A randomized phase II study of stem cell mobilization with cyclophosphamide+G-CSF or G-CSF alone after lenalidomide-based induction in multiple myeloma.

The most common means of mobilizing autologous stem cells is G-CSF alone or combined with cyclophosphamide (CY) to obtain sufficient CD34+ cells for one to two transplants. There are few prospective, randomized studies investigating mobilization regimens in multiple myeloma (MM), especially after lenalidomide-based induction. We designed this prospective, randomized study to compare low-dose CY 2 g/m2 +G-CSF (arm A) and G-CSF alone (arm B) after lenalidomide-based up-front induction in MM. Of the 80 initially randomized patients, 69 patients were evaluable, 34 and 35 patients in arms A and B, respectively. The primary end point was the proportion of patients achieving a yield of ⩾3 × 10(6)/kg CD34+ cells with 1-2 aphereses, which was achieved in 94% and 77% in arms A and B, respectively (P=0.084). The median number of aphereses needed to reach the yield of ⩾3 × 10(6)/kg was lower in arm A than in arm B (1 vs. 2, P=0.035). Two patients needed plerixafor in arm A and five patients in arm B (P=0.428). Although CY-based mobilization was more effective, G-CSF alone was successful in a great majority of patients to reach the defined collection target after three cycles of lenalidomide-based induction.

Autologous stem cell transplantation versus novel drugs or conventional chemotherapy for patients with relapsed multiple myeloma after previous ASCT.

High-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) is the most common first-line treatment for patients with multiple myeloma (MM) under 65 years of age. A second ASCT at first relapse is frequently used but is challenged by the use of novel drugs. We retrospectively studied the outcome of second-line treatment in MM patients from the Nordic countries with relapse after first-line HDT and ASCT. Patients that underwent a second ASCT (n=111) were compared with patients re-treated with conventional cytotoxic drugs only (n=91) or with regimens including novel drugs (proteasome inhibitors and/or immunomodulatory drugs) (n=362) without a second ASCT. For patients receiving a second ASCT median overall survival was 4.0 years compared with 3.3 years (P<0.001) for the group treated with novel drugs and 2.5 years (P<0.001) for those receiving conventional cytotoxic drugs only. A second ASCT also resulted in a significantly longer second time to progression and a significantly longer time to next treatment. We conclude that, irrespective of the addition of novel drugs, MM patients in first relapse after ASCT still appear to benefit from a second ASCT. A second ASCT should be considered for all physically fit patients.

Comparative analysis of minimal residual disease detection by multiparameter flow cytometry and enhanced ASO RQ-PCR in multiple myeloma.

Multiparameter flow cytometry (MFC) and allele-specific oligonucleotide real-time quantitative PCR (ASO RQ-PCR) are the two most sensitive methods to detect minimal residual disease (MRD) in multiple myeloma (MM). We compared these methods in 129 paired post-therapy samples from 22 unselected, consecutive MM patients in complete/near complete remission. Appropriate immunophenotypic and ASO RQ-PCR-MRD targets could be detected and MRD analyses constructed for all patients. The high PCR coverage could be achieved by gradual widening of the primer sets used for clonality detection. In addition, for 13 (55%) of the patients, reverse orientation of the ASO primer and individual design of the TaqMan probe improved the sensitivity and specificity of ASO RQ-PCR analysis. A significant nonlinear correlation prevailed between MFC-MRD and PCR-MRD when both were positive. Discordance between the methods was found in 32 (35%) paired samples, which were negative by MFC-MRD, but positive by ASO RQ-PCR. The findings suggest that with the described technique, ASO RQ-PCR can be constructed for all patients with MM. ASO RQ-PCR is slightly more sensitive in MRD detection than 6-10-color flow cytometry. Owing to technical demands ASO RQ-PCR could be reserved for patients in immunophenotypic remission, especially in efficacy comparisons between different drugs and treatment modalities.

Risk factors for physical child abuse in infants and toddlers.

BACKGROUND: We examined the risk factors and injuries in physical child abuse between November 2003 and February 2007. PATIENTS AND METHODS: The uptake area of the University Hospital of Turku, Finland, consists of about 700 000 inhabitants. Forty-eight cases of physical child abuse were examined. The median age of the abused children was 2.2 years, for children with skull fractures it was 0.5 years. The incidence of child physical abuse increased during the study period; it was 0.6/month in 2004 and 1.7/month in 2006. Mortality in the study group was 2.1 %. RESULTS: Depression, overactivity, crying and prematurity were risk factors in the physically abused children. Parental risk factors were alcohol and drug abuse. Most often the perpetrator was the father or stepfather; when the perpetrator was unknown, the children were mostly in their mothers' care. The average delay of 3 weeks until starting the investigation into abuse was mostly due to delays by health centers or homes. Radiographs were the cornerstones of the medical examination but magnetic resonance examinations were essential for the examination protocol. CONCLUSIONS: All levels of public health services, day care facilities and schools must be aware of possible physical child abuse and initiate an investigation as soon as possible by contacting the authorities. Physically abused children and their families must be followed up and supported for a sufficiently long period by social pediatric outpatient wards. The general information on child maltreatment provided to the public needs to be increased to prevent abuse. A child welfare report must be made to social workers in every maltreatment case examined in hospital, and in most cases the offence must also be reported to the police. Nevertheless, in certain cases even permanent custody of the child cannot be avoided.

Are signs of temporomandibular disorders stable and predictable in adolescents with headache?

The aim of the present study was to study changes in signs and symptoms of temporomandibular disorders (TMD) and factors predicting TMD signs in adolescents with and without headache. A population-based sample (n = 212) of 13-year-olds with and without headache was re-examined at the age of 16. The study included a questionnaire, face-to-face interview and somatic examination. In addition, a neurological examination, a muscle evaluation and a stomatognathic examination were performed. Significant changes were seen in TMD signs during the follow-up, but TMD signs at the end of the follow-up could not be predicted by baseline headache, sleeping difficulties, depression or muscle pain. TMD signs at the age of 16 were associated with female gender and muscle pain. We conclude that considerable changes in TMD signs occur in the follow-up of adolescents with and without headache. Headache-related TMD are not predictable in adolescents with and without headache.

Epidemiology of Gyrodactylus salaris (Monogenea) in the River Tornionjoki, a Baltic wild salmon river.

The occurrence of Gyrodactylus salaris in the River Tornionjoki was investigated in 2000-2004. Infection of salmon parr, Salmo salar, was common in the uppermost reach of the river system but decreased downstream and was rare in the lowermost reach. This pattern was consistent across the study period regardless of varying water temperatures. The oldest age groups of parr were more often infected than younger ones throughout the river system, irrespective of their origin (wild or stocked). Parasite-free hatchery-reared 1-year-old parr became infected during their first summer in the wild. Downmigrating salmon smolts had a high prevalence of infection, but their role in the distribution of infection seemed unimportant. On grayling, Thymallus thymallus, we observed only the grayling-specific clade of Gyrodactylus. We found no indication of grayling participating in the epidemiology of infection on salmon. The salmon parr and smolt population in the Tornionjoki has been at its height during the late 1990s and 2000s. Our results indicate that G. salaris infection in this Baltic river has no devastating effects on the salmon population as it has had in salmon rivers flowing into the North Atlantic and White Sea.

Characteristics of neck pain associated with adolescent headache.

The objective of the study was to find out what kind of neck pain (NP) is associated with headache (HA) and with various headache variables: frequency, type, intensity, disturbance, and relief with analgesics. A population-based sample of 12-year-olds with and without HA (n = 304) was followed for 4 years. At the age of 16 years, NP was evaluated on the basis of self-reported symptoms and a thorough physical examination of the neck region. Both self-reported and measured NP were associated with HA variables. Co-occurrent NP was found in adolescents with migraine as often as in those with tension-type HA. Especially, muscle pain and intensive, frequent NP were associated with disturbing HA unresponsive to analgesics. The study indicates that concomitant NP should be considered in adolescent HA sufferers, and a thorough cervical and muscle evaluation is recommended when planning the treatment of HA.

Obesity and the clinical use of serum GGT activity as a marker of heavy drinking.

OBJECTIVE: Gamma-glutamyl transferase (GGT) is a widely used clinical marker of alcohol abuse. However, although obesity may also elevate serum GGT activities, the effects of overweight on the interpretation of GGT testing have remained poorly defined. MATERIAL AND METHODS: GGT activities from 1147 moderate drinkers and 449 abstainers who were classified according to body mass index (BMI) were compared with those of 208 heavy drinkers admitted for detoxification. RESULTS: GGT upper normal limits, defined based on normal weight abstainers (men 53 U/L; women 45 U/L) were lower than those based on moderate drinkers (men 68 U/L; women 50 U/L). The relative increases in GGT activities in male moderate drinkers with overweight (54%) or obesity (125%) exceeded the corresponding changes found in women (25% and 75%, respectively). The BMI-dependent variation on the sensitivity of GGT for correctly classifying heavy drinkers ranged from 29% to 67%. The rates of false-positive values in the subgroups from low to high BMI varied from 0% to 27%, respectively. CONCLUSIONS: The data indicate that the diagnostic value of serum GGT testing could be improved by using reference data derived from databases of abstainers with normal weight or BMI-based categorization of reference ranges.

Does neck pain determine the outcome of adolescent headache?

The aim of the study was to examine the influence of concomitant neck pain (NP) on the outcome of headache (HA) frequency and HA type in adolescence. A population-based sample of 13-year-olds with or without HA (n = 228) was followed for 3 years. NP was evaluated at the beginning of the follow-up on the basis of recorded muscle tenderness and self-reported symptoms. During the 3 years of follow-up, changes in both HA type and frequency were common. NP interfering with daily activities at the age of 13 years predicted change from non-frequent (0-1/month) to monthly HA (>1/month), especially in boys (P = 0.03 boys, P = 0.06 girls). The use of physiotherapy predicted persistence of monthly HA in boys (P = 0.004). The changes in HA type were not predictable by NP. In conclusion, the risk of worsening HA in adolescence is more probable if the HA is associated with NP interfering with daily activities.

Changing headache from preschool age to puberty. A controlled study.

The characteristics of disturbing primary headache and the occurrence of headache types were studied by sending a questionnaire to 1132 Finnish families of 6-year-old children. Children with headache in the preceding 6 months and their controls were clinically examined at the ages of 6 and 13. During the follow-up, half of the headaches, classified as migraine at age 6 years, were unchanged and 32% turned into tension-type headache. In children with tension-type headache, the situation was unchanged in 35%, and in 38% of children the headache type had changed to migraine. At preschool age the most common location of headache was bilateral and supraorbital, and at puberty bilateral and temporal. During the follow-up, symptoms concurrent with headache, such as odour phobia, dizziness and balance disturbances became more typical, whereas restlessness, flushing and abdominal symptoms became less marked. The early manifestation of both migraine and tension-type headache predict equally often migraine in puberty with marked changes in concurrent symptoms and pain localization.

Adolescent disc degeneration--no headache association.

The objective of the study was to determine whether adolescents with headache have more disc degeneration in the cervical spine than headache-free controls. This study is part of a population-based follow-up study of adolescents with and without headache. At the age of 17 years, adolescents with headache at least three times a month (N = 47) and adolescents with no headache (N = 22) participated in a magnetic resonance imaging (MRI) study of the cervical spine. Of the 47 headache sufferers, 17 also had weekly neck pain and 30 had neck pain less than once a month. MRI scans were interpreted independently by three neuroradiologists. Disc degeneration was found in 67% of participants, with no difference between adolescents with and without headache. Most of the degenerative changes were located in the lower cervical spine. In adolescence, mild degenerative changes of the cervical spine are surprisingly common but do not contribute to headache.

Outcome of headache frequency in adolescence.

Only a few studies have been published of the outcome of adolescent headache (HA). The aim of this study was to examine the predictors of the outcome of headache frequency. A population-based sample of 13-year-olds with or without HA (N=228) was followed to the age of 16 years. HA was classified on the basis of a face-to-face interview and clinical examination. The outcomes of monthly HA (>1/month) and non-frequent HA (0-1/month) were studied. Frequent use of analgesics, female gender and multiple non-headache pain predicted the persistence of monthly HA (>1/month). Significant predictors for worsening non-frequent HA (from 0 to 1/month to >1/month) were female gender, consistent migraine and high basic educational level of one parent. Adolescents frequently using analgesics constitute a risk group for a poor outcome of HA. Especially girls meeting this criterion should be considered a target group in the planning and implementing of preventive measures.

Headache children with temporomandibular disorders have several types of pain and other symptoms.

The aim was to investigate the association between temporomandibular disorders (TMD) and overall muscle tenderness, depressive symptoms, sleep difficulties, headache frequency and related symptoms in children with primary headache in comparison with controls. Based on an unselected population sample of 1135 Finnish schoolchildren classified according to the type of headache at age 12, altogether 297 children aged 13-14 from different headache groups and healthy controls were randomly selected for an interview and clinical examinations. Children with migraine had more TMD signs than children with nonmigrainous headaches or healthy controls. High TMD total scores were associated with palpation tenderness in other parts of the body and with frequent headache attacks. We conclude that children with overall headache, migraine in particular, and high total TMD scores showed an increased overall tenderness to muscle palpation and multiply manifested hypersensitivity pain.

Leisure activities in adolescents with headache.

AIM: To investigate the association between different types of headache and leisure activities in 13-y-old schoolchildren. METHODS: A population-based, cross-sectional study was performed through face-to-face interviews with age-matched cohorts with headache and asymptomatic controls. The present study comprised 59 children with migraine, 65 with episodic tension-type headache (TTHA) and 59 headache-free controls. In the interview, besides questions concerning headache, the children were asked open and structured questions about the type and amount of their leisure activities. RESULTS: Children with migraine spent more time in sports activities than children with episodic tension-type headache or children without headache (test for trend, p<0.01; migraine: OR 1.4, 95% CI 1.1-1.9; tension-type headache: OR 0.9, 95% CI 0.7-1.1). The type of leisure activity was not significantly associated with headache type (p>0.05). Children with both migraine and episodic tension-type headache used computers more often than children without headache (test for trend, p<0.05; migraine: OR 1.2, 95% CI 1.1-1.5; tension-type headache: OR 1.3, 95% CI 1.1-1.5). CONCLUSION: This study provides additional data on the activity status and headache complaints in adolescents. The results indicate that frequent computer use is associated with both tension-type headache and migraine, and intensive overall sports activities are characteristic of adolescents with migraine.

Biomarkers of alcohol consumption in patients classified according to the degree of liver disease severity.

OBJECTIVE: In the search for optimal biomarkers of excessive drinking, only a few studies have been conducted to compare the relationships between ethanol consumption, liver status, and various laboratory markers of ethanol-induced diseases. MATERIAL AND METHODS: Concentrations of carbohydrate-deficient transferrin (%CDT and CDTect methods), serum sialic acid (SA), gamma-glutamyl transferase (gamma-GT), aspartate aminotransferase (ASAT), mean corpuscular volume (MCV), and a marker of fibrogenesis (PIIINP) were studied in 102 alcoholics with (n=59) or without (n=43) alcoholic liver disease. Controls were 34 healthy volunteers who were either social drinkers or abstainers. RESULTS: Although concentrations of all markers were significantly higher in the alcoholic patients than in the healthy controls, their diagnostic characteristics showed a considerable degree of variation. The %CDT, SA, and MCV showed the strongest correlations with the amount of recent alcohol intake. The presence of liver pathology notably influenced the results of CDTect, GT, ASAT, and PIIINP. In ROC analyses, the highest rates of diagnostic accuracy for detecting hazardous drinking were reached with GT (0.94), CDT (0.86), and SA (0.85), followed by MCV (0.79) and ASAT (0.77). Upon abstinence, the estimated times for normalization varied between 10 days (CDTect) and 25 days (GT). CONCLUSIONS: Our data suggest distinct differences in the clinical characteristics of biological markers of ethanol consumption. While the overall accuracy of CDT and GT appear to be highest in the detection of problem drinking, serum SA and PIIINP measurements are of further value when the effects of liver pathology and ethanol drinking need to be differentiated.

Diplostomum spathaceum metacercarial infection and colour change in salmonid fish.

Colour changes in two salmonid fish, the salmon (Salmo salar) and sea trout (S. trutta), were examined in relation to infection with the trematode Diplostomum spathaceum. This parasite had no effect on the rate of colour change in these fish, although species specific differences in colour adjustment times were observed. Increasing asymmetry in parasite numbers between the right and left eye, which could lead to the retention of vision in one eye, nevertheless tended to reduce the colour change time in salmon with moderate infection (P=0.08). This first experimental attempt to examine colour changes in fish in relation to eye fluke infections provides grounds for future investigations. The darker appearance of the heavily infected fish described in the literature suggests that a high parasite burden actually causes colour changes. We emphasise that detailed quantitative studies using fish with higher parasite loads, especially from the tail of the aggregated parasite distribution, are needed to describe these relationships in detail.

Oral treatment of acute myeloid leukaemia with etoposide, thioguanine, and idarubicin (ETI) in elderly patients: a prospective randomised comparison with intravenous cytarabine, idarubicin, and thioguanine in the second and third treatment cycle.

A randomised multicentre study was conducted among patients over 65 yr of age with newly diagnosed acute myeloid leukaemia (AML) to compare oral treatment with etoposide 80 mg/m(2) and thioguanine 100 mg/m(2) twice daily on 5 d and idarubicin 15 mg/m(2) on 3 d (ETI) to a mainly i.v. combination of cytarabine 100 mg/m(2) twice daily on 5 d, idarubicin 12 mg/m(2) x 1, and thioguanine (TAI). Ninety-two patients were enrolled. Their median age was 72 yr, range 65-84 yr. Sixty-five patients had de novo AML, 21 AML subsequent to myelodysplastic syndrome, and six treatment-related AML. They received at first a 6-d i.v. treatment with cytarabine and idarubicin. After the first treatment, 68 patients were randomised to receive two cycles of ETI (n = 36) or TAI (n = 32) and thereafter maintenance with mercaptopurine and methotrexate. Of the 92 patients, 52 (57%) achieved remission at some stage. The median survival was 10 months. There were no significant differences between the patients randomised to ETI or TAI in the remission rate (67% vs. 72%), survival (12 months from randomisation in both arms), event-free survival or relapse rate. The patients randomised to receive ETI spent significantly fewer days at hospital during the two randomised cycles (20 vs. 41 d, P = 0.010), and they had fewer days with infusions, shorter neutropenias and thrombocytopenias and fewer and less severe infections. In conclusion, treatment with oral ETI resulted in a similar antileukaemic effect as obtained with mainly i.v. TAI, with less toxicity and reduced need for hospitalisation.

Muscle tenderness in pericranial and neck-shoulder region in children with headache. A controlled study.

Increased pericranial muscle tenderness is connected with tension-type headache in adults. In children, the importance of muscle tenderness in the pericranial or neck-shoulder region in the pathogenesis of different types of headache is unknown. The present study evaluated muscle tenderness in the pericranial and neck-shoulder region in children with migraine, those with tension-type headache and those without headache. An unselected population-based questionnaire study concerning headache was carried out in 1135 Finnish schoolchildren aged 12 years. Of them, 183 children were randomly selected for a face-to-face interview and a clinical examination. Muscle tenderness was recorded by manual palpation and dolorimeter. Children with migraine had increased overall tenderness, recorded by manual palpation, compared with those without headache. They also self-reported tenderness in the neck-shoulder region during daily activities more often than the children of the other groups. Muscle tenderness was not associated with paediatric tension-type headache. The mean pressure pain thresholds did not differ among the three groups. However, a negative correlation between the total tenderness score and the dolorimeter score was found in each group. In conclusion, children with migraine had increased muscle tenderness at palpation of the pericranial and neck-shoulder muscles and they also reported pain symptoms in the neck-shoulder region most frequently. Instead, increased pericranial and neck-shoulder muscle tenderness was not associated with tension-type headache in children.

Determinants of tension-type headache in children.

The objective of this study was to study the prevalence, characteristics and predisposing factors of tension-type headache in children. An unselected population-based questionnaire study was carried out in 1409 Finnish schoolchildren aged 12 years. Of them, 1135 (81%) returned an acceptably completed questionnaire. The prevalence of episodic tension-type headache in children was 12% (138 of 1135). Children with episodic tension-type headache also often reported characteristics of pain typical for migraine. Children with frequent and persistent episodic tension-type headache reported stabbing and severe occipital pain, phonophobia and abdominal pain significantly more often than children with infrequent episodic tension-type headache. Neck-shoulder symptoms, symptoms of depression and oromandibular dysfunction were each independently associated with episodic tension-type headache. The father's occupation of a lower-level white-collar worker put the child at a four-fold risk for episodic tension-type headache. We conclude that episodic tension-type headache is as common as migraine in children. It can be associated with depression, oromandibular dysfunction and muscular stress. Especially children with frequent and persistent episodic tension-type headache report characteristics of pain typical for migraine.