Presynaptic inhibition of soleus Ia afferents does not vary with center of pressure displacements during upright standing.

The present work was designed to investigate the presynaptic modulation of soleus Ia afferents with the position and the direction of the displacement of the center of pressure (CoP) during unperturbed upright standing and exaggerated CoP displacements in young adults. Hoffmann (H) reflex was evoked in the soleus by stimulating the tibial nerve at the knee level. Modulation of Ia presynaptic inhibition was assessed by conditioning the H reflex with fibular nerve (D1 inhibition) and femoral nerve (heteronymous facilitation) stimulation. Leg muscle activity was assessed by electromyography (EMG). The results indicate that in unperturbed standing and exaggerated CoP displacements, the H-reflex amplitude was greater during forward than backward CoP direction (p<0.05). However, the amplitude of the conditioned H reflex (expressed relative to unconditioned H reflex) did not vary with CoP displacement, regardless of the experimental condition. The soleus EMG was greater during forward than backward CoP direction and during anterior than posterior position in both experimental conditions (p<0.05). The modulation of the unconditioned H reflex with CoP direction was positively associated with the corresponding changes in soleus EMG (r(2)>0.34). The tibialis anterior EMG did not change during unperturbed standing, but was greater for backward than forward CoP direction during exaggerated CoP displacements. In this experimental condition, soleus EMG was negatively associated with tibialis anterior EMG (r(2)=0.81). These results indicate that Ia presynaptic inhibition is not modulated with CoP direction and position, but rather suggest that CoP displacements induced changes in excitability of the soleus motor neuron pool.

[Fungemia and other invasive fungal infections in Icelandic children. A nationwide study.].

INTRODUCTION: Invasive fungal infections are increasing in incidence. Among those who are at increased risk of fungal blood stream infections (fungemia) and disseminated fungal infections are premature infants and immunosuppressed children. These infections are associated with high morbidity and mortality. Invasive fungal infections have not yet been studied in Iceland. MATERIAL AND METHODS: We studied all cases of fungemia and/or disseminated fungal infections in Icelandic children (16 years) during a 20 year period. Histopathology reports and autopsies were reviewed. Information on predisposing factors, symptoms, treatment and outcome was collected. All obtainable fungal blood stream isolates were subcultured and their susceptibility to common antifungals determined. RESULTS: In the 20 year period from 1980-1999, 19 episodes of invasive fungal infections were diagnosed in 18 infants and children in Iceland. Twelve episodes of fungemia occured in 11 children and the nationwide annual incidence increased from 0.28 to 1.90 cases/100,000/year (p=0.037) during the study period. Half of the children were premature infants. All patients had a central venous catheter at the time of blood culture and most had received intravenous antibiotics or corticosteroids. Candida albicans was the most commonly isolated species (nine of 12 episodes, 75%). In addition to patients with fungemia, three children were diagnosed with disseminated fungal infection by histology or autopsy. Two cases of fungal meningitis, without fungemia, were identified. Furthermore, two children had invasive infections with Aspergillus fumigatus and both patients survived. Three children (3/16; 19%) with invasive Candida-infections died. CONCLUSIONS: In this study of invasive fungal infections among Icelandic children we demonstrate that the incidence of fungemia has risen significantly in the past 20 years. Diagnosis of invasive fungal infections can be complicated and negative blood cultures do not exclude disseminated infection. Given the high attributable mortality, timely diagnosis and aggressive treatment is extremely important.

Prognostic impact of karyotypic findings in childhood acute lymphoblastic leukaemia: a Nordic series comparing two treatment periods. For the Nordic Society of Paediatric Haematology and Oncology (NOPHO) Leukaemia Cytogenetic Study Group.

The prognostic impact of acquired chromosome abnormalities was evaluated in a population-based consecutive series of 768 children (< 15 years of age) with acute lymphoblastic leukaemia (ALL). The study cohort included all cases of cytogenetically abnormal childhood ALL diagnosed between 1986 and 1997 in the five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden). The probability of event-free survival (pEFS) for the total cohort was 0. 72 +/- 0.02. When comparing the two treatment periods of July 1986 to December 1991 and January 1992 to December 1997, a better survival was seen for the latter time period (pEFS of 0.69 +/- 0.02 vs. 0.76 +/- 0.02, P = 0.05). Hypodiploidy with less than 45 chromosomes, t(9;22)(q34;q11) and 11q23 translocations were associated with a dismal outcome during the whole study period (pEFS of 0.57 +/- 0.12, 0.41 +/- 0.14 and 0.37 +/- 0.10 respectively). The poor prognostic influence of 11q23 rearrangements seemed to be restricted to infants and older children (> 10 years), who differed significantly from children aged 1-10 years in this regard (P < 0. 01). Patients with t(9;22)-positive ALL seemed to benefit from allogeneic bone marrow transplantation in first remission (P = 0.05). The pEFS for children with t(1;19)(q23;p13)-positive ALL was intermediate (0.63 +/- 0.17), with a tendency to a better outcome for patients with the unbalanced variant der(19)t(1;19). Hyperdiploid ALL patients, subdivided into moderate hyperdiploidy (47-51 chromosomes), massive hyperdiploidy (52-60 chromosomes) and cases in the tri-/tetraploid range (> 60 chromosomes) had the best outcome in the last treatment period (pEFS of 0.81 +/- 0.06, 0.80 +/- 0.04 and 0.88 +/- 0.07 respectively), unless t(1;19), t(8;14), t(9;22) or 11q23 translocations were present. In a multivariate analysis including white blood cell (WBC) count, immunophenotype, age, mediastinal mass, central nervous system involvement and leukaemia karyotype, only WBC and modal chromosome number were shown to be significant independent risk factors (P < 0.01).

Inflammatory bowel disease in Iceland, 1990-1994: a prospective, nationwide, epidemiological study.

BACKGROUND: Two separate nationwide, retrospective epidemiological studies of inflammatory bowel disease (IBD) in Iceland over a combined 40-year period, 1950-1989, have shown a continually rising incidence. The main objective of this study was to investigate the incidence of IBD prospectively for the 5-year period 1990-1994 to determine whether there still was an ongoing increase. METHODS: The retrieval of new cases of ulcerative colitis (UC) and Crohn's disease (CD) was based on a monthly review of all small and large intestinal tissue specimens with any type of inflammation submitted to all three departments of pathology in Iceland. All small intestinal X-ray records suggestive of CD were also reviewed. All possible new cases of IBD were then scrutinized by examination of the clinical records, using accepted criteria for confirmation or exclusion of IBD. RESULTS: A total of 215 cases of UC and 72 cases of CD were diagnosed, yielding a mean annual incidence for UC 16.5/100000 (95% confidence interval (CI) 14.4-18.9), and for CD 5.5/100000 (95% CI 4.3-7.0). The highest combined age related incidence for UC was 28.7/100000 in the group aged 30-39 years, and for CD 8.5/100000 in the groups aged 10-19 and 20-29 years. The most common extent in UC was proctosigmoid and the most frequent localization in CD was colonic only. CONCLUSIONS: This prospective study demonstrates a continuing and statistically significant increase in the incidence of both UC and CD in Iceland. The general changes identified for a few previously suggested environmental factors do not allow any firm conclusions as to their role in the observed increase in incidence. It is possible that there are some other causative factor(s).

[Gastroschisis in Iceland, a population study.].

INTRODUCTION: Gastroschisis, a congenital abdominal wall defect, is a rare disorder. The incidence of gastroschisis in Iceland is neither known nor is the results of surgery. OBJECTIVE: To determine the incidence of gastroschisis in Iceland, treatment results and mortality rate. MATERIAL AND METHODS: A retrospective study was performed. Hospital records, birth records and autopsy records were reviewed. The period was divided in two, 1970-1982 and 1983-1994. RESULTS: Twenty-eight children with gastroschisis were born in Iceland 1970-1994. Ten children with gastroschisis were born in the first period and 18 in the second, making the incidence 1.78/10,000 births vs. 3.45/10,000 (p<0.09). No abortion was performed because of gastroschisis and no child was stillborn with it. Associated anomalies were detected in 13 children, eight of which were gut atresias or stenosis. Other anomalies were found in seven children (21.4%). Of the mothers 82% (23/28) were primiparous, mean age 21.5 years. Gestational age was 30-40 weeks. Vaginal delivery was in 16 cases and Caesarean section in 12 cases, six of which were elective. Eighteen children were diagnosed at birth, 10 by ultrasound at 19 weeks of gestations. Birth weight was 2650 g (mean, range 1500-3720 g). Primary closure was done in 15 cases and delayed closure in 11, mostly in the first period. Hospital stay was 55 days (mean, median 26 days). Mortality rate was 10.7% (3/28) in two cases associated with major congenital anomalies. Long term complications are few 5/28 and consist of recurrent abdominal pain and constipation. CONCLUSIONS: This study indicates that the incidence of gastroschisis is increasing in Iceland, and although the study is too small to be significant, the trend is obviously there. In accordance with other studies the predominance of young primiparous mothers and small for gestational age children is observed. The results in treating gastroschisis in Iceland is at least as good as in bigger centers and the mortality rate is well within acceptable range, especially if taken into account that no abortions were performed because of gastroschisis.

Inflammatory bowel disease in Iceland, 1980-89. A retrospective nationwide epidemiologic study.

BACKGROUND: A previous nationwide epidemiologic study of inflammatory bowel disease (IBD) in Iceland in 1950-79 showed a low but steadily rising incidence. The incidence of IBD in Iceland in 1980-89 was investigated and compared with reports from neighboring countries. METHODS: Cases were retrieved by a review of all small- and large-intestinal tissue specimens with any type of inflammation submitted to the only two departments of pathology in Iceland. All small-intestinal X-ray records suggestive of Crohn's disease (CD) in the three major hospitals were also screened. All hospital and outpatient records of cases suggestive of IBD were then reviewed using accepted criteria for confirmation or exclusion. RESULTS: The mean annual incidence of ulcerative colitis (UC) was 11.7/100,000, and that of CD 3.1/100,000. The highest age-specific incidence of UC was in the group 30-39 years old and for CD in the group 60-69 years old. The most frequent involvement at diagnosis of UC was proctitis only, in 54%, and in CD colon only, in 54.7% of the patients. CONCLUSIONS: This study shows a continuing increase in the incidence of both diseases. Compared with the period 1970-79, there has been an almost twofold increase in the mean annual incidence of UC and more than a threefold increase of CD, a statistically significant increase in both instances.

[Feeding patterns and risk factors in an epidemic of neonatal necrotizing enterocolitis.].

OBJECTIVE: To study the relationship between neonatal feeding patterns and the emergence of neonatal necrotizing enterocolitis during the epidemic of this disease in Iceland in 1987-1990. MATERIAL AND METHODS: This was a retrospective case-controlled study of 18 newborns that developed neonatal necrotizing enterocolitis during a four year epidemic of the disease. Two newborns of similar weight and gestational age served as controls for each case. The amount of food given per kilogram of body weigth was recorded every 12 hours for each group and plotted against time. The differences in amount of food for the individuals of each group were calculated, regression lines found and these compared by t-test. The type of food the children received was also noted and compared, as was the presence of several other possible risk factors. RESULTS: The statistical calculation (t-test) showed that there was no significant difference between the patients and the controls as regards the amount of food given and the increase in the amount of each feeding (p=0.6). Sixteen (88.9%) of the patients had been fed before the occurrence of the disease. All had been fed through a gastric tube but only 20 (55.6%) of the controls, this is a significant difference (p=0.03). Three (18.8%) of the patients and 18 (50%) of the controls were given breast milk at their first feed. This difference however is not statistically significant (p=0.07). Comparison was also made of the occurrence of the following risk factors: umbilical catheter, perinatal asphyxia, polycythemia, acute or semiacute cesarian section, respiratory distress and being small for gestational age. Only births by cesarian section showed a significant difference between the groups (p= 0.004). Comparison of the number of risk factors did not show a statistically significant difference (p= 0.05). However there was a linear trend towards the patients having more risk factors than the controls (p=0.01). CONCLUSION: The study did not show that the epidemic of neonatal necrotizing enterocolitis in Iceland in 1987-1990 was caused by the increments in feeding given prior to the development of the disease. Two possible risk factors, feeding by gastric tube and birth by acute or semiacute cesarian section, were significantly more often found in the patient group than in the control group.

[Wilms' tumor in Iceland 1961-1995. A retrospective study.].

OBJECTIVE: Wilms' tumor is a malignant disease in the kidneys that usually affects young children. Information about the clinical behaviour of this tumor in Iceland has been scarce. The aim of this study was to find the incidence, clinical presentation, treatment and survival of patients with Wilms' tumor. MATERIAL AND METHODS: Included in the study were all patients diagnosed with Wilms' tumor in Iceland from 1st of January 1961 to 31st of December 1995. Altogether, there were 17 patients, 15 children, mean age 33 months (standard deviation 19, range 5-77 months) and two adults (age 25 and 29), with M/F ratio 0.7. Information was gained from each patient's record and the cancer registry of the Icelandic Cancer Society. All the tumors were re-evaluated by a pathologist and staged according to the NWTS staging system. RESULTS: Age adjusted incidence during the study period was 0.2/100,000 per year (1.0 for children under 15 years). Abdominal mass (65%) and abdominal pain (53%) were the most common symptoms. Histology was typical in all cases except one with anaplasia and another with sarcomatous growth. One patient was diagnosed in stage I (6%), six in stage II (35%) and seven in stage III (41 %). Two patients had pulmonary metastases (stage IV) and one had bilateral tumor (stage V). Nephrectomy was performed in all cases. The operative mortality was 12%. Of the 15 patients surviving surgery, 12 received radiotherapy, 12 chemotherapy and nine both treatments. Crude five-year-survival for the whole group was 42%, 25% for the patients diagnosed 1961-1976 and 61% for those diagnosed 1977-1995 (p=0.13). The patient with bilateral tumor was still alive 13 years after diagnosis. CONCLUSION: As in other Western countries, Wilms' tumor is rare in Iceland and has similar incidence and clinical presentation. Two thirds of the patients were diagnosed in stage II or III. Even patients with distant metastases can be cured with multimodal treatment: surgery, chemotherapy and radiotherapy. There was a trend toward better survival during the study period.

Malignant nasopharyngeal tumours in Iceland.

From 1965 to 1990, 46 cases of malignant nasopharyngeal tumours were diagnosed in Iceland. The incidence rate is as low as in other Western countries, 0.6/100,000 per year. Histo-pathological diagnosis were as follows: Undifferentiated carcinoma 45%; squamous cell carcinoma 30%; non-keratinizing carcinoma 7%; and plasmacytoma 9%; lymphoma 7%; rhabdomyosarcoma 2%. Four per cent were diagnosed at stage I, 13% at stage II, 29% at stage III and 54% at stage IV. The overall crude survival at 10 years from diagnosis was 28.3%. The following factors were found to have a prognostic value: Stage of disease, size of tumour (T-classification) and age at diagnosis. Nodal stage (N-classification) alone and sex were not found to be prognostic factors. There was no difference in survival among the different WHO types of cancer. Patients with carcinoma were all treated with radiotherapy. The survival of those who received more than 60 Gy was better than of those who received 60 Gy or less (p = 0.04).

Macular corneal dystrophy in Iceland. A clinical, genealogic, and immunohistochemical study of 28 patients.

BACKGROUND: The frequency of different types of macular corneal dystrophy (MCD) was determined in Iceland where MCD accounts for one third of every penetrating keratoplasty. METHODS: The authors determined the serum levels of antigenic keratan sulfate (aKS) in 27 patients with MCD and 53 unaffected family members by an enzyme-linked immunosorbent assay that uses an anti-KS monoclonal antibody (5-D-4). The authors also stained sections from 37 corneal buttons (including 2 regrafts) from 23 patients with MCD by the avidin-biotin complex method using the same anti-KS monoclonal antibody. RESULTS: Based on the serum analyses, 22 patients had MCD type I and 5 had MCD type II. The corneas from patients without detectable KS in the serum lacked immunohistochemical reactivity to the anti-KS antibody. Every MCD cornea examined from individuals with normal serum KS levels showed KS reactivity. All 53 unaffected siblings and parents carrying the recessive gene had normal serum KS levels. CONCLUSIONS: Macular corneal dystrophy types I (78.6%) and II (21.4%) both occur in Iceland. Members of affected sibships had only one of these types, not both. Nine patients with MCD type I and four persons with MCD type II belonged to a large pedigree in which individuals have been traced as far back as the beginning of the 16th century. The linking of patients with MCD types I and II in an inbred pedigree suggests that both types may be manifestations of the same abnormal gene rather than independent entities. The serum KS levels were not helpful in detecting heterozygous MCD carriers.

[Prevalence and diagnosis of neural tube malformations in Iceland 1972-1991.].

OBJECTIVE: The incidence and types of central nervous system (CNS) defects diagnosed in fetuses and newborns over a 20-year period, 1972-1991, were investigated. Concurrently the effect of prenatal ultrasound screening on the rates of delivered babies with neural tube defects were evaluated. MATERIAL AND METHOD: All CNS defects diagnosed in newborn babies and in miscarried or legally aborted fetuses in Iceland during the study period were searched for using the Icelandic Birth and Abortion Registries. For ascertainment maternity case records, hospital records and autopsy and pathology reports were scrutinized. The number and types of defects were noted for each year and the prevalence evaluated for five- and 10-year periods as well as for the time after introduction of organised obstetric ultrasound screening. RESULTS: There was considerable yearly variation in the incidence of CNS defects. In the first five-year period no CNS defect was diagnosed prenatally, but thereafter the number of cases diagnosed before birth rose, partly because of improved identification of more subtle defects. In spite of an increase in the number of cases to 2.2/1000 births, the incidence of babies born with CNS defects was more than halved to 0.8/1000 births. Organised nationwide ultrasound screening in and after 1984 had a marked lowering effect on the number of births with these defects. In 60% of cases the diagnosis was obtained before birth, most often before 22 weeks gestation. Most severe malformations were diagnosed, except for spina bifida, where after 1984 only 40% were diagnosed early enough to allow termination of pregnancy. CONCLUSION: The incidence of CNS defects has risen, probably because of improved recognition of these malformations during pregnancy and to some extent after birth. Organised obstetric ultrasound allowed diagnosis of most severe defects, although 1/3 of defects leading to severe handicap went undiagnosed until after birth, particularly in smaller hospitals and health centers outside Reykjavik. Improving the diagnostic possibilities through training of staff handling obstetric screening is important, but the introduction of nationwide biochemical screening must also be considered.

[Ulcerative colitis in Iceland 1980-1989. A retrospective epidemiological study.].

OBJECTIVE: To find the incidence of ulcerative colitis in Iceland during the past decade for comparison with previous study and incidence figures from neighbouring countries. METHODS: This was a nationwide retrospective study of the period 1980-1989. Cases were retrieved by reviewing all reports on tissue specimens from the large and small intestine with any type of inflammation referred to the two departments of pathology in Iceland. All possible cases of ulcerative colitis were then followed by a review of the clinical information. Only those cases fulfilling accepted diagnostic criteria were included in the study. RESULTS: Thus 282 cases of ulcerative colitis were found, 166 men and 116 women, M/F ratio 1.43. The mean annual incidence for the 10 year period was 11.7/100,000. The highest age specific incidence was found in the group 30-39 years, 21/100,000/year. Most frequently the inflammation was limited to the rectum (proctitis), found in 53.9% of the patients. Proctosigmoiditis was seen in 29.8%, left-sided col notitis in 5.3% and extensive colitis in 11%. Approximately 63% of the patients had been symptomatic for less than six months before diagnosis. Information on familial cases of inflammatory bowel disease was obtained from 8.9% of the patients. CONCLUSION: There has been a steady and significant increase in the incidence of ulcerative colitis in Iceland in the past four decades and the mean annual incidence has almost doubled from the last decade 1970-1979. This increase in incidence is considered real, i.e. not due to better methods of detection or a change in diagnostic criteria.

[Crohn's disease in Iceland 1980-1989. A retrospective epidemiological study.].

OBJECTIVE: To find the incidence of Crohn's disease in Iceland during the past decade for comparison with previous study and incidence figures from neighbouring countries. METHODS: A nationwide retrospective study of the incidence of Crohn's disease in Iceland for the 10-year period 1980-1989 was conducted. New cases were retrieved by review of all small and large intestinal tissue specimens with any type of inflammation submitted to the two departments of pathology in Iceland. All cases with the slightest possibility of Crohn's disease were followed clinically by examining their hospital, outpatient and x-ray records. In addition all small intestinal x-rays with the diagnosis of Crohn's disease were screened. The criteria of Lennard-Jones were used to confirm or exclude Crohn's disease. RESULTS: Thus 75 patients were found, 36 men and 39 women, M/F ratio 0.9. The mean annual incidence was 3.1/100,000, which is a three fold increase compared to the period 1970-1979. The incidence of Crohn's disease in Iceland is still the lowest among the neighbouring countries. The highest age specific incidence was in the age group 60-69 years, 8.9/ 100,000, which is unusual. The most frequent localization of the intestinal inflammation at diagnosis was colon only (54.7%). The second most common localization was ileum only (25.3%), but in 18.7% of the patients the disease involved both ileum and colon. Inflammation limited to the colon was significantly more frequent in the older age groups. There was a family history of inflammatory bowel disease (IBD) in 8% of the cases. CONCLUSION: The incidence of Crohn's disease in Iceland, while still low compared to that of the neighbouring countries, is rising. The reason for this increase is unknown.

Relation of antiphospholipid antibody and placental bed inflammatory vascular changes to the outcome of pregnancy in successive pregnancies of 2 women with systemic lupus erythematosus.

Histological changes in biopsies from the placental and placental bed in 2 successive pregnancies of 2 women with systemic lupus erythematosus and antiphospholipid antibodies were studied. In one of the first 2 pregnancies vasculitis was found in the spiral arteries of the placental bed biopsy, while the other showed perivascular inflammatory infiltration and deciduitis. This was associated with poor pregnancy outcome and elevated antiphospholipid antibodies (aPL). In the subsequent 2 pregnancies prednisolone treatment was tailored to suppress the aPL titer with markedly decreased inflammatory changes and no evidence of vasculitis in the spiral arteries of the placental bed was found. This was associated with a normal pregnancy outcome. A causal relationship between aPL and inflammatory vascular changes in the placental bed as well as a beneficial effect of the corticosteroid treatment in those two women in suggested.

Carcinoid tumors of the appendix in children younger than 16 years. A retrospective clinical and pathologic study.

Eighteen cases of appendiceal carcinoid in children aged 4 to 15 years, 14 of them girls, are reviewed. Most (73%) of the tumors were located in the distal third of the appendix. Tumor size, measured in histologic sections, ranged from 0.1 to 1.2 cm. In three cases the tumor had invaded the mesoappendix. No metastases were found. Standard appendectomy was performed in all cases as the only surgical procedure. The preoperative clinical diagnosis in 15 cases was acute appendicitis, which was histologically confirmed in 53%. At follow-up 2.2 to 29.3 years postoperatively (mean 16.4 years), all the patients were alive and without suspected or verified recurrence of carcinoid.

Classification of perinatal and late neonatal deaths in Iceland. A survey from a defined population.

A retrospective case record analysis of all perinatal and late neonatal deaths in Iceland in the periods 1976-80 and 1981-85 was done and the causes of death classified according to the extended Aberdeen classification. There was a significant (p less than 0.0001) reduction in number of deaths between the two periods with perinatal mortality rates declining from 10.6/1000 in 1976-80 to 6.8/1000 in 1981-85. In 1976-80 there were 81 (33%) antepartum, 37 (15%) intrapartum and 128 (52%) neonatal deaths compared to 61 (38%) antepartum, 13 (8%) intrapartum and 86 (54%) neonatal deaths in 1981-85. Fetal abnormality was the most common cause of death in both periods followed by the category Low birthweight in 1976-80. In 1981-85 increased morphological detection of infection in infants of very low birthweight by placental examination and autopsies lead to a shift from the category Low birthweight to Maternal Disease, the second most common cause in that period. To achieve lower perinatal mortality rates efforts should be directed towards lowering antepartum losses near term and increasing survival of very low birthweight infants.