Hippocampal volumes and cognitive performance in children born extremely preterm with and without low-grade intraventricular haemorrhage.

Children born extremely preterm, especially those with intraventricular haemorrhage (IVH), are at increased risk of adverse cognitive outcomes during childhood. The present study aimed to explore the effects of IVH (grades I-II) on hippocampal volumes, and their correlates with cognitive performance. The sample consisted of 94 participants, including 54 children born extremely preterm (19 with IVH, grades I-II), and 40 children born at term. All participants underwent a magnetic resonance imaging study at the age of 10 (Mage = 10.20 years; SDage = 0.78), and 74 of them (45 extremely preterm and 29 full-term) carried out a cognitive assessment at 12 years old. Children born extremely preterm had lower scores in cognitive performance compared to their full-term peers. Significant positive partial correlations were observed between global bilateral hippocampus, left CA-field, and left subiculum volumes with processing speed in the full-term group, while no significant correlations were found in the extremely preterm group. Moderation analyses in the extremely preterm sample revealed that low-grade IVH moderated the relationship between right hippocampal volume and full-IQ (F(4,40) = 5.42, p = 0.001, R2 = 0.35). Having greater right hippocampal volume had a protective effect on full-IQ in those children born extremely preterm with low-grade IVH.

Destruction rate of h3+ by low-energy electrons measured in a storage-ring experiment.

Knowledge of the abundance of H(3)(+) is needed in interstellar and planetary atmospheric chemistry. An important destruction mechanism of H(3)(+) is low-energy electron impact followed by dissociation, but estimates of the reaction rate span several orders of magnitude. As an attempt to resolve this uncertainty, the cross section for dissociative recombination of vibrationally cold H(3)(+) has been measured with an ion storage ring down to collision energies below 1 millielectron volt. A rate coefficient of 1.15 x 10(-7) cubic centimeters per second at 300 kelvin was deduced. The cross section scaled with collision energy according to E(-1.15), giving thee rate a temperature dependence of T(-0.65).

Effect of the antineoplastic agent methotrexate on experimental heterotopic new bone formation in rats.

Heterotopic new bone formation was induced by implanting pieces of demineralized bone matrix in the abdominal wall of 22 growing Sprague-Dawley rats. The animals were divided into three groups and were given, 24 hr after initiation of the bone induction process, a single i.v. injection of methotrexate, 100 or 250 mg/kg body weight, or placebo, followed after 2 hr by leucovorin rescue. A slight and transient arrest in weight gain was noted in the methotrexate-treated animals. New bone formation during 3 weeks after implantation was analyzed by the amount of ash in implants, and as a measure of bone formation at the end of the experiment, short-time incorporation of 45Ca and [3H]proline was used. The ash content of implants was reduced by 56 and 68% in the two methotrexate groups. Uptake of both nucleotides was also greatly reduced in heterotopic bone, whereas metaphysial and diaphysial tibia and teeth were not affected. The results indicate a pronounced inhibition of methotrexate on bone induction, persisting for at least 3 weeks. Methotrexate reduces the bone-forming potential, with possible consequences for the success of limb-saving surgery and fracture healing.

Growth inhibition of human osteosarcomas in nude mice by human interferon-alpha: significance of dose and tumor differentiation.

The sensitivity of 11 human osteosarcoma xenografts in nude mice to human interferon-alpha (IFN-alpha) was studied. Growth inhibition could be demonstrated in all tumors but the necessary IFN-alpha dose ranged from 1 X 10(5)-1 X 10(6) IU/day. IFN-alpha had to be given daily to attain growth arrest and growth resumed after reduction of the IFN-alpha dose. The xenografts could be divided in two groups based on their sensitivity to IFN-alpha: one group of five xenografts that were growth arrested by IFN-alpha, 2 X 10(5) IU/day, and another group of six xenografts in which this dose was insufficient to arrest growth. The proportions of S-phase cells, determined by DNA flow cytometry of untreated control xenografts, were lower in the former group compared to the latter less IFN-alpha sensitive group. Histological examination revealed that in four of the five more IFN-alpha sensitive xenografts, tumor tissue was replaced by normal bone and marrow tissue. This was not seen in the respective control xenografts and not in any of the six less sensitive IFN-alpha treated xenografts. It appears that less proliferative osteosarcoma xenografts are more sensitive to growth inhibition by IFN-alpha. Interestingly the antitumor effect by IFN-alpha on these xenografts was expressed not only by growth arrest but also by tumor differentiation.

Influence of human alpha-interferon on four human osteosarcoma xenografts in nude mice.

Growth-inhibiting effects of human alpha-interferon (HuIFN-alpha) were investigated in four human osteosarcoma xenografts in nude mice. In addition to effects on growth, the HuIFN-alpha treatment was evaluated by histological examination and DNA flow cytometric analysis. Daily doses of 2 X 10(5) IU HuIFN-alpha completely arrested the growth of two osteosarcoma xenografts and partially inhibited one, whereas 1 X 10(6) IU/day were necessary to arrest the growth of the fourth. Growth inhibition was reversible and tumor size independent. The histological appearance, including mitotic indices, and S-phase proportions were unchanged in three xenografts. The mechanism of the HuIFN-alpha-induced growth inhibition of these three xenografts was therefore not considered to be a direct antiproliferative effect, but rather due to increased cell loss and/or increased cell cycle time. The modal DNA value of one xenograft was changed from aneuploid to diploid during HuIFN-alpha treatment. Histologically, these xenografts were partly replaced by normal appearing bone and bone marrow. The S-phase proportion was also reduced in these xenografts, implying that HuIFN-alpha can also have a direct antiproliferative effect.

A novel spontaneous metastasis model of human osteosarcoma developed using orthotopic transplantation of intact tumor tissue into tibia of nude mice.

Evaluation of potential new treatment strategies requires adequate experimental tumor models which resemble the clinical situation as closely as possible. The purpose of the present study was to establish a new human osteosarcoma spontaneous metastasis model using orthotopic transplantation of histologically intact tumor tissue into the tibia of nude mice. Intact tumor pieces, obtained from the 32nd serial passage of subcutaneously growing human osteosarcoma xenografts, were implanted into the proximal tibia in 31 nude mice. Animals were sacrificed and autopsied 2, 4, 6, and 8 weeks after transplantation and examined macroscopically and microscopically for local tumor growth and metastases. All mice developed local intratibial bone tumors that were radiographically and histologically similar to primary human osteosarcoma. Lung metastases were observed in all mice, local and distant lymph node metastases in 15 (48%), and liver metastases in 6 (19%) mice. The microscopic appearance of the metastases was similar to that observed in the donor patient's tumor, corresponding subcutaneous xenografts and orthotopically transplanted intratibial tumors. This spontaneous metastasis model of human osteosarcoma in nude mice may resemble a clinical situation and could thus be useful for studies on local tumor growth, metastasis formation and therapy.

The combined effect of interferon and methotrexate on human osteosarcoma and lymphoma cell lines.

Two human osteosarcoma cell lines and 1 human lymphoblastoid cell line were tested for the growth inhibitory effect of methotrexate and human leukocyte interferon, both separately and in various combinations. Both agents inhibited the cell lines. No synergistic, inhibitory or blocking effects on tumor cell growth were detected.

Structure, growth and cell proliferation of human osteosarcoma and malignant fibrous histiocytoma xenografts in serial transplantation in nude mice.

Tumour specimens from one patient with osteosarcoma and one with malignant fibrous histiocytoma were transplanted in serial passages in nude mice. Structure, growth and cell kinetics of the xenografts were studied in order to assess the validity of the two tumour models. Cell proliferation was analysed using in vivo labelling with the thymidine analogue iododeoxyuridine (IdUrd) and the IdUrd labelling index (LI) was determined by immunohistochemistry. The DNA index (DI) was examined by flow cytometry. The c-myc oncoprotein expression was studied by immunohistochemistry. More intense proliferation was observed in the peripheral parts of the tumours. There was no correlation between tumour growth and cell proliferation in the two tumour groups. Stability of the tumour models was indicated by low intrapassage and interpassage variations of DI, LI, and volume doubling time, and also by retained histopathological characteristics and c-myc staining patterns of donor patients' tumours during serial transplantation.

Growth patterns and cell kinetics of human osteosarcoma xenografts in serial passages in nude mice analyzed by in vivo labelling with iododeoxyuridine.

A human osteoblastic osteosarcoma was transplanted in nude mice and followed in seven serial passages. Tumor cell kinetics was analyzed by in vivo labelling with the thymidine analogue iododeoxyuridine (IdUrd). Immunohistochemistry was used to measure the IdUrd labelling index. Duration of S phase (ts) was estimated by flow cytometry. From these two parameters potential doubling time (tpot) was calculated. Cell kinetic parameters showed low variations between passages and also between xenografts in same passage. Smaller variations of ts compared to labelling index and tpot were found. tpot was generally short with an interpassageal mean of 1.3 days and CV=14.8%. All xenografts showed DNA aneuploidy (mean DNA index --1.6). Homogeneous tumor growth was indicated by low variations of volume doubling time and lag time. There was no correlation between tumor growth and cell proliferation. Histopathological characteristics of the donor patients tumor were retained during serial transplantation.

The circulating hormonal milieu of the endocrine pancreas in healthy individuals, organ donors, and the isolated perfused human pancreas.

Although basal circulating levels of individual islet cell hormones have been measured, few studies compared the molar ratios of the major hormones secreted by the endocrine pancreas. This study examined the basal levels of four major islet hormones: insulin, C-peptide (C-P), glucagon (G), and pancreatic polypeptide (PP) in normal subjects, in organ donors with brain death, and in the isolated perfused human pancreas. Basal blood samples were taken from normal, fasted control subjects (NCs). Pancreata were obtained from 17 organ donors (ODs) with donor portal vein (DPV) and radial arterial (DRA) blood samples taken before organ procurement. Single-pass perfusion was performed on the procured pancreata, and after rewarming and equilibration, basal samples were collected from the splenic vein (SV) for 30 min. Radioimmunoassays of insulin, C-P, G, and PP were performed on all samples, and basal levels of all hormones were expressed as a common unit, femtomoles per milliliter. The data suggest that in the basal state, these four major islet hormones circulate in a relatively constant molar ratio. The ratio of the hormones is altered in brain death and with in vitro perfusion of the pancreas. The isolated perfused human pancreas secretes a relatively constant molar ratio of these hormones; however, this ratio is markedly different from the circulating ratio seen in either the NC group or the OD group. We conclude that a relatively constant hormonal milieu is secreted from the normal endocrine pancreas, and this hormonal milieu is altered after brain death and with isolation and perfusion of the human pancreas.

Adjuvant interferon treatment of human osteosarcoma.

This paper updates the results of the clinical trial to examine the efficacy of exogenous leukocyte interferon therapy as adjuvant treatment for osteosarcoma. So far the incidence of metastases is lower and the survival rate is better for the interferon-treated group than for the concurrent control group. The number of treated patients is too small at present to allow proper statistical calculations to be made.

Characterisation of human deltoid muscle in patients with impingement syndrome.

Muscle biopsies from the anterior and medial parts of the deltoid of 11 male patients and six male controls were analysed with morphological and immunohistochemical methods. The distribution, area, and capillarization of the muscle fibres were determined, and the amount of connective tissue was measured with staining for type-III collagen. Compared with the controls, the patients with impingement syndrome had more type-I than type-II fibres, but the areas of the different types were almost the same. There was no difference in capillarization per fibre type between patients and controls, but the patients had more connective tissue. The results indicate that patients with impingement syndrome have morphological changes in the deltoid muscle, probably due to immobilisation and pain. They support the hypothesis that the deltoid muscle, the medial part in particular, is affected in patients with impingement syndrome.

Electromyogram (EMG) recordings from the subscapularis muscle: description of a technique.

Operative treatments for recurrent dislocation of the shoulder usually focus on the subscapularis muscle because it is supposed to contribute to the joint stability. It is of clinical interest to record the EMG from the subscapularis muscle in order to interpret its function. The purpose of the present study was to describe a safe and reliable route to reach the muscle, deeply located between the scapula and the thoracic cage, with fine-wire EMG electrodes. Twenty-four shoulders were investigated in 12 volunteers. A hypodermic needle containing bipolar fine-wire electrodes was inserted in the posterior axillary line with the subjects in the supine position, and the arm held in an abducted and externally rotated position. Three criteria confirmed the location of the electrodes: experience of periosteal pain when the needle reached the costal surface of the scapula, drawing-in of the wires 3-4 cm when the subject adducted his arm, thereby rotating his scapula downward, and raw EMG recorded during typical movements. Additionally, in four shoulders, the electrode location was checked with computed tomography. There were no complications from this technique, and the subjects felt no pain from the fine-wire electrodes during arm movements. We conclude that the described technique is a safe and reliable method of reaching the subscapularis muscle with EMG electrodes.

Comparison of the effects of adriamycin and methotrexate on orthotopic and induced heterotopic bone in rats.

The effect of the two antineoplastic drugs, Adriamycin and methotrexate, on orthotopic bone, and on the induction of experimental heterotopic bone in rats was analyzed. The drugs were administered as single injections: Adriamycin in s.c. doses of 0.5 and 2 mg/kg body weight and methotrexate i.v. 100 and 250 mg/kg body weight followed by leucovorin rescue after 2 h. A passing, but significant, decrease in body weights occurred in the methotrexate-treated animals, but not in those given Adriamycin. Analysis of the amount of heterotopic bone formed 4 weeks after induction by demineralized bone matrix revealed a 30-40% decrease in the groups treated with either of the antineoplastic agents, whereas orthotopic bone was unaffected. Six weeks after the treatment the net effect on the induced bone had decreased. The present study shows that the two antineoplastic drugs Adriamycin and methotrexate inhibit heterotopic new bone formation induced by demineralized bone matrix in rats to an equal extent, although their mode of action on the cellular level is entirely different, and that the inhibitory effect of a single treatment diminishes in the presence of a continuous inductive process.

Interaction between amphotericin B, carboplatin, and radiation in human osteosarcoma xenografts in nude mice.

In order to evaluate and modify the radiosensitizing effect of carboplatin, amphotericin B (AmB) was given as pre-treatment to nude mice with bilateral subcutaneous human osteosarcoma xenografts. One of the two tumours in each animal was irradiated with a single dose of 12 Gy following treatment with AmB (5 mg kg(-1)), or carboplatin (20 mg kg(-1)), or AmB (5 mg kg(-1)) plus carboplatin (20 mg kg(-1)), respectively. Tumour growth was compared with non-treated tumours. A significant reduction of tumour growth was observed after irradiation. Carboplatin in itself reduced tumour growth and also added to the effect of radiation. An unexpected interaction was seen where AmB obviously decreased the effect of either carboplatin or radiation alone or the two given concomitantly. The presented results are contradictory to some earlier in vitro studies and imply that the interactive effect in general and especially with regard to AmB can not be universally applied to all experimental situations.

Gait in rheumatoid arthritis: an electrogoniometric investigation.

For the purpose of detecting early aberrations of gait in rheumatoid arthritis 17 women suffering from that disease were examined. They were all under 50 years of age and had an essentially normal range of motility in the hips, knees and ankles. Eleven healthy women walking at voluntary speed and 6 healthy women walking at the same slow speed as the RA patients were included as controls. The recordings were made while the subject walked on a treadmill with a computerized electrogoniometer measuring the angular excursions of the hip, knee and ankle in three planes simultaneously. The patients with RA walked at a slower speed than did the healthy subjects (0.6 vs 1.2 ms-1). The angular excursions, i.e. inward and outward rotation, abduction and adduction, flexion and extension, were significantly less in the RA patients than in the healthy subjects who walked at voluntary speed. As compared to the healthy subjects walking at a slow speed, the differences in range of motility were much smaller. The major aberrations of the gait pattern were found in the ankles and feet, which showed reduced internal rotation (7 vs 10 degrees), adduction (6 vs 12 degrees) and a less pronounced plantar flexion at toe off (1 vs 8 degrees).

Radiographic measurement of the lumbar spine. A clinical and experimental study in man.

The accuracy of radiographic measurements of lumbosacral lordosis, vertebral size, spondylolisthesis, and disc height were studied. Errors caused by lateral tilt or longitudinal axis rotation of the lumbosacral spine were assessed in an experimental study on 12 cadavers. In a series of 170 normal individuals, the distribution of radiographic variables describing lumbosacral lordosis, size of vertebrae, and disc height was investigated. The interobserver measurement variation was studied with respect to all measured variables. The differences between radiographs of 125 spondylolytic patients in the recumbent and standing positions were analyzed with respect to vertebral slipping and lumbosacral lordosis. There were only minor projectional and interobserver measurement errors in the variables describing vertebral size and lumbosacral lordosis, which make these variables suitable for radiographic assessment at repeated examination. The absolute measurements of disc height were too inaccurate to be used as a basis for conclusions. A semiquantitative approach is more reliable, and can be recommended for the comparison of radiographic assessments of disc height. In adults, the radiographic evaluation of vertebral slipping and lumbosacral lordosis is equally reliable in the recumbent and standing positions.

Rotation osteotomy of the proximal humerus to stabilise the shoulder. Five years' experience.

A reduced retroversion angle of the humeral head may predispose to recurrent anterior shoulder dislocation and may also be a factor in persistent instability after soft-tissue repair. We performed rotational osteotomy of the proximal humerus in 20 patients with recurrent anterior shoulder dislocations (10 traumatic, 10 non-traumatic) and a decreased retroversion angle of the humeral head. The mean preoperative retroversion angle was 12 degrees, which was increased after surgery to a mean value of 32 degrees. All patients regained a normal range of shoulder motion and normal function within three months after surgery. At the five-year review all shoulders were stable, pain-free and had no radiological signs of osteoarthritis.

The effect of biopsy on survival of patients with osteosarcoma.

A retrospective study of patients with osteosarcoma was undertaken to determine whether there was a relationship between biopsy and survival. Fifty-seven patients treated at the Karolinska Hospital, Stockholm, between 1938 and 1959 were included in this study, all of whom were less than thirty years old, had a metaphysial osteosarcoma in a long bone but had no pulmonary metastases at the time of diagnosis; all were treated by amputation. No clinical variants of osteosarcoma were included. Twenty-four of the fifty-seven patients had an amputation without a prior biopsy; the others had biopsies before amputation. These two groups were fairly closely matched in age, sex, site and size of tumour, and in the level of amputation; some patients in each group received radiation before operation. Evaluation of these two groups of patients revealed that the performance of a biopsy, with or without a delay of not more than thirty days between the biopsy and the definitive operation, had no adverse effect on survival.

Proximal humeral osteotomy to correct the anatomy in patients with recurrent shoulder dislocations.

Surgical treatment of patients with traumatic shoulder dislocations is usually successful, but soft-tissue surgery in patients with nontraumatic shoulder dislocation often fails to stabilize the joint. Previous studies have shown that decreased humeral head retroversion might be one cause of anterior shoulder instability. Eleven patients with anterior recurrent dislocations, five traumatic and six nontraumatic, and all with a small humeral head retroversion angle, have been operated on using a proximal humerus osteotomy to correct the abnormal anatomy. After surgery, the humeral head retroversion was normalized to a mean angle of 34 degrees. All shoulders became stable. External rotation increased 7 degrees on the average, and internal rotation decreased 10 degrees on the average. One year after surgery, shoulder function was excellent in all operated shoulders.