Differential expression pattern of Bcl-2 family members in B and T cells in systemic lupus erythematosus and rheumatoid arthritis.

OBJECTIVE: This study aimed to evaluate the expression level of anti-apoptotic Bcl-2 family proteins in B and T cells in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in relation to disease activity and the effect of various Bcl-2 family inhibitors (BH3 mimetics) as potential treatment. METHODS: We included 14 SLE patients, 12 RA patients, and 13 healthy controls to study anti-apoptotic Bcl-2, Bcl-XL, and Mcl-1 expression and cell survival in different B and T cell subsets using stimulation assays and intracellular flow cytometry. Effect of various BH3 mimetics was assessed by cell viability analyses. RESULTS: In SLE, significant differences in Bcl-2 family members were confined to the B cell compartment with decreased induction of Bcl-XL (p ≤ 0.05) and Mcl-1 (p ≤ 0.001) upon CpG stimulation. In RA, we did not observe any differences in expression levels of Bcl-2 family proteins. Expression patterns did not correlate with disease activity apart from decreased induction of Mcl-1 in B cells in active SLE. After in vitro stimulation with CpG, plasmablasts were more viable after treatment with three different BH3 mimetics compared to naïve or memory B cells in control and patient cells. After activation, Mcl-1 inhibition was most effective in reducing plasmablast and T cell viability, however, less in patients than controls. CONCLUSION: Our study provides evidence for the increased differential expression pattern of Bcl-2 family members in B and T cell subsets of patients with SLE compared to controls. Tested BH3 mimetics showed higher efficacy in controls compared to both autoimmune diseases, though nonsignificant due to low patient numbers.

Sensitivity and specificity in a longitudinal temporomandibular disease study.

A longitudinal prospective study on the development of temporomandibular disease (TMD) in children was initiated in 1970. The study ended in 1990. One of several diagnostic TMD criteria applied was osteoarthrosis, defined as a 'morphological and/or structural deformity of the condyle' diagnosed on radiographs. Although these radiographic techniques are suspect in terms of falsenegative findings, 'morphological and/or structural deformity of the condyle' has been shown to be associated with a characteristic craniofacial form. As such, it has confirmed diagnostic significance. The present study will test the reliability of this diagnosis using cross-sectional and longitudinal findings for objective signs and subjective symptoms that are attributed to TMD. Signs and symptoms of TMD performed poorly as predictors for 'morphological and/or structural deformity of the condyle'. Thirty-seven percent of the participants had a 'morphological and/or structural deformity of the condyle' diagnosed at least once during the 20-year study period. In two thirds of the cases, 'morphological and/or structural deformity of the condyle' was not a stable characteristic through time. Normal radiographic anatomy of the condyle was often associated with signs and symptoms. We arrive at the conclusion that TMD is an umbrella, housing several overlapping problems that may manifest themselves at irregular intervals or even may disappear completely.

Correlation between arthroscopically observed changes and synovial light microscopic findings in osteoarthritic temporomandibular joints.

The aim of this study was to determine the correlation between arthroscopically observed (ASC) changes in the synovial membrane and other joint components and synovial light microscopic (LM) findings in the temporomandibular joint (TMJ). Synovial membrane biopsies were obtained during unilateral arthroscopy in forty patients. Thirty-one patients were diagnosed with TMJ osteoarthritis (OA) and nine patients with non-osteoarthritic conditions of their TMJs. Correlations between ASC and synovial LM findings were analyzed with Cohen's Kappa and Spearman's rank correlation tests. Values for Kappa of 0.6 and higher and values for a correlation coefficient of 0.7 and higher were considered satisfactory. No correlations were found in the retrodiscal tissue biopsies. In the anterodiscal tissue biopsies, ASC hypervascularity correlated with LM intima cell shape and cell density. ASC lowered attachment to the anterior slope of the articular eminence correlated with the LM presence of a fibrous intima matrix. In several TMJs, a high concurrence was observed between ASC and LM pathologic changes. The severity of pathologic changes as observed by LM was, however, often less than was suggested arthroscopically.

A placebo-controlled study of intravesical pentosanpolysulphate for the treatment of interstitial cystitis.

OBJECTIVE: To evaluate the therapeutic efficacy of intravesical pentosanpolysulphate (PPS) compared with placebo in patients with interstitial cystitis (IC). PATIENTS AND METHODS: Twenty patients who fulfilled the diagnostic criteria for IC participated in a double-blind placebo-controlled study; 10 received intravesical PPS (300 mg in 50 mL of 0.9% sodium chloride) applied twice a week for 3 months and the other 10 received a placebo. Symptomatic relief and objective variables (bladder capacity voiding volumes and urinary frequency) were assessed after 3 months and the long-term outcome of those continuing treatment was determined. RESULTS: Of the patients treated with PPS, four gained significant symptomatic relief compared with only two receiving placebo. Only the urodynamic bladder capacity showed a statistically significant increase in patients treated with PPS (P = 0.047). At 18 months from the start of the study, the symptoms were relieved in eight patients while still receiving PPS instillations and in four without treatment. CONCLUSIONS: These results suggest that intravesical PPS is an effective option for the treatment of IC and shows that the intravesical application of PPS is a safe treatment with no important side-effects.

Multiple linear regression as an analytical tool in cephalometric studies.

When the effect is studied of a factor like 'orthodontic therapy' on linear craniofacial growth, the concomitant consequence of age and gender on size cannot be ignored. The methodologically correct solution is division of the study group into smaller units, each of which is homogeneous with respect to age, gender, and therapy, and to compare these with matched controls. Yet, apart from matched controls being hard to find, this method of subdivision has the serious drawback that smaller groups decrease statistical power. A solution without the need to create sub-groups lies in the application of multiple linear regression analysis. It has been applied to biological data in other studies, but verification of the outcome has not been reported so far. Indeed, testing the mathematical assumptions underlying the regression model created unresolvable obstacles and, therefore, it was decided to perform verification by means of practical examples. Two separate tests for the applicability of the multiple linear regression method, on different data, with differing predictor sets, and with different control samples have been performed.

Association of lip posture and the dimensions of the tonsils and sagittal airway with facial morphology.

The specific contribution of enlarged tonsils or adenoids to craniofacial growth remains unknown, and there is no agreement in the literature as to the significance of lip posture. This study assessed the separate associations of lip posture, sagittal airway size, and tonsil size with selected cephalometric measures. Clinical and cephalometric data of 207 children who presented for evaluation of tonsil and/or adenoid problems were evaluated. Multiple linear regression was used to assess the linear relationship between each of the three parameters and the cephalometric dependent variables. Open lip posture, reduced sagittal airway, and large tonsils were each associated statistically with a characteristic but different skeletal configuration. This association was proportional. Specifically, a more open lip posture was associated with a more backwardly rotated face and larger lower facial height. Reduced sagittal airway size was associated with en bloc backward relocation of the maxilla and mandible. Because the sella-nasion dimension shortened proportionally, the SNA and SNB angles were not affected. Larger tonsils were associated with more forward relocation and rotation of the maxilla and mandible and increased SNA and SNB angles. Because each of the three parameters was associated proportionally with a different craniofacial morphology, it is concluded that lip posture, sagittal airway size, and tonsil size represent three different and unrelated phenomena with respect to their effects on craniofacial growth and form.

The role of caries recognition: treatment decisions from bitewing radiographs.

OBJECTIVE: To describe the effect of the ability to estimate caries depth from bitewing radiographs on restorative treatment decisions. METHODS: A 10% random sample of Dutch dental practitioners (n = 444) was sent a two-part questionnaire based on an analytic approach to radiographic caries diagnosis and restorative treatment decision making. In the second part the dentists were asked to diagnose radiographs of 105 tooth surfaces with and without dentine caries and then to make a treatment decision for each surface. A regression analysis was carried out using the negative predictive value (TN/[TN + FN]) of the restorative treatment decision for dentine caries as the dependent variable. RESULTS: The mean negative predictive value for the dentists' proposals from radiographs to leave surfaces untreated was 0.77 (SD 0.05; min. 0.60, max 0.87). Nine significant (P < 0.05) variables explained 65% (R2 = 0.65) of the variation in decision making. One diagnostic ability variable explained 48% of the variation found. CONCLUSIONS: Dentists appear to take the seriousness of errors in restorative decisions into account when deciding on treatment. The ability of dental practitioners to identify and discriminate between lesions in the inner half of the enamel and the outer half of the dentine, however, plays a dominant role in their treatment decision making.

Increased urinary levels of Tamm-Horsfall glycoprotein suggest a systemic etiology of interstitial cystitis.

PURPOSE: We investigated the role of Tamm-Horsfall protein in interstitial cystitis. MATERIALS AND METHODS: Urinary Tamm-Horsfall protein excretion was analyzed in interstitial cystitis patients and controls, and bladder biopsy specimens were stained immunohistochemically for Tamm-Horsfall protein. RESULTS: Urinary Tamm-Horsfall protein levels in 28 women with interstitial cystitis were statistically significantly greater than those in 25 female controls. No positive staining for Tamm-Horsfall protein was demonstrated in the bladder tissue from 10 interstitial cystitis cases. CONCLUSIONS: The results support the notion that interstitial cystitis may have a systemic etiology. In addition, this assay might have clinical value in the diagnosis of interstitial cystitis.

Signs and symptoms of temporomandibular disorder (TMD) and craniofacial form.

Signs and symptoms attributed to temporomandibular disorder (TMD) were registered in 170 persons at an average age of 12.5 years. One hundred and ten were reexamined at an average age of 26.4 years. Craniofacial form was defined on standardized lateral cephalograms, taken at the time points mentioned, by 22 linear and 8 angular measurements. The symptoms, clicking and pain, never appeared to be associated with craniofacial form. The signs, clicking and crepitation, in children did not appear to be associated with craniofacial form either. However, adults with signs were characterized by horizontal facial deficiencies. Adults with clicking joints had a saggitally shorter maxilla and mandibular diagonal, whereas adults with crepitating joints had, in addition, a shorter anterior and posterior cranial base and pharynx. This sagittal "shortness" could already be demonstrated for many of the reported dimensions at the corresponding cephalograms taken about the age of 12.5 years, and did not appear to have changed much over time. It is concluded that the reported TMD signs in adults were associated with a sagittal shorter midface. Part of the typical structure associated with signs antedated the actual detection of these signs by 14 years. This implies that not all TMD signs in adults can be regarded as the exclusive result of some etiologic factor operating after the teenage period. This finding of an association cannot be interpreted as a causal relationship.

The relationship between temporomandibular joint mobility and peripheral joint mobility reconsidered.

The purpose of this paper was to study the relationship between temporomandibular joint (TMJ) mobility and mobility of joints and to study the general character of joint mobility in 83 subjects, 55 females and 28 males (mean age 26.7, range 13-46 years). The subjects were recruited from the Department of Oral and Maxillofacial Surgery of the University Hospital of Groningen. All participants had a good general health and did not present anamnestically, clinically or radiographically TMJ disorders. Of these subjects, angular displacement of the mandible relative to the cranium during maximal mouth opening (AMO) was measured. Furthermore, the maximal range of motion of passive digit five hyperextension, passive thumb apposition to the wrist, active elbow and knee hyperextension, active ankle dorsal flexion and trunk flexion were measured. All measurements were performed bilaterally, except trunk flexion. Calculation of product moment correlations (Pearson) revealed a weak relationship between AMO and mobility of right digit five and elbows for the total group and between AMO and mobility of both digits five and elbows for women. The correlations were never stronger than 0.4. Multiple regression revealed that only 25.9% of the total variance of AMO could be explained by mobility of peripheral joints, age and sex. Calculation of product moment correlations between mobility of peripheral joints, trunk flexion and age revealed weak correlations between the different joints, with the exception of paired joints. Principal component analysis revealed a weak general character of joint mobility.(ABSTRACT TRUNCATED AT 250 WORDS)

Prediction of the neonatal crown-heel length from femur diaphysis length measurements.

The usefulness of the Rossavik growth model in predicting crown-heel length (CHL) was evaluated in 50 women with normal singleton pregnancies in a Dutch population. The femur diaphysis lengths (FDL) were predicted assuming growth cessation at 38, 39, 39.5, and 40 weeks, menstrual age (MA), and at birth using Rossavik growth models determined from two second-trimester FDL measurements. Predicted CHLs were then calculated from predicted FDLs using six different equations. Predicted CHLs were compared with the actual neonatal CHLs and the percent differences calculated. The growth potential realization index (GPRI) values were also determined. With all six equations, regression analysis revealed a significant relationship between the percent differences and birth ages for those infants delivering after 38 and 39 weeks, MA, respectively. The signs of the slopes of the regression lines were negative, indicating continued growth of these fetuses. With the Vintzileos equation, no evidence of continued growth was obtained after 39.5 weeks, MA. The systematic prediction error at this time point was 0.9%, whereas the random error was 3.3%. The mean GPRICHL was 99%, with a 95% range of 93% to 104%. These findings indicate that the CHL can be predicted with a high degree of accuracy in this Dutch population if the appropriate growth cessation age and FDL-CHL function are used.

[Treatment with soft laser. The effect on complaints after the removal of wisdom teeth in the mandible]. / Behandeling met softlaser. Invloed op klachten na de verwijdering van verstandskiezen in de onderkaak.

In a placebo controlled double-blind randomized study the effect of low level laser therapy on postoperative complaints after removal of lower third molars was examined. Several parameters were investigated in two groups of patients; in one group low level laser was applied during and following third molar removal, in the other no active additional laser treatment was given. The results of this study show that therapeutic low level laser treatment could not statistically reduce the postoperative pain, swelling, trismus and function impairment after extraction of lower third molars.

Joint mobility measurements: reliability of a standardized method.

Assessment of hypermobility and hypomobility is frequently performed visually with all its limitations. In this study, a standardized joint mobility measurement method is suggested, and its reliability is tested. The maximal range of motion of passive digit five hyperextension, passive thumb apposition to the wrist, active elbow and knee hyperextension, active ankle dorsal flexion and trunk flexion was measured in 30 healthy subjects. All measurements were performed bilaterally, except for trunk flexion. Three experienced observers performed the measurements according to a rigidly standardized protocol, using appropriate goniometers and rules. During one measurement session each observer measured each subject. Two consecutive measurement sessions were organized. Analysis of variance, with subject and time as explaining variables, was performed on the data obtained. The inter-observer variability ranged from 1.42 degrees (left knee hyperextension) to 4.05 mm (right thumb apposition) in the first measurement session and from 1.35 degrees (left knee hyperextension) to 4.58 degrees (right digit five hyperextension) in the second measurement session. The intra-observer variability ranged for observer A from 0.75 degree (left knee hyperextension) to 3.67 mm (left thumb apposition), and from 0.93 degree (left knee hyperextension) to 3.88 degrees (left digit five hyperextension) for observer B. Observer C ranged from 0.71 degree (left knee hyperextension) to 4.01 mm (right thumb apposition). Based on the results of this study, the authors conclude that joint mobility can be measured reliably and accurately with the presented simple tools.(ABSTRACT TRUNCATED AT 250 WORDS)

Variability of forced oscillation (Siemens Siregnost FD 5) measurements of total respiratory resistance in patients and healthy subjects.

The reproducibility of total respiratory resistance (Rrs) measured with a simplified forced oscillatory method (Siemens Siregnost FD 5) was measured and compared with that of slow inspiratory vital capacity (IVC) and forced expiratory volume in one second (FEV1). The former technique has the advantage that assessment of bronchial obstruction can be made without a forced maneuver, which may be difficult in patients with chronic obstructive pulmonary disease (COPD). We used the criteria proposed by the American Thoracic Society for the diagnosis of COPD. Pulmonary function tests (IVC, FEV1 and Rrs) were measured in seven healthy subjects and in two groups of patients with COPD. First one technician performed six measurements of IVC, FEV1 and Rrs in all subjects during a period of 90 minutes on the same day. Second to evaluate intraindividual variability the measurements were performed on ten subsequent days. The median interval (range) between the first and last measurements in days was 38 (20-186). The mean +/- SD coefficient of variation (CV) Rrs in patients was 15.7% +/- 5.0% and in normals, 10.8% +/- 3.2%. There was less variation in the FEV1 value of 11.0% +/- 6.2% and normals, 2.2% +/- 1.0%; and IVC, 6.9% +/- 5.0% and normals, 2.4% +/- 0.7%. There is no correlation between age and CV. It is concluded from the study that oscillatory Rrs has a larger coefficient of variation within one patient than FEV1 or IVC. If Rrs is used for longitudinal follow-up in COPD patients, we suggest that variations less than 26% (mean +/- 2 SD) can be considered the result of "spontaneous" variation in lung function.

[The relationships between orthodontics and temporomandibular joint dysfunction. A review of the literature and longitudinal study]. / Zusammenhänge zwischen Kieferorthopdie und Kiefergelenksdysfunktion. Literaturübersicht und longitudinale Untersuchung.

The fist part of this study concerns a literature review on temporomandibular dysfunction (TMD). There exists an equal amount of literature relating occlusal interferences to TMD, as there are reports denying any causal relationship. It is remarkable, however, that the latter reports are relatively recent. The relationship between the Angle classification and TMD is reported to be only weak in a "normal" orthodontic population. The relationship between morphologic malocclusion, e.g. deep bites or crossbites, with TMD seems to be somewhat stronger. The vast majority of the reports did not find any relationship between TMD and orthodontic treatment or extractions. Our own longitudinal prospective study could not reveal any systematic relationship between orthodontic treatment or extractions and TMD.

Factors influencing the likelihood of successful decisions to treat dentin caries from bitewing radiographs.

The purpose of this study was to describe the role played by the ability to estimate caries depth in successfully deciding to treat dentin caries when making use of bitewing radiographs as a diagnostic test. A 10% random sample (n = 444) of Dutch dental practitioners was sent a two-wave questionnaire concerning radiographic caries diagnosis and restorative treatment decision making. The second wave consisted of simulated bitewing radiographs of 105 tooth surfaces with and without dentin caries according to two measuring standards: (a) a micro-radiographic "gold" standard and (b) a norm of expert observers. The dentists were asked to diagnose caries at 4 depths of penetration using a 5-point certainty scoring system to measure diagnostic ability; and to make a treatment decision for each surface. The overall response was 61% (273). A regression analysis was carried out using the chance per dentist of correctly deciding to treat dentin caries as the dependent variable. The degree of agreement with the experts' diagnosis of radiographic caries depth was used to create variables measuring diagnostic ability. Five significant (P less than 0.05) variables explained 60% (R2 = 0.60) of the variation in decision making. The best diagnostic ability variable explained 47% of the variation while the treatment criterion reportedly used explained 3%. We conclude that the ability of practitioners to interpret radiographs plays a major role in treatment decision making and that their reported treatment decision making criteria should not be taken at face value.

Groin dissection in the treatment of lower-extremity melanoma. Short-term and long-term morbidity.

Groin dissection was performed in 151 consecutive patients from 1970 to 1984. Groin dissections were therapeutic in 138 cases (91%) and elective in 13 (9%). One hundred forty-three patients (95%) underwent an ilioinguinal node dissection, while eight (5%) were treated with an inguinal node dissection. In 88 patients, the groin dissection was combined with isolated regional perfusion. Primary wound closure was performed in 140 patients (93%). There was no 30-day postoperative mortality. Complications included temporary seroma (26 [17%] of 151 patients), wound infection (14 patients [9%]), wound necrosis (five patients [3%]), and edema (30 patients [20%]). Residual inguinal node metastases after groin dissection did not occur. Morbidity of groin dissection did not increase when the groin dissection was combined with isolated regional perfusion. Quantification of the degree of edema in 66 patients revealed functional limitation due to edema in three patients (4.5%). This technique of groin dissection gives good results with minimal functional morbidity of the affected leg.

Long-term effects of orthodontic treatment, including extraction, on signs and symptoms attributed to CMD.

The prevalence of signs and symptoms attributed to craniomandibular disorders (CMD) was established in an orthodontically treated sample. The effect of orthodontic therapy upon this prevalence was studied by monitoring three groups of patients whose treatment procedures were different. The first group was treated with functional appliances, the second with Begg light wire, and the third with chin cups. In addition, the effect of extraction upon the prevalence was studied by monitoring three groups in which different extraction decisions had been made: four first premolars extracted, all other types of extraction, and no extraction. Based upon the finding of similar prevalences after 20 years of observation, it appears that neither orthodontic treatment nor extraction has a causal relationship with the signs and symptoms of CMD recorded during this study.

Forced oscillation technique. Reference values for total respiratory resistance obtained with the Siemens Siregnost FD5.

Total respiratory resistance (Rrs) was measured by the application of a sine wave of airflow to the mouth at an oscillation frequency of 10 Hz. The instrument used was the Siemens Siregnost FD5. The Rrs data were correlated with height, age, sex, and weight in 73 patients and 29 healthy subjects. The patients took part in a rehabilitation program for restoration of their locomotion function. Both groups had normal lung function (VC, FEV1) and no signs of pulmonary disease. The only important determining factor for the value of the Rrs was height. The mean Rrs of 102 subjects was 0.29 +/- 0.08 kPa.1-1.s. Other studies gave values between 0.23 +/- 0.05 and 0.32 +/- 0.10 kPa.1-1.s.

Prevalence of structural bony change in the mandibular condyle.

Estimated on data derived from a longitudinal study of 172 orthodontic subjects, structural bony change in the mandibular condyle occurs in 5% of the individuals documented from childhood to adulthood. The first appearance generally was between 12 and 16 years of age. Differential diagnosis based upon signs and symptoms of CMD registered simultaneously, as proposed in the 1990 guidelines for craniomandibular disorders appeared to be inconsistent. To illustrate how suddenly the process of bony change may proceed, a case report is presented in which a severe change transpired within a 1-year interval in a 13-year-old patient.