concordance of diagnosis, efficacy and reproducibility of features were investigated. DN were distinguished well from the other entities (mean Po 0.87). Agreement on the degree of atypia of DN was low. The reproducibility of the scoring was best for the following features: irregular nests, lymphohistiocytic infiltrate, marked junctional proliferation and large nuclei. The overall values of these features to discriminate between DN and non-DN were better than for the other features studied. Using the presence of at least three of the four features as a condition for the diagnosis of DN, values for sensitivity, specificity and positive and negative predictive values were 0.86, 0.91, 0.96 and 0.73, respectively. On the basis of the results these features seem best suited as histological criteria for the diagnosis of DN.

Multiple primary melanomas in a patient with familial-type DNS during clomiphene-induced pregnancy.

A 35-year old woman developed six primary cutaneous melanomas during her third pregnancy. She had received clomiphene treatment for nearly 2 years previously. She developed two more primary melanomas 15 and 21 months after giving birth. All melanomas were histologically associated with preexisting dysplastic naevi. The patient showed the characteristic phenotype of the dysplastic naevus syndrome; a cousin and an aunt were treated for malignant melanoma and the patient's brother had histologically confirmed dysplastic naevi. The course of her first two pregnancies was not complicated by the development of melanomas. We suggest that clomiphene may have played a role in the activation or progression of these 'precursor lesions' into malignant melanoma.

Cutaneous pseudo-T-cell lymphomas. A clinicopathologic study of 20 patients.

The histologic features of 20 patients with cutaneous pseudo-T-cell lymphomas other than actinic reticuloid and lymphomatoid papulosis were investigated. Two histologic types of cutaneous pseudo-T-cell lymphomas were designated. The band-like (MF-like) pattern that simulated mycosis fungoides (MF) and a nodular pattern that mimicked cutaneous T-cell lymphomas (CTCL) other than MF. Both patterns showed histologic features that generally are not found in CTCL and thus may be helpful in the differential diagnosis from CTCL. However, at present the differential diagnosis between pseudo-T-cell lymphomas and CTCL should be based on a combination of clinical and histologic data.

Differential diagnosis of cutaneous large cell lymphomas using monoclonal antibodies reactive in paraffin-embedded skin biopsy specimens.

We studied a large panel of monoclonal antibodies reactive on routinely processed paraffin-embedded tissue to determine their sensitivity and specificity in the diagnosis of 35 primary cutaneous large cell lymphomas of B- (n = 14) and T-cell origin (n = 21). The findings show that differentiation between clinically relevant subgroups can be obtained by a small panel of antibodies including L26, MB2, LN1, MT1, UCHL1, and Ber-H2. Pitfalls in the use of the reagents are discussed.

Mycosis fungoides-like lesions associated with phenytoin and carbamazepine therapy.

We report the cases of four patients who were taking the anticonvulsant drugs phenytoin or carbamazepine and in whom skin lesions developed that showed histologic features suggestive of mycosis fungoides. Two patients had a solitary lesion on the trunk, whereas the other two patients had multiple plaques. In all four patients systemic signs were absent.

Serum-sickness-like illness as a complication after streptokinase therapy for acute myocardial infarction.

We report a case of serum-sickness-like illness in a 47-year-old patient who received early high-dose intravenous and intracoronary streptokinase following acute myocardial infarction. The picture comprised severe arthralgias, fever, an urticarial rash and marked elevation of circulating immune complexes. This case represents a rare complication of streptokinase therapy.

Prognostic significance of CD30 (Ki-1/Ber-H2) expression in primary cutaneous large-cell lymphomas of T-cell origin. A clinicopathologic and immunohistochemical study in 20 patients.

The histologic and immunophenotypical features of 20 primary cutaneous large-cell lymphomas of T-cell origin were investigated and correlated with clinical data to obtain prognostically relevant criteria. Histologic evaluation, using the updated Kiel classification, showed that these large-cell lymphomas represent a morphologic spectrum, often making classification rather arbitrary. It is therefore concluded that the clinical relevance of histologic subtyping is limited for this group of lymphomas. Immunophenotypical studies revealed significant differences between CD30-positive and CD30-negative lymphomas. CD30-positive lymphomas generally presented with localized skin disease, and had a favorable prognosis (9 of 10 patients alive and in complete remission; median survival, 37 months). In contrast, CD30-negative lymphomas often presented with or rapidly developed generalized disease; all patients died of lymphoma (median survival, 17 months). These findings suggest that CD30 expression is an important prognostic parameter for this group of primary cutaneous large-cell lymphomas.