Low dose thalidomide in patients with relapsed or refractory multiple myeloma.

Remarkable results of the treatment of refractory multiple myeloma with thalidomide have been reported. In most preceding studies, the given thalidomide dose was escalated to a maximum tolerated dose of up to 800 mg/d. The frequency of adverse effects correlates with dose intensity. Since a significant gain of therapeutic effects could not be observed as thalidomide dosage was escalated, the optimal dose of thalidomide remains to be determined. We report the results of a study with low dose thalidomide (median administered dose 100 mg/d, range 50-400 mg/d). Twenty-four relapsed (n = 19) or resistant (n = 5) multiple myeloma patients were included in the study. Twelve patients (50%) received thalidomide as monotherapy, 8 patients (33%) received a combination of thalidomide and dexamethasone (every 4 weeks 40 mg/day for 4 days) and 4 patients (17%) who were resistant to vincristine, doxorubicin, dexamethasone (VAD) received VAD combined with thalidomide. Overall, a response was observed in 12 patients (50%). Of the 12 patients treated with low dose thalidomide alone 5 (42%) responded, of the 8 patients who received a combination of thalidomide and dexamethasone 5 (63%) responded and of the 4 patients who had thalidomide in addition to VAD 2 patients (50%) responded. In 3 patients, thalidomide treatment had to be discontinued because of side effects and 1 patient died before response could be assessed. We conclude that low dose thalidomide is an effective and safe rescue therapy in relapsing or refractory multiple myeloma. Response to thalidomide might be dependent on prognostic parameters and tumor burden. To answer these questions larger prospective studies are necessary.

Chorea as a manifestation of the antiphospholipid syndrome in childhood.

Chorea has been related to the presence of antiphospholipid antibodies (a-PL) in the context of systemic lupus erythematosus (SLE). Here we report the case of a 13-year-old girl with a-PL antibodies, who had developed thrombophlebitis at the age of 11 years and chorea two years later, in the absence of clinically evident SLE. Serological tests revealed a false positive test for syphilis, a prolonged activated partial thromboplastin time, hypocomplementaemia and positive anti-DNA antibodies.

HLA alloantigens in Greek patients with systemic lupus erythematosus.

The frequency of the HLA-A, -B and -DR alloantigens was studied in 74 unselected, consecutive, unrelated Greek patients with systemic lupus erythematosus (SLE) and the results were compared with those of healthy controls (380 for the class I antigens and 154 for the class II antigens). No statistically significant differences were noted between patients and controls regarding the prevalence of any class II antigen. Furthermore, no such differences were observed between our 36 anti-Ro (SSA) positive and the rest of our SLE patients. However, the coexistence of anti-Ro (SSA) and anti-La (SSB) antibodies (9 patients) correlated significantly with HLA-B8, whereas the haplotype HLA-B8DR3 was more common in the anti-Ro (SSA) positive patients than in the rest-although the difference did not reach statistical significance. The combination of high anti-ds-DNA and low C4 serum levels correlated with absence of HLA-DR5. Our findings, while in agreement with those of certain previous studies, are somewhat different from those of others. The differences may at least partly be related to variations in the control populations employed. On the other hand some of the differences, in accordance with other peculiarities of Greeks with connective tissue disease, emphasize the role of racial and/or ethnic background in the HLA-association of various autoimmune diseases and the fact that the detectable HLA alloantigens in certain diseases modify disease and autoantibody expression rather than being responsible for the autoimmune process itself.

Clinical and serological spectrum of systemic lupus erythematosus in Greek children.

In the present study 19 Greek Caucasian children with systemic lupus erythematosus (SLE), onset before the age of 16, were followed up for 1-12 years (mean 5.6 yrs.). Diagnosis was determined early in 14 patients and delayed by 2 to 6 years in 5. The clinical manifestations and laboratory findings did not differ significantly from those reported in adults with lupus. The major organ system involvement at onset and early course were skin and joints (80%) followed by kidneys (42%). During the course of the disease 26% of the children developed central nervous system (CNS) involvement. All the patients were treated with steroids and/or cytotoxic drugs in severe uncontrolled progressive disease. At the mean 5.6 years follow-up most patients were in remission on small doses of steroids; one patient still presents signs of active lupus nephritis and one patient died from sepsis. All the patients with CNS involvement recovered without permanent CNS residue.

Retention of fissure sealants using two different methods of application in teeth with hypomineralised molars (MIH): a 4 year clinical study.

AIM: This was to evaluate the retention rate of fissure sealants applied to MIH molars with occlusal enamel opacities, using two different application methods after 4 years. METHODS: 54 children exhibiting molars with MIH aged 6-7 years, participated in the study. SELECTION CRITERIA: presence of at least 2 fully erupted caries-free maxillary or mandibular first permanent molars in the opposite sides of the mouth, both with occlusal enamel opacities without breakdown. Following parental consent, sealants were applied using a half-mouth experimental design. Group A: On a randomly assigned first molar on one side of the mouth sealants Fissurit were placed using a single bottle adhesive system (One-step prior to sealant application. Group B: Sealants were applied on the contra-lateral molar using the conventional etch and seal technique. Children were seen biannually when a preventive program was applied, without replacing any lost sealant. RESULTS: After 4 years, 47 sets of molars (94 teeth) were available for blind evaluation. Teeth in Group A presented a better retention rate; 70.2% were fully sealed, 29.7% partly sealed and none unsealed (lost sealant). Group B revealed 25.5% fully sealed, 44.6% partly sealed and 29.7% unsealed teeth. STATISTICS: Differences between groups A and B were statistically significant (p<0.001). Also both groups revealed a decreasing retention rate over the 4-year period (p<0.001). There was no difference in dental caries increment rate and enamel breakdowns at the end of the study (p>0.01). CONCLUSIONS: In hypomineralised molars with occlusal opacities sealants appear to have greater retention when applied using 5th generation adhesive systems prior to sealant.

Parental attitudes and perceptions affecting children's dental behaviour in Greek population. A clinical study.

AIM: This was to investigate the relationship of children's behaviour during dental treatment to parental dental attitudes and perceptions in a definitive population of Greek children in Athens. METHODS: 88 children aged 3-11 years and their parents, attending the Community Dental Centre for Children in Athens, participated. A questionnaire including demographic information, questions regarding parents' dental experience and anxiety (M-DAS test), as well as questions regarding expectant behaviour of each child and his/her dental anxiety level (parental version of the CFSS -Dental Subscale), was completed by the parents during the first examination appointment. During the two following operative sessions each child's behaviour was recorded and evaluated using the Frankl Scale. Collected data were statistically analyzed using a SPSS statistical program. RESULTS: No significant difference was found between a child's actual behaviour and gender, nationality, frequency of parent's dental visits, parental dental fear (M-DAS) and previous medical experience of the child (p>0.001). In contrast, age (p=0.005), previous child's dental fear (p=0.081), previous child's dental behaviour (p<0.0001), predicted by the parent behaviour (p<0.0001) and parental version of CFSS-DS (p<0.001), revealed statistically significant associations to child's behaviour during treatment. CONCLUSION: According to the present study in Greek children, children's behaviour during dental treatment is related to age, previous dental fear and experience and behaviour prediction by the parents. Parents' estimations regarding their children's fear and behaviour could be a useful predictor of child's level of cooperation during dental treatment.

Molar-incisor-hypomineralisation (MIH). Retrospective clinical study in Greek children. I. Prevalence and defect characteristics.

AIM: This was to evaluate the prevalence and the clinical characteristics of MIH in a group of Greek children. METHODS: During the years 2003--2005, all MIH cases diagnosed according to the recently set criteria were selected from the new patients clinic of a Community Dental Centre for Children (Athens). Age, gender and teeth involved were recorded. The severity of MIH was determined collectively by dividing the affected teeth in two groups; a) mild defect (demarcated opacities) and b) moderate/severe defect (enamel breakdown and atypical restorations). Evaluation of the distribution of the affected teeth within MIH cases was performed in a separate group of 225 affected children aged 8-12 years with their entire 12 'index' teeth erupted. RESULTS: From the 3,518, 5.5 to 12 year old children that were examined, there were 360 (10.2%) children with MIH, 211 (58.6%) females and 149 (41.4%) males, with 1,926 affected teeth, 1,231 molars and 695 incisors. In the molars group, maxillary molars were more frequently affected (87.8/90.3%) than mandibular (81.7/82.2%). In the central incisor group, maxillary teeth were also more frequently affected (50/55%) than mandibular (24.4/25%), while laterals were the least affected. In all there were 37.9% molars with moderate/severe defects as compared with 4.9% incisors, the remaining 62.1% and 95.1% respectively being mild. The various associations between the affected teeth were evaluated in the sub-group of 225 MIH children with all 'index' teeth erupted (1,286 affected teeth, 776 molars and 510 incisors), with mean number of affected teeth per child being 5.7; separately for molars 3.4 and for incisors 2.2. In these cases 28.4% of the children had only molars affected and 71.6% had both molars and incisors. In descending order the associations of affected teeth more frequently found were: 4 molars/2 incisors (23.5%), 4 molars/4 incisors (16.8%), 4 molars alone (15.1%) and 2 molars alone (9.7%), the remaining being much less. STATISTICAL ANALYSIS: As age increased the clinical severity of the affected teeth became more prevalent (p=0.0001), and when the total number of affected teeth was assessed the likelihood of having severe defect was also increased (p=0.001). CONCLUSION: The prevalence of the defect in the present study was 10.2% with maxillary teeth being more frequently affected. Severity increased with age. Mild defects were much more frequent, particularly in incisors. The total number of teeth affected and the most frequently found associations were, 4 molars/2 incisors, 4 molars/4 incisors, 4 molars alone and 2 molars alone.

Molar-incisor-hypomineralisation (MIH). A retrospective clinical study in Greek children. II. Possible medical aetiological factors.

AIM: This was to examine the potential medical aetiological factors involved in the development of MIH. METHODS: During the years 2003--2005, all MIH cases diagnosed according to set criteria were selected from the new patients clinic of a Community Dental Centre for Children (Athens). The age, gender and teeth involved were recorded. A control group of socio-demographically matched controls was also identified. The potential aetiological factors were retrieved through personal interview with the parents and from each child and mother's medical book. Only verified aetiological factors were recorded. Evaluation of the correlation of affected teeth and the timing of the insult was performed in a separate group of 225 affected children aged 8-12 with their entire 12 'index' teeth erupted. RESULTS: From the 3,518, 5.5 to 12 years old children examined, 360 (10.2%) had MIH. Aetiology of MIH: 44 children (12.2%), presented without any relevant medical history, the remaining 316 (87.8%) recorded various medical problems associated with MIH, compared with 18.9% for controls. Perinatal (163, 33.6%) and postnatal (162, 33.9%) problems were the most frequently found and prenatal the least (33, 8.6%). For 42 children (11.7%) problems occurred in more than one chronological period, mainly during both the perinatal and postnatal period (11.1%). The most common prenatal problem was repeated episodes of high fever (12/33), in the perinatal period birth by Caesarean section (92/163) and other birth complications (34/163). Various respiratory conditions (88/162), repeated episodes of high fever (31/162) and neonatal illness (28/162) were the commonly reported problems in the postnatal period. Many MIH cases presented with more than one medical problem during the peri-and postnatal period. STATISTICAL ANALYSIS: Children with MIH recorded 68.9% more frequent medical problems than controls (p<0.0001). A positive correlation (p<0.001) between the total number and type of affected teeth with the timing of the insult was observed in the 225 MIH children with all their 'index' teeth erupted. CONCLUSION: Children with MIH present with more medical problems than controls during their prenatal, perinatal and postnatal period. The majority of these illnesses may produce hypocalcaemia, hypoxia and pyrexia to the child or the mother. The number of affected teeth was associated with the timing of the possible insult; children with prenatal, perinatal and postnatal problems present more affected teeth in increasing order.

Subacute cutaneous lupus erythematosus in Greece. A clinical, serological and genetic study.

We present herein clinical, serological and genetic findings on 27 Greek, subacute cutaneous lupus erythematosus (SCLE) patients. Twenty-three (85 p. 100) presented with a psoriasifom rash in a photosensitive distribution. Two patients (7.5 p. 100) had an annular rash in a polycyclic pattern. Two other patients exhibited both types of lesions. The majority of our patients also had other skin manifestations, including butterfly rash, discoid lesions and maculopapular rash. Systemic manifestations were: arthralgias or arthritis in 50 p. 100, low grade fever in 35 p. 100, central nervous system involvement in 15 p. 100, Sjögren's syndrome in 18 p. 100 and serositis in 8 p. 100. Anti-nuclear antibodies were found in 93 p. 100; antibodies to Ro (SSA) and/or La (SSB) in 70 p. 100. Twenty-one (78 p. 100) satisfied the ARA criteria for systemic lupus erythematosus (SLE). No HLA-DR3 antigen association was found in the 16 patients tested. These findings are somewhat different from those reported previously: a) the frequency of the psoriasiform rash rather than the annular one is the highest in Greek SCLE patients; b) most patients also have other skin manifestations mimicking the full spectrum of SLE with prominent cutaneous lesions; and c) no HLA-DR3 antigen association was found in Greek patients. Environmental, ethnic or genetic factors may be responsible for these differences.

Sjögren's syndrome in systemic lupus erythematosus.

Sixty unselected consecutive patients with systemic lupus erythematosus (SLE) were prospectively evaluated for evidence of Sjögren's syndrome. This was diagnosed in the patients whose minor labial salivary gland biopsy was graded greater than or equal to 3 (according to Chisolm and Mason), who also had keratoconjunctivitis sicca (positive rose bengal eye test) and/or xerostomia (subjective xerostomia and decreased stimulated parotid flow rate). Lip biopsy revealed focal round cell infiltration compatible with a greater than or equal to 3 grade in 11 patients, minimal perivascular infiltration in 21 patients and no infiltration in 28. In the positive biopsy group (greater than or equal to 3 grade) subjective xerophthalmia, decreased parotid flow rate, parotid gland enlargement, lymphadenopathy, presence of rheumatoid factor and anti-La (SSB) antibodies were significantly commoner than in the others. Of the 11 patients of this group, 5 had keratoconjunctivitis sicca which sufficed for the diagnosis of Sjögren's syndrome, suggesting a prevalence of 8.3% in our population with SLE. In these individuals subjective xerophthalmia (40%), positive Schirmer's I eye test (60%), decreased parotid flow rate (80%), parotid gland enlargement (80%) and presence of rheumatoid factor (80%) and anti-La (SSB) antibodies (80%) were significantly more frequent than in the remaining patients, whereas significant differences regarding other features of SLE were not observed. Our results suggest that Sjögren's syndrome in SLE is relatively rare and usually mild. Furthermore, it may present more similarities to primary Sjögren's syndrome than to secondary Sjögren's syndrome accompanying rheumatoid arthritis.

Histologic lesion in labial salivary glands of patients with systemic lupus erythematosus.

In an attempt to evaluate the presence or incidence of Sjögren's syndrome in patients with systemic lupus erythematosus (SLE), 72 randomly selected patients with SLE, regardless of sicca manifestations, underwent labial salivary gland biopsy. Thirty-seven patients (51%) had normal labial salivary gland tissue. Seventeen patients (24%) had a mild perivascular infiltration of 15 to 20 lymphocytes per focus. In the remaining 18 patients (25%) heavy infiltration of more than 50 lymphocytes per focus was observed. From the latter group five specimens showed perivascular distribution of the infiltrates. About 40% of patients with any infiltration had keratoconjunctivitis sicca. Patients with severe lymphocytic infiltration in minor salivary gland tissue rarely had kidney involvement and often had lymphadenopathy and circulating rheumatoid factor, cryoglobulins, and antibodies to SS-A (Ro) and SS-B (La) antigens. Vasculitis was not found more frequently in any group of patients. Our results suggest that perivascular lymphocytic infiltrates in the labial salivary glands of patients with SLE may be the initial histologic lesion of Sjögren's syndrome.

Epidemiology of adult rheumatoid arthritis in northwest Greece 1987-1995.

OBJECTIVE: Rheumatoid arthritis (RA) in Greece differs in its clinical, serological, and genetic aspects from that of Northern European countries. We investigated the incidence and prevalence of RA in the district of Ioannina in northwest Greece for the period 1987-1995. METHODS: We investigated records of patients at rheumatology clinics of university and general hospitals and private clinics in Ioannnina. Diagnosis was by 1987 ACR criteria, and the population data were based on the 1991 national census. Crude and age specific rates were calculated as number of cases per 1000 inhabitants. Age adjusted rates were obtained by the direct method using the European standard population. RESULTS: A total of 428 cases of RA were identified during the study period. Total prevalence of RA was for men 2.05 and for women 4.78 cases/1000 inhabitants, and the total women/men ratio was 2.33. Annual incidence rates fluctuated between 0.15 and 0.36/1000 inhabitants. CONCLUSION: Our findings suggest a low prevalence and low incidence of RA in northwest Greece. Environmental and/or genetic factors may explain this low frequency of the disease in the population studied.