Microstructural white matter alterations and hippocampal volumes are associated with cognitive deficits in craniopharyngioma.

CONTEXT: Patients with craniopharyngioma (CP) and hypothalamic lesions (HL) have cognitive deficits. Which neural pathways are affected is unknown. OBJECTIVE: To determine whether there is a relationship between microstructural white matter (WM) alterations detected with diffusion tensor imaging (DTI) and cognition in adults with childhood-onset CP. DESIGN: A cross-sectional study with a median follow-up time of 22 (6-49) years after operation. SETTING: The South Medical Region of Sweden (2.5 million inhabitants). PARTICIPANTS: Included were 41 patients (24 women, ≥17 years) surgically treated for childhood-onset CP between 1958-2010 and 32 controls with similar age and gender distributions. HL was found in 23 patients. MAIN OUTCOME MEASURES: Subjects performed cognitive tests and magnetic resonance imaging, and images were analyzed using DTI of uncinate fasciculus, fornix, cingulum, hippocampus and hypothalamus as well as hippocampal volumetry. RESULTS: Right uncinate fasciculus was significantly altered (P ≤ 0.01). Microstructural WM alterations in left ventral cingulum were significantly associated with worse performance in visual episodic memory, explaining approximately 50% of the variation. Alterations in dorsal cingulum were associated with worse performance in immediate, delayed recall and recognition, explaining 26-38% of the variation, and with visuospatial ability and executive function, explaining 19-29%. Patients who had smaller hippocampal volume had worse general knowledge (P = 0.028), and microstructural WM alterations in hippocampus were associated with a decline in general knowledge and episodic visual memory. CONCLUSIONS: A structure to function relationship is suggested between microstructural WM alterations in cingulum and in hippocampus with cognitive deficits in CP.

Hippocampal volume in relation to clinical and cognitive outcome after electroconvulsive therapy in depression.

OBJECTIVE: In a previous magnetic resonance imaging (MRI) study, we found a significant increase in hippocampal volume immediately after electroconvulsive therapy (ECT) in patients with depression. The aim of this study was to evaluate hippocampal volume up to 1 year after ECT and investigate its possible relation to clinical and cognitive outcome. METHOD: Clinical and cognitive outcome in 12 in-patients with depression receiving antidepressive pharmacological treatment referred for ECT were investigated with the Montgomery-Asberg Depression Rating Scale (MADRS) and a broad neuropsychological test battery within 1 week before and after ECT. The assessments were repeated 6 and 12 months after baseline in 10 and seven of these patients, respectively. Hippocampal volumes were measured on all four occasions with 3 Tesla MRI. RESULTS: Hippocampal volume returned to baseline during the follow-up period of 6 months. Neither the significant antidepressant effect nor the significant transient decrease in executive and verbal episodic memory tests after ECT could be related to changes in hippocampal volume. No persistent cognitive side effects were observed 1 year after ECT. CONCLUSION: The immediate increase in hippocampal volume after ECT is reversible and is not related to clinical or cognitive outcome.

[Importance of echocardiography and MRI in periventricular leukomalacia]. / Apport de l'échographie et de I'IRM dans la leucomalacie périventriculaire.

Periventricular leukomalacia (PVL) consists of focal coagulation necrosis and of more diffuse and mild white matter involvement as gliosis and lesions of immature oligodendrocytes. PVL affects essentially the premature newborn and has become the dominant form of perinatal neurological insults. Its diagnosis remains difficult to assess as neurological examination is poorly contributive. Diagnostic imaging plays an important role as it completes clinical, biological and electrophysiological data in depicting the cerebral lesions. Cerebral ultrasound remains the first imaging modality to perform in order to investigate and follow ill neonates. However ultrasound has a low sensitivity and specificity in depicting non cavitated PVL. Magnetic resonance imaging (MRI), in the acute stage, provides additional information about the extension and the depiction of hemorrhagic component of the lesions. Furthermore, diffusion-weighted MRI appears useful for the early identification of the diffuse component of PVL. MRI in the chronic stage is the only imaging method to study the progress of myelination and precise the extension of sequellar lesions.

Magnetic resonance imaging of the fifth metatarsophalangeal joint compared with conventional radiography in patients with early rheumatoid arthritis.

OBJECTIVE: To evaluate if magnetic resonance imaging (MRI) is superior to conventional radiography for detection of erosions in the fifth metatarsophalangeal (MTP5) joint. METHODS: Within one year from the onset of rheumatoid arthritis (RA) (baseline), one and three years thereafter MRI and conventional radiographs of the MTP5 joint were performed in 23 patients. RESULTS: MRI revealed erosions in 10 patients at baseline, in 15 after one year and in 15 patients after 3 years. On conventional radiography, there were erosions in 10 patients at baseline, 16 after one year as well as after 3 years. The agreement between the two imaging methods was fair to good at baseline and after one and three years (kappa 0,65, 0,51 and 0,51 respectively). The number of patients with clinical evidence of synovitis decreased considerably over time although the number of patients with MRI-synovitis was unchanged and the number of patients with erosions increased. CONCLUSIONS: MRI was not superior to conventional radiography in detecting erosions in MTP5 joints in patients with early RA. Most erosions developed during the first year of observation. Synovitis on MRI may be a marker of future development of erosions in the MTP5 joint.

A PCR-based method to distinguish fungi of the rice sheath-blight complex, Rhizoctonia solani, R. oryzae and R. oryzae-sativae.

Identification of Rhizoctonia solani, R. oryzae and R. oryzae-sativae, components of the rice sheath disease complex, is extremely difficult and often inaccurate and as a result may hinder the success of extensive breeding programmes throughout Asia. In this study, primers designed from unique regions within the rDNA internal transcribed spacers have been used to develop a rapid PCR-based diagnostic test to provide an accurate identification of the species on rice. Tests on the specificity of the primers concerned showed that they provide the means for accurate identification of the Rhizoctonia species responsible for sheath diseases in rice.

Growth hormone therapy of Turner's syndrome: beneficial effect on adult height.

OBJECTIVE: To carry out a multicenter, prospective, randomized trial of human growth hormone (GH), alone or in combination with oxandrolone (OX), in patients with Turner's syndrome (TS). METHODS: In an initial phase lasting 12 to 24 months, 70 girls with TS, verified by karyotype, were randomly assigned to one of four groups: (1) observation, (2) OX, (3) GH, or (4) GH plus OX. After completion of the first phase, group 3 subjects continued to receive GH only. All other subjects were treated with GH plus OX. Subjects were followed up until attainment of adult height and/or cessation of treatment. Data from this trial were compared with growth characteristics of 25 American historical subjects with TS (matched for age, height, parental target height, and karyotype) who never received either GH or androgens. RESULTS: Of the 70 subjects enrolled, 60 completed the clinical trial. The 17 subjects receiving GH alone all completed the trial and reached a height of 150.4+/-5.5 cm (mean +/- SD), 8.4+/-4.5 cm taller than their mean projected adult height at enrollment (95% confidence interval [CI]: 6.3 to 10.6 cm). The 43 subjects receiving GH plus OX attained a mean height of 152.1+/-5.9 cm, 10.3+/-4.7 cm taller than their mean projected adult height (95% CI: 8.9 to 11.7 cm). The historical control subjects had a mean adult height of 144.2+/-6.0 cm, precisely matching their original projected adult height of 144.2+/-6.1 cm. CONCLUSIONS: GH, either alone or in combination with OX, is capable of stimulating short-term growth and augmenting adult height in girls with TS. With early diagnosis and initiation of treatment, an adult height of more than 150 cm is a reasonable goal for most girls with TS.

Brain function in spider phobia.

Measurements of regional cerebral blood flow (rCBF) were performed in 16 women suffering from spider phobia. The non-invasive 133Xe inhalation method, giving information about the blood flow of superficial areas, was used. The subjects were studied under three conditions: during resting, when exposed to a videotape showing nature scenery, and finally when watching a video with living spiders. During the rCBF measurements the subjects' behaviour was registered systematically and respiration, blood pressure, Pco2, and heart rate were monitored. Eight subjects who showed and reported severe panic during the spider exposure had marked rCBF decreases in frontal areas, especially in the right hemisphere. The remaining eight subjects displayed a more efficient control of their emotions and became frightened, but not panic-stricken, during the spider exposure. These showed a consistent rCBF increase in the right frontal area compared to neutral stimulation. Thus, results revealed significant functional changes in the frontal cortex in subjects with spider phobia during phobogenic exposure. It seems likely that these frontal changes are related to the experience and control of phobic anxiety.

Adult height in growth hormone (GH)-deficient children treated with biosynthetic GH. The Genentech Growth Study Group.

Near-adult height (AH) was determined in 121 children (72 males and 49 females) with GH deficiency (GHD) who were prepubertal when they began treatment with recombinant DNA-derived preparations of human GH. AH as a SD score was -0.7 +/- 1.2 (mean +/- SD), significantly greater than the pretreatment height SD score (-3.1 +/- 1.2), the predicted AH SD score (-2.2 +/- 1.2; Bayley-Pinneau method), and the height SD score at the start of puberty (-1.9 +/- 1.3). In contrast to studies of GH treatment outcome, which used pituitary-derived GH (pit-GH) in lower doses, we found that males did not have a higher AH SD score than females, spontaneous puberty did not diminish AH, and AH was significantly greater than that predicted at the start of GH treatment. In a multiple regression equation, the statistically significant variables (all P < 0.0001) related to AH (r2 = 0.70) were the following: duration of treatment with GH, sex (males were taller than females, as expected for the normal population), age (younger children had a greater AH) and height at the start of GH, and growth rate during first year of GH. For the AH SD score (r2 = 0.47), pretreatment predicted AH, duration of GH, and bone age delay were significant (P < 0.0002) explanatory variables. Bone age delay (chronological age-bone age) had a negative impact on the AH SD score. Target height, etiology of GHD, previous treatment with pituitary GH, and the presence or absence of spontaneous puberty did not significantly improve the prediction of AH. Early diagnosis of GHD and continuous treatment with larger doses of GH to near AH should improve the outcome in children with short stature due to GHD.

Brain tumor recurrence in children treated with growth hormone: the National Cooperative Growth Study experience.

As of October 1993 the National Cooperative Growth Study included 1262 children with brain tumor who were treated with growth hormone. The type of brain tumor was specified in 947 (75%) of these children. The most common types were glioma, medulloblastoma, and craniopharyngioma, accounting for 91.3% of all those for which type was specified. Brain tumor recurred in 83 (6.6%) of the 1262 children over a total of 6115 patient-years at risk. The frequencies of tumor recurrence in children with low-grade glioma (18.1%), medulloblastoma (7.2%), and craniopharyngioma (6.4%) are lower than those in published reports of tumor recurrence in the general pediatric population with the same types of tumors. The analysis cannot conclusively show that no increased risk of tumor recurrence exists, however, because of the potential incompleteness of data reporting in the National Cooperative Growth Study. Nevertheless the findings are reassuring that children with the more common types of brain tumor who are treated with growth hormone do not seem to be at excessive risk for tumor recurrence.

Outcome of a four-year randomized study of daily versus three times weekly somatropin treatment in prepubertal naive growth hormone-deficient children. Genentech Study Group.

A comparison was made of the growth responses of prepubertal naive GH-deficient children who were randomly assigned to receive 0.3 mg/kg.week recombinant human GH administered either daily (QD) or three times weekly (TIW) over 4 yr. The effects of the two regimens on annual growth velocity, change in height SD score, bone maturation, and age at onset of puberty are presented as the mean +/- SD. During each of the 4 yr, the annual growth velocity was significantly greater in the QD vs. TIW group. At 48 months, the mean total gain in height was 9.7 cm greater in the QD group (38.4 +/- 5.5) than that in the TIW group 28.7 +/- 3.2; P = 0.0002). The mean height SD score at the end of each year was significantly greater in the QD group. After 4 yr, the total gain in height SD score was 3.2 +/- 1.2 in the QD group compared to 1.5 +/- 0.5 in the TIW group (P = 0.0003). The height SD score at 4 yr was 0.2 in the QD group (pretreatment, -2.9) compared to -1.4 in the TIW group (pretreatment, -2.9). After 4 yr of rhGH treatment, the increment in bone age was similar in the QD (4.9 +/- 1.0 yr) and TIW (4.8 +/- 1.1 yr) groups. The change in height age minus the change in bone age was more favorable in the QD (1.2 +/- 0.8 yr) than in the TIW (0.0 +/- 0.9 yr) group (P = 0.003). The mean age at onset of puberty in boys was the same in the QD (13.2 yr) and TIW (13.0 yr) groups (P = 0.71), and the mean bone age at the start of puberty was also similar (11.5 in QD and 11.3 in TIW groups; P = 0.66). The advantages of QD rhGH treatment in prepubertal GH-deficient children after 4 yr were additional gains of 1.7 height SD score and 9.7 cm in height over those treated with the TIW regimen (P = 0.0002).

Neuropsychological assessment of dementia: state of the art.

A comprehensive neuropsychological examination includes an assessment of both cognitive functions and personality characteristics. In order to evaluate dementia, the patient's present as well as the premorbid functioning has to be assessed, which is performed by means of tests, behavioral observations, rating scales, and inquiries. These methods are used for diagnostic purposes, for differential diagnostics, follow-up studies, and for evaluation of treatment effects. Recent research has shown that neuropsychological methods have a high sensitivity and specificity in detection of dementia, utilizing measures of episodic memory. For staging of dementia, episodic memory as well as other cognitive functions are necessary. The effectiveness of dementia differentiation by means of neuropsychological methods varies from quite good regarding frontal lobe degeneration to less good regarding cerebrovascular dementias, probably due to the variation in site, extent, number, and temporal characteristics of the lesion. Future development is required regarding methods for evaluation of premorbid functioning, instruments for assessment of executive functions, and personality characteristics in dementia. Furthermore, brain-behavior studies are needed to learn more about the relation between neuropsychological measures vs neuropathology, neurochemistry, and neuroimaging.

Lack of increased risk for extracranial, nonleukemic neoplasms in recipients of recombinant deoxyribonucleic acid growth hormone.

This report describes cases of new extracranial nonleukemic neoplasms in recombinant human GH (rhGH) recipients. The data are largely from the National Cooperative Growth Study (NCGS), with over 51,000 patient-years at risk from 12,209 patients treated with Protropin rhGH. In addition to case reports of extracranial tumors from the NCGS enrollees, there have been reports from non-NCGS patients. Ten cases of new extracranial neoplasms have been reported from this total study population, and there have been eight cases whose second neoplasms were extracranial in nature. For the new cases, the number of observed cases is compared with the number of expected cases, as derived from incidence rates published by the National Cancer Institute's SEER (Surveillance, Epidemiology, and End Results) Program. The standard morbidity ratio (SMR), defined as the number of observed cases/expected cases, is calculated for males and females separately, with further subgroup analysis based upon age. For the NCGS population, the SMRs were not statistically distinguishable from unity (i.e. 1). When the number of non-NCGS Protropin patients is estimated and SMRs are calculated for the total Protropin-treated group, the SMRs remain statistically indistinguishable from one. At present, these data suggest that rhGH does not increase the risk for developing nonleukemic extracranial neoplasms. Because a small number of additional cases could significantly alter the SMR calculations, meticulous reporting and continued surveillance must continue.

Growth response of children with non-growth-hormone deficiency and marked short stature during three years of growth hormone therapy.

Short-term administration of human growth hormone to children with idiopathic short stature can improve mean growth rate and predicted adult height. It is yet unknown whether therapy would alter pubertal development or affect final height. Three-year treatment results in a group of children with idiopathic short stature are reported. For year 1 of the study, 121 prepubertal children were randomly selected to receive somatotropin, 0.3 mg/kg per week, administered subcutaneously three times weekly (n = 63), or to be nontreatment control subjects (n = 58). After 1 year, all subjects were again randomly selected to receive either three-times-weekly or daily dosing at the same total dose. For the 92 subjects who completed 36 months of treatment, mean growth rate increased from a mean of 4.6 cm/yr before treatment to a mean of 8.0 cm/yr in the first year of treatment. Daily dosing resulted in a significantly faster mean growth rate (9.0 cm/yr) than three-times-weekly dosing (7.8 cm/yr) (p = 0.0005). Mean growth rates were 7.6 and 7.2 cm/yr during years 2 and 3, respectively, and did not differ by dosing group. Mean standardized height for all subjects improved from -2.7 to -1.6 after 3 years. When the growth rate was standardized for bone age, however, subjects who remained prepubertal had a significantly greater gain in mean height SD score than subjects who became pubertal during that 3-year period (p < 0.02). Mean standardized Bayley-Pinneau predicted adult height SD score increased from -2.7 to -1.6 and was independent of the timing of pubertal onset, but for individuals this score was more variable. Year-1 growth response, expressed as growth rate or change in height SD score, was the best predictor of growth in subsequent years. Responses to therapy could not be reliably predicted from baseline anthropometric variables, plasma insulin-like growth factor I SD score, growth hormone levels. Final height assessment will be needed to determine the ultimate benefit of therapy.

Factors predicting the response to growth hormone (GH) therapy in prepubertal children with GH deficiency.

To identify factors influencing the response to GH therapy, we used a multiple regression model to analyze data from 632 naive prepubertal children with GH deficiency (GHD). There were 523 children with idiopathic and 109 children with organic GHD. They were treated with the same preparation of biosynthetic methionyl GH (somatrem, Protropin) for at least 1 yr. In children with idiopathic GHD, six variables predicted 40% of the response to treatment. They were (listed in relative importance, all P < 0.0001): age, log maximum GH, weight adjusted for height, dosing schedule, dose, and midparental height. Three variables, pretreatment growth rate, log maximum GH, and age, predicted 20% of the GH response in children with organic GHD. When data for all children were analyzed using analysis of covariance, children with idiopathic GHD grew better than those with organic GHD (mean +/- SD, 9.2 +/- 2.4 vs. 8.8 +/- 2.6 cm/yr; P < 0.0001). The children (both organic and idiopathic GHD) who did not respond well to treatment were younger and thinner than those who did. Early diagnosis and initiation of therapy should be beneficial to ultimate height attainment. The best response to GH therapy should be in young children with severe idiopathic GHD who receive daily weight-adjusted doses. The use of GH daily in higher doses would be expected to be most beneficial in older children with acquired and/or less severe GHD or in children who are underweight for height.

Urinary growth hormone and insulin-like growth factor I. Effects of growth-hormone injection schedule.

Urinary growth hormone (GH) and insulin-like growth factor I (IGF-I) excretion profiles were compared in children receiving biosynthetic GH. Group 1 included 18 healthy controls. Group 2 included nine children given biosynthetic GH three times a week. Group 3 included 14 children given daily GH injections. Overnight urine samples were collected for three consecutive nights in all groups. No significant day-to-day variation in urinary GH output was observed in group 1. In group 2, urinary GH output was significantly higher on day one following injection than on days two and three. Urine GH outputs in group 2 were significantly lower on days two and three than the values observed on all days in group 3. Throughout the three-day study, subjects in group 3 excreted similar amounts of GH significantly higher than those of controls. Urinary IGF-I output (nmol/kg) was similar on all three study days in groups 1 and 3. Group 2 had significantly lower urinary IGF-I output on day three compared with day one. Urinary IGF-I output on day three was also significantly lower in group 2 than in group 3. We conclude that urinary GH and IGF-I outputs are influenced by the frequency of GH administration.

[Local recurrence of breast cancer after breast preserving surgery. Experiences with a triple test as a routine control]. / Lokalt residiv av cancer mammae etter brystbevarende behandling. Erfaringer med trippeldiagnostikk som kontrollrutine.

Patients treated for breast cancer with breast-conserving surgery and radiotherapy were followed up by physical examination, mammography, and fine needle aspiration ("triple test") at The Norwegian Radium Hospital. Local recurrence was found in six cases. Two recurrences were detected by physical examination only, one by physical examination and mammography, and three by mammography only. Fine needle aspiration is useful when recurrence of cancer is suspected at mammographic or physical examination. Follow-up after breast-conserving treatment requires considerable experience in the field. Follow-up using the "triple test" should take place at regional centres.

Diagnostic significance of urinary growth hormone measurements in children with growth failure: correlation between serum and urine growth hormone.

Twelve-h overnight urine and serum samples obtained simultaneously at 20-min intervals were assayed for growth hormone (GH). Ninety-one children, 5 to 16 y (Tanner stage 1 to 3) participated; group 1 were healthy children, group 2 were children with organic GH deficiency, and group 3 had idiopathic growth failure and normal GH stimulation tests. Serum pool GH concentrations in group 1 were similar to those in group 3 (3.3 +/- 0.3 versus 3.4 +/- 0.2 micrograms/L); group 2 had significantly lower GH concentrations (1.6 +/- 0.2 micrograms/L). Plasma IGF-I levels were significantly greater in groups 1 (14.2 +/- 2.6 nmol/L, p less than 0.001) than in groups 2 and 3 (2.6 +/- 0.5 and 5.5 +/- 0.7 nmol/L, respectively). Urinary GH (mean +/- SEM) standardized for body weight (micrograms/kg) in group 1 (0.31 +/- 0.02) was significantly greater than in group 2 (0.14 +/- 0.01) and group 3 (0.20 +/- 0.01). However, when expressed as microgram/mol creatinine, the output of GH was similar in group 1 (4.0 +/- 0.3) and group 3 (3.4 +/- 0.3); both groups had significantly greater output compared to group 2 (1.3 +/- 0.2). Urinary IGF-I (nmol/kg) in group 1 (0.22 +/- 0.02) was significantly greater than in group 2 (0.12 +/- 0.01) or group 3 (0.07 +/- 0.01). Urinary GH correlated with serum pool GH concentration (r = 0.64, p less than 0.001). Although urinary GH output reflects endogenous GH secretion, the overlap between groups 1 and 3 precludes using urinary GH measurements as a diagnostic test for GH deficiency in children with idiopathic growth failure.

Growth hormone for short stature not due to classic growth hormone deficiency.

The advent of recombinant DNA technology has resulted in potentially unlimited supplies of growth hormone. Sufficient quantities are now available not only for the long-term, uninterrupted treatment of GH-deficient children but potentially for the treatment of non-GH-deficient patients with other short stature or growth attenuating disorders. Short-term studies have demonstrated an improvement in the growth rates of subjects with isolated short stature, Turner syndrome, and chronic renal failure; and additional studies are under way to assess the efficacy of GH therapy of other short stature syndromes. However, the long-term efficacy and possible adverse effects of GH treatment in these situations is not known. Until there has been more experience, GH deficiency should remain the primary indication for GH treatment. Growth hormone should not be considered routine therapy for other conditions associated with or resulting in short stature. However, research should continue in these areas to define which children may benefit from GH treatment.

[Contrast mammography in spontaneous bloody secretion from the nipple]. / Kontrastmammografi ved spontan blodig sekresjon fra mammae.

43 women with spontaneous bloody nipple discharge were examined by galactography performed with water soluble contrast medium. The purpose of this study was to evaluate the use of galactography in these patients, to localize the cause of this particular type of discharge and to register the therapeutic consequences of the findings. Surgical resection was carried out in all cases where galactography showed intraductal pathology. The remaining patients (except for four who also underwent surgery) were observed without treatment. No sign of carcinoma was found in a follow-up examination of the non-operated patients after two to four years. The results show that galactography can be suitably used to demonstrate and localize intraductal pathology, and may therefore be of importance in the preoperative investigation of spontaneous blood-stained secretion.