The outcome of traditional or comprehensive outpatient care for rheumatoid arthritis (RA). Results of an open, non-randomized, 2-year prospective study. This work presents results of a quasiexperimental prospective cohort study of the medium-term course of chronic rheumatoid arthritis (RA) under two different conditions of care. During 1984-1986 a total of 262 patients was recruited. All were new referrals to a university outpatient department. 121 came from the city of Hannover, FRG, and were assigned to comprehensive team care (cc) provided by two rheumatologists, a nurse, physician's assistant, occupational therapist, psychologist, and social worker; 141 came from outside Hannover and received care from a physician in training for internal medicine/rheumatology and a nurse, supervised by a senior registrar (TC). The patients in the first group were significantly older (57 vs 51 years), had more active disease (ESR 44 vs 31 mm/h), were more disabled (functional capacity 69 vs 78%), more often lived alone (27 vs 10%) and were more depressed compared with patients in the second group. There were no significant differences in gender (80% female), number of Rome criteria (5.2), and disease duration (6 years) between the two groups. 179 patients were followed for 2 years. There was no demonstrable difference between those who dropped out and those who continued in the study. Patients from both groups showed significant and clinically important improvements in ESR and number of swollen joints, whereas functional capacity and pain intensity did not change. Depression and patients' global self-rating improved only in the CC-group. Analyses adjusting for differences between the two groups were unable to show a different efficacy for either form of care.(ABSTRACT TRUNCATED AT 250 WORDS)


[The mobile rheumatoid health unit--an ambulatory consultation from the viewpoint of the physician and patient]. The acceptance of a university-based outpatient department (Department of Rheumatology, Hannover Medical School, FRG) has been investigated. Ninety-five former patients with RA, previously treated in the department were interviewed by phone. 312 general practitioners from the city of Hannover received a mailed questionnaire. Patients were asked why they had left outpatient department care; questions for general practitioners dealt with types of referral. Despite high satisfaction with the outpatient unit in both groups, we found several shortcomings which possibly might influence discontinuation of treatment and non-utilization of the department: patients and physicians criticized the scheduling system and waiting times. Both groups complained of frequently changing doctors. The general practitioners wanted more contact with the department and more information about the unit. A small group of patients and referring physicians expressed resignation.


[Special problems of young rheumatic patients with occupational placement]. In a study initiated by the German League against Rheumatism, 433 young patients with rheumatic disorders (mean age 27 years, disease duration 7.5 years, 60% female, 40% male) were questioned in 1989 for the first time to ascertain disease-related problems encountered at school or during professional training. Their self-reported diagnoses were 68.2% chronic arthritis and 23.6% Ankylosing spondylitis (definite or probable diagnosis). From 181 patients who had been affected at school age, 84.5% reported the following main problems: absence related to illness, exclusion from excursions and school-related activities. Nevertheless, a majority of the patients (60.5%) reached a qualified graduation. 25.3% of the study sample was still attending school, 50.3% were employed, 8.6% were unemployed, and 4.5% had been retired early. Only 37.7% of the Arthritis patients and 22.3% of the Spondylitis patients had sought advice and help from the labour exchange services; 26.9% of the arthritis patients and 21.9% of the Spondylitis patients assessed this advice to be helpful. Regarding vocational guidance, the patients main criticism was a lack of knowledge about rheumatic disorders. There is a demand for an adjustment of the individual physical abilities and the requirements of the respective jobs, and continuous supervision by a rheumatologist is necessary.


[Population epidemiologic evaluation of the Hannover Mobile Rheumatoid Health Service]. The aim of the study was the evaluation of a potential selection process for patients with rheumatoid arthritis (RA) referred to the Mobile Service for Rheumatics in Hannover (MSRH). The MSRH is the only referral center for patients with inflammatory rheumatic diseases in Hannover. A comparison of the health status was made between 58 individuals with RA identified in a population study, and 103 RA patients from the MSRH. The following disease parameters were less favorable in the clinical group: duration of morning stiffness, functional capacity, number of swollen joints, rheumatoid factor, ESR, disease activity, and classical RA according to the Rome-criteria. Only 22% of the individuals with RA identified in the population study have been referred to the MSRH. These patients more frequently had definite or classical RA (statistically not significant: p = 0.17, p = 0.11, respectively). It was shown that the clinical group comprised more severe RA cases. Thus, data from such patients may not be generalized for the entire group of RA cases in the population.


Isolation of promoter sequences from Brevibacterium sp. R312. Promoter sequences recognized by Escherichia coli RNA polymerase were isolated from Brevibacterium sp. R312, a coryneform strain producing nitrile hydratase and amidase. Ten Escherichia coli clones containing promoter sequences were selected for their ability to grow with chloramphenicol concentrations of up to 1500 micrograms/ml. The strength of these promoter sequences was determined. We carried out a preliminary study of the strongest promoter having a chloramphenicol acetyl-transferase/beta-lactamase activities ratio of 18.4.


Keratinolytic fungi in Egyptian soils. I. Baited with hair and wool. 150 soil samples were collected, 90 from Nile Valley and Delta, 36 from desert and 24 from salt marshes. Human, buffalo and cow hair and sheep wool were used as baits at three incubation temperatures. Forty-four species which belong to twenty-one genera at 27 degrees C and forty-two which belong to twenty-two genera at 37 degrees C were collected. We isolated the following keratinophilic fungi Chrysosporium tropicum, C. keratinophilum, C. indicum, C. pannicola, C. queenslandicum, Trichophyton terrestre, T. mentagrophytes and Microsporum gypseum. Several other saprophytic fungi were isolated. No fungi were isolated at 45 degrees C.


Anaerobic facultative bacteria isolated from the gut of rabbits fed different diets. Anaerobic facultative bacteria colonizing the intestinal tract of conventional rabbits fed three different diets (standard pellet, hay and pellet/hay mixture) were enumerated in brain heart infusion agar. Colony counts recovered from homogenized samples of small intestine, caecum and rectum differed with reference to the diet given. Among anaerobic groups, identified from rabbit fed pellet/hay mixture, Enterococci (E. faecalis, E. avium, E. faecium and E. durans) represented the predominant flora. Enterobacters (E. cloacae and E. aerogenes) accounted for about 10 to 25% of the bacteria in the rectum and colon respectively, whereas Staphylococci (S. intermedius, S. epidermidis and S. lentus) represented 11% of the bacteria isolated from colon.


Bacillus species associated with wheat and sorghum dusts from combine harvester. 14 species and one species variety belonging to genus Bacillus were collected from wheat and sorghum dusts of combine harvester on either nutrient agar (NA) or sheep blood agar (SBA) at 30 degrees C (14 spp.), 45 degrees C (13 spp.) and 55 degrees C (5 spp.). The flora of Bacillus on both substrates and on the two isolation media were basically similar and the most common species were B. brevis, B. cereus, B. circulans, B. coagulans, B. licheniformis, B. stearothermophilus and B. subtilis. The total viable count of airborne bacteria in the two atmospheres were lower in wheat than in sorghum hay sites. The percentage count of haemolytic bacteria on SBA comprised 10% and 15% of the total viable count, respectively.


Purification and general properties of xylanase from Aspergillus terreus. Aspergillus terreus THOM produced appreciable yield of xylanase on medium containing acid pretreated rice straw as sole carbon source. The enzyme was purified approximately 25-fold by ammonium sulfate precipitation, gel filtration through Sephadex G-50 and ion-exchange chromatography on DEAE-cellulose with a yield of about 23% and specific activity of 15.38 units/mg protein. Optimum activity against xylan was at 45 degrees C and pH 4.5. Relative stability of the enzyme was recorded at pH range of 4-5.5. Heating the enzyme preparation at 60 degrees C for one hour resulted in a 82.61% loss of activity. After exposing to 90 degrees C for 10 minutes xylanase retained 4.28% of its original activity. The purified enzyme lost 25% of the original activity after keeping at 4 degrees C for 9 months in 0.05 M acetate buffer (pH 4.5). The Km value of the enzyme was found to be 0.83 mM. Zn2+ was the most enhancing agent for xylanase activity. Cu2+ followed by Co2+ and K+ were the more deterrent cations. Xylanolytic activity of A. terreus was strongly inhibited by HgCl2, 2,4-dinitrophenol (DNP), phloridzin and ethylene diamino tetra acetic acid (EDTA).


[Experiences with 216 manual esophageal anastomoses and with mechanical single and double row suture technique (SPTU, EEA, ILS) in stomach cancers]. From 1973 to 1990 we have performed 216 anastomoses of the oesophagus after resection of gastric malignancy. Both resection due to a carcinoma of the oesophagus and subtotal gastric resection due to distal carcinoma of the stomach have not been considered. In a retrospective study we present the results of our oesophageal anastomoses performed by hand-suture and stapling. The perioperative complications are shown with special regard to the insufficiency rate of the oesophageal anastomosis and the resulting mortality. In 70 by hand suturing performed anastomoses (1973-80) we have seen 3 (4.4%) leaks of the oesophagojejuno-/oesophagogastrostomy, in 146 stapled anastomoses (1980-90) 6 (4.2%) insufficiencies were seen. Two of 3 dehiscences in the hand-sewn group and one of the 6 leaks in the stapler group had a lethal outcome. The overall hospital mortality could be reduced from 18.5% to 6.9%.


[Boerhaave syndrome in pyloric hyperplasia]. Boerhaave's-syndrome is a rare illness, usually caused when sudden intense vomiting leads to a spontaneous rupture of the healthy esophagus. Alcoholism and neurological diseases are considered to be the main predisposing factors. Because the complaint is so rare the casuistic of Boerhaave's-syndrome is described in connection with pyloric stenosis. In order to confirm the diagnosis the following practice is recommended: During gastrografin swallowing the pylorus should be examined in order to remedy the possible cause of the complaint when the operative therapy is carried out.


[Pedicle torsion of the accessory spleen within the scope of the "polysplenia-asplenia complex" as a rare differential diagnosis of acute abdomen]. A 25 year old female patient with a painful palpable tumour in the right flank was admitted to our hospital presenting signs and symptoms of an acute abdomen. During explorative laparotomy unexpected haemorrhagic infarction of a splenula caused by a volvulus of the vascular pedicle was found. In spite of the documentation of multiple positional abnormalities of visceral organs preoperative diagnostic imaging techniques were unable to point to the diagnosis because of an uncommon rightsideness of the polysplenism. In the case of an indefinite rightsided abdominal mass defects of embryonic morphogenesis should be always taken into consideration.


Constitutional delay of growth and adolescence. Results of short-term and long-term treatment with GH. During recent years numerous reports on the favourable results of short-term trials with GH in patients with constitutional delay of growth and adolescence (CDGA) have been published, but it has been unclear whether such treatment affects final height. In the present study, the results of long-term therapy with GH in replacement doses have been evaluated in 15 patients who were treated with GH for several years (three years on average). At the start of treatment, 10 of the children were prepubertal and 5 were in puberty. All patients were followed up until final height was reached. Mean final height of the 13 male patients was 170.0 +/- 4.4 cm, i.e. -1.58 SDS. In the two female patients, final height was 150.0 cm (-3.5 SDS) and 164.0 cm (-0.8 SDS), respectively. Adult height of the patients lagged behind target height by 5.4 +/- 3.2 cm (mean +/- SD). Measured adult height corresponded to adult height as predicted prior to treatment. In conclusion, GH treatment of patients with CDGA did not increase final height.


In vitro synthesis of glycosaminoglycans in endocrine ophthalmopathy. The effects of humoral and cell-mediated immunity on the glycosaminoglycan synthesis of retrobulbar fibroblasts was evaluated in patients with endocrine ophthalmopathy. After incubation with IgG and sera, secreted glycosaminoglycans, radiolabeled with D-6-3H-glucosamine and 35sulfate, were precipitated with cetylpyridinium chloride and ethanol. Hyaluronic acid synthesis of human retrobulbar fibroblasts after incubation with sera and IgG and after co-culture with lymphocytes was assessed by means of a radiometric test. Patients' IgG, compared to controls', accounted for a higher secretory stimulation of porcine retrobulbar fibroblasts (as measured by cetylpyridinium chloride precipitation) after 24 and 48 h. Contrasting with 24 h incubation time, glycosaminoglycan values after 48 h were increased two to threefold. Patients' and controls' sera caused earlier and stronger, yet indistinguishable glycosaminoglycan production. Non-sulfated hyaluronic acid was the preponderant glycosaminoglycan secreted into the media by retrobulbar fibroblasts. As assessed with the radiometric test, incubation with patients' and controls' sera and IgG did not reveal a significant difference in stimulating the hyaluronic synthesis of patients' and controls' retrobulbar fibroblasts. When measuring the hyaluronic acid synthesis of controls' and patients' retrobulbar fibroblasts after co-cultivation of lymphocytes, however, patients' lymphocytes had a marked ability to increase the hyaluronic acid concentration compared to controls' lymphocytes. The hyaluronic acid concentration after incubation of a patient's retrobulbar fibroblasts with autologous lymphocytes was markedly more elevated than the intrinsic hyaluronic acid production of retrobulbar fibroblasts.(ABSTRACT TRUNCATED AT 250 WORDS)


Adrenal hormones in human follicular fluid. Considerable evidence indicates that adrenal hormones may affect gonadal function. To assess the role of some adrenal hormones in human follicular fluid and their relationship with the ability of the oocyte to be fertilized and then to cleave in vitro, cortisol and dehydroepiandrosterone sulfate were measured in follicular fluid obtained at the time of oocyte recovery for in vitro fertilization from cycles stimulated by clomiphene citrate, human menopausal gonadotropin and human chorionic gonadotropin. Thirty-six follicular fluid containing mature oocyte-corona-cumulus complexes and free of visible blood contamination were included in this study. There was no significant difference in follicular fluid dehydroepiandrosterone sulfate concentration between follicles with oocytes which did or did not fertilize (5.1 +/- 1.1 vs 5.8 +/- 2.0 mumol/l). However, follicular fluid from follicles whose oocytes were not fertilized had levels of cortisol significantly higher than those in follicular fluid from follicles containing successfully fertilized oocytes (406.0 +/- 75.9 vs 339.2 +/- 37.0 nmol/l; p < 0.005). No significant correlations were found between rates of embryo cleavage and cortisol and dehydroepiandrosterone levels in follicular fluid. We conclude that cortisol levels in follicular fluid may provide an index of fertilization outcome, at least in stimulated cycles by clomiphene citrate, human menopausal gonadotropin and human chorionic gonadotropin.


TSH-dependent production of T4 and T3 by metastases of a thyroid carcinoma. A patient with T4 and T3 production by metastases of a follicular thyroid carcinoma leading to TSH suppression is described. During a period of three years, plasma T4, T3 and TSH levels were measured in the substitution-free periods before the successive iodine-131 retention measurements and iodine-131 therapies, when the patient was at least two weeks without thyroid hormones. From the presented data it can be derived that the production of thyroid hormones by metastases was enhanced by endogenous TSH.


Effect of dopamine injection into the anteroventral third ventricular region and the paraventricular nucleus on vasopressin secretion in conscious rats. To investigate the role of dopamine receptors situated in the paraventricular nucleus and the anteroventral third ventricular region in regulating vasopressin release, responses of plasma AVP and its controlling factors to injections of dopamine into these regions and the lateral cerebral ventricle were examined in conscious rats. The injections of 156 nmol (30 micrograms) dopamine into the cerebral ventricle produced transient rises in plasma AVP 5 min later. When the dose of dopamine was reduced to 26 nmol (5 micrograms), the increase in plasma AVP was not provoked any more. However, injections of 26 nmol dopamine into the paraventricular nucleus greatly augmented plasma AVP 5 and 15 min later. This dose of dopamine was without effect on plasma AVP when injected into the anteroventral third ventricular region, including the organum vasculosum lamina terminalis, median preoptic nucleus, medial preoptic area and the periventricular preoptic nucleus. These dopamine administrations in the cerebral ventricle, paraventricular nucleus and the anteroventral third ventricular region did not significantly change AVP-controlling factors such as plasma osmolality, sodium and arterial pressure. On the basis of these results, we conclude that dopamine receptors in the paraventricular nucleus may function to facilitate AVP secretion, whereas those in the anteroventral third ventricular region may not play an important role in the regulation of AVP release.


Iodide and T4 kinetics in plasma, thyroid gland and skin of 10-day-old rats: effects of iodine deficiency. The effects of iodine deficiency on the peripheral metabolism of thyroid hormone in immature rat were evaluated by measuring the kinetics of iodide and thyroxine (T4) in control and iodine-deficient 10-day-old rats. Iodine-deficient pups were obtained by giving the mother drinking water containing perchlorate; this anion is not transferred but prevents iodine transfer in the mother's milk. Labelled iodocompounds were measured in plasma, thyroid and skin for 48 h following intravenous injection of Na131I plus [125I]T4. Data were interpreted by compartmental analysis. The iodide plasma clearance rate, plasma equivalent distribution volume, plasma concentration, production and iodine thyroid content of iodine-deficient rats were significantly lower (-29%, -31%, -84%, -89% and -87% respectively) than in control 10-day-old rats. The iodide thyroid uptake was reduced (-47%) but remained higher than the release of iodine as T4. Cutaneous iodine was lost much more quickly by iodine-deficient pups than by control pups, explaining the decreased iodide distribution volume. The parameters of T4 metabolism were not changed by iodine deficiency, except for a slight but significant reduction of the thyroxinemia and T4 pools (-13%). Thence, T4 production was not significantly changed (about 8 pmol/h in control and iodine-deficient rats). The labelled T4 curves in iodine-deficient and control skin were superimposed and the patterns of labelled T3 derived from [125I]T4 were identical. Thus, the skin of immature rats converts T4 to T3; this process was not disturbed by iodine deficiency. The thyroid function of immature rats is particularly resistant to iodine deficiency, but the mechanisms remain unknown.


Effects of metyrapone infusion on corticotropin-releasing factor and arginine vasopressin secretion into the hypophysial portal blood of conscious, unrestrained rams. The effects of rapid changes of circulating cortisol levels on ACTH secretion and on corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) concentrations into hypophysial portal blood were studied in six adult rams. Pharmacological adrenalectomy was obtained by 3 h metyrapone infusion (100 mg.kg-1.h-1). Blockade of cortisol synthesis induced a tenfold increase of plasma ACTH levels accompanied by a moderate increase of CRF secretion (150% vs preinjection levels) and a large increment of AVP secretion (535% vs preinjection levels). ACTH levels remained high during the 3 h following the end of metyrapone infusion. During the same period, CRF secretion was still elevated (231% vs preinjection levels), while AVP secretion was further stimulated (2,151% vs preinjection levels). Subsequent hydrocortisone infusion (66 micrograms.kg-1.h-1) for 2 h induced a rapid decrease of both ACTH and AVP secretion, while CRF levels in hypophysial portal blood still remained elevated. These data suggest that changes in ACTH secretion induced by acute modifications of the negative glucocorticoid feedback are, in addition to the well documented direct effect of cortisol on the corticotropes, mainly mediated by variations of hypothalamic AVP secretion.


Re-expression of thyroxine-binding globulin in post-weaning rats during protein or energy malnutrition. Thyroxine-binding globulin, the highest affinity thyroid hormone binder of rat serum, was studied during 28 days of dietary protein restriction (6% protein vs 18% protein in isocaloric control diet) or energy restriction (60% intake of control diet). Studies were performed on male rats aged four weeks at the beginning of experiments: the animals had reached the ontogenic stage when the thyroxine-binding globulin had declined, after its high postnatal surge, to undetectable levels. Short-term administration (seven days) of one or the other restricted diet similarly induced resynthesis of the protein. Its serum concentrations reached 26-46% of those measured in eight-day pups (peak of the neonatal surge) and its liver mRNAs showed corresponding enhanced signals. Serum T4 binding activities were increased, although concomitantly transthyretin, second specific T4 carrier of the rat serum, decreased markedly (65-75% of controls) in response to the dietary restrictions. Longer-term diet administration (14 or 28 days) resulted in the further increase of the thyroxine-binding globulin in the protein-restricted rats, in contrast to its decline and eventual disappearance in the energy-restricted animals. Protein restriction was associated with increased total and free T3 serum concentrations, in contrast to energy restriction which little affected these parameters. These studies reveal rat thyroxine-binding globulin as a positive (increasing), highly sensitive reactant of malnutrition, able to discriminate between energy deficiency and composition dysequilibrium of diets. They suggest that up-regulation of its synthesis in the two dietary models involves differential mechanisms.


Development of gonadal feedback regulation of gonadotropin gene expression and secretion in female rats. The postnatal development of the gonadal negative feedback control of gonadotropins was studied in female rats. Neonatal (5-day-old) and randomly cycling young (60-day-old) and more mature (180-day-old) adult rats were ovariectomized, and half of them received Silastic implants containing the synthetic estrogen, diethylstilbestrol. The neonatal rats were killed 5, 10 or 15 days, and the adult rats 7 days after the operation. Age-matched and sham-operated animals served as controls. There were no statistically significant responses of serum LH or FSH concentrations or of the pituitary gonadotropin subunit mRNA levels to ovariectomy at any of the neonatal ages. A marked increase (p < 0.01) after ovariectomy was seen in serum gonadotropins and in the cognate mRNA levels at both adult ages. In spite of the weak feedback response of the neonatal rats to ovariectomy, diethylstilbestrol suppressed the basal pituitary gonadotropin concentrations and the specific LH and FSH beta-chain mRNAs (p < 0.01-0.05). These results demonstrate that the gonadal negative feedback regulation of gonadotropin synthesis and secretion is not fully developed in neonatal and prepubertal female rats before 20 days of age. This is probably due to the steroidogenic quiescence of the ovaries in early life. However, the capability of the pituitary to respond to negative estrogen feedback has developed in the neonatal female, as demonstrated by the suppressive effects of diethylstilbestrol treatment on gonadotropin secretion.


Evidence for specific binding and stimulatory effects of recombinant human erythropoietin on isolated adult rat Leydig cells. The presence of specific binding of recombinant human erythropoietin and its effect on testosterone production were evaluated in isolated intact adult rat Leydig cells. Maximal specific binding was observed after 135 min incubation at 34 degrees C. Scatchard analysis of the binding data revealed two distinct classes of binding sites for [125I]-recombinant human erythropoietin with dissociation constant of (Kd1) 1.9 x 10(-10) mol/l and (Kd2) 1.37 x 10(-8) mol/l respectively and binding capacity of (Bmax1) 12.3 fmol/10(6) cells and (Bmax2) 42.8 fmol/10(6) cells, respectively. GnRH, hCG, IGF-I and EGF did not induce any modification of recombinant human erythropoietin-specific binding. Recombinant human erythropoietin added to isolated adult rat Leydig cells exerted a stimulatory effect on testosterone production reaching its maximal effect at the dose of 10(-10) mol/l (testosterone production from 14.9 +/- 1.7 to 45.1 +/- 6.2 pmol/10(6) cells/3 h). Addition of anti-recombinant human erythropoietin serum completely blocked the recombinant human erythropoietin-stimulated testosterone production. These results show that purified adult rat Leydig cells possess recombinant human erythropoietin specific binding, and suggest that this glycoprotein directly influences rat Leydig steroidogenesis.


Effect of adenosine analogues on plasma corticosterone concentration in rats. In this study we examined the effect of the adenosine analogues: N6-cyclohexyladenosine, L-N6-phenylisopropyladenosine and 5'-N-ethylcarboxamidoadenosine on the plasma corticosterone concentration in rats. It was found that N6-cyclohexyladenosine (0.1-3.0 mg/kg), L-N6-phenylisopropyladenosine (0.1-1.0 mg/kg) and 5'-N-ethylcarboxamidoadenosine (0.01-1.0 mg/kg) dose-dependently increased the plasma corticosterone level. The effects of N6-cyclohexyladenosine (0.1 mg/kg) and L-N6-phenylisopropyladenosine (0.1 mg/kg) were completely blocked in animals pretreated with dexamethasone (3 x 1 mg/kg), as well as in animals with a pharmacological blockade of the release of hypothalamic corticotropin-releasing factor induced by chloropromazine (10 mg/kg), morphine (20 mg/kg) and nembutal (25 mg/kg), whereas the corticosterone response to 5'-N-ethylcarboxamidoadenosine (0.01 mg/kg) was blocked in dexamethasone-pretreated rats only. On the other hand, the adenosine receptor antagonists: 8-(p-sulfophenyl)-theophylline (30 mg/kg), 8-phenyltheophylline (10 and 30 mg/kg), 1,3-dipropyl-8-(2-amino-4-chloro)-phenylxanthine (1 and 3 mg/kg) and 1,3-dipropyl-7-methylxanthine (1 mg/kg) did not affect the corticosterone response to N6-cyclohexyladenosine, L-N6-phenylisopropyladenosine or 5'-N-ethylcarboxamidoadenosine. The obtained results indicate that N6-cyclohexyladenosine and L-N6-phenylisopropyladenosine stimulate the corticosterone secretion at the hypothalamic level, whereas 5'-N-ethylcarboxamidoadenosine is likely to act at the pituitary level. Although the effects produced by the adenosine analogues show that both A1 and A2 receptors are involved in the corticosterone response, negative results of the interaction studies with adenosine receptor antagonists indicate that further experiments are necessary to elucidate this problem.


Malignant prolactinoma.

Malignant prolactinoma. Malignant prolactinoma is a rare entity and only a few cases have been published. The diagnostic criteria and the clinical course remain unclear. We present a case of malignant prolactinoma in a woman with a 30-year duration of the disease. In the terminal stage of the disease the prolactinoma metastasized to the left eye, the prolactin level reaching 196000 mU/l. Bromocriptine in high doses was not effective. The response to pergolide was good in the first two years of treatment; thereafter an escape effect was observed. The patient died in a comatose state. A review of previously published cases follows.


[Memory disorders and symptoms of frontal dysfunction in 29 patients operated on for an aneurysm of the anterior communicating artery]. Twenty-nine patients operated for an aneurysm of the anterior communicating artery have been submitted to short-term and long-term memory tests and to tests said to be sensitive to frontal lobe dysfunction; anosognosia was also studied. Their performance, as compared to that of 29 matched control subjects, revealed: (a) that this neurological condition induces often memory deficits (with anosognosia) and, even more often, signs of frontal dysfunction; (b) that these deficiencies are not homogeneous, however; and (c) that the classical amnesic syndrome can be observed in some cases. It appears useful to make an in-depth analysis of memory deficits of this kind of patients to reach a better understanding of normal memory processes.


[Intracranial plasmocytoma manifesting multiple myeloma: apropos of a case]. Neurological complications of myeloma are multiple and various. Cranial and intracranial locations have been rarely reported. They can be classified into three clinical groups: (1) cranial nerve palsies secondary to single or multiple lesions in the base of the skull, (2) intraorbital tumors, (3) intracranial tumors, either cranial myeloma extending intracranially or pure intracranial tumor (dural and/or cerebral). In our case, macroscopic and microscopic examination of the brain showed dural and cerebral involvement, confirmed by immunohistochemical studies. The radiological features are discussed (CT scan, MRI, angiography). To our knowledge, a single report of intracranial plasmacytoma documented by MRI has been reported in the literature.


Factitious hemiplegia and Munchausen's syndrome. We report a case of a thirty-year-old woman suffering from chronic factitious disorder with hemiplegia. Such a pathomimia is very uncommon in Munchausen's syndrome. Indeed, most often, the clinical picture is characterised by acute abdominal pain, fainting, haemoptysis, precordialgia, hematemesis or dermatological lesions.


[Non-ischemic borderline brachial paralysis]. Non ischemic anterior borderzone brachial paralysis. Anterior borderzone brachial paralysis (ABBP) is a hemodynamic ischemic syndrome of the watershed zone between the anterior and middle cerebral arteries. Two cases of non ischemic reversible ABBP are reported. The first suffered from multiple sclerosis; a CT-scan showed a lesion of the corona radiata, at the level of the anterior hemispheric borderzone. The second suffered from lung adenocarcinoma. A CT-scan showed multiple metastases, one being surrounded with oedema at the level of the anterior borderzone. According to its reversibility, the ABBP was reported to the inflammatory-oedematous reaction and not to a demyelinating or metastatic lesion itself. As ABBP may occur unilaterally, the name "one-armed man syndrome" should be used instead of "man-in-the-barrel syndrome" (which always implies a bilateral paralysis).


In situ hybridization with digoxigenin-labeled probes: sensitive and reliable detection method applied to myelinating rat brain. A method for in situ hybridization of digoxigenin-labeled cDNA and cRNA probes to myelin protein mRNA is described. This technique has dual advantages of high structural resolution and high sensitivity and avoids problems associated with handling of radioactive materials. Furthermore, it can be readily combined in double labeling with immunocytochemical protein detection. We have used this technique to detect and locate mRNA for myelin basic protein (MBP), proteolipid protein (PLP), 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and myelin-associated glycoprotein (MAG) in oligodendrocytes of 7-day-old and adult rat brains. PLP and MAG mRNA were restricted to the perinuclear cytoplasm, whereas MBP and CNPase mRNA was additionally present in peripheral oligodendrocyte processes.


The microglial reaction in the rat hippocampus following global ischemia: immuno-electron microscopy. Transient arrest of the cerebral circulation leads to neuronal cell death in selectively vulnerable regions of the central nervous system. It has recently been shown at the light microscopical level that neuronal necrosis is accompanied by a rapid microglial reaction in ischemia (Gehrmann et al. (1992) J. Cereb. Blood Flow Metab. 12:257-269). In the present study we have examined the postischemic microglial reaction in the dorsal rat hippocampus at the ultrastructural level using immuno-electron microscopy. Global ischemia was produced by 30 min of four-vessel occlusion and the microglial reaction then studied after 8, 24 and 72 h. In sham-operated controls microglial cells were not phagocytic; they were randomly distributed throughout the neuropil and occasionally made contacts with other structures such as dendrites in CA1. Ultrastructural signs of activation were observed from 1 day postlesion onward. Reactive microglial cells were consistently seen to phagocytose degenerating neurons particularly in the CA1 stratum pyramidale and in the CA4 sector. They were sometimes interposed between two morphologically distinct types of CA1 neurons, i.e., "dark" (degenerating) and "pale" (surviving) types of neurons. Phagocytic microglial cells also became positive for major histocompatibility complex (MHC) class II antigens at these locations from 1 day after ischemia onward. Furthermore, activated microglial cells were frequent along degenerating dendrites in the stratum radiatum of CA1. After survival times of up to 72 h microglial cells, but not astrocytes, were occasionally observed to undergo mitosis. In addition to their random distribution across the neuropil, microglial cells were frequently observed in a perivascular position under normal conditions.(ABSTRACT TRUNCATED AT 250 WORDS)


Exudation of fibronectin and albumin after spinal cord injury in rats. Spinal cord of the rat was investigated immunohistochemically to detect signs of extravasation of fibronectin in animals in which the cord was subjected to different degrees of compression trauma. Immunohistochemistry was performed after survival periods of 4 and 24 h and parallel sections were incubated for albumin immunoreactivity to detect signs of breakdown of the blood-spinal cord barrier. Extravascular reaction products indicating the presence of fibronectin were found within and in the vicinity of the compression provided that bleeding had occurred in the spinal cord, i.e., in rats with severe trauma. Immunoreactive material indicating extravascular albumin was present in the traumatized region and in many segments of the cord located away from the compressed part. Such material was seen both proximal and distal to the primary injury and even in rats with a low magnitude of compression. Generally, with more severe trauma and longer survival periods extravascular albumin was more extensively distributed along the cord. No signs of fibronectin antigen were detected in spinal cord segments away from the compression even though such regions showed albumin immunoreactivity outside the vessels. The results indicate that within and close to the primary injury of compressed spinal cord exudation of fibronectin may occur from the plasma of microvessels provided that the impact is severe enough to cause intramedullary hemorrhages.


Intraventricular infusion of N-methyl-D-aspartate. 1. Acute blood-brain barrier consequences. The purpose of this study was to document the early cerebrovascular consequences of excessive N-methyl-D-aspartate (NMDA) receptor activation. Five microliters of NMDA (100 nmol/microliters) or vehicle was infused over a 15-min period into the lateral ventricle of adult rats. The protein tracer horseradish peroxidase (HRP) was injected intravenously for blood-brain barrier (BBB) studies. The intraventricular infusion of vehicle (n = 5) caused no alterations in arterial blood pressure or microvascular damage away from the intraventricular probe tract. In contrast, NMDA infusion (n = 8) led to a gradual increase in arterial blood pressure (mean 36 mm Hg). Multifocal regions of HRP extravasation were observed bilaterally throughout the neuraxis following NMDA infusion. Sites of BBB disruption and hemorrhage included brain regions bordering ventricular spaces. In addition, isolated foci of protein extravasation were commonly detected in the cerebral cortex, thalamus, basal forebrain, septum and cerebellum. Pretreatment with the noncompetitive NMDA antagonist MK-801 (2 mg/kg) substantially reduced the BBB responses to NMDA. However, microvascular abnormalities were seen in NMDA-infused rats where blood pressure elevations were inhibited by blood removal. In addition to neurons, cerebral blood vessels are also acutely affected by NMDA receptor activation. Blockage of NMDA receptor channels following brain injury may potentially provide protection by attenuating BBB breakdown and subsequent brain edema.


A morphometric and immunohistochemical study of the vestibular nuclear complex in bovine spongiform encephalopathy. A morphometric and immunohistochemical study of the vestibular nuclear complex was performed on five bovine spongiform encephalopathy (BSE) and five control cow brains. Neurons of the lateral and superior vestibular nuclei were counted at 500-microns intervals in 10-microns-thick sections, using an image analysis system comprising a projection microscope and digitising pad linked to a computer. A bimodal distribution of neuron diameters was recognised in the brains of normal cattle. One population of neurons had a mean diameter of 30 microns and the other had a mean diameter of 60 microns. The vestibular nuclei from BSE cattle had an approximately 50% reduction in total numbers of neurons when compared with controls (P < 0.01). Cattle which were clinically diseased longer had the fewest number of neurons preserved. Diminished numbers of neurons were detected throughout the area studied and affected neurons of all diameters. Immunohistochemical staining for synaptophysin, a protein present in synapses throughout the CNS, showed no significant reduction in axon terminals synapsing with vestibular neurons, including vacuolated neurons of BSE brains, when controls and BSE brains were compared. This suggests that de-afferentation of neurons is not the cause of neuronal loss. Prion protein was detected in the neuropil of the vestibular nuclear complex of BSE brains but not control brains. These studies show that previously unsuspected neuronal loss is a significant feature of BSE.


Adult onset lysosomal storage disease in a Tibetan terrier: clinical, morphological and biochemical studies. We describe a novel late-onset lysosomal lipid storage disease affecting a Tibetan terrier. The principal clinical manifestations include visual loss, progressive cerebellar ataxia and dementia. A necropsy of an affected 10-year-old dog demonstrated cerebellar atrophy. Histological analysis revealed extensive loss of retinal ganglion cells and cerebellar Purkinje cells, and mild to moderate loss of neurons in the cerebrum, basal ganglia and spinal cord. There were generalized neuronal hypertrophy and multifocal neuronal necrosis associated with the presence of enlarged macrophages. Neurons and perineuronal macrophages contained cytoplasmic granules that stained with PAS, luxol fast blue and several lectins. The granules were sudanophilic and autofluorescent. Electron microscopic analysis revealed lysosomes laden with lamellated membrane structures in neurons, pancreatic ductal and centroacinar cells and in cultured fibroblasts. These findings indicate lysosomal storage of both lipid and carbohydrate. Biochemical analysis of brain lipids and numerous lysosomal enzyme assays of leukocytes and cultured fibroblasts were unsuccessful in elucidating the underlying enzyme defect, although a generalized increase of brain gangliosides was noted.


Morphology of cerebral plaque-like lesions in hereditary cerebral hemorrhage with amyloidosis (Dutch). We studied the presence and morphology of plaque-like lesions in the frontal cortex of six patients, aged 40 to 76 years, with hereditary cerebral hemorrhage with amyloidosis--Dutch type (HCHWA-D), using beta/A4 immuno-, silver, Congo red and thioflavin S staining. Two types of beta/A4 immunoreactive and Congo red-negative plaques were detected. The first type was composed of argyrophilic fibrous material in periodic acid-methenamine silver (PAM) and modified Bielschowsky staining and lacked silver-stained degenerating neurites. Therefore, this type of plaque has the same staining properties as the diffuse plaque described in Alzheimer's disease, Down's syndrome and nondemented elderly. The second type of plaque, occurring only in the three oldest patients and numerically increasing with age, consisted of a spherical non-argyrophilic area of granular texture with a rim of PAM-positive material. The PAM-positive fibrous material of both types of plaques was mingled with coarser and compact, irregular-shaped argyrophilic structures in the oldest patient. The described plaques did not show bright fluorescence with thioflavin S staining. These results indicate, that the morphology of plaques, encountered in HCHWA-D, is diverse and changes with age.


Cerebral granular cell tumors: report of a case and a note on their nature and expected behavior. A case of cerebral granular cell tumor (GCT) is reported. Histologically, the growth was composed of benign astrocytes, granular cells and transitional forms between both elements. Glial fibrillary acidic protein was detected in the glial component and, to a lesser extent, in the granular cells. Alpha-1-antichymotrypsin was demonstrated in the latter component only. Ultrastructural study also supported the evidence that neoplastic astrocytes became granular cells. The survey of the literature and our own results suggest that GCTs in this particular location, even when histologically benign, seem to have a worse prognosis than the low-grade supratentorial astrocytomas.


The coexistence of Alzheimer's disease and Creutzfeldt-Jakob disease in a patient with dementia of long duration. We report here a 75-year-old-male with a slowly progressive dementia of 5-year duration along with a rapid exacerbation of symptoms in the terminal 3 months. Neuropathological examinations revealed findings consistent with conspicuous Alzheimer's disease and mild Creutzfeldt-Jakob disease (CJD). The plaque amyloid was exclusively composed of beta-protein. The immunohistochemistry of prion protein using hydrolytic autoclaving pretreatment showed diffuse gray matter stainings in the sections of both the cerebral and cerebellar cortices. This method was thus considered useful in confirming the diagnosis of CJD for this case.


Long-term kinetic vitreous fluorophotometry. Fluorophotometric measurements of vitreous and plasma fluorescence were performed in 14 normal subjects up to 24 h after injection of a single intravenous dose of sodium fluorescein. The data were subjected to a kinetic two-compartmental analysis, including the determination of the transfer rate constants between the central and the peripheral compartment (K12 and K21) as well as between the central and vitreous compartment (K(in) and K(out)). In the central compartment (plasma) a mean terminal disposition rate constant (beta) of free fluorescein of 0.23 h-1 was found, corresponding to a half-life of 3.01 h. The vitreous fluorescence reached a maximum 2-5 h after the injection and then declined monoexponentially and very slowly (t1/2 = 9.6 h). The rate constant of permeation into the eye (K(in)) was found to be 0.66 h-1, while the rate constant of elimination of fluorescein from the vitreous was 0.072 h-1 (K(out)). Kin was found to be significantly higher than K12, presumably indicating an active transport mechanism for fluorescein located at the blood-ocular barrier. K(out) was significantly lower than K21, reflecting a slow vitreous elimination of fluorescein. A permeability index defined as the percentage ratio between the areas under the vitreous and the plasma concentration curves was found to be 3.5%, illustrating the poor penetration of fluorescein into the vitreous. Kinetic long-term fluorophotometry appears to be a promising new tool in the study of the blood-ocular barrier.


Long-term kinetic vitreous fluorophotometry in normal and diabetic subjects. Nine normal and 24 diabetic subjects were examined by long-term vitreous and plasma fluorescein fluorophotometry and the observed concentration profiles were described by biexponential time courses. The rate constant of elimination of fluorescein from the body (K10) was significantly decreased in diabetics with background and proliferative retinopathy, presumably caused by affection of the liver and possibly representing alterations in membranes of liver cells. Increased kidney albumin excretion was observed with increasing degree of retinopathy. The apparent rate constant of fluorescein penetration into the eye (Kin) was found significantly decreased in background as well as in proliferative retinopathy; while the permeability index, calculated as areas under vitreous and plasma fluorescein curves, was significantly increased. In the normal subjects Kin was significantly higher than the rate constant of fluorescein transfer (K12) from the apparent central to the peripheral tissue compartment, whereas in the diabetics this difference was only found in the group with background retinopathy. The findings seem compatible with the concept that the breakdown of the blood-ocular barrier could be caused at least partly by affection of an active transport system for fluorescein, but thickening and compositional changes of the basement membranes in the eye might also be of importance.


Excimer laser refractive keratectomy for high myopia. 6-month follow-up of patients treated bilaterally. Both eyes of twenty patients were treated for myopia with refractive keratectomy using an excimer laser (193 nm), and followed for six months. The 40 eyes were divided into Group I (22 eyes) with an attempted refraction change of 5-8 diopters; and Group I (18 eyes) with 9-12 diopters of attempted refraction change. In Group I the corrected visual acuity improved or was unchanged in 16/22 eyes. Two eyes with high preoperative corrected visual acuity had experienced a significant loss in corrected visual acuity after 6 months. In Group II, the corrected visual acuity decreased in 10/18 eyes, in 4 eyes significantly. Among the 40 eyes, 39 had a refraction change less than intended after 6 months. Overcorrection was seen in only 1 eye. In Group I, 20/22 eyes were corrected up to 2.5 diopters less than attempted. In Group II, 9/18 eyes were more than 2.5 diopters from the attempted correction. All eyes developed subepithelial opacification ('haze'), which, in spite of steroid treatment, was still present after 6 months. The haze was more severe in eyes treated with 9-12 diopters of attempted refraction change. The achieved refraction change in the two eyes of the same patient was found to be correlated, possibly due to an individual factor in corneal wound healing.


Critical frequency of photic driving: which part of the visual pathway do we examine? Studies on critical frequency of photic driving were performed on patients with optic atrophy, moderately expressed suprachiasmal lesions and normal subjects. A reduction was present only in optic atrophy patients. The critical frequency of photic driving showed significant correlations with visual acuity and differential light sensitivity of the areas located within 15 degrees from the fixation point. The correlation proved higher for foveal sensitivity expressed in non-logarithmic rather than in logarithmic units, the opposite being the case for the sensitivity of parafoveal areas. It may be concluded that critical frequency of photic driving is conditioned by the cortical projection zones and visual pathways corresponding to the central 15 degrees of the visual field, but with predominant role of foveal projections.


Scotopization and pseudoprotanomaly in blue-yellow/colour vision defects. With a routine clinical colour vision test battery we found scotopization in 32% of retinal diseases presenting with pseudoprotanomaly as sign of an acquired type III blue-yellow colour vision defect. In blue-yellow colour vision defects of retinal origin scotopization is a transient phenomenon, present in early stages of the disease, but it is not an obligatory finding. There is no evident relationship between visual acuity and scotopization.


Visual impairment in Nordic children. III. Diagnoses. The diagnoses, according to type and site and the degree of visual impairment, responsible for severe visual impairment in children below the age of 18, were analyzed in a material compiled from the national registers of visually impaired in Denmark, Finland, Iceland and Norway. Among 2527 children the predominant causes of visual impairment are ascribed to congenital malformations, neuro-ophthalmological diseases and retinal diseases. Optic atrophy is the leading single cause of severe visual impairment when all diagnoses are compared, and this also applies when all categories of visual impairment are included. Retinopathy of prematurity is the second principal cause of severe visual impairment, while cerebral amblyopia rates as the third most significant cause. Congenital cataract is also of considerable importance when all categories of visual impairment are compared. The differences registered between the Nordic countries were found to be within reasonable limits, except for a preponderance of neuro-ophthalmological diseases in the Danish material. This could be explained by a better medical supervision of mentally retarded patients in Denmark. Additional impairments occur in a large percentage of patients, but are unevenly distributed in the disease groups. A high frequency of additional impairments are found in the neuro-ophthalmological group and in the groups with congenital malformations, emphasizing the importance of a multidisciplinary evaluation when dealing with the visually impaired child.


Visual impairment in Nordic children. IV. Sex distribution. A Nordic study group of ophthalmologists, NORDSYN, has compiled registers in Denmark, Finland, Iceland and Norway of 2527 visually impaired children aged 0-17 years. This paper is concerned with the sex-distribution in the registers and has documented a statistically significant excess of males in two of the registers (Denmark and Finland). The dominance of males seems to be related to two main conditions: 1. Genetic factors. 2. Perinatal factors. The genetic factors are mainly concerned with X-linked inheritance. The fact that perinatal influences involve visual impairment in males more than in females is difficult to account for. It may be conjectured, that the basis for perinatal visual damage is determined by unknown prenatal, possibly genetic, factors.


Contrast sensitivity deficits in subjects with glaucoma-like discs using an oscilloscope-based method. The central visual function of 20 subjects with glaucoma-like discs, normal intraocular pressures and normal visual fields and 20 age-matched normal subjects was assessed by measuring contrast sensitivity using an oscilloscope technique. The subjects with glaucoma-like discs exhibited a significant reduction in contrast sensitivity compared to the age-matched normal; these differences were greatest at spatial frequencies of 2 and 4 cdeg-1.


Prevalence of retinitis pigmentosa and allied disorders in Denmark. III. Hereditary pattern. A national epidemiological study revealed 1301 prevalent cases of retinitis pigmentosa (RP) in the Danish population on January 1, 1988. The corresponding number of 974 families were analyzed with respect to Mendelian inheritance groups. Thirty families, comprising 6.9% of the prevalent RP-cases, were categorized with an autosomal dominant inheritance pattern. In 187 families, 22.6% of RP-cases, autosomal recessive heredity was encountered. X-linked heredity was found in 45 families, 10.8% of the RP-cases. Simplex RP-cases comprised 562 persons (43.2% of RP-cases). About a fourth of the non-systemic X-linked cases were females. Half of these had an age at onset after 30 years, but a third had their first RP-symptoms before age 18 years. A representative fraction of parents to non-systemic autosomal dominant, autosomal recessive, X-linked, and simplex cases were evaluated concerning their age at the time they had their first affected child. Mothers of the male simplex cases were of statistically significant higher age than mothers of the other inheritance groups. This may imply a high rate of new mutations among simplex cases, especially on the X-chromosome.


Immunofluorescence localization of cystatins in human lacrimal gland and in the exorbital lacrimal gland of the rat. Cystatins are widely distributed natural inhibitors of cysteine proteinase. They occur both intra and extracellularly in various cells and tissue fluids including tears. Using an immunofluorescence technique with antibodies against rat cystatin S, an inhibitor of submandibular gland origin, cystatin-like immunoreactive material was demonstrated in the acinar cells of the exorbital lacrimal gland of the rat. Administration of the cholinergic agonist carbachol caused a depletion of cystatin from the acinar cells. This depletion was followed by a partial restitution in 6-8 h. Administration of the beta-adrenergic agonist isoproterenol for 4 days, which caused a marked hypertrophy of the submandibular gland, had no effect on the structure, weight, or cystatin content of the exorbital lacrimal gland. After such treatment, however, single large cells with intense staining for cystatin were encountered. Cystatin-like immunoreactive material was also demonstrated in human lacrimal gland using antibodies against human cystatin S. These data suggest the notion that tear cystatins are secreted by the lacrimal glands.


Results of pneumatic retinopexy with air. Although scleral buckling yields good results in retinal reattachment surgery, we search for less laborious methods which could give the same high cure rate. Fifty-one consecutive patients with phakic, rhegmatogenous retinal detachment and breaks within 60 degrees of the upper retinal quadrants were treated by retino-cryopexy, drainage of subretinal fluid (under an operating microscope), and intravitreal injection of air (0.8 to 2.0 ml). Follow-up examinations (after 6 to 12 months) disclosed retinal reattachment in 44 of 51 eyes (86%). Cases with macular detachment showed good visual recovery, and 15 of 23 eyes (65%) achieved 0.5 (20/40) or more in visual acuity. Postoperatively, new retinal breaks occurred in 6%, proliferative vitreoretinopathy in 2%, and macular pucker also in 2%. Pneumatic retinopexy with air is an easy procedure, it is associated with few complications, and enables rapid postoperative recovery.


Topical anesthesia and adjustable sutures in strabismus surgery. Our experience with the use of topical anesthesia and adjustable sutures in a one-stage operation for treatment of strabismus is discussed, and selected cases are presented. In addition to using the method in recession, we have also developed a method for using adjustable sutures in resection of muscles. We have also found the method useful in reoperations and in operations on paretic muscles.


Limbus-based versus fornix-based conjunctival flap in glaucoma filtering surgery. Eighteen consecutive patients suffering from the same type of glaucoma in both eyes were treated with bilateral trabeculectomy. Surgery with both fornix-based and limbus-based flap was performed on each patient, one procedure in each eye. Pre- and postoperative intraocular pressure, morphology of the fistulation bleb, anterior chamber depth and need for additional treatment were recorded. Half a year after surgery, the fornix-based flap procedure was superior (p < 0.05) concerning high success rate, little additional therapy and good morphology of the bleb.


Trabeculectomy and gelatin implants. A retrospective, long-term follow-up study. In a retrospective follow-up study including 60 eyes with simple or capsular glaucoma, the results obtained by using a gelatin implant under the scleral flap during trabeculectomy were compared with those obtained without such implants. One month postoperatively the mean IOP was significantly lower in the gelatin group than in the control group (15.0 mmHg and 17.9 mmHg, respectively) (p = 0.024). At the long-term follow-up, however, the mean IOP in the two groups were very similar (13.6 mmHg and 14.8 mmHg, respectively).


Intravitreal silicone and fluorosilicone oils: pathologic findings in rabbit eyes. The effects of medical-grade intraocular silicone and commercial-grade fluorosilicone oils were studied in rabbit eyes. The experimental model consisted of lensectomized and vitrectomized eyes that did not undergo further treatment (Group 1), and three groups of lensectomized and vitrectomized eyes that were injected intravitreously 3 months earlier with medical-grade silicone oil of 1000 cs (Group 3), and 10,000 cs (Group 4). The silicone oil-injected eyes developed proliferative membranes. The fluorosilicone oil caused an intravitreous inflammatory reaction with vacuolated macrophages present around the oil that may have been due to the higher concentration of low-molecular-weight components found in the oil.


Visual dysfunction in type II diabetic patients revealed by a hyperacuity test. Displacement thresholds for an oscillating bar, which fall into the hyperacuity range, were determined in 21 subjects with non-insulin dependent diabetes mellitus and 19 age-matched visually normal controls. The diabetic subjects were classed as either having minimal or no retinopathy. Whilst thresholds for the diabetic group were significantly raised above those of the normal group, there were no significant differences in thresholds between the diabetic subgroup with retinopathy and the subgroup without. Greater thresholds tended to be found at higher frequencies of oscillation as the known duration of the diabetes increased.


Association of reliability with reproducibility of the glaucomatous visual field. We studied 207 glaucoma patients (207 eyes) who had two successive visual tests on the Humphrey Field Analyzer to determine the association of unreliability (> 10% incidence of a missed catch trial test) with threshold variation. We found that in patients where one visual field showed > 30% false negative or positive errors, and the other visual field also was unreliable, a significant increase in the variance of the mean defect existed from reliable patients (p < 0.05). Of patients who had only one of two visual fields which was unreliable (from false negative errors), only those with marked glaucomatous visual field loss (< -15 dB depth of defect) showed a greater variance in mean defect between examinations over reliable patients (p < 0.05). In total, 41 patients (19.8%) had unreliable visual fields associated with statistically increased threshold variation. This study suggests that patient reliability should be considered when interpreting changes in threshold between automated visual field examinations.


Weighting according to location in computer-assisted glaucoma visual field analysis. In recent years several aids for automated interpretation of visual field data have been suggested. We believed that incorporation of thorough knowledge of normal visual field variability would allow improvements in the performance of such aids since more attention would be paid to field results in areas with low physiological variability. Two visual field models for classification of fields in glaucoma based on comparisons of sensitivity values in the upper and lower hemifields and on analysis of test point clusters with diminished sensitivity were compared. Both models were constructed using logistic regression analysis in 101 normal eyes and 101 eyes with glaucoma. The first, more traditional model assumed Gaussian distributions of deviations from age-corrected normal thresholds and constant variability across the field (non-weighted model). The second model took into account empirically determined variability of pointwise threshold results and of cluster volumes in various visual field regions (weighted model). The two models were subsequently tested on an independent material of 163 normal eyes and 76 eyes with glaucoma. The weighted model gave significantly better classification of the fields in both materials. Accounting for physiological threshold variability can offer significant advantages in the construction of perimetric analysis aids for detection of glaucoma.


Spatial analyses of glaucomatous visual fields; a comparison with traditional visual field indices. Interpretation of numeric automated threshold visual field results is often difficult. A large amount of data is obtained for every single field tested. Various approaches to summarize this data have been suggested, most commonly the mean and standard deviation of departures from age-corrected normal threshold values. These visual field indices differ substantially from subjective field interpretation where spatial relationships are important. We have previously devised two methods for automated field interpretation which take spatial information into account--regional up-down comparisons and arcuate cluster analysis. We now studied the merits of using these new spatial methods and compared them to traditional visual field indices for discrimination between normal and glaucomatous field results. Central static 30 degree field results in 101 eyes of 101 normal subjects and 101 eyes of 101 patients with glaucoma were discriminated using logistic regression analysis. The best field classification was obtained with a spatial visual field model combining up-down differences and arcuate clusters. The advantages of the spatial model were confirmed in an independent material of 163 eyes of 163 normal subjects and 76 eyes of 76 patients with glaucoma where eyes with large field defects had been removed. In this material the spatial model gave 87% sensitivity and 83% specificity while the best non-spatial model gave 82% sensitivity and 80% specificity. Visual field interpretation in glaucoma may be significantly enhanced if detection is focused on circumscribed field loss rather than on averages of differential light sensitivities and similar indices which do not take spatial relationships into consideration.


Choroidal melanoma responses after brachytherapy treatment. Serial ultrasonic measurements performed on 85 melanoma patients who were treated with radioactive plaques and followed for up to 141 months revealed that no 2 patients had identical patterns of change. Eighty-two of the patients were categorized into one of four patterns after treatment: Type D (decrease in height, 57 patients), Type S (same height, 12 patients), Type I (increase in height, 9 patients), and Type RG (tumour regrowth, 4 patients). The calculated mean total change in tumor height for Type D was 1.92 mm at 6 months, 2.58 mm at 12 months, 2.97 mm at 24 months and 3.61 mm at 48 months. For Type I, the mean total change in tumor height was 0.80 mm at 6 months, 0.95 mm at 12 months, 2.28 mm at 24 months, and 3.0 mm at 48 months.


Birdshot retinochoroidopathy in monozygotic twins. Birdshot retinochoroidopathy is a rare ocular disorder which was named and delineated as a separate clinical entity by Ryan & Maumenee in 1980. We diagnosed birdshot retinochoroidopathy in a monozygotic pair of twins, who were affected with a time interval of 12 years, respectively. These are the first with birdshot retinochoroidopathy to be reported from the Nordic countries and the first report on this disorder in monozygotic twins. Due to night-blindness, visual field defects and a severely affected electroretinogram one of our cases initially was diagnosed as a choroidoretinal dystrophy. Birdshot retinochoroidopathy should be kept in mind as a differential diagnosis in retinitis pigmentosa-like disorders with widespread choroidal involvement. Our cases substantiated the evidence of a strong correlation with the presence of HLA-A29 antigen.


Acanthamoeba keratitis; report of the first Norwegian cases. Two patients with therapy resistant keratitis are described. There were no predisposing diseases. Both patients had been using rigid contact lenses for more than 10 years and both cleaned their lenses in cold tap water. The patients presented with keratitis of several weeks duration resistant to antibacterial and antiviral treatment and not responding to high doses of corticosteroids. Ultimately, after the possibility of a protozoan aetiology had been considered, culture of corneal scrapings from both patients yielded growth of Acanthamoeba trophozoites. Acanthamoeba keratitis is very rare in northern European countries and has never before been diagnosed in Norway. The present cases show that Acanthamoeba should be added to the list of possible pathogenic agents even in northern low temperature areas.


Recurrent choroidal detachment following timolol therapy in previously filtered eye. Choroidal detachment post filtering surgery. A 64-year-old patient with open-angle glaucoma was treated with timolol following two unsuccessful filtering procedures. While on timolol therapy, she developed three episodes of choroidal detachment, hypotony and shallow anterior chamber. These findings resolved upon cessation of timolol and reappeared on 3 occasions shortly after reinstitution of the beta blocker therapy.


Immunologic studies of nonunited fractures. We studied tissue samples of noninfected delayed union or nonunion of diaphyseal bones in 10 patients immunopathologically and neuroimmunologically 4 to 25 months after the primary injury. Samples mostly consisted of vascularized connective tissue of varying density with the proline-4-hydroxylase-containing fibroblast as the major cell type. Most inflammatory cells were CD4 T-lymphocytes and their number was always twice that of the CD8 positive cells. Staining for CD11b positive monocyte/macrophages showed in all samples positive cells scattered in the connective tissue stroma with perivascular enrichments. Mast cells were absent or very rare. Our findings suggest that delayed union and nonunion tissue consists of vascularized connective tissue, which mostly contains 5B5 fibroblasts, CD11b macrophages and vascular endothelial cells with only few immigrant recently recruited monocytes or lymphoid cells. Almost all resident cells seem to be involved in tissue remodeling as suggested by their content of fibroblast-type MMP-1 and its proteolytic activator MMP-3 or stromelysin. The most striking finding was the paucity or total lack of peripheral innervation, which may have to do with the nonunion of the fracture.


Lengthening of anterior cruciate ligament graft. Roentgen stereophotogrammetry of 32 cases 2 years after repair. 32 patients with old anterior cruciate ligament injuries were operated on with patellar tendon-prepatellar tissue-quadriceps tendon graft over the top without and with augmentation (Kennedy-LAD). The anteroposterior (AP) laxity was assessed preoperatively, and at 6, 12, and 24 months after the operation with roentgen stereophotogrammetry. 6 months postoperatively the instability had decreased 5.4 mm in the nonaugmented and 1.9 mm in the augmented group, but not to normal values. During the following 18 months the AP laxity increased and returned to the preoperative level. At 2 years, 28 of the 32 patients were considered good or excellent, according to the Lysholm score. There was a lack of correlation between AP laxity and functional tests.


Instability after anterior cruciate ligament rupture. Measurements of sagittal laxity compared in 11 cases. Manual tests and 2 external devices were used together with roentgen stereophotogrammetry (RSA) and an active weight-bearing radiographic method to measure the sagittal laxity in 11 knees with anterior-cruciate-ligament rupture. In 5 knees no ligament surgery had been performed (unstable knees) and in 6 knees a reconstruction had been performed one year before the examination (stable knees). There were positive correlations between all methods, including the manual tests when all knees, both stable and unstable, were analyzed together. However, the mean values of the total displacement differed between the methods, especially when comparing the weight-bearing radiographs with the three other methods. Some knees with substantial displacement during passive loading did not show any displacement when weight bearing; the measurements thus depended on both the ligamentous laxity and the patient's neuromuscular control of the joint. When the stable knees were analyzed separately, higher mean values were recorded with the external devices than with RSA using 180 N load. This could be explained by an error from soft tissue deformation which added to the skeletal displacement when the external devices were used.


Bone formation after distraction osteotomy of the radius in sheep. Gradual distraction by external fixation was performed one week after osteotomy of the radius in 12 sheep. Bone regeneration in the distraction area was studied by light and electron microscopy. One week after starting the distraction the gap was composed of hematopoietic cells and fibroblasts. The collagen production had already started and it continued actively throughout the distraction period. The collagen produced by the fibroblasts in the central interzone of the gap was organized according to the direction of the distraction. The osteoblasts were lined up along the collagen bundles and osteoid formation was most active around the capillaries. Mineralization started two weeks after the beginning of the distraction. After cessation of the distraction, separate groups of cartilaginous cells were found in some specimens among the newly formed bone. Our findings suggest that osteogenesis as a result of gradual distraction occurs through the whole distraction area with preceding formation of organized collagen matrix. The bone structure in the distracted segment represents an organized lamellar structure at an early stage of the osteogenesis.


Delayed distraction in bone lengthening. Improved healing in lambs. We compared delayed distraction (DD) with immediate distraction (ID) in bone-lengthening. Open femoral diaphyseal osteotomy was performed on 24 three-month-old lambs, and external distractor fixators were applied. In the ID group (n 12), distraction commenced on the first postoperative day; in the DD group (n 12), distraction was delayed until the tenth day after surgery. In all the animals, the femur was lengthened by 2 cm at the rate of 1 mm/day. The animals were killed 1, 2, and 3 months postoperatively. Radiography and densitometry of the lengthened callus showed that DD, compared with ID, improved the quality of the callus with quicker, denser, and more homogeneous bone formation.


Effects of short-term treatment with corticosteroids and indomethacin on bone healing. A mechanical study of osteotomies in rats. We studied the effects of short-term therapy with methylprednisolone and indomethacin on healing of intramedullary pinned osteotomies of the femur in rats. When the osteotomy was complete and healing occurred under unstable conditions with callus formation, indomethacin inhibited healing when estimated by mechanical tests of bending moment, energy expenditure before refracture, and bending rigidity 6 weeks after surgery. No inhibitory effects were seen following corticosteroid treatment. When the osteotomy was incomplete and healing occurred under stable conditions, similar tendencies were observed. Thus, short-term medication with indomethacin inhibits fracture healing. This was not the case with short-term methylprednisolone.


Fracture healing monitored with strain gauges. External fixation of 7 humeral neck fractures. We measured healing in 7 cases of surgical neck fracture of the humerus by applying a strain gauge measuring bar between the external fixation pins. Repeated measurements provided a healing curve for the individual cases. The gradual decrease in deflection of the fracture zone reached a plateau of about 50 percent after 2 to 4 weeks in 6 cases. Removal of the frame at this time proved safe, as solid healing occurred. In one fracture no such decrease was seen and nonunion developed.


Calcitonin effects on rabbit bone. Bending tests on ulnar osteotomies. 30 adult male New Zealand white rabbits underwent osteotomy and plate fixation of the left ulna for 6 or 12 weeks. The right ulna served as control. In half of the rabbits 6 IU calcitonin was given daily until death, and in the other half placebo injections in the same manner. A three-point bending test was performed on both ulnae. Sections of bone, covered or uncovered by the plates, were examined histologically. Long-term administration of calcitonin increased the mechanical properties of both fractured and intact bones and reduced porosity of the cortex under the plate.


Bone morphogenetic protein induces bone in the squirrel monkey, but bone matrix does not. Demineralized bone matrix (DBM) reproducibly induces extraskeletal bone formation in rodents, but its effects in dogs and primates are negative or uncertain. In previous studies on the squirrel monkey, DBM did not induce bone, although the same implants were effective in nude rats. In the present study, the DBM was augmented with recombinant human bone morphogenetic protein-2 (BMP-2). Bone was formed in 10 of 12 monkeys, as verified by histology and calcium content. However, in 4 monkeys, the induced bone mass appeared smaller than the original implant. DBM controls induced microscopic amounts of bone in 2 out of 10 monkeys. In the nude rats, all DBM controls and augmented implants induced bone. The difficulties in achieving bone induction in higher animals may be overcome, at least partially, by using a higher concentration of the inductive protein than is present in DBM.


Effect of local prostaglandin E2 on periosteum and muscle in rabbits. We assessed the target tissue for the stimulatory effect of prostaglandin E2 (PGE2) on bone formation previously observed during fracture healing. PGE2 was infused into tibial periosteal tissue in the right leg of 7 rabbits and into the anterior tibial muscle in the right leg of 7 other rabbits for 6 weeks. Solvent solution was infused into the left leg. PGE2 infusion at the periosteum caused the formation of primitive woven bone with large amounts of connective tissue; solvent infusion caused small amounts of normal periosteal bone formation. In the neighboring cortical bone, remodeling was increased after PGE2 infusion compared to solvent infusion. In the muscle, PGE2 infusion caused the formation of connective tissue with small amounts of woven bone. Thus, the major effects of PGE2 infusion at the site of the periosteum was the formation of primitive woven bone and in muscles the formation of connective tissue.


Indomethacin for prevention of ectopic ossification in cementless hip arthroplasties. A prospective 1-year study of 100 cases. In a prospective series of 100 patients we investigated the effect of indomethacin for 6 weeks in the prophylaxis of ectopic bone formation in hip replacements with cementless fixation. Indomethacin prophylaxis reduced (P < 0.0001) ectopic bone formation compared to a retrospective control group of equal size. Side-effects occurred in one-fifth of the patients, but most of these could continue the medication for at least 4 weeks.


No effect of piroxicam on achilles tendinopathy. A randomized study of 70 patients. 70 consecutive adult, nonrheumatic patients with a painful achilles tendinopathy were randomized to treatment with either a nonsteroid antiinflammatory drug (piroxicam) or placebo. Both groups received adjunct treatment with a period of rest combined with stretching and strengthening exercises. 52/70 cases were engaged in various sports, notably running. All subjects were evaluated on days 3, 7, 14, and 28 with respect to pain, tenderness, swelling, ankle joint movement and muscle strength. Results were judged from residual symptoms and an overall assessment of the efficacy. No differences were seen between the groups at any time during the study. The overall result was identical with a rate of success slightly better than 50 percent which corresponds to the placebo response reported in other studies.


Hip fracture patients may be vitamin B6 deficient. Controlled study of serum pyridoxal-5'-phosphate. Deficiency of vitamin B6 in rats may result in defective bone formation, possibly due to decreased activity of the enzyme ornithine decarboxylase which requires pyridoxal-5'-phosphate (PLP) as a co-factor and is responsible for production of intracellular putrescine, a metabolic regulator. We studied 3 groups of patients (62 fit ambulant out-patients, 21 elective arthroplasty patients, and 20 hip fracture patients) and assayed their PLP status by high performance liquid chromatography. The reference range derived from the out-patients was 13-106 nmol/L. 3 of the arthroplasty group and 10 of the fracture group had serum PLP concentrations less than 13 nmol/L (P < 0.01). We conclude that PLP may be an etiologic factor in hip fracture by virtue of its role in the activity of a key regulatory protein.


Prediction of disturbed healing in femoral neck fracture. Radiographic analysis of 149 cases. To determine factors predictive of early healing disturbances after fixation of femoral neck fracture, the radiographic and clinical data of 149 patients were subjected to a logistic regression analysis comparing them with the results 3 months postoperatively. As in previous studies, fracture reduction distinguished between fractures with or without healing disturbances. The following signs in the preoperative radiographs were predictive of unfavorable outcome: small head fragment, comminution of the calcar femorale, and varus angulation of the head. Fractures with negative predictive signs may be selected for primary arthroplasty.


Survival after trochanteric fracture. Biological factors analyzed in 270 patients. Factors that influence mortality were analyzed in 270 patients operated on for trochanteric hip fracture. Survival was closely related to age and medical condition at the time of injury; methods of treatment had little influence on survival.


Motion of the bipolar hip prosthesis components. Friction studied in cadavers. It has been postulated that most hip motion occurs at the inner bearing in bipolar hip prosthesis. However, radiography and cineradiography analyses have shown that the inner bearing is not always the primary articulation. We studied the frictional behavior of bipolar prosthesis and Austin-Moore prostheses and the motion of the bipolar prosthesis using a pendulum apparatus. The primary articulation was altered according to the amount of loading. When a load of 10 kg was applied to the joint, motion occurred at both bearings with friction coefficients 0.061 at the inner bearing and 0.026 at the outer bearing. With loads of over 20 kg, the outer bearing was the primary articulation. The inner bearing was the dominant articulation only when the acetabular cartilage had been removed. Our results suggest that the motion of bipolar prostheses occurs mainly at the outer bearing during normal walking, and that this prosthesis cannot be expected to reduce wear of articular cartilage.


Ultrasonography for diagnosis of slipped capital femoral epiphysis. Comparison with radiography in 9 cases. In 7 of 8 patients with non-acute slipped capital femoral epiphysis, the slip was visualized by ultrasound. The mean epiphyseal displacement was 6.0 mm, measured on an anterior ultrasound scan. Grading of slip severity by ultrasound was consistent with the radiographic assessment. Two patients had a moderate hip joint effusion which did not affect the final outcome, whereas one patient with an acute slip had a pronounced effusion, and necrosis of the epiphysis occurred. The anteversion angles of the affected hips were reduced as compared to those of the normal hips. It was concluded that ultrasonography was reliable in detecting pronounced and mild degrees of epiphyseal slips, whereas minimal slips could be missed. The detection of hip effusion is important because a tamponade may cause vascular impairment of the epiphysis, unless aspirated.


Piroxicam spares buprenorphine after total joint replacement. Controlled study of pain treatment in 81 patients. In a blinded, placebo-controlled study, the nonsteroidal antiinflammatory drug piroxicam, in combination with the partial morphine agonist/antagonist buprenorphine, was compared with buprenorphine alone for analgesic effect and side-effects in a 10-day period following total replacement of the hip or knee. 117 patients entered and 81 completed the study. The patients receiving piroxicam consumed less buprenorphine. There were no differences concerning side-effects between the two treatment groups, apart from a tendency towards less nausea after the third postoperative day in the group receiving piroxicam.


Increased resistance of bacteria after adherence to polymethyl methacrylate. An in vitro study. The pathobiology of total joint prosthesis infection was investigated in vitro. Discs of polymethylmethacrylate (PMMA) were exposed to a suspension containing cells of 10(8) per mL Staphylococcus epidermidis E-46. After 12 hours, exposed discs were rinsed with phosphate-buffered saline and placed in brain heart infusion broth containing antibiotics (2.5 mg per mL of Cephaloridine). After gentle shaking for 24 hours at 37 degrees C, the bacteria on the PMMA surface were detached and washed with phosphate-buffered saline to remove the antibiotics. Compared with the free bacteria which were detached from the PMMA by sonication immediately after exposure to the antibiotic solution, those allowed to remain adhered to the PMMA surface were more resistant to antibiotics. Scanning electron microscopy showed accumulation of bacteria surrounded by slime on PMMA discs exposed for 12 hours. Our results indicate that resistance of bacteria to antibiotics is increased after adherence to the biomaterial and formation of a slime layer.


Perioperative factors associated with septic arthritis after arthroplasty. Prospective multicenter study of 362 knee and 2,651 hip operations. Perioperative factors associated with late septic arthritis after knee and hip arthroplasties were prospectively investigated. All patients received a short course of perioperative cefuroxime. After a follow-up of 1 year, septic arthritis was diagnosed in 9/362 patients (2.5 percent) after knee arthroplasty and in 17/2651 patients (0.64 percent) after hip arthroplasty. For the knee, factors associated with septic arthritis after arthroplasty were rheumatoid arthritis, wound infection, an unhealed wound, and a painful, limited knee function at discharge from the hospital. For the hip, corresponding risk factors were diabetes, failed fracture osteosynthesis, a breakdown of sterility during operation, wound infection, postoperative urinary tract infection, and an unhealed wound at discharge from the hospital or a difficult rehabilitation course. Reoperation after knee and hip arthroplasty was also clearly associated with a higher incidence of septic arthritis.


Timing of physiodesis in limb length inequality. The Straight Line Graph applied in 30 patients. In a prospective study 30 children underwent 33 physiodeses for lower limb length inequality (LLI). Timing of surgery was based on (bi)annual orthoradiographic measurements and skeletal age, and in accordance with Moseley's Straight Line Graph. The mean predicted LLI was 5.2 (3.0-11) cm and the mean LLI at the end of growth was 1.4 (0.0-4.3) cm. In 9 patients final LLI exceeded 1.5 cm, and one of these patients was operated on twice. In total, secondary operations were performed three times. After analysis of the failures it is concluded that the accuracy of the Straight Line Graph is mainly limited by the pattern of skeletal maturation. Recommendations to prevent failures from other causes are given.


Nutrition as a prognostic indicator in amputations. A prospective study of 47 cases. The nutritional status was evaluated prospectively in 47 consecutive patients who were amputated for lower extremity ischemia. It was good in 13 patients, reduced in 18, and poor in 16. Malnourished patients had a higher frequency of impaired wound healing, and an increased risk of postoperative cardiopulmonary and septic complications; all 6 deaths occurred in these groups.


Synovitis of the knee after intraarticular fracture fixation with Biofix. Report of two cases. We report two cases of severe aseptic synovitis of the knee 8 and 13 weeks after biodegradable internal fixation (Biofix rods) of a fracture of the intercondylar eminence. Both knees were treated by surgical revision and synovectomy. Histologic examination revealed a severe foreign-body type of reactive synovitis in the absence of infection. It is not advisable to use Biofix intraarticularly.


Peroneal tendon subluxation in a case of anomalous peroneus brevis muscle. We report a case of peroneal tendon subluxation as a result of an anomalous extension of the peroneus brevis muscle into the fibular groove, causing an encroachment phenomenon, stretching-out of the superior peroneal retinaculum, longitudinal splitting of the peroneus brevis tendon, subluxation of the peroneal tendons, and peroneal tenosynovitis. We describe a simple surgical technique for tendon stabilization, after decompression of the fibular groove.


Mitochondrial enlargement and basement membrane thickening of renal proximal tubules, possible initiators of microalbuminuria in non-insulin-dependent diabetics (NIDDM). To clarify the morphological changes in renal proximal tubules at the onset of diabetic nephropathy, we observed 177 biopsy samples from patients with Non-Insulin-Dependent Diabetics (NIDDM) using light and electron microscopy. Group I had no proteinuria (p.u.), group II had p.u. < or = 0.5 g/day, group III had p.u. > 0.5 g/day, group IV had serum creatine level (Cr) > 1.5 mg/dl. Twenty age-matched normal patients and 80 patients with IgA nephropathy were used as controls. In groups I and II, the following features were significantly different from those in the controls: spherical enlargement of mitochondria (MT) in proximal tubule cells, hypertrophy of proximal tubule cells and their nuclei, and thickening of both the proximal tubule basement membrane (TBM) and the glomerular basement membrane (GBM). Among the histological changes observed in group I, the thickness of the GBM and TBM indicated that the disease would lead to diabetic nephropathy. MT enlargement was positively correlated with nuclear and cytoplasmic enlargement of the proximal tubule cells in diabetic patients (p < 0.05), but was not correlated with other morphological changes or disease prognosis. Glomerular nodular lesions, glomerular sclerotic change, and cortical tubulointerstitial fibrosis became evident in groups III and IV. From the above, we concluded that MT enlargement and thickening of the TBM are possible causes of reduced active transport in the proximal tubules, causing microalbuminuria in diabetics, and initial impairment of post-tubule transport.


Appearance of Ulex europaeus agglutinin-1 and Griffonia simplicifolia agglutinin-1 binding sites on cancer cells in sigmo-rectal polyps. Ninety-three polypectomized cases from the sigmo-rectal region were examined by lectin histochemistry. On the apical surface, the UEA-1 binding sites were positive in 24/29 carcinomas and in 25/62 adenomas; while the GSA-1 binding sites were positive in 16/29 carcinomas and in 0/62 adenomas. In 2 non-neoplastic polyps, only one case was UEA-1 positive; none was GSA-1 positive. In neighbouring regions, adenomas adjacent to carcinomas were UEA-1 positive in 9/27 cases and GSA-1 positive in 3/37 cases. Thus, the GSA-1 binding sites were expressed more specifically on carcinomas. In the Golgi area, none of the polyps was UEA-1 positive while most of the cells showing GSA-1 positivity were apt to do so within the cells without showing GSA-1 positivity on the apical surface. There were no correlations between the positive rate of the lectin binding sites on the apical surface and the stage of cancer development or the histology of the adenoma on which a cancer developed. The meaning of this restricted appearance of the GSA-1 binding sites on the cancer cell surface was discussed in relation to observations previously reported in the literature.


An autopsy case of mitochondrial encephalomyopathy (MELAS) with special reference to extra-neuromuscular abnormalities. An autopsy case of a 37-year-old man with mitochondrial encephalomyopathy is reported. Ragged-red fibers and crystalline inclusions in mitochondria were revealed by biopsy of the striated muscle of the patient. Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) was diagnosed clinically. In addition to severe atrophy and degeneration of the generalized striated muscles and many foci of laminar necrosis of the cerebral cortex, the following abnormalities were observed: 1) hypertrophy of the myocardium, 2) fatty change of the liver, 3) focal sclerosis of the glomeruli and dilatation of the tubules of the kidneys, 4) hyalinous degeneration of the Langerhans' islands of the pancreas and 5) wavy change of the smooth muscle fibers of the muscularis propria of the gastrointestinal tract. We suggest that mitochondrial encephalomyopathy affects various organs and tissues, among which susceptibility of the muscular tissues--skeletal muscle, myocardium and smooth muscle--is high.


Diffuse Mallory bodies in the liver, diffuse Lewy bodies in the brain and diffuse fat replacement (lipomatous pseudohypertrophy) of the pancreas in a patient with juvenile Parkinson's disease. A 38-year-old male patient with the juvenile variant of Parkinson's disease, in whom onset had occurred at the age of 24 yr, was autopsied. There were no clear symptoms of pancreatic or hepatic insufficiency during the entire clinical course. The only notable features were a slightly delayed decrease of the blood glucose level in an oral glucose tolerance test, slightly elevated levels of serum alkaline phosphatase and serum lactate dehydrogenase, and episodic loose stools. Autopsy revealed uniform enlargement of the pancreas due to massive fat replacement (lipomatous pseudohypertrophy): the exocrine glandular elements showed marked atrophy and loss, while the islets of Langerhans were preserved. The liver exhibited a histology closely mimicking alcoholic hepatitis associated with the diffuse presence of Mallory bodies (MBs), possibly indicative of a disturbance of protein metabolism. The nervous system showed the diffuse presence of Lewy bodies (LBs) in the cerebrum in addition to the ordinary lesions of Parkinson's disease. Although the etiopathogenesis of none of these three lesions has been well elucidated, common epitopes of MBs and LBs have recently been demonstrated. Therefore, the present case study suggests that a specific underlying toxic agent may cause diffuse LBs in the brain on the one hand, and diffuse MBs in the liver and lipomatous pseudohypertrophy of the pancreas on the other.


An autopsy case of invasive pituitary adenoma (prolactinoma) with rapid fatal clinical course due to streptococcal meningitis. A 44-year-old male suffered epistaxis and headache of sudden onset and was diagnosed as having suppurative meningitis due to streptococci. Four days after the onset of symptoms, he died despite treatment with antibiotics. Destruction and ballooning of the sella turcica was revealed by a plain head X-ray examination during the clinical course. At autopsy, a massive tumorous lesion extended from the ballooned sella turcica to the paranasal cavities, nasopharynx and facial bone, and this had resulted in suppurative meningitis. The tumor was also disseminated to the basal skull. The tumor cells possessed prominent nuclear atypia and were immunohistochemically positive for prolactin. This was diagnosed as a case of pituitary adenoma with markedly invasive pathological findings and a rapid and fatal clinical course.


An autopsy case report of diffuse esophageal intramural pseudodiverticulosis. A case report of diffuse esophageal intramural pseudodiverticulosis (EIPD) we encountered at autopsy is described. The pseudodiverticula represented dilated excretory ducts of esophageal submucosal glands with squamous metaplasia of the epithelium. They contained keratin flakes, mucin and/or inflammatory cells which were mainly neutrophils. Submucosal chronic inflammation surrounding the glands was prominent. The findings suggested that the ductal dilatation resulted from obstruction of the ducts by inflammatory material, mucus and desquamated epithelium. To the best of our knowledge, this is the first autopsy report of diffuse EIPD in Japan.


A case of adenocarcinoma of the lung with a spindle cell component. We report a 60-year-old man, who was admitted to the hospital with complaints of cough and sputum. His chest x-ray showed an abnormal mass in the right upper lobe. After admission he noticed the painful gingival tumor. Right upper lobectomy and resection of the gingival tumor were performed. Their histological features showed that the tumor consisted of a papillary and tubular adenocarcinoma mixed with a component of spindle cells. Immunohistochemical study demonstrated a positive reaction in the epithelial component for keratin and epithelial membrane antigen, and not only these epithelial markers but also vimentin were expressed in some spindle tumor cells. Electron microscopic study confirmed the biphasic pattern, showing gland formation and undifferentiated cells. We diagnose this case as adenocarcinoma of the lung with a spindle cell component and the gingival tumor was metastatic. Autopsy showed that metastatic lesions were found in the left adrenal gland and in the left kidney. The tumor cells in the left adrenal gland were composed of spindle cells and the tumor in the left kidney showed gland formation. Immunohistochemical and electron microscopic findings of surgical and autopsy specimen suggest that this tumor is of epithelial origin, and the spindle cells are derived from immature mesenchymal cell transformation of epithelial cells.


Anorexia nervosa and bulimia: a prevalence study. We determined the prevalence of anorexia nervosa and bulimia in a large sample of students attending a secondary school on the island of São Miguel (Azores) using the Diagnostic Interview for Children and Adolescents, which enabled us to collect the information necessary to make DSM-III diagnoses. Although the prevalence of anorectic and bulimic behaviour was rather high, the partial syndrome of anorexia nervosa was found in only 0.48% of the students (0.76% for girls and 0.17% for boys) and the syndrome of bulimia in only 0.16% (0.30% of the girls; there were no boys with bulimia). The overall prevalence of eating disorders, including partial syndromes, was rather low (0.64%). These results stand in sharp contrast to reports that eating disorders are common and probably getting more common. The low prevalence found in the present survey is probably due to the absence of sociocultural pressures to control eating and weight.


Paroxetine and imipramine in the treatment of depressive patients in psychiatric practice. A total of 151 outpatients with endogenous or mixed endogenous and reactive depression were included in a 6-week double-blind study, with extension for up to 1 year, in psychiatric practice. The results showed trends in efficacy variables and a statistically significant difference in a benefit-risk ratio in favour of paroxetine (Seroxat, Paxil) compared with imipramine. Efficacy was largely maintained in both groups during long-term treatment. The frequency and severity of side effects in paroxetine patients declined markedly from short-term to long-term treatment, whereas changes in imipramine patients were less pronounced. Significantly more imipramine patients gained weight during long-term treatment. In conclusion, paroxetine is an effective and well tolerated antidepressant, well suited for outpatients in psychiatric practice.


Does case management reduce the rehospitalization rate? It was expected from deinstitutionalization that outpatient care could replace hospital care. But many empirical studies proved that the number of admissions to psychiatric hospitals rose when community-based care developed. This might be due to the lack of coordination and cooperation of extramural services. The concept of case management therefore originated in the last few years. In this study the effect of case management on the rehospitalization rate is examined by analyzing the data of 4 social-psychiatric services responsible for defined catchment areas. During the evaluation period of 2.5 years, 162 patients dismissed from psychiatric hospitals were referred to those services. For each of these index patients a matched control patient was identified, each identical in diagnosis, sex, age, living conditions and number of previous inpatient episodes. The results of a survival analysis show that there are no significant effects of case management on the rate of rehospitalization nor on the length of time in hospital in case of a rehospitalization.