Longitudinal Speech Outcome at 5 and 10 Years in UCLP: Influence of Speech Therapy and Secondary Velopharyngeal Surgery.

OBJECTIVE: To investigate speech development of children aged 5 and 10 years with repaired unilateral cleft lip and palate (UCLP) and identify speech characteristics when speech proficiency is not at 'peer level' at 10 years. Estimate how the number of speech therapy visits are related to speech proficiency at 10 years, and what factors are predictive of whether a child's speech proficiency at 10 years is at 'peer level' or not. DESIGN: Longitudinal complete datasets from the Scandcleft project. PARTICIPANTS: 320 children from nine cleft palate teams in five countries, operated on with one out of four surgical methods. INTERVENTIONS: Secondary velopharyngeal surgery (VP-surgery) and number of speech therapy visits (ST-visits), a proxy for speech intervention. MAIN OUTCOME MEASURES: 'Peer level' of percentage of consonants correct (PCC, > 91%) and the composite score of velopharyngeal competence (VPC-Sum, 0-1). RESULTS: Speech proficiency improved, with only 23% of the participants at 'peer level' at 5 years, compared to 56% at 10 years. A poorer PCC score was the most sensitive marker for the 44% below 'peer level' at 10-year-of-age. The best predictor of 'peer level' speech proficiency at 10 years was speech proficiency at 5 years. A high number of ST-visits received did not improve the probability of achieving 'peer level' speech, and many children seemed to have received excessive amounts of ST-visits without substantial improvement. CONCLUSIONS: It is important to strive for speech at 'peer level' before age 5. Criteria for speech therapy intervention and for methods used needs to be evidence-based.

Expression of integrins and E-cadherin in squamous cell carcinomas of the head and neck.

Integrins and cadherins are cell adhesion molecules suggested to play an important role in malignant progression and tumour differentiation. Our aim was to characterise the pattern of expression and the relations between integrin beta1, beta4, beta6 and E-cadherin and the different histopathological features important when judging tumour differentiation, using a well-defined scoring system. Formalin-fixed paraffin-embedded pre-irradiation biopsies from 85 patients with head and neck squamous cell carcinomas (HNSCC) were stained and evaluated for the expression of integrin beta1, beta4 and beta6 and E-cadherin. The integrins were upregulated in carcinomas compared to the adjacent mucosa and E-cadherin was downregulated. However, differences were found within the tumour: Expression of E-cadherin was lost and the three integrins were upregulated at the tumour borders, compared to central parts of the tumour biopsy. Expression of the integrins did not correlate with tumour or histopathological parameters, whereas expression of E-cadherin was correlated with high degree of keratinisation, high nuclear maturation and few mitoses - factors that characterise well-differentiated carcinomas -and E-cadherin can therefore be considered as a marker of differentiation. Furthermore, loss of adhesion expressed by low E-cadherin and integrin beta4 correlated with the presence of nodal metastases at the time of diagnosis.

Prognostic indicators for malignant tumours of the parotid gland.

The best treatment of malignant parotid tumours still remains to be defined, and a better knowledge about the tumour features that predict the treatment result is needed. The histological classification of parotid tumours may present difficulties on account of their great morphological diversity. In a series of 152 patients with a malignant tumour of the parotid gland, the prognostic factors and treatment results were investigated over a 25-year period. Treatment consisted of surgery, radiation therapy or a combination (49%, 13% and 38% respectively). Crude 5-year survival was 50% with significant differences related to stage (stage I, 65%; stage II, 50%; stage III, 21%; and stage IV, 9%). With respect to histopathology, the adenoid cystic carcinomas and the acinic cell carcinomas had the best prognosis (76% and 67% 5-year crude survival and 53% and 67% 10-year crude survival respectively). There was a significant difference in crude survival between well/intermediate and poorly differentiated tumours (P = 0.007). In a Cox hazard regression analysis including 136 patients and using death from cancer as the end-point, the following parameters were independent prognostic predictors: T-classification (P = 0.002), M-classification (P < 0.0001), N-classification (N+versus N0) (P = 0.005), local invasion (P = 0.003) and histological differentiation of the tumour (P = 0.03). The TNM system is a good predictor of treatment outcome for malignant parotid tumours. The use of a combination of clinical and histological factors will assist the design of treatment strategies for parotid gland tumours.

The value of amino-terminal propeptide of type III procollagen in routine screening for methotrexate-induced liver fibrosis: a 10-year follow-up.

BACKGROUND: Methotrexate (MTX) -induced liver damage is an important complication in patients treated with this drug for skin disease. Reliable non-invasive monitoring tests would have considerable importance. OBJECTIVES: This retrospective study was designed in order to evaluate if serial normal serum levels of amino-terminal propeptide of type III procollagen (PIIINP) might indicate that no significant fibrosis is taking place in the liver, and thereby reduce the need for repeated liver biopsies in psoriatic patients treated with MTX. METHODS: The clinical records of 70 patients with psoriasis, who in the years 1989/90 were on MTX and had both a liver biopsy without fibrosis and a normal PIIINP, were examined and followed until the patient stopped taking the drug. The follow-up time was from 1 to 11 years. RESULTS: A total of 189 liver biopsies and 329 analyses of PIIINP were recorded. Twenty-one patients had only one and no further biopsies, but their data included at least two to three PIIINP samples obtained within a year around the time of the biopsy, and at least two were taken either prior to or at the time of the biopsy. The remaining patients had from two to seven liver biopsies each and a total of 267 analyses of PIIINP. In the study period only four patients developed fibrosis of the liver as shown by liver biopsies, and all four of these patients developed elevated serum PIIINP levels. In addition two further patients, one of them with psoriatic arthritis, had elevated PIIINP, but normal liver biopsy. Thus no liver fibrosis was missed in the 63 patients with consistently normal PIIINP levels. CONCLUSIONS: Present data support the view that, as long as PIIINP is consistently normal in serial investigations, there is minimal risk of development of substantial liver fibrosis.

Intracutaneous injection of lysophosphatidylcholine induces skin inflammation and accumulation of leukocytes.

Various cell stimuli act through activation of phospholipase A2, which hydrolyses fatty acids from membrane phospholipids, resulting in the formation of fatty acids and lysophospholipids. One of the lysophospholipid classes, lysophosphatidylcholine, is a chemoattractant for monocytes and T-lymphocytes and induces the expression of adhesion molecules on cultured endothelial cells. The purpose of the present study was to determine whether lysophosphatidylcholine possesses proinflammatory properties in vivo. This was assessed clinically and histologically by intracutaneous injection of 200-800 nmol lysophosphatidylcholine in healthy volunteers. Lysophosphatidylcholine elicited a dose- and time-dependent local erythema and oedema. The erythema disappeared within 4 h, while the induration lasted for up to 48 h. HE-stained biopsies taken after 24 h showed a leukocytoclastic vasculitis in 2 of the 6 subjects. Microscopic examination of immunohistochemically stained biopsies taken 24 h after the injection showed a significant increase in the number of T-lymphocytes, monocytes and neutrophils, whereas the number of Langerhans' cells was unchanged after lysophosphatidylcholine injection. In addition, the number of intercellular cell adhesion molecule-1 and -3-positive cells was increased approximately 3-fold after injection of lysophosphatidylcholine. In conclusion, the phospholipase A2 hydrolysis product lysophosphatidylcholine can induce erythema, oedema, a mixed cellular infiltrate and the expression of adhesion molecules.

[Child psychiatric in-patient treatment]. / Behandlingsformer under børnepsykiatrisk indlaeggelse.

This article describes the Danish part of a multinational epidemiological point-prevalence study concerning child psychiatric in-patient treatment, which aims to describe different kinds of treatment methods used in child psychiatric in-patient care. The study includes all 10 child psychiatric in-patient units in Denmark. Data on psychiatric treatment modalities were collected by means of a questionnaire in spring 1990 on 192 children, which included all of the actual in-patients (100%). Primary caretaking was the main treatment method (100%), individual psychotherapy was offered to one third, as was family therapy. Eight percent were medicated, 6% with psychoactive drugs. The study showed that medication in child psychiatric in-patient care was rare, and was never the only treatment method. A range of psychotherapeutic methods were used.

Lack of predictive value of potential doubling time and iododeoxyuridine labelling index in radiotherapy of squamous cell carcinoma of the head and neck.

PURPOSE: To investigate the prognostic value of T(POT), S-phase time (TS), iododeoxyuridine (IdUrd) labelling index (LI) and DNA index with loco-regional tumour control as the end-point. MATERIALS AND METHODS: Iododeoxyuridine was given to 99 patients with squamous cell carcinomas of the head and neck before the start of radiotherapy. The analysis included FCM parameters (LI, TS, T[POT] and DNA index, n = 87) and LI determined by immunohistology (IHC, n = 45). A hybrid T(POT) was determined by combining the FCM TS and the IHC LI (n = 45). In diploid tumours (n = 39), the FCM LI was underestimated and the FCM T(POT) was overestimated because the flow cytometer was unable to distinguish between tumour and normal cells. The 'tumour LI' was defined as the IHC LI or the FCM LI of aneuploid tumours when a biopsy for IHC evaluation was not available and similarly the 'tumour T(POT)' was determined by the hybrid T(POT) or the FCM T(POT) of aneuploid tumours (n = 63). RESULTS: There was good agreement between the IHC LI and the FCM LI for aneuploid tumours, but there was disagreement for diploid tumours. The median tumour T(POT) was 4.1 days (range 0.6-19.5 days) and the median tumour LI was 12.9% (range 3.1-46.0%). In a univariate analysis there was no prediction of loco-regional tumour control by the LI, the TS or the T(POT) determined by either of the methods. T-classification, N-classification, clinical stage and tumour diameter were related with loco-regional tumour control, whereas clinical stage was the only parameter that yielded independent prognostic significance in a multivariate analysis. CONCLUSIONS: This study does not confirm the significant prognostic value of T(POT) as indicated in some previous reports. Larger clinical studies are needed to draw final conclusions.

Immunohistochemical expression of IL-10 in mycosis fungoides.

Immunoreactivity of the cytokine IL-10 has been investigated in situ in mycosis fungoides (MF). Expression of IL-10 was detected using immunohistochemistry in skin biopsies (n = 8) and T-cell lines (n = 2) from mycosis fungoides patients. IL-10 positivity was seen in the dermal cell infiltrates and in T-cell lines in mycosis fungoides. The dermal IL-10 reaction in a skin biopsy from an active lesion in MF indicates the possibility for disease progression.

The flashlamp-pumped dye laser and dermabrasion in psoriasis--further studies on the reversed Köbner phenomenon.

Eleven patients with chronic plaque psoriasis were treated with the flashlamp-pumped pulsed dye laser and 6 of the same patients were at the same time treated by dermabrasion. Complete remissions were observed in 3 patients following laser-treatment and in 5 of 6 after dermabrasion. The observation periods were from 4 to 9 months. Our data suggest that the mechanism of the reversed Köbner phenomenon, which is thought to be responsible for the results of dermabrasion, is partly due to destruction of the dermal papillary vasculature. Partial responses were seen in 6 laser-treated and in one patient treated by dermabrasion. Two patients showed no response to laser treatment. These clinically unsatisfactory results can be explained by the great variety in thickness of plaques and in variability of penetration of the laser light. Measurements of absorption and scattering properties of plaques scheduled for laser treatment could probably allow improvements in the technique by optimizing laser beam diameter and pulse duration as well as wavelength and energy levels. The use of the dye laser is far less traumatic to the patient than dermabrasion.

Cancer of the nasal cavity and paranasal sinuses. A clinico-pathological study of 277 patients.

In the period 1963-1991, a total of 277 consecutive patients with malignant tumours of the nasal cavity and paranasal sinuses were treated at Aarhus University Hospital. The major histological types included squamous cell carcinoma (46%), lymphoma (14%), adenocarcinoma (13%), and malignant melanoma (9%). Kaplan-Meier estimates of 5-year corrected survival (death from cancer) showed the best prognosis for adenoid cystic carcinoma (87%), adenocarcinoma (65%) and lymphoma (56%), and the poorest prognosis for undifferentiated carcinoma (17%) and malignant melanoma (24%). The 5-year corrected survival for squamous cell carcinoma was 35%. Of the 180 patients with treatment failure, the vast majority occurred locally (n = 166); a minor proportion was regional (n = 23) or distant (n = 30). For the 195 patients with carcinoma, the following parameters were of statistical prognostic significance (5-year corrected survival): histological differentiation (moderate-well 65% vs. poor 22%), primary T-site (nasal cavity 56% vs. maxillary antrum 39% vs. other sinuses 24%), tumour stage (T2 68% vs. T3 37% vs. T4 29%), nodal stage (N0 48% vs. N1-3 21%), treatment (radiotherapy + surgery 56% vs. radiation alone 35%).

Determinants of decision-making in the screening procedure of a community psychiatric service.

This study is a predictor analysis of the screening procedure followed by a psychiatric service for a period of 1 year preceding and a period of 1 year following the introduction of community psychiatry. Throughout this period, the psychiatric service consisted of a local service within the catchment area and a central service at a psychiatric hospital outside the area. At the time of the reorganization, the responsibility for the psychiatric service was transferred from the public health authorities to the social services. Before the reorganization, screenings were conducted on the basis of referral papers or simply as a result of telephone communication. After the reorganization, the screening procedure was intensified by means of a pre-examination. One aim of the reorganization was to ensure that the severely mentally ill take priority over patients characterized predominantly by social strain. Patients with manic-depressive psychosis and other psychoses showed a significantly increased probability of being accepted for treatment, whereas those with schizophrenia showed no significant increase, irrespective of the service reorganization. Similarly, manic-depressive psychosis and other psychoses (not schizophrenia) were significant predictors of hospitalization at the mental hospital outside the catchment area as well as hospitalization in the local facilities, irrespective of the service reorganization. Indicators of social strain were not given higher priority following the service reorganization.

Histopathologic, stereologic, epidemiologic, and clinical parameters in the prognostic evaluation of squamous cell carcinoma of the oral cavity.

BACKGROUND: Prognostic indicators that could assist in a more precise selection of patients with oral cancer for differentiated therapy would be clinically valuable. METHODS: A consecutive series of 161 cases of intraoral squamous cell carcinoma (SCC) occurring during a 5-year period in a population of 1.4 million inhabitants, was evaluated by histopathologic (the modified classification of Jakobsson et al.), stereologic, clinical, and epidemiologic parameters and the serum markers hemoglobin and rhesus blood group. RESULTS: Univariate analysis established a significant prognostic value in terms of cause-specific survival for T stage (P < .0001), stage (P < .0001), maximum tumor diameter (P < .0001), N stage (N+/NO) (P < .0001), alcohol consumption (P = .03), stereologic estimates of nuclear volume (P = .04), and the histomorphologic parameters mode of invasion (P = .001), pattern (P = .01), vascular invasion (P = .02), depth (P = .006), and mean histologic score. Tobacco consumption was borderline significant (P = .055). A multivariate analysis using the Cox proportional hazard analysis showed that both clinical (stage, P < .0001; size, P = .0027), epidemiologic (tobacco consumption, P = .0054), morphohistopathologic (mode of invasion P < .0001), and stereologic (nuclear volume, P = .0010) parameters had an independent significant effect on survival. Inversely, the mean histologic score had no prognostic value. From the final regression model prognostic forecasts were calculated. Twelve patients (25%) with stage I disease had unfavorable histologic and stereologic parameters. The observed survival (+/- 1 standard error of the estimate) for these patients was 33% +/- 18%. The observed survival for stage I patients with more favorable histologic and stereologic characteristics (n = 36) was 76% +/- 8%. CONCLUSION: The use of a combination of clinical, histologic, epidemiologic, and stereologic parameters will assist the design of treatment strategies for intraoral SCC.

Methotrexate-induced liver cirrhosis. Clinical, histological and serological studies--a further 10-year follow-up.

BACKGROUND: Methotrexate (MTX) may induce liver damage, which in some psoriatics will lead to fibrosis or cirrhosis. Studies performed 10 years ago on 25 patients with MTX-induced liver cirrhosis indicated that this type of cirrhosis was not of an aggressive nature. OBJECTIVE: The aim of this study was to evaluate the present status of surviving patients 10 years later, together with the latest clinical and histological data on patients who had died. METHODS: The investigations were carried out on 186 liver biopsies and 5 autopsies. All biopsies were studied by the same pathologist. Eleven surviving patients were also studied by analysis of serum aminoterminal propeptide of type III procollagen (PIIINP), which is an indicator of fibrogenesis, which is especially suitable for follow-up of fibrotic liver disease. RESULTS: Thirteen patients had died; 1 of these died of liver failure. Another patient died form an overdose due to misunderstanding of the prescribed dosage given elsewhere. The remaining deaths were non-MTX related, but all 5 autopsies showed some degree of cirrhosis. On the other hand, 13 patients had no histologically verified liver cirrhosis in their latest biopsy, and PIIINP was within the normal range in all 11 patients investigated, this in spite of total cumulative MTX doses from 1,120 to 18,645 mg (mean 7,171 mg). CONCLUSIONS: This study confirmed that in most patients MTX-induced liver cirrhosis is not aggressive. However, continued low-dose MTX led, in spite of normal liver tests, 8 years after the last biopsy to liver failure and death in 1 of our patients. Our data support the continued use of liver biopsies in the surveillance of MTX-treated psoriatics.

Observer variation in histological classification of cutaneous malignant melanoma.

To evaluate the variations within and between observers in the interpretation of important histological prognostic factors, a series of 96 melanoma patients was randomly selected from a database of 1691 patients with cutaneous malignant melanoma. The stained sections were examined on two occasions by four experienced pathologists. Analysis by observed agreement and kappa statistics showed maximal tumour thickness to be the best reproducible variable, with ulceration the second best. Regression was the least reproducible, with level of invasion and type of melanoma in the mid range. Intra-observer variation was uniformly less than inter-observer variation for each variable. For tumour thickness a variance component analysis was done to quantify the variability further. The clinician should not base his choice of treatment entirely on the microscopic classification but take into consideration the clinical course and appearance of the tumour.

Histological differentiation of oral squamous cell cancer in relation to tobacco smoking.

The aim of this study was to assess the potential effect of tobacco and alcohol consumption on the histological differentiation of oral squamous cell carcinomas in 161 consecutive patients. The patients were included in a prospective study to secure valid data on tobacco and alcohol consumption. The histopathological grading system included eight morphological qualities describing both the tumour cell population and the interaction between tumour and host. A mean histological score was calculated as the arithmetic mean of the scored individual morphological parameters. Tobacco consumption, as opposed to alcohol consumption, was shown to be significantly correlated with the mean histological score (P = 0.0009), and with the four morphological qualities describing the tumour cell population: pattern (P = 0.0044), cytoplasmic differentiation (P = 0.0008), nuclear differentiation (P = 0.0054) and mitosis (P = 0.0001). Thus, tobacco consumption seems to cause the tumour cells of oral squamous cell carcinomas to undergo a more pronounced dedifferentiation which makes them more aggressive. This effect is enhanced with increasing exposure to tobacco smoke.

Prognostic value of pretreatment factors in patients with locally advanced carcinoma of the uterine cervix treated by radiotherapy alone.

The prognostic effect of pretreatment patient- and tumor characteristics, and the influence of radiotherapy schedule on local control, distant metastases, and crude survival were analyzed in 424 consecutive patients with FIGO stage IIB (n = 137), IIIA (n = 10), IIIB (n = 211) and IVA (n = 66) cancer of the uterine cervix. All patients were given radiotherapy alone. From 1974 and through 1977, the external and intracavitary combined radiotherapy was given continuously in 4 to 6 weeks. From 1978 and through 1983, the treatment policy was changed to split-course radiotherapy by introducing planned pauses, resulting in an overall treatment time of 10 to 12 weeks. The results were estimated by univariate actuarial- and Cox multivariate regression analyses. Multivariate analysis showed that significant adverse variables for local control were large lateral tumor diameter, young age, low hemoglobin at time of admission, many pregnancies, split-course strategy, and high FIGO stage. Risk of metastases increased with decreasing hemoglobin, increasing malignancy grade and split-course treatment. Poor survival probability were related to large lateral tumor diameter, high malignancy grade and FIGO stage, low hemoglobin, split-course therapy, and adeno/adenosquamous tumor type.

Photopheresis in the red man or pre-Sézary syndrome.

BACKGROUND: The beneficial effect of extracorporeal photochemotherapy has clearly been established for patients with cutaneous T-cell lymphoma with Sézary's syndrome. But this treatment has not been used in the red man syndrome or pre-Sézary syndrome. Some of these patients do not respond sufficiently or do not tolerate other therapies. OBJECTIVE: The purpose of this open study was to evaluate the clinical efficacy of photopheresis in this group of patients. METHODS: Seven patients with the red man syndrome were treated on 2 consecutive days every 4 weeks for 6-22 months. Six had been on systemic steroids and 3 had also received retinoids without sufficient effects. All were initially treated with topical nitrogen mustard but no longer tolerated this treatment. RESULTS: All signs of erythroderma disappeared in 6 of the 7 patients. All systemic therapy could be discontinued in all but 2 patients. No side effects were observed. CONCLUSION: Photopheresis may be an effective alternative treatment for this group of patients, when other types of therapy have failed.

Toxic epidermal necrolysis and erythema multiforme following therapy with terbinafine.

We report two cases with severe skin reactions following oral terbinafine (Lamisil) therapy. The first case was a 49-year-old woman with onychomycosis of the toe nails. She had suffered from diabetes for 3 years, but it was well controlled on insulin. Five days after start of terbinafine 250 mg once daily she developed erythema. The treatment was continued for 2 days, but the skin eruption progressed, and a clinical diagnosis of toxic epidermal necrolysis was confirmed histologically. The second case was a 51-year-old woman with dermatomycosis on the right foot. She developed a papular eruption in the second week after taking terbinafine 250 mg once daily. Despite this eruption she continued treatment for 6 days. Generalized erythema multiforme developed in the following days. Terbinafine is a recently introduced efficacious fungicidal drug. This is the first report of toxic epidermal necrolysis following terbinafine.

[Malignant parotid tumors. Therapeutic results and prognosis in 110 consecutive patients]. / Maligne parotistumorer. Behandlingsresultater og prognose hos 110 konsekutive patienter.

The UICC 1987 TNM classification system was used to retrospectively analyze the treatment results and prognostic factors in 110 consecutive patients diagnosed and treated from 1970 to 1986. Treatment consisted of surgery, radiotherapy, or a combination. Malignant mixed tumours were seen in 28% of the patients, mucoepidermoid tumours in 18%, adenoid cystic tumours in 15%, acinic tumours in 13%, undifferentiated tumours in 11%, adenocarcinomas in 10%, and other types in 5%. Ten-year corrected survival was 52%, and significant differences in survival were found between: 1. patients with disease stage I-IV (I: 85%, II: 69%, III: 43%, IV: 14%); 2. those with local tumour extension (34%) and without local tumour extension (79%); 3. patients with facial nerve palsy (0%) and without facial nerve palsy (57%); 4. those with low- or intermediate-grade tumours (69% combined) and those with high-grade malignant tumours (30%). Forty-five percent of the patients were cured after primary treatment, as were an additional 22% of those treated for local or neck node recurrences. It is concluded that there is a good correlation between TNM classification of UICC 1987 (stage and local extension of tumour) and prognosis, and that facial nerve palsy and grade of malignancy are important prognostic factors.