Growth hormone secretion in patients with Turner's syndrome as determined by time series analysis.

Twenty-four-hour growth hormone (GH) profiles in 26 girls with Turner's syndrome were compared with those of 26 normally growing short children and 24 slowly growing short children. All children were prepubertal and below 12 years of age. A subgroup of 13 girls was treated with ethinyl estradiol and a 24-h GH profile was reassessed. In an additional group of 45 girls with Turner's syndrome (aged 6.7-18.9 years) the effect of age, spontaneous breast development and ethinyl estradiol treatment was studied. The profiles were assessed by Fourier analysis. The oscillatory activity and the mean 24-h GH concentration were similar in children with Turner's syndrome and the normally growing short children, in contrast to lower levels in the slowly growing short children. The periodicity of GH secretion was similar in all groups. In the longitudinal study, ethinyl estradiol treatment resulted in a significant increase in pulse amplitude, but not in periodicity. In the cross-sectional study there was no significant difference between the subgroups of girls with either presence or absence of breast development or ethinyl estradiol treatment. GH secretion was not significantly related to age, height in standard deviation score or height velocity. These data imply that there is no abnormality in GH secretion in girls with Turner's syndrome.


Effects of thyroid hormones on mitochondrial oxygen consumption in brown adipose tissue and heart from cold-exposed hypothyroid rats.

The present work measured brown adipose tissue and heart mitochondrial oxygen consumption in hypothyroid rats treated with replacement doses of T3, T4 or T4 plus iopanoic acid and kept at 4 degrees C for 24 h. Heart oxygen consumption in normal, untreated hypothyroid and T4-treated hypothyroid rats was unaffected by cold exposure. In rats treated with T4 plus iopanoic acid, rates of oxygen consumption were normal in those maintained at 4 degrees C as well as in those kept at room temperature, despite serum T3 concentration being significantly decreased. The cold-exposed T3-treated hypothyroid rats showed a marked decrease in oxygen consumption (p less than 0.02) and alpha-glycerophosphate dehydrogenase activity, a T3-dependent enzyme. Mitochondrial oxygen consumption in brown fat from normal (p less than 0.01), T4 (p less than 0.02) and T4 plus iopanoic acid-treated (p less than 0.01) rats rose more than twofold in response to cold. In the T3-treated group, oxygen consumption at room temperature was higher (p less than 0.02) than in any other group at similar temperatures. However, the T3-treated group showed no changes in oxygen consumption in response to cold, perhaps because this group reached the maximal response at room temperature. The untreated and the T3-treated hypothyroid rats (both groups devoid of T4) did not survive at 4 degrees C unless T4 or several-fold replacement amounts of T3 were administered. The data demonstrate the crucial role of T4 in thermogenesis during cold exposure.


Decrease of testosterone level during an experimental African trypanosomiasis: involvement of a testicular LH receptor desensitization.

To investigate gonadal disorders and changes of the testicular receptors occurring during the sleeping sickness disease (African trypanosomiasis), an experimental model was developed with 10-month-old rats infested by bloodstream forms of two variants of Trypanosoma brucei brucei (AnTat 1.1 A and AnTat 1.8). At the acute phase, three days after inoculation, the animals were sacrificed for estimating the serum levels of LH and testosterone and the number of testicular LH receptors. Considering a possible intervention of the stress during the infestation and to improve our investigations on gonadal imbalance related to trypanosomasis, levels of additional parameters [corticosterone, glucose and transaminases (glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase)] were determined. Stimulation testing with hCG was likewise assessed in infested rats to analyse the testicular testosterone response to gonadotropin. A significant decrease was demonstrated for serum LH and testosterone levels in the infested rats, as well as the loss of: (i) the testicular responsiveness to exogenous gonadotropin; (ii) the number of testicular LH receptors. Moreover, the remaining testicular receptors of infested rats showed an increase in their equilibrium association constant (Ka). Our study suggests that dysfunction of Leydig cells occurring during African trypanosomiasis is in part related to stress induced by the presence of the parasites.


Effects of growth hormone releasing hormone on insulin action and insulin secretion in a hypopituitary patient evaluated by the clamp technique.

The effect of growth hormone releasing hormone (GHRH-44) therapy on insulin action and secretion was evaluated in a hypopituitary patient after one month and one year of treatment. Hepatic and peripheral insulin action was studied with the hyperinsulinemic-euglycemic clamp in combination with [6,6-2H2]glucose tracer infusion. First and second phase insulin secretion was assessed with the hyperglycemic clamp. Prior to GHRH-44 therapy the hypopituitary patient had higher insulin mediated glucose disposal rate and lower basal and stimulated insulin concentrations by more than two standard deviations from the mean of a control group. Following therapy there was no change in basal hepatic glucose production; however, there was evidence of diminished peripheral insulin action. This was manifested by decreased insulin mediated glucose disposal during the hyperinsulinemic-euglycemic clamp, and increased insulin secretion during the hyperglycemic clamp. We conclude that GHRH-44 therapy in this patient was associated with decreased peripheral insulin action which was compensated for by increased insulin secretion.


Deformability of the erythrocyte membrane in patients with myelodysplastic syndromes.

One of the major determinants of erythrocyte survival is membrane deformability, and an important intrinsic parameter of membrane deformability is the shear elastic modulus (mu) with higher mu values corresponding to increased membrane rigidity. Using a micropipette technique, we determined the shear elastic modulus of erythrocytes from 21 patients with myelodysplastic syndromes (MDS). Ten thalassemic patients and 15 healthy subjects served as controls. The shear elastic modulus of MDS erythrocytes was very significantly increased in all the patients studied, reflecting the rigidity of the membrane; the value of mu was also significantly higher in comparison with thalassemic cells. These data point to a fundamental change in the mechanical properties of the erythrocyte membrane in MDS. Biochemical studies of the membrane composition are clearly needed.


Aggressive chemotherapy for acute leukemia relapsed after bone marrow transplantation: a second chance?

Eight patients, 5 with acute non lymphoid leukemia and 3 with lymphoid leukemia, were treated at relapse after bone marrow transplantation (BMT; 4 autologous BMT and 4 allogeneic BMT). Of these, 2 relapsed within 3 months after BMT (2 allogeneic BMT) and 6 (2 allogeneic and 4 autologous BMT) after more than 9 months after BMT. The 2 patients relapsing early showed no response to treatment and died. Five out of 6 patients relapsing late achieved complete remission (4 of them with intensive chemotherapy). Four patients are currently alive. Aggressive combination chemotherapy can produce long-term survival in selected patients relapsed after BMT.


Splenic megakaryocytopoiesis in primary (idiopathic) osteomyelofibrosis. An immunohistological and morphometric study with comparison of corresponding bone marrow features.

An immunohistochemical and morphometric study has been performed on splenic tissue of 10 patients with primary (idiopathic) osteomyelofibrosis (OMF) to determine characteristic features of megakaryocytopoiesis in myeloid metaplasia. Using the periodic acid-Schiff reaction (PAS) and particularly the monoclonal antibody CD61 (Y2/51), all elements of this cell lineage including precursors could be identified. In comparison with bone marrow specimens from our file material (40 patients with OMF, 15 control cases) which were processed in a similar way, megakaryocytes in the spleen revealed significant differences. These differences included smaller cell sizes, a disturbed nuclear-cytoplasmic ratio, and a conspicuous increase in the relative frequency of promegakaryoblasts. In conclusion, extramedullary megakaryocytopoiesis in OMF did not only show more pronounced abnormalities of differentiation, but also a higher degree of immaturity. Our finding of a significant accumulation of megakaryocytic precursors in the spleen as opposed to the bone marrow, corroborates the so-called filtration theory which has been introduced to explain the evolution of splenic myeloid metaplasia in OMF.


Felty's syndrome: favorable response to granulocyte-macrophage colony-stimulating factor in the acute phase.

We report a case of Felty's syndrome in which infectious complications due to severe neutropenia could be overcome by short-term treatment with recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF, 7 micrograms/kg/day s.c.). Leukocyte counts rose from 1,050/mm3 at presentation to 4,470/mm3 after 15 days of treatment. A flare-up of arthritis was not noted. Defects in granulocyte function and clinical improvement prior to leukocyte rise suggest that the beneficial effect of GM-CSF is mainly due to an improvement of granulocyte function.


Anemia and neutropenia in a case of copper deficiency: role of copper in normal hematopoiesis.

We present a patient who developed severe anemia and neutropenia after receiving parenteral nutrition for 2.5 years. The serum levels of copper and ceruloplasmin were low, and the bone marrow showed the presence of ringed sideroblasts and vacuolated immature cells. The administration of copper chloride by bolus injection led to a rapid improvement in anemia and neutropenia. The number of progenitor cells (colony-forming unit-granulocyte-macrophage and erythrocyte) present before the copper supplementation was well preserved. It is therefore suggested that copper enzymes play an important role in the maturation of hematopoietic cells.


11;13 translocation in acute nonlymphocytic leukemia.

In this paper, we report on a 9-year-old girl with acute nonlymphocytic leukemia (FAB-M5) with a rare chromosome abnormality, t(11;23)(q21;p11). Peripheral blood showed Hb 7.5 g/dl, WBC 3,600 cells/microliters (10% blasts), and platelet count 110 x 10(3) cells/microliters. The bone marrow aspirates showed normal cellularity with 36.7% blasts. On morphological characteristics, micromegakaryocytes were observed, and on chromosome examination the karyotype was shown to be 46,XX,t(11;13)(q21;p11) in all metaphases.


Primary adult T-cell lymphoma of the breast.

A case of primary adult T-cell lymphoma (ATL) of the breast is described. A 69-year-old woman presented with a painless, rapidly growing lump in her left breast. Staging procedures demonstrated no sign of generalized disease. Following a Patey's mastectomy, 10 courses of adjuvant chemotherapy (CHOP) were successfully administered. The light microscopic, immunohistochemical and molecular genetic analyses of the surgical specimen revealed a primary ATL. Seropositive mothers who breast-feed their children may facilitate the accumulation of T cells carrying HTLV-I in their breasts and thereby increase their risks of developing breast ATL.


Pearson's marrow-pancreas syndrome in 2 Turkish children.

Two unrelated infants, 1 female and 1 male, with Pearson's syndrome are presented. Both patients presented with severe macrocytic refractory anemia starting early in infancy. Investigation of the mitochondrial (mt), DNA showed that one of the patients had a 4,977 bp deletion, and the other had a 4.5 kb mtDNA deletion. It is concluded that Pearson's syndrome should be borne in mind in the differential diagnosis of refractory anemia especially when there are accompanying gastrointestinal disturbances and metabolic acidosis.


Myelokathexis and monocytosis in a patient with gastric cancer.

A 66-year-old patient developed leukocytosis, neutrophilia and monocytosis following surgery for gastric carcinoma. The polymorphonuclear cells showed a marked shift to the right and abnormally hypersegmented or pyknotic nuclei, whereas the monocytes were vacuolized. The bone marrow was hypercellular with an increased number of multilobed polymorphonuclear cells. This myeloid cell defect is compatible with the nuclear abnormalities described as myelokathexis. The combination of the nuclear abnormalities of the polymorphonuclear cells with persistent monocytosis suggests the possibility of a paraneoplastic variant of myelodysplasia.


Thyroid hormones influence perceptual processing in a visual search paradigm.

The mechanisms that mediate the effects of thyroid hormones on higher cognitive processes are not well understood. In the present experiments, event-related potentials (ERPs) and behavioral measurements were recorded in a visual search paradigm where a target item had to be detected in a number of distractor items. 10 healthy subjects were given a daily dose 300 micrograms thyroxine (T4) p.o. and recordings were made before and after 3 weeks of treatment. All subjects developed hyperthyroidism with a completely suppressed TSH (1.6 +/- 0.5 mU/l vs. non detectable), a significant increase in T3 (1.5 +/- 0.2 vs. 1.9 +/- 0.2 ng/ml). T4 (6.6 +/- 1.6 micrograms/dl vs 11.9 +/- 2.7 micrograms/dl) and sex-hormone binding globulin (2.9 +/- 1.1 vs. 3.8 +/- 1.3 micrograms/ml; all p less than 0.0005). Compared to the control group (n = 15), thyroid hormones improved controlled serial visual processing, as indexed by changes of the late positive ERP component and target detection hit rate (in both cases p less than 0.01), whereas parallel detection of salient features remained unchanged. The data suggest a differential impact of thyroid hormones on visual information processing.


Effects of thyroxine, triiodothyronine and reverse triiodothyronine on the neonatal hypothyroid rat cerebellum.

In order to develop a model of thyroid hormone action, we studied the effect of small doses of T3 and T4 on the development of the hypothyroid neonatal cerebellum of rat pubs. Using granulosa cell death at postnatal d15 (picnotic index) as a criterion of hypothyroidism, it was found that a single injection of 50 ng T3/10g bw or 180 ng T4/10 g bw would reduce the picnotic index to levels found in euthyroid rat cerebelli. We further tested if rT3, known to be an excellent blocker of deiodinase type 2 activity, would be able to block the effects of T4. 20 micrograms rT3/10g bw had to be given to be an effective inhibitor in vivo. This dose did not affect the potency of T4 and control experiments with rT3 alone indicated that rT3 was capable of reducing the picnotic index to euthyroid levels. It is speculated that rT3 might act at the nuclear receptor but also at the cell membrane.


Homeostasis of brain T3 in rat fetuses and their mothers: effects of thyroid status and iodine deficiency.

Faced with large variations in iodine, T4 or T3 supply, the fetal brain is able to maintain T3 homeostasis to a greater degree than apparent from changes in plasma and other tissues, such as the liver. Changes in the activity of 5'D-II play an important role in this homeostasis, although this does not exclude other regulatory mechanism(s), such as changes in type III (5D) activity, in uptake of the iodothyronines by the brain, or in cerebral iodothyronine turnover rates. T3 generated locally from T4 is more important than plasma derived T3 as determinant of the total T3 available to the brain throughout the life cycle of the rat. It is especially important during the fetal and neonatal phases of brain development, when the brain depends almost exclusively on the supply of T4. Fetal brain T3 homeostasis is maintained despite large fluctuations in the supply of T4. An excess of T3 also affects brain T3 to a lesser degree than it does other tissues. If present results are relevant to man, they suggest that overtreatment of mother of a congenital hypothyroid fetus with T4 is not likely to be harmful for the fetal brain. Treatment with T3 should be avoided, as it deprives the fetal brain of the main regulatory mechanism involved in homeostasis of brain T3, namely generation of T3 from T4.


The trace components--selenium and flavonoids--affect iodothyronine deiodinases, thyroid hormone transport and TSH regulation.

The trace elements iodine and selenium exert major control function on thyroid hormone homeostasis. Appropriate production, transport to target cells, activation of prohormones to yield receptor ligands, and metabolism resulting in the termination of the hormonal signals are influenced by these two trace elements but also by dietary compounds such as flavonoids. Flavonoids, ubiquitous secondary metabolites of plants and their synthetic derivatives such as EMD 21388 interfere with hormone binding to transthyretin and activation by the selenoenzyme Type I 5'deiodinase. The resulting alterations of free thyroid hormone fractions in serum effect pituitary feedback regulation, hormone action and elimination. Selenium dependent regulation of expression of Type I 5'deiodinase and glutathione peroxidase was studied in the porcine kidney epithelial cell line LLC-PK1 at the enzyme activity, protein and steady-state mRNA levels. A cellular hierarchy of selenite utilization with preferential incorporation into Type I 5'deiodinase compared to glutathione peroxidase was found under limiting selenite supply. These mechanisms together with hierarchic selenium redistribution between brain and endocrine organs might contribute to maintain thyroid hormone homeostasis during development and pathophysiological situations.


Characteristics of type III iodothyronine deiodinase.

Type III iodothyronine deiodinase (ID-III) catalyzes the inner ring deiodination of T4 to rT3 and of T3 to 3,3'-T2, representing an important pathway for the inactivation of thyroid hormone. High activities of this "oncofetal" enzyme are found in rat brain, skin and fetal intestine, rat and human placenta, chick embryo liver, monkey hepatocarcinoma cells, human colon carcinoma cells, and tadpole liver. ID-III shows substrate preference for T3 over T4; Km values are approximately 10-fold lower for T3 than for T4 but Vmax values are similar. In contrast to the marked ontogenic pattern of ID-III in different tissues, the enzyme shows little change under pathophysiological conditions, such as fasting and thyroid dysfunction. Brain ID-III activity is decreased in hypo- and increased in hyperthyroidism, but the changes are small. Reaction of brain and placenta microsomes with BrAc 125I-T3 results in extensive labeling of a 32 kDa protein (p32). However, the relationship of p32 with ID-III is not clear, since labeling of p32 is also observed in tissues without ID-III activity and is not inhibited with a large excess of substrate.


The movement of thyroid hormones in the central nervous system.

Thyroid hormones in the central nervous system (CNS) present a number of complexities which include a marked difference in hormone effects on the developing brain compared to the mature brain, extensive regional heterogeneity within the brain, and alternate ways by which the hormones gain entry to the CNS and its cells. Furthermore, most of the T3 found within brain cells is derived from the T4 that they have accumulated. This brief review concerns the movement of the thyroid hormones as they leave the bloodstream and make their way into and through the CNS. There are many sites for potential control of thyroid hormone transport into the central nervous system. The blood brain barrier and the choroid plexus may work in tandem as two parallel resistors subjected to different controls to maintain brain interstitial levels of thyroid hormone at near constant levels. Thyroid hormone may enter neurons directly from the interstitial fluid or indirectly from the glial cells. Nonetheless, both neurons, perhaps at the synaptosome, and glial cells are capable of transporting and concentrating thyroid hormones at physiological levels.


The role of transthyretin in the transport of thyroid hormone to cerebrospinal fluid and brain.

Cerebrospinal fluid (CSF) transthyretin (TTR), the main CSF thyroxine (T4) carrier protein in the rat and the human is synthesized in the choroid plexus (CP). After injection of 125I-T4 in the rat, radioactive T4 accumulates first in the CP, then in the CSF and later in the brain. We have shown that competitive inhibition of T4-TTR binding sites in the CP and CSF by a flavonoid results in a decrease in the radioactivity present in the brain after i.v. injection of 125I-T4, suggesting that T4 transported to the CSF via the CP is a significant pathway for the supply of thyroid hormones to the brain.


Cerebral expression of transthyretin: evolution, ontogeny and function.

This paper reviews studies on the synthesis and secretion of the thyroid hormone-binding protein, transthyretin by the choroid plexus. The secretion of transthyretin by the choroid plexus into the cerebrospinal fluid may have an important function in the transport of thyroxine from the blood to the brain. The transthyretin gene is expressed in the choroid plexus of most vertebrates and synthesis of this protein may have evolved in the brain before the liver.


Influence of thyroid hormone on brain gene expression.

Brain development in mammals is dependent on thyroid hormone. In the rat, the T3 receptor is present as early as the 14th day of fetal life and increases during the periods of neuroblast proliferation and oligodendrocyte differentiation. The mRNAs encoding the receptor isoforms can also be demonstrated by in situ hybridization, with different distribution of the alpha or beta forms. Expression of several genes was studied in hypothyroid animals during the neonatal period. The lack of thyroid hormone affects the expression of most oligodendrocyte genes in a time- and region-dependent fashion. The major role of thyroid hormone on myelin genes is on their timing of expression. Among the neuronal genes studied, thyroid hormone influences the expression of RC3, a brain specific gene encoding a protein kinase C substrate. Thyroid hormone is not require for the timing of expression of this gene, but is needed for its full expression both during the neonatal period and in adult animals.


Thyroid hormone effects on neuronal differentiation during brain development.

Neurite outgrowth and acquisition of neuronal polarity depend on microtubule assembly and this process is impaired when hypothyroidism is established at late fetal stages in the rat. Taking in account these observations the effects of thyroid hormone deficiency in the developing cerebellum were studied with probes for different tubulin isoforms and for two microtubule-associated proteins, tau and MAP2, which are specific for the axons and the dendrites, respectively. The results showed that thyroid hormone deficiency: 1) desynchronizes the spatio-temporal program of axonal and dendritic differentiation in the cerebellum. 2) Modifies the developmental pattern of expression of various tubulin isoforms. 3) Delays replacement of the immature tau variants by the mature forms. The adult variants of tau proteins specify adult and stable axons whereas the juvenile forms are expressed when axons are growing actively. According to these criteria the hypothyroid brain remains immature at stages when proper connectivity is normally established. Thyroid hormone appears therefore as an epigenic signal that synchronizes axonal and dendritic outgrowth, two major parameters of the construction of the neuronal network.


Maternal hypothyroxinemia and brain development: I. A hypothetical control system governing fetal exposure to maternal thyroid hormones.

Maternal hypothyroxinemia consequent on endemic iodine deficiency is associated with an increased incidence of neurological disorders in the offspring. Such correlations were originally postulated as reflecting direct effects of elemental iodine on fetal brain development during early pregnancy, it being generally believed that maternal thyroid hormones do not cross the placenta in significant amount in consequence of the presence of elevated concentrations of TBG in maternal blood. However TBG possesses the capacity to enhance T4 transport to particular target organs during pregnancy. This realization led us to hypothesize a) that maternal T4 is transported to the fetus, and is of crucial importance to early fetal development, and b) that TBG forms part of a control system specifically designed to maintain at an optimal level the T4 environment to which the developing fetus is exposed. Subsequent studies in rats demonstrated that maternal T4 traverses the placenta in significant amounts prior to the development of the fetal thyroid. Other studies have led us to suggest that one or more isoforms of HCG may be implicated in a feed-back system interacting with the hypothalamic/pituitary system governing maternal thyroid hormone secretion. Though our experimental work has primarily focused on the effects of thyroid hormones on the fetal brain, we believe it to be likely that fetal exposure to maternal hormones is under placental control, and that other components of this putative system are worthy of study.


Maternal hypothyroxinemia and brain development: II. Biochemical, metabolic and behavioural correlates.

Using a rat model, we have investigated the influence of maternal hypothyroxinemia throughout pregnancy on brain development in young and adult progeny. Although no consistent change was observed in whole brain total protein concentration, the subcellular distribution of protein was adversely affected. Isolation of glycoprotein from developing brain by concanavalin A-affinity chromatography and subsequent resolution by gel electrophoresis revealed the selective compromise of particular glycoprotein species. Furthermore, both control and experimental progeny expressed unique glycoprotein species which either persisted over the period studied or were transient. Calcineurin, a regulator of neurite elongation, was compromised in young progeny, as were a number of lysosomal enzymes (beta-D-glucosidase and aryl sulphatase). In adult progeny, the content of cerebroside sulphate (a major myelin galactolipid) was reduced in midbrain and paleocortex, and brain region-specific compromise was observed for acetylcholine metabolic enzymes. These changes were associated with alterations in behavioural output. We conclude that the availability of maternal thyroxine to the fetus may be a critical determinant for normal brain development and function.


Regulation of T3 production in the brain.

Intracerebral thyroid hormone metabolism is responsible for maintaining intracellular T3 levels within narrow limits. A coordinated regulation of brain T4 to T3 conversion and T3 degradation allows the brain to respond to changes in the availability of circulating T4 and thereby isolates the brain from environmentally influenced changes in thyroid hormone status. T4 to T3 conversion is regulated by dynamic increases or decreases in the cellular content of the enzyme that catalyzes this reaction that are due to changes in enzyme degradation not enzyme synthesis. Little is known about the molecular events regulating the other deiodinating enzymes in the brain. In addition to the dynamic regulation of T4 to T3 conversion, anatomical segregation of the deiodinases that activate and inactivate thyroid hormone contributes to the minimal contribution of circulating T3 to the intracerebral pool of bioactive thyroid hormone.


Mild iodine deficiency in fetal/neonatal life and neuropsychological performances.

The effects of mild/moderate iodine deficiency during the fetal/neonatal life on neuropsychological performances are still poorly defined. In this research we analyzed some parameters of cognitive performance with sensitive psychometric tests in children living in an area with moderate iodine deficiency. Each subject was submitted to the following neuropsychological tests: 1) a reaction time (RT) session, 2) the block design subtest of the WISC-R, 3) the coding subtest of the WISC-R. No significant difference was found between children with mild iodine deficiency and controls, for block design and coding tests. On the other hand controls had significantly faster RTs. Our data show that exposure to mild iodine deficiency in fetal/neonatal life does not affect general cognitive performance but influences the velocity of motor response to visual stimuli, which may be due to an alteration of the efficiency of the information processing mechanism.


Intellectual assessment of hypothyroid children detected by screening.

The IQ was studied in 50 children with CH. Normal distribution of IQ was found in patients detected by neonatal screening. Close relationship was observed between subnormal IQ values (less than 90) and undetectable serum Tg levels (less than 0.3 ng/ml). The intellectual outcome in children with CH depends considerably from the intrauterine hypothyroidism.


The possible etiological role of psychological disturbances in Graves' disease.

In the discussion of possible factors in the etiology of Graves' disease, stress has always played a major role. We investigated the possible influence of present depression (depressivity scale DS) and anxiety (State Trait Angstinventar STAI X1) on peripheral lymphocyte subpopulations in 10 patients with Graves' disease. The tests were done in hyperthyroidism and after 2-4 months in stable euthyroidism. Parallel to the psychometric testing, peripheral lymphocyte subpopulations were investigated. Elevated anxiety as a constant personality trait was investigated with the State Trait Angstinventar STAI X2 in 19 hyperthyroid patients with Graves' disease. 5 of the 10 patients had a pathological T4:T8 ratio and very high raw values for present anxiety (mean = 53,8; STAI X1), as well as a a high percentile for depression (median 93,1; DS). The other 5 patients with a normal T4:T8 ratio had much lower values for anxiety (mean = 37,8; STAI X1) and depression (median 78,4; DS). In those patients, the T4:T8 ratio remained normal in stable euthyroidism, while the values for anxiety and depression decreased. This also happened in the patients with a formerly pathologic T4:T8 ratio. However, the pathologic T4:T8 ratio persisted in those patients. The STAI X2 percentage ranking for the 19 hyperthyroid patients was 76,5. The value for healthy people is 55,5. Therefore a significantly elevated anxiety--representing a constantly elevated internal psychological stress--seems to be present in patients with Graves' disease. Since psychological stress is known to influence the immune system, such a constant personality trait could be a predisposing factor for Graves' disease.(ABSTRACT TRUNCATED AT 250 WORDS)


Integration of thyroid hormones with hypothalamic factors on pituitary TSH secretion.

A study employing a newly developed fourth generation immunometric serum TSH assay (assay limit 0.001 mu/l was performed to determine the temporal pattern of inhibition of serum TSH in response to a maximal suppressive dose of thyroid hormone (T3, T4 and TRIAC) as compared to the pattern produced by dopamine (DA) and dexamethasone (DEX). Mean onset of inhibition was 24, 48 and 68 minutes for thyroid hormone, DA and DEX, respectively. The inhibitory pattern was uniform and reproducible for the same or different individuals if data were normalized respective to basal TSH values. Inhibitory pattern with thyroid hormone formed two distinct log linear functions: A rapid phase (phase 1) spanning 48 minutes to 24 hours and a slower phase (phase 2) bridging 24 to 1,000 hours. A diurnal variation in phase 1, but not in phase 2 suppression, was observed. A phase 1 response was also produced by DA and DEX but not phase 2. Low dose TRH infusion studies indicated that thyroid hormone and DEX inhibited thyrotroph response at or beyond the TRH receptor, while DEX appeared to inhibit endogenous TRH secretion. No additive effects of DA or DEX on T3 inhibition were seen in phase 1. These studies provide new insight into the mechanism by which these endocrine factors complementarily regulate TSH secretion in man.


Maturation of pituitary-thyroid function in the anencephalic fetus.

The recent availability of both cordocentesis and ultrasensitive/highly specific immunometric assays for TSH and its subunit determination along with direct "two-step" assays for free thyroid hormone measurement, prompted us to study the maturation of hypothalamic-pituitary-thyroid axis in normal and anencephalic human fetuses from 17 to 26 weeks of gestation. In addition, TSH bioactivity was measured as cAMP accumulation in CHO cells transfected with recombinant human TSH receptor and TSH carbohydrate structure was studied by lectin chromatography. In both normal and anencephalic fetuses, circulating TSH and FT4 levels significantly increased from 17 to 26 weeks of gestation. Circulating FT3 concentrations were very low (0.5-3.1 pmol/l), while alpha-SU levels were very high (20-417 mg/l). Both FT3 and alpha-SU levels did not change from 17 to 26 weeks of gestation and, again, no differences between normal and anencephalic fetuses were recorded. Circulating TSH from both normal and anencephalic fetuses showed an enhanced bioactivity and was more retained on the lectin column than adult TSH, thus indicating that molecules with different carbohydrate structure are circulating during fetal development. In conclusion, the present data demonstrate that the absence of the hypothalamus does not compromise the maturation of pituitary-thyroid function and that the mechanisms underlying the secretion of TSH molecules with elevated bioactivity and different structure of glycosylated chains are not dependent on hypothalamic neuroendocrine control.


Regulation of hypothalamic TRH production and release in the rat.

Thyrotropin-releasing hormone (TRH) is produced in the hypothalamic paraventricular nucleus (PVN) as a 255-amino acid precursor (pro-TRH) with 5 TRH progenitor sequences. Pro-TRH is enzymatically processed to yield TRH and other peptides, which are transported to the median eminence and released into hypophysial portal blood. To elucidate the role of TRH in the control of thyroid function, we studied hypothalamic TRH synthesis and release in many conditions. TRH synthesis and release were assessed by pro-TRH mRNA measurement, and by sampling portal blood or push-pull perfusate, respectively. Destruction of the PVN reduced TRH and TSH secretion dramatically, while electrical stimulation of this nucleus enhanced their release. Hence, the PVN is important for normal TSH secretion. TRH synthesis and release decreased in hyperthyroid rats, but increased in hypothyroid rats. The magnitude of these changes, however, was small compared with alterations in TSH, suggesting that the feedback of thyroid hormones on TSH release is mainly exerted at the pituitary level. TRH synthesis and release increased during cold exposure, and decreased during starvation and diabetes. Thus, altered thyroid function during cold exposure, diabetes and starvation seems due to modified hypothalamic TRH synthesis and release.


Effects of selenium and iodine deficiency on iodothyronine deiodinases in brain, thyroid and peripheral tissue.

Long term nutritional selenium (Se) deficiency had only marginal effects on the thyroid T4 and T3 content and on the activity of the selenoenzyme type I deiodinase (5'D-I) in the thyroid gland. These findings reveal a remarkable resistance of the thyroid to Se-deficiency which may substantially contribute to the observed maintenance of T4 and T3 levels in circulating blood. In contrast to its maintained thyroidal activity, 5'D-I in peripheral tissues like liver and kidney was strongly decreased by Se-deficiency. The observed decrease of type II deiodinase (5'D-II) in the cerebral cortex of Se-deficient rats was obviously caused by the suppressing regulatory effect of elevated cortex T4 concentrations. The severalfold 5'D-II enhancement in iodine depleted animals was not abolished by additional Se-deficiency, suggesting that brain type II deiodinase is not a selenoenzyme. The role of selenium for cortex type III 5-deiodinase, which was moderately decreased in selenium as well as iodine-deficient rats, awaits definite evaluation by further studies. The different responsiveness to thyroidal and hepatic 5'D-I to Se restriction is further evidence for priorities in the selenium supply to different tissues.


Radioimmunoassay of thyrotropin-releasing hormone in euthyroid subjects and in patients with thyroid diseases.

An episodic pattern of fluctuation in serum TRH level was demonstrated in euthyroid males. It is suggested that these rises in serum TRH-IR are due to its pulsatile hypothalamic release, however, it must be remembered that a high proportion of circulating TRH is derived from extrahypothalamic sources. The conception that the TSH surge during late evening is secondary to an increased TRH release could not be proved in the present study. In the euthyroid and primary hypothyroid groups the mean values of serum TRH-IR did not differ, while its level was slightly, but not significantly lower in hyperthyroid patients. The evaluation of a single TRH determination is impeded by the short half-life, low serum level and its production in extrahypothalamic sites, too.


Monoamine regulation of prolactin and TSH secretion in hypothyroidism.

Dopaminergic and serotoninergic systems are involved in regulation of prolactin (PRL) and TSH secretion. About 10% of patients presented because of an galactorrhea and hyperprolactinemia (HP) have uncompensated primary hypothyroidism (PH). Two groups of patients were investigated using metoclopramide (MCP, DA antagonist, 10 mg i.v.), cyproheptadine (serotonin antagonist, 4 mg per os) and TRH tests. Group A consisted of 12 females with PH and hyperprolactinemia (HP). Group B presented 4 females with PH, HP and pituitary microadenoma on CT-scan. In control group of healthy euthyroid women basal PRL and TSH levels were in the normal range and statistically significant increase of both hormones was observed after MCP and TRH injections. Marked increase of basal TSH and PRL levels was found in both clinical groups. In contrast to control group no TSH reaction in MCP test was observed. PRL response to MCP was declined in group B versus group A. Cyproheptadine inhibited TSH secretion in patients with HP and PH, while this effect was absent in control group. TRH stimulated TSH and PRL response in group B was declined. Presented data shows that HP in PH may be due to the presence of subclinical microadenoma made manifest by hypothyroid state and/or due to disturbances in monamine control of PRL and TSH secretion.


The pituitary control of rat thyroxine binding globulin.

Thyroxine-binding globulin (TBG) is in the rat a developmentally regulated protein, actively synthesized in postnatal developing pups and in aging animals, but undetectable in adults. Experimental depletion of thyroid hormones (TH) in adults by thyroidectomy (Tx) or by hypophysectomy (Hx) results in marked reexpression of TBG synthesis. T3 replacement in both cases antagonizes this effect, though only moderately in Hx rats. These observations point to a regulatory pathway of TBG synthesis common to TX and Hx rats, characterized by an inverse relationship between TBG and TH levels. However, along with this thyroid-dependent TBG regulation, important differences between Tx and Hx rats are evidenced, pointing to specific pituitary factors of TBG control. The most striking difference concerns the effect of growth hormone (GH) replacement: the TBG of Tx rats is not affected, in contrast to that of Hx rats which is further increased by GH administration. The TBG response of the GH-treated Hx rats, which is strongly resistant to inhibition by T3, might involve deshomeostasis of GH-controlled functions not necessarily linked to the thyroid, e.g. the pancreatic functions regulating carbohydrate or lipid metabolism. In the light of these studies, it may be envisaged that the high surge of rat TBG during postnatal development involves a transient sensitivity of the TBG gene to stimulation by endogenous GH, and that this sensitivity lasts until functional maturity of the hypothalamic-pituitary-thyroid axis has been achieved.


Thyroid autoimmunity and neuropsychological development.

Thyroid autoimmunity may affect neuropsychological development by interfering with the fetal and/or neonatal thyroid status; indeed, both hypo- and hyperthyroidism during the fetal-neonatal life may be associated with a subsequent impairment of intellectual and psychomotor performances. Maternal thyroid status during early pregnancy, and in particular hypothyroidism due to autoimmune thyroiditis, can also affect the fetal neurological development. Finally, anti-thyroid drugs used to control hyperthyroidism in pregnant women with Graves' disease have been widely investigated for their possible effect on the intellectual development of the offspring.


Antidepressants and thyroid hormone levels.

We assessed the effect of treatment with the tricyclic antidepressant, desipramine, on peripheral thyroid hormone levels in 28 severely depressed patients. Only those whose depression responded showed a decrease in their thyroxine levels without alteration of other thyroid function tests. In a second study involving 38 depressed patients, we observed an increased response to antidepressant treatment with the addition of triiodothyronine but not equivalent doses of thyroxine (T4). The finding is consistent with the decreases in plasma T4 levels which accompany an antidepressant response to desipramine.


Thyroid hormones and depressive illness: implications for clinical and basic research.

It has been well-known for at least 100 years that both hypo- and hyperthyroidism may cause almost any psychiatric symptom, depending on the severity of the illness. No thyroid disorder, however, induces symptoms that are specific for a psychiatric disorder. Laboratory tests show depressed patients to be euthyroid. Any abnormalities that have been found, such as slightly elevated T4 levels or decreased T3 or TSH concentrations, have frequently failed to be replicated and do not fit any endocrinological diagnosis. They could reflect either "intervening factors" such as stress, methodological problems or a disturbance of central thyroid hormone metabolism. All antidepressant therapies (antidepressant drugs, carbamazepine, lithium, electroconvulsive therapy and sleep deprivation) have a marked influence on peripheral thyroid hormone levels. In particular, decreases in serum T4 and rT3 levels are often correlated to antidepressant response, suggesting that an effect on central thyroid hormone metabolism is involved in the as yet unknown mechanism of action of these therapies. Indeed, animal studies have shown that antidepressants do affect deiodinase activities and T3 and T4 concentrations in rat brain. However, the effects are highly area specific and dependent on the drug administered and the time of day at which the investigation was conducted. Although the mechanism of thyroid hormone action on CSF signal transduction is as yet unknown, effects on "general CNS functions" such as second messengers, G-proteins or calcium homeostasis seem more likely than specific effects on the different receptor systems.


Multimodal sensory and motor evoked potentials in a two-year follow-up study of MS patients with relapsing course.

Serial recording of multimodal sensory (pattern reversal visual, brainstem auditory, median and tibial somatosensory) and motor evoked potentials during a 2-year period was performed on a group of 25 patients with relapsing multiple sclerosis. A new, 10-degree evoked potentials abnormality scale was introduced. In contrast to the insignificant common trend of both the mean individual EP latency parameters and the mean expanded disability status scale and evoked potentials abnormality scale to deteriorate the changes in both expanded disability status scale (p less than 0.05) and evoked potentials abnormality scale (p less than 0.01) were significant using a 1-point criterion for change and non-parametric testing. Changes in both scales differed in about 50% of patients; contrary to bidirectional changes in the clinical scale, no improvement in the evoked potential scale was found. The introduction of an evoked potentials abnormality scale based on separate cut-off step-like criteria may increase the robustness of evoked potential changes due to the activity of the disease in longitudinal studies.


Influence of caffeine, sweating and local hyperemisation on "Marstock" thermotesting.

Marstock thermotesting evaluates A-delta- and C-fiber functions. To optimize this method, intraindividual variations of vasodilatation, blood flow and sympathetic activity probably biasing thermotest results were imitated by exogenous stimuli which strongly exaggerated these intraindividual variations. In 20 healthy subjects, warm (WT), cold (CT), and heat-pain (HT) thresholds were determined in the morning at the thenar (th), the volar wrist (wr), and behind the malleolus internus (mi). Thresholds at the thenar and the volar wrist were compared with those during severe sweating induced by Minor's test, and to those measured when sympathetic activity had been increased by the ingestion of a high dose of caffeine (0.5 g). Furthermore, the intraindividual variation of local capillary blood flow and vasodilatation was imitated by a rubefacient liniment (Forapin) applied to the three sites. After a local hyperemisation had been induced thermal thresholds were measured and compared to those measured without any stimulation. Local hyperemia did not influence thermal thresholds significantly. Sweating only lowered cold thresholds at the thenar significantly and only slightly raised warm and heat-pain thresholds at the thenar. Caffeine significantly lowered warm thresholds and raised heat-pain thresholds at the thenar. To conclude, the tested exogenous interferences do not disturb thermal perception markedly, especially when testing is not performed at the thenar, but at the volar wrist and when the testing-procedure and parameters are standardised.


Epilepsy and anomalies of neuronal migration: MRI and clinical aspects.

Neuronal migration disorders are the result of disturbed brain development. In such disorders, neurons are abnormally located. In diagnosing these conditions, magnetic resonance imaging is superior to any other imaging technique. This enables us to improve our knowledge of the clinical correlates of neuronal migration. With reference to migrational disorder, a retrospective study of all 303 patients with epileptic seizures referred for magnetic resonance imaging during a 3-year period was performed, 13 patients (aged 12-41, mean age 27) were identified. They represent 4.3% of the entire study group. Of the patients with known epilepsy, 6.7% and of the mentally retarded, 13.7% had migrational disorders. Four patients had schizencephaly as the dominant finding, one was classified as hemimegalencephaly, 2 had isolated heterotopias, and 6 had localized pachy- and/or poly-microgyria. The clinical pictures are complex. Ectopias of grey matter are recognised foci of epilepsy, but from an epileptological and a clinical viewpoint little attention has been given to these disorders. The present study shows that malmigration is not rare in epilepsy patients, especially not in the mentally retarded.


Driving with Parkinson's disease. A controlled laboratory investigation.

The part played in traffic safety by illness or disability is unknown, as is the identity and degree of the disorders which necessitate the use of driving aids or completely incapacitate a person from driving. By means of a mock car, 28 persons suffering from Parkinson's disease were compared with 109 healthy controls. Only patients in presumed optimal drug regimen and without complicating disorders were included in the study group. The main results were failure to react to stimuli on several occasions, a high frequency of erroneous reactions in particular directional errors, reduced strength and speed of movement and increased reaction times. Typically the latter would entail a prolongation of the reaction distance with more than 1/3, i.e. 6 m when driving a car at a speed of 80 km/h. The Webster score proved to be an unreliable predictor of the results of the mock car test, and the UPDRS is suggested for future studies.


Is the prevalence of Parkinson's disease in New Zealand really changing?

The prevalence of idiopathic Parkinson's Disease (IPD) in Dunedin, New Zealand on 31st July 1990 was 110.4/100,000. When corrected to a standard population based on the 1960 U.S. census, the prevalence fell to 76.0/100,000 due to changes in the age structure of the population. The corrected prevalence in Wellington (another New Zealand city), in 1962 was 99.6 (before the introduction of levodopa), and in Aberdeen, Scotland in 1984 was 102.7. The principal difference was fewer people under 65 years of age in our study. Case finding methods and diagnostic criteria were similar in all three studies, and case ascertainment was adequate. Under representation of younger people could be due to either a lower incidence rate or poorer survival due to treatment with high doses of levodopa compounds. Prospective research is required to explain our findings.


A prospective double-blind clinical trial, comparing the sharp Quincke needle (22G) with an "atraumatic" needle (22G) in the induction of post-lumbar puncture headache.

Posture-dependent, post-lumbar puncture headache is most likely caused by continuous leakage of cerebrospinal fluid through the dura mater perforation with a consecutive downward sagging of the intracranial content and an irritation of pain-sensitive structures of meninges and blood vessels. A psychogenic co-factor may also play a role. It is generally acknowledged that the incidence and intensity of the headache correlate significantly with the diameter of the needles used. A second factor, the shape of the needle point plays a crucial role as is shown in our prospective, double-blind, clinical trial with 75 patients: employment of the "atraumatic" Sprotte needle with a rounded off point significantly reduced the incidence of post-puncture headache from 36% to 4%. Beside the discussion of pathogenic factors, remarks on a rational therapy are made.


Effect of physical exercise on mortality in patients with Parkinson's disease.

Public health nurses visited and followed up for more than one year 438 patients with Parkinson's disease living in Osaka. The follow-up period averaged 4.1 years, during which 71 deaths were observed. The patients were classified according to the degree of physical exercise they performed, and the ratios of observed to expected deaths were calculated. The exercising group showed the lowest ratio of 1.68 (1.45 for patients able to walk independently, and 1.89 for those could not) while all patients exhibited a ratio of 2.47. Multivariate analysis using Cox's proportional hazard model, adjusted for age, sex, walking ability and duration of disease at study entry, showed that, compared with the exercising group, the non-exercising patients had a hazard ratio of 1.83.


Vibratory stimulation increases and decreases the regional cerebral blood flow and oxidative metabolism: a positron emission tomography (PET) study.

The aim of this study was to examine the hypothesis, if the activation of some cerebral structures due to physiological stimulation is accompanied by deactivations of other structures elsewhere in the brain. A vibratory stimulus was applied to the right hand palm of healthy volunteers and the regional cerebral blood flow (rCBF) and regional cerebral oxygen metabolism (rCMRO2) were measured with positron emission tomography (PET). Regional analysis and voxel-by-voxel plots indicated that the stimulation induced increases and decreases of the rCBF were coupled to increases and decreases of the rCMRO2. The increases were localized in the left primary somatosensory area (SI), the left secondary somatosensory area (SII), the left retroinsular field (RI), the left anterior parietal cortex, the left primary motor area (MI), and the left supplementary motor area (SMA). The decreases occurred bilaterally in the superior parietal cortex, in paralimbic association areas, and the left globus pallidus. The increases and decreases of the rCBF and rCMRO2 were balanced in such a way that the mean global CBF and CMRO2 did not change compared with rest. We conclude that the decreases of the cerebral oxidative metabolism indicated regional depressions of synaptic activity.


Myasthenia gravis in Hong Kong Chinese. 2. Paediatric disease.

In a study covering 85% of the population of Hong Kong, 39% of all myasthenia gravis (MG) patients, i.e. 103 individuals (54 girls and 49 boys) were found to have had MG with onset before puberty. Two patients had transient neonatal MG, 20 had early onset juvenile MG and 81 had late onset juvenile MG. Restricted ocular MG occurred in 71% of patients and the remainder had generalised MG. The median age at onset was 4 years. Complete remission occurred in 34 patients (34%), a good response in 14 (14%), and fair response in 32 (32%). The clinical course remained static in 16 patients (16%) and 3 patients deteriorated. Two patients died, 1 with myasthenic crisis and the other with cholinergic crisis. All patients, except 2 with neonatal MG, were initially treated with anticholinesterase, but 24% also required steroid therapy. Thymectomy was performed for 12 patients, of whom 5 (42%) showed marked improvement. Thymic histology was normal in 3, showed hyperplasia in 6, non-invasive thymoma in 1 and involution in 2. The most commonly associated disease was Graves' disease which occurred in 7 patients (7%).


Antibodies to Borrelia burgdorferi in patients with carpal tunnel syndrome.

In a study of 94 consecutive patients with neurophysiologically verified carpal tunnel syndrome (CTS) 7/94 had IgG and 0/94 IgM serum titers to Borrelia burgdorferi above the 98th percentile value of age and sex matched controls (n = 127). The difference in prevalence of positive IgG serum titers in patients, compared to controls, was not statistically significant. Even in patients, living in an area, highly endemic for Lyme borreliosis, routine serological screening for borrelia infection does not seem indicated in the investigation of CTS.


Slowly progressive limb-kinetic apraxia with a decrease in unilateral cerebral blood flow.

We report two patients with slowly progressive motor disorders, whose principal manifestations were asymmetric limb-kinetic apraxia and muscle rigidity. In both patients MRI revealed no responsible lesion, whereas single photon emission computed tomography (SPECT) showed a decrease in cerebral blood flow (CBF) in the unilateral hemisphere. One patient with mainly right-sided apraxia had a decreased CBF in the left central region between the frontal and parietal cortices, and the other patient with left-sided apraxia in the right parietal cortex. In agreement with asymmetric clinical symptoms, the regional CBF decrease in the unilateral cortical areas including the frontal and parietal cortices may suggest a degenerative disease, presumably diagnosed as having cortico-basal degeneration.


Dystrophin or a "related protein" in Duchenne muscular dystrophy?

Previously we have shown low levels of dystrophin immunoreactivity in muscle from patients with DMD. According to the "frame-shift hypothesis" DMD muscle should not synthesize any dystrophin through to the C-terminus and it has been suggested that the protein detected is not dystrophin, but a related autosomal homologue. We have labelled serial sections of DMD muscle with specific monoclonal antibodies to the amino, rod and C-terminal domains of dystrophin and find labelling on the same individual fibres, allowing us to conclude that the protein detected is Xp21-encoded dystrophin. This has an impact on the interpretation of myoblast transfer experiments. The abundance (on blots) of "C-terminal dystrophin" appears lower than "rod dystrophin" in both BMD and DMD.


Systemic interferon-alpha in the treatment of HTLV-I-associated myelopathy.

Treatment with interferon-alpha (IFN-alpha) was undertaken in 16 patients with human T-lymphotropic virus type I-associated myelopathy (HAM). All patients had progressive spastic paraparesis before treatment. Twelve patients were enrolled in an open therapeutic trial with a dose of 3.0 x 10(6) IU/day of IFN-alpha and 4 in a randomized, double-blind, multidose (3.0 x 10(6), 1.0 x 10(6) or 0.3 x 10(6) IU/day) trial. IFN-alpha was injected intramuscularly for 28 days. Eight of 12 patients enrolled in an open trial and 2 patients receiving a dose of 3.0 x 10(6) IU/day of IFN-alpha in a randomized trial showed clinical improvements during and after the treatment. The results showed that, although not for all patients, systemic IFN-alpha with a dose of 3.0 x 10(6) IU/day is effective in the treatment of HAM.


Evidence for an electrically silent, neurogenic fluid secretion in the rat jejunum in vivo.

The aim of this study was to evaluate the mechanism behind neurogenic fluid secretion in the rat jejunum. In vitro, short-circuit current (SCC) and potential difference (PD) were measured with the conventional Ussing technique. In vivo, electric parameters and net fluid transport (NFT) were simultaneously recorded with two different techniques. In separate in vivo experiments alkaline secretion (As) was estimated. In vitro, the chloride channel blocking substance 5-nitro-2(-3-phenylpropyl-amino)benzoic acid (NPPB) and the loop diuretic substance furosemide (F) inhibited SCC, whereas the carbonic anhydrase inhibitor acetazolamide (Ace) lacked effect. Noradrenaline inhibited SCC and this effect was antagonized by NPPB and F. In vivo, cholera toxin induced a parallel increase in PD/SCC and fluid secretion. Conversely, mesenteric nerve stimulation (MNS) or administration of the nicotinic antagonist hexamethonium (Hx), concomitantly inhibited PD/SCC and fluid secretion. However, there was a poor correlation between the magnitudes of these effects. F inhibited SCC in vivo and also the SCC-effect of MNS. However, F had no effect on fluid secretion in vivo, nor on the NFT-effect of MNS. Jejunal As was stimulated by cholera toxin and MNS significantly inhibited As. The present results challenge the current view on the role of electrogenic chloride secretion in intestinal secretion. Alternative mechanisms are tentatively discussed.


Contractions induced by angiotensin I, angiotensin II and bradykinin in isolated smooth muscle from the human detrusor.

In isolated human detrusor preparations angiotensin (At)II 10(-9)-10(-5) M caused concentration-dependent contractions. The contractile effect was immediate, and had an amplitude which at the highest concentration used, 10(-5) M, reached 103 +/- 16% of the mean contraction produced by K+ 124 mM (27.6 +/- 1.4 mN). The AtII effect was completely blocked by saralasin 10(-6) M, but was not affected by pre-treatment of the preparations with captopril or enalaprilate. There was a marked tachyphylaxis to the actions of the peptide. AtI (10(-8)-10(-5) M) also caused contractions which were rapidly developing, and subject to a marked tachyphylaxis. At a concentration of 10(-5) M, the mean amplitude was 66 +/- 9% of the K(+)-induced contraction. The contractions were blocked by saralasin 10(-6) M, but not by captopril or enalaprilate 10(-5) M. In contrast, contractions produced by AtI in rabbit mesenteric arteries were practically abolished by the angiotensin converting enzyme (ACE) inhibitors. The contractions induced by both AtI and AtII were practically abolished after pre-treatment in a nominally calcium-free Krebs solution. However, blockade of L-type calcium channels by nifedipine 10(-6) M reduced the responses to both AtI 10(-6) M (by 38 +/- 4%) and AtII 10(-6) M (by 39 +/- 7%), but never abolished the contractions. Bradykinin (Bk; 3 x 10(-8)-10(-5) M) had a contractile effect in detrusor preparations which varied widely between strips. At a concentration of 3 x 10(-6) M, a maximum was reached amounting to 30 +/- 10% of the K(+)-induced contraction.(ABSTRACT TRUNCATED AT 250 WORDS)


Renal response to volume depletion and expansion in Milan hypertensive rats.

In previous studies on Milan hypertensive (MHS) rats, we found an impaired tubuloglomerular feedback (TGF) response before, during and after development of hypertension. In the present study MHS rats and rats of the Milan normotensive strain (MNS) were investigated after 24 hours of volume depletion (VD) and subsequently after 5% isotonic volume expansion (VE) with respect to whole kidney function, interstitial hydrostatic (P(int)) and oncotic (IIint) pressures, stop-flow pressure characteristics of TGF and changes in early proximal flow rate in response to increased loop of Henle flow. MHS rats had higher mean arterial blood pressure (Pa) than MNS rats (129 vs. 101 mmHg) both after VD and after subsequent VE. No difference in glomerular filtration rate (GFR) was found. Both strains had a low urine flow rate (approximately 1.5 microliters min-1) during VD, which increased fourfold after VE. The interstitium was significantly more dehydrated in MHS, as indicated by a more negative net interstitial pressure (P(int)-IIint than in MNS (-1.3 +/- 0.3 vs. +/- 0.0 +/- 0.5 mmHg) after VE. The TGF mechanism was more activated in MHS during volume depletion, as indicated by a larger drop in stop-flow pressure (Psf) in response to loop of Henle perfusion (7.1 +/- 0.7 vs. 4.7 +/- 0.2 mmHg, P less than 0.05). However, during VD the loop of Henle flow that elicited half maximal response in Psf, the turning point (TP), was equally low in MHS and MNS (13.5 +/- 0.6 and 14.3 +/- 0.4, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)


Effects on renal sodium and potassium excretion of vasopressin and oxytocin in conscious dogs.

Renal effects of arginine vasopressin and oxytocin were studied in conscious dogs, made water-diuretic by a waterload equivalent to 2% of body weight. Body water and content of sodium were maintained by separate servo-controlled infusions. Peptides were infused for 60 min at rates of 50 pg kg-1 min-1 (arginine vasopressin) or 1 ng kg-1 min-1 (oxytocin), either separately or combined. Infusions increased plasma arginine vasopressin to 1.9 +/- 0.2 (arginine vasopressin alone) and 1.8 +/- 0.3 pg kg-1 (arginine vasopressin plus oxytocin and plasma oxytocin to 72 +/- 5 (oxytocin alone) and 77 +/- 8 pg ml-1 (oxytocin plus arginine vasopressin). Arginine vasopressin or arginine vasopressin plus oxytocin increased urine osmolality similarly by a factor of 13, decreased urine flow to between 5 and 7% of control and decreased free water clearance. Oxytocin reduced urine flow and free water clearance and increased urine osmolality by a factor of 2. Oxytocin and arginine vasopressin separately increased excretion of sodium from 4 +/- 2 to 15 +/- 6 mumol min-1 and from 7 +/- 4 to 25 +/- 13 mumol min-1, respectively. Arginine vasopressin plus oxytocin led to a pronounced natriuresis (13 +/- 4 to 101 +/- 27 mumol min-1). Arginine vasopressin and arginine vasopressin plus oxytocin increased the excretion of potassium by a factor of 2.5. Oxytocin and arginine vasopressin plus oxytocin increased urinary Na+/K+ ratio by a factor of 3.7.(ABSTRACT TRUNCATED AT 250 WORDS)


Three years' experience with levonorgestrel-releasing intrauterine device and Norplant-2 implants: a randomized comparative study.

A randomized comparative study of levonorgestrel-releasing intrauterine device (LNG-IUD) and Norplant-2 implants was carried out in 200 women for 36 months. Three thousand one hundred woman-months of use were observed with each device. Only one pregnancy occurred in users of LNG-IUD at the 12th month of use. The change in bleeding pattern was the most frequent reason for discontinuation. The discontinuation rate for irregular bleeding with Norplant-2 was 17.3 and 26.8 at 24 and 36 months, respectively, as compared to 3.3 with LNG-IUD at both 24 and 36 months. The differences were statistically significant. Removal for amenorrhea and pain only occurred in acceptors of LNG-IUD. About 20-40% of women using Norplant-2 had prolonged bleeding through 36 months. The percentage of amenorrhea in LNG-IUD was the highest (29.3%) at the end of two years of use. More than 97% of subjects reported satisfaction with the methods used by themselves.


Assessing potential demand for Norplant implants in Sri Lanka.

This study assesses potential demand for Norplant implants using data from a population-based survey conducted in rural Sri Lanka. Overall, 35% of currently married non-sterilized women of childbearing age expressed interest in using the implants, 52% did not want to use the method, and 13% were unsure about using it. The demand was substantially higher (44% vs 28%) among younger age groups (less than 30 years) than among older age groups (30-44). The results showed that life-cycle variables (age, parity and marital duration) and fertility preference variables (desire for another child and desired birth-interval) were generally more important than socioeconomic variables in determining variations in potential demand for Norplant in Sri Lanka. Desired birth spacing was found to be a powerful indicator of the potential demand. The majority (85%) of respondents interested in using Norplant were also willing to absorb at least some of the cost of the implants. Among older age groups, those who were using modern temporary methods of contraception either exclusively or in combination with traditional methods had a higher demand for Norplant than non-users or exclusive users of traditional methods. For the younger women, however, potential demand did not vary significantly according to whether they were currently using a method or the type of method used.


Changes in contraceptive practice in a multiracial urban-based community over a ten-year period.

There have been changes in the national policy regarding population growth in Malaysia from 1982. This report studies the changes in contraceptive practice among the three racial groups in this country, i.e. Malays, Chinese and Indians, over a 5-year period with an interval of 10 years. This is a retrospective study based on the attendance at the same family planning clinic in an urban setting. The striking change noted is the change in the racial composition of contraceptive usage in the two study periods with a shift from the Chinese being predominant in 1975-1979 to Malays in 1985-1989. There was no change among the numbers of Indians using contraception. The results also reveal a significant trend of change for users of the pill and those undergoing sterilization. There were no significant changes in IUD, condom and injectable usage. The study demonstrates how national policies, level of education and rural urban migration can significantly alter contraceptive practice.


Clinical evaluation of quinacrine pellets for chemical female sterilization.

Under the auspices of the Coordinating Board of Indonesian Fertility Research (BKS PENFIN), a clinical trial was undertaken to examine the safety and effectiveness of the quinacrine pellet method for nonsurgical female sterilization. One hundred women were selected to receive 3 monthly insertions of 250 mg of quinacrine and were followed up at 1, 3, 6 and 12 months after the third insertion. Socioeconomic data and complaints and menstrual patterns at each insertion and every follow-up visit were recorded, as were all failures. The life-table failure rate was determined to be 3.1. The continuation rate in this study was 96% at 1 year. Just over one-fifth of the women had amenorrhea by the third insertion, but most returned to normal by 1 year, and it appears that this amenorrhea was transient in nature. The method proved to be safe and effective, suggesting that larger clinical trials are in order.


A New Zealand randomized comparative study of three IUDs (Nova-T, MLCu375, MLAgCu250): 1-, 2- and 3-year results.

A randomized comparative study was made in New Zealand of 3 models of copper IUDs, the Nova-T, MLCu375 and MLAgCu250, with interval acceptors. Completing 3 years of use, there were 608 Nova-T (14,011 woman-months), 586 MLCu375 (14,161 woman-months) and 596 MLAgCu250 (14,614 woman-months). At 3 years, loss to follow-up was 5.2% for the Nova-T, 5.1% for the MLCu375 and 4.1% for the MLAgCu250. The Multiloads were significantly easier to insert and were preferred by the operators, as the insertion technique for the Nova-T was complicated. However, the Nova-T was significantly easier to remove. There was one perforation with a Nova-T in a puerperal breastfeeding woman. In the only 2 parameters that are comparable between series, accidental pregnancy and expulsion [1], the Multiloads have been shown to be superior with higher relevant continuation rates. At 3 years, the MLCu375 had a significantly lower accidental pregnancy rate and higher relevant continuation rate. The results obtained with the Nova-T are similar to those of the WHO study [2]. The MLCu375, with its potential for use up to 5 years, has been shown to be the superior device.


A randomized comparative trial of the MLCu375, TCu220C, steel ring and uterine cavity-shaped IUDs.

The Stainless Steel Ring, Uterine Cavity-Shaped Device, TCu220C and MLCu375 IUDs were evaluated in a randomized trial of 1536 women in Guangdong Province, China. The first-year continuation and expulsion rates were significantly lower (p less than 0.05) for the latter 3 IUDs than for the Stainless Steel Ring. The first year pregnancy rates for the MLCu375 (0.76 per 100 women) and TCu220C (1.2 per 100 women) were significantly lower (p less than 0.05) than those of the other two devices (6.1 and 4.1 per 100 women). The results of the study show that the MLCu375 and TCu220C are the most suitable IUDs for women in Guangdong Province.


The progestin-only oral contraceptive--its place in postpartum contraception.

The progestin-only oral contraceptive (POC) is not a widely-used method of contraception, possibly due to competition from other contemporary contraceptive methods or misunderstanding and prejudices among clients and/or service providers. Because of its underuse, the POC, as a contraceptive method, is under-studied. This article evaluates the general merits of the POC and its disadvantages relative to combined oral contraceptives (COCs) and other contraceptive methods, specifically during the postpartum period and particularly for breastfeeding women. We find that the POC appears to be a safe and acceptable contraceptive method for postpartum women who are fully or nearly fully breastfeeding at six months postpartum or when menstruation returns. The POC could be considered for use at any time by non-breastfeeding postpartum women. The need for empirical studies of the POC is also discussed.


[Aqueous protein concentration in diabetics. Report 5. Relationship between aqueous protein concentration and pathological findings of iridial vessels].

The relationship between aqueous protein concentration (APC) and pathological changes in the iridial blood vessels was investigated in 49 eyes of 45 diabetic patients who underwent cataract surgery. APC was measured with a laser flare-cell meter before surgery. The quantification analysis method (type I, multivariate analysis) revealed that the most relevant factor to APC was the existence of nephropathy followed by, in descending order, the degree of retinopathy and changes in iridial vessels as demonstrated by electron microscopy. When data were reanalyzed after exclusion of the iridial vessels were found to be strongly relevant to APC. These results suggest that breakdown of the blood-retinal barrier contributes to the APC increase in eyes with advanced diabetic retinopathy, and that changes in iridial vessels may mainly influence APC in non- and milder-retinopathy groups.


[Relationship of the office intraocular pressure (IOP) to diurnal fluctuation of IOP in low-tension glaucoma: a multivariate analysis].

In 288 eyes of 114 low-tension glaucoma (LTG) patients, the mean, peak, trough and magnitude of the diurnal fluctuation of the intraocular pressure (IOP) determined over a period of 24 hours (diurnal IOP) were correlated with the IOPs recorded at the daytime office (office IOP), refraction, extent of visual field loss, age, sex, blood pressure and obesity index by the method of multivariate analysis. Only the mean office IOP was found to have a statistically significant contribution for estimating the mean, peak and trough of the diurnal IOP with the proportion (R) of 0.71 0.67 and 0.68 respectively. Furthermore, an analysis of the IOP data obtained from 118 LTG suspects using the receiver operating characteristics (ROC) curve showed that a patient whose peak diurnal IOP exceeds 21 mmHg could be detected with a sensitivity of 100% and a specificity of 46% if around-the-clock IOP measurements were carried out in patients whose mean office IOP are above 16 mmHg at least in one eye. In view of high prevalence of LTG in Japanese, estimation of mean diurnal IOP from mean office IOP and exclusion of primary open angle glaucoma using the mean office IOP of 16 mmHg as a cutoff IOP level are thought to be clinically useful.


[Postoperative lens location calculated by ray tracing error correction (RTEC) in relation to axial length and corneal curvature].

Postoperative lens location, defined as the distance between the posterior corneal surface and the loop-lens connection, was calculated by ray tracing error correction (RTEC) method. Parameters needed were the anterior corneal curvature and axial length before surgery; IOL power; shape factor; diameter; and postoperative refraction. Under the hypothesis that lens location is a linear function of axial length and corneal curvature, 72 X lenses (A hospital), 94 Y lenses (A hospital), 26 Z lenses (B hospital) and 32 W lenses (B hospital) inserted eyes were analyzed. Mean lens locations were 3.68, 4.28, 4.29 and 4.73 mm, respectively. Regression coefficients of the axial length were 0.291, 0.294, 0.212 and 0.189, respectively. Regression coefficients of the corneal curvature were -0.984, -0.921, -0.626 and -0.019, respectively. These results show that longer axial length or smaller corneal curvature has deeper postoperative lens location, and that the regression coefficients are similar if the hospital is the same and measuring instruments are the same.


[Preretinal membrane in the macular area before and after the scleral buckling procedure].

In 100 consecutive eyes with successful repair for rhegmatogenous retinal detachment, a prospective study was performed for preretinal membranes in the macular area by assessing before and after scleral buckling surgery. The preoperative prevalence of the preretinal membrane was 23% in the eyes with macula-on detachment, although not feasible in the eyes with preoperative macula-off. After surgery, preretinal membranes were revealed in 59%, and macular puckers associated with retinal distortion were observed in 9%. Approximately half of the eyes without a preretinal membrane before surgery developed a postoperative preretinal membrane, suggesting that the preoperative preretinal membrane, which has been considered to be a remnant of the vitreous cortex, was not always necessary for the development of postoperative preretinal membrane.


[Histopathological study of retinopathy of prematurity].

Using light and electron microscopy, we studied the histopathological findings of retinopathy of prematurity (zone II, stage 3). The infant was born at 32-week gestational period and the birth weight was 1,255 g. He suffered from intracranial hemorrhage and hydrocephalus, and died at 78 days old. The ophthalmoscopic findings of both eyes at 72 days after birth showed that the intermedia was clear. The optic disc and posterior pole showed normal findings. Ridge formation with non-vascularized retina was seen at the equator of all quadrants of the fundus except the nasal quadrant of retina. Light and electron microscopic studies showed the following; in the most periphery of the vascularized retina, endothelial cell proliferation with the capillary lumen of glomeruloid tufts (rearguard) were seen. There were the aggregation of immature mesenchymal cells (vanguard) near to the rearguard. The cytoplasmic organelles of spindle cells in the non-vascularized retina were different from those of surrounding glial cell. Therefore, they were thought to be mesenchymal cells in the non-vascularized retina. Between the vanguard and the rearguard, the proliferative tissues composed of immature endothelial cells and mesenchymal cells extended into the vitreous body through the inner limiting membranes, and they formed the fibrovascular membranes on the retina. It was concluded that fibrovascular proliferation on the retinal surface in the active case of retinopathy of prematurity was composed of immature endothelial cells with vascular lumen and mesenchymal cells.


[Clinicopathological and immunohistochemical study of malignant lymphoma of the orbit].

The authors performed histopathological and immunohistochemical studies of 14 cases of orbital malignant lymphoma except for the conjunctival one. The patients were composed of 9 males and 5 females, and the average age of the cases was 61.5 +/- 12.3 years old. All cases were unilateral malignant lymphomas, 5 cases were right and 9 cases were left. Two patients had stage I disease, 10 patients had stage II disease, and 2 patients had stage III disease. The 5 year-survival rate was in 7/12 (58%). Histopathological examination revealed that 3 cases belonged to small lymphocytic, 4 cases diffuse small cleaved, 3 cases diffuse mixed and 4 cases diffuse large cell type by the working formulation. Immunohistochemical examination showed that all cases reacted positively against the B cell markers, while negatively against the T cell markers except for 1 case, indicating the cases were B cell lymphomas. Additionally, an immunoglobulin study contributed to elucidate the monoclonal proliferation of the tumor cells.


[Quantitative analysis of the slow phase in congenital nystagmus during convergence].

A previous report described that congenital nystagmus (CN) shows a lower intensity (frequency x amplitude) of spontaneous oscillation during convergence than for distance viewing. However, there has been no detailed report of quantitative analysis of the slow phase of CN during convergence. Therefore, in the present study, the slow phase of CN during convergence was analyzed in 7 patients horizontal and jerky type CN. The time constant of the slow phases were estimated using the repetitive non-linear least square method by a personal computer (NEC, PC 9801). The slow phases of CN for distance viewing were increasing-velocity exponentials, while those of CN during convergence were constant-velocity exponentials. The frequency, amplitude and mean velocity of the slow phase decreased during convergence. Thus, it was suggested that the velocity of the retinal image in CN decreased during convergence.


[Quantitative analysis of eye movement during VDT work].

The point of fixation during visual display terminal (VDT) work was analyzed by using Eye Mark Recorder-NAC with their corneal reflexes. The subjects were categorized into 2 groups, expert VDT worker and non-expert with VDT work. As for the VDT task, Japanese sentences were loaded. On the other hand, ordinary desk work copying was loaded using the same Japanese sentences. The following results were obtained. VDT work needed more complex eye movements in both vertical and horizontal directions compared with desk work. The point of fixation was mainly located on the surface of the oscilloscope in the expert subjects, whereas, it was mainly located on the keyboard in non-expert subjects. In analyzing the velocity of eye movements during VDT work, the expert moved the eyes more slowly than the non-expert. These results suggested that the VDT experts can move their eyes more effectively and slowly.


[Motor adaptation in the Bielschowsky head-tilt test in cases of superior oblique palsy].

To elucidate a motor adaptation phenomenon in the Bielschowsky head-tilt test in cases of superior oblique palsy, a gain of the otolith-ocular reflex was studied. The amplitude of ocular counter-rolling (OCR) of the non-paretic eye was measured with a photographic method, using limbal conjunctival marks as landmarks which were marked with indigo carmine. The average preoperative OCR of the non-paretic eye was 10.49 degrees at 30 degrees of head tilt to both sides, but after corrective surgery in the paretic eye the OCR of the non-paretic eye decreased to 8.43 degrees. To clarify the relation between OCR, duration of palsy and vertical deviation of the Bielschowsky head-tilt test (BHP), which was the difference of vertical deviation measured with the head tilted to the left and right shoulders at an angle of 30 degrees, the BHP/OCR ratio was calculated. We found no relation between BHP and OCR, but the BHP/OCR ratio increased proportionally in cases of long-standing palsy, From these results an increased BHP/OCR ratio could be an adaptive phenomenon caused by secondary innervational changes or muscle contracture to minimizing the contralateral head tilt to maintain binocular single vision.


[A case of lamellar keratoplasty and autoscleroplasty combined with keratoepithelioplasty for Wegener's sclerocorneal ulcer].

A 62-year-old man with Wegener's granulomatosis developed sclerocorneal ulcer. The general condition of the patient became well with steroid and presented cyclophosphamide therapy, he developed sclerocorneal ulcer. The sclerocorneal ulcer was present at the nasal limbus of the right eye. The ulcer was marked and presented descemetocele. Although lamellar keratoplasty was performed, the scleral ulcer recurred after two weeks. Excision of the affected sclera and autoscleroplasty was performed. The ulcer disappeared after 6 months, and the corneal graft was covered with corneal epithelium and conjunctiva. Ten months after autoscleroplasty was performed, a sclerocorneal ulcer was again recurred. We performed lamellar excision of the affected corneal area, resected the adjacent conjunctiva and performed keratoepithelioplasty. These surgical procedures were effective in preventing perforation of the cornea. Specular microscopic study of the corneal epithelium revealed nucleated epithelium and large epithelial cells. The endothelium appeared normal.


[Experimental study on possibility of corneal injury by electromagnetic wave].

The possibility of epithelial injury of BALB/C mice cornea exposed to a cathode ray tube (CRT) of a commercially available television was investigated. Epithelial injury of the cornea was confirmed by fluorescein-positive staining after 24 hours of CRT exposure approximately 3-9 cm from the surface of the CRT. The corneal epithelial injury was shown to be mainly limited to the most superficial layer by transmission electron microscope finding showing slight deterioration of the basal cell layer. The corneal epithelial defect was further measured by a scanning electron microscope in relation to the time of exposure to the CRT. The impaired area increased in dose-dependent manner to the some extent. The epithelial defect increased at 5 hours of CRT exposure and reached a maximum, that is 46.6% of the entire area of the cornea, by 12 hours of exposure, thereafter maintaining an equilibrium. The mechanism of corneal epithelial injury by CRT was discussed.


[Ultrastructural, immunohistochemical and immunoelectron microscopic studies on the transitional part of the trabecular meshwork and the ciliary muscle in human and porcine eyes].

The authors demonstrated the ultrastructure of the transitional portion of the human trabecular meshwork (TM) of the ciliary muscle (CM) by transmission electron microscopy, together with the porcine TM and CM, which have not been reported so far. In the transitional portion of the human eye, bundles of smooth muscle cells showed tapering in the anterior portion, and long slender processes of TM cells covered the outside of muscle bundles occasionally, in association with intervening nerve fibers. In the human transitional portion, there were many stick-like or irregular-shaped structures consisted of collagen fibrils. In the porcine eye, although the fine structure of the TM was similar to that of human TM, the shape of each porcine CM cell was irregular and their cytoplasm were invaginated into the adjoining cells, like herniation. In the immunohistochemical study, the positive immunoreactions were found in TM cells for vimentin, Schwann cells for S-100 and S-100b, and the CM cells for muscle (m)-actin and desmin in both species by using each antibody. Only the porcine TM cells were positive for S-100 and S-100b. In the human eye, smooth muscle-like cells similar to TM cells in the transitional portion were detected, and these cells were positive for m-actin. Moreover, the cells covering Schlemm's canal were positive for factor VIII and UEA-1. These immune positivities were confirmed at the ultrastructural level. These immunohistochemical reactions may be useful tools to evaluate cell at the light and electron microscopic levels in human and porcine TM and CM regions.


[Blood flow in the optic nervehead following intravenous administration of calcium antagonist].

The authors quantitated the blood flow of the optic nervehead after intravenous administration of calcium antagonist. The hydrogen clearance method was used to measure the blood flow after placing an electrode sensor in the optic nervehead of 9 eyes of 5 Macaca fuscata monkeys, under general anesthesia by intravenous pentobarbital sodium. 5 micrograms/kg of nicardipine, a calcium antagonist, was rapidly injected into the femoral vein. Measurement of blood flow in the optic nervehead was started 5 minutes after injection until 90 minutes at intervals of 15 minutes. A dose of 2 micrograms/kg/min nicardipine was then administered intravenously for another 90 minutes. During the experiment, intraocular pressure was maintained at 15 mmHg under continuous monitoring of systemic blood pressure. The blood flow in the optic nervehead decreased to 83% 5 minutes after injection. It increased slowly and reached the initial value 50 minutes later. It reached 108% of the initial value 80 minutes after injection. During the additional infusion of nicardipine, the blood flow decreased slowly and reached 85% of the initial value. It is concluded that the blood flow in the optic nervehead changed depending on the method, quantity and duration after injection of intravenous calcium antagonist. The blood flow decreased immediately after administration. The main cause of this phenomenon was thought to be due to decrease of perfusion pressure secondary to decrease of systemic blood pressure.


[Effects of timolol and carteolol on ocular pulsatile blood flow].

Effects of timolol (0.5%) and carteolol (2%) on ocular pulsatile blood flow (PBF) were studied in healthy adult volunteers. PBF was measured with the BFA system, analyzing the ocular pressure waves. Each drug was instilled in one eye and PBF was measured in both eyes before and fifteen minutes after the instillation. In each drug, the PBF change between the two measurements was evaluated with a control study, which was performed in the same manner with physiological saline solution. In the non-instilled eyes, both timolol (n = 6) and carteolol (n = 9) had no significant change on PBF. In the instilled eyes, timolol (n = 6) caused no significant change, whereas carteolol (n = 9) increased PBF significantly. The range of the BFA system measurement error was within 4.7 +/- 2.4 microliters/min (P = 95%). Taking the error into account in each instilled eye, timolol (n = 6) increased PBF in 3 eyes and decreased it in 3 eyes, while carteolol (n = 9) increased PBF in 7 eyes, did not change it in one eye and decreased it in one eye. It is thought the effect of carteolol to increase PBF may be explained by endothelium-dependent relaxing factor (EDRF).


[The effect of stimulus intensity and background luminance on the b-wave implicit time of photopic electroretinogram in normal human eyes].

The authors studied the effect of stimulus intensity and background luminance on the b-wave implicit time of photopic electroretinogram in normal human eyes. Photopic electroretinograms were recorded at various stimulus intensities and background luminances in the range of 2.5 log scale using an integrating sphere of 30 cm diameter in the first experiment. The results from two normal eyes showed that with increasing stimulus intensity or with decreasing background luminance the b-wave implicit time of photopic electroretinogram prolonged and one or three wavelets superimposed on the ascending limb of the b-wave. The second experiment was performed using a half dome sphere of 60 cm diameter to study the b-wave implicit time at three different stimulus intensities. The results from 30 normal eyes disclosed a statistically significantly longer implicit time at the greater stimulus intensities. These results suggest that b-wave implicit time in photopic electroretinogram becomes delayed with increasing stimulus intensity and becomes shorter with brighter background luminance.


[Depth perception and amplitude of VEPs for variations of dot density in static random dot stereograms].

Relative changes in depth perception and amplitude of VEPs were compared when the dot density in static random dot stereograms was altered. The maximum amplitudes of negative potentials evoked by either stereogram or uncorrelogram were recorded from the occipital region of human scalp. The peak latency was in the range of 160 to 260 msec, averaging 197 msec in 18 subjects. The amplitude of negative potentials evoked by either stereogram or uncorrelogram was always larger than that evoked by correlogram. The amplitudes on either stereograms, uncorrelograms or correlograms did not significantly increase when the dot density was increased, and there was no significant difference in amplitude on either stereogram or uncorrelogram. Depth perception did not closely correlate with the dot density nor with the amplitude of negative potentials. These results suggest that the amplitude of negative potentials may represent activities of disparity-sensitive neurons elicited in a trigger feature manner, but it does not reflect activities of the higher order process of depth perception.


[Electrophysiological experiment on neuronal pathway controlling horizontal eye-head coordination in the cat].

Tectal di-synaptic postsynaptic potentials (EPSPs) recorded in the abducens internuclear neurons (6 IN) were invariably facilitated by conditioning peduncular stimulation in the cat, which indicated that tectal and cortical excitation of 6 IN were mediated by a common set of interneurons. Using an extracellular recording technique, those common interneurons were identified as reticulospinal neurons by showing axonal projection to C2-3 spinal segment; they were also found to distribute mainly to the medial region of the nucleus reticularis pontis caudalis immediately rostral to the abducens nucleus, and not in the medullary reticular formation caudal to the abducens nucleus. The present experiment suggested that integration of tectal and cortical commands for horizontal eye-head coordination are taking place in the reticular formation rostral to the abducens nucleus which has been called the paramedian pontine reticular formation in the cat.


Identification of viable myocardium by dipyridamole-induced improvement in regional left ventricular function assessed by echocardiography in myocardial infarction and comparison with thallium scintigraphy at rest.

In patients with coronary artery disease and left ventricular impairment, the distinction between ventricular dysfunction due to myocardial fibrosis and postischemic, viable, although dys-synergic, myocardium has important clinical implications. Experimental studies have shown that dipyridamole can increase myocardial function in stunned segments, outlining a potential role of dipyridamole-induced functional recovery as an ultrasonic marker of myocardial viability. The aim of this study was to assess whether the increase of regional left ventricular function early during dipyridamole infusion in basally asynergic segments could identify viable myocardium recognized by rest injected, delayed (greater than 14 hours from tracer injection) thallium and (in a subset of patients) late functional recovery evaluated by a follow-up echocardiogram at rest. Twenty-two patients with angiographically documented coronary artery disease and regional dysfunction in resting conditions (average left ventricular ejection fraction 43 +/- 8%) were studied by echocardiography. All patients underwent a dipyridamole-echocardiographic test (up to 0.84 mg/kg over 10 minutes) and a delayed planar thallium study. A 13-segment model was used for both techniques. A score index ranging from 1 (normokinesia) to 4 (dyskinesia) was used for echocardiography. Thallium-201 activity was expressed in each segment as the percentage of maximal activity in the corresponding view. After dipyridamole, the wall motion score was assigned to each segment in resting conditions and at peak hyperkinesia before possible mechanical signs of ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)


Doppler echocardiographic patterns of left ventricular filling in patients early after acute myocardial infarction.

Diastolic function is routinely assessed using Doppler-derived left ventricular (LV) filling patterns. Ratios between peak flow velocities during early filling and atrial contraction (E/A) of less than 1 are considered pathologic and diagnostic of impaired relaxation. Myocardial stiffness can normalize the E/A ratio, and thus, in some clinical settings, a normal E/A ratio may identify patients with high filling pressures. LV filling patterns were studied with Doppler echocardiography in 15 healthy subjects and 38 patients with recent acute myocardial infarction. The results were correlated with clinical and hemodynamic variables. E/A ratio less than 1 was found in 14 patients (37%) and in only 1 control subject; E/A ratio greater than 2 found in 5 patients (13%) and in only 1 control subject; 19 patients (50%) had an apparently normal E/A ratio. No correlation was found between LV filling pattern and ejection fraction or presence of diabetes or arterial hypertension. LV end-diastolic pressures were low to normal in patients with an E/A ratio less than 1 and were usually greater than 15 mm Hg in those with normal or abnormally increased (greater than 2) E/A ratios. Thus, an apparently normal E/A ratio in patients after myocardial infarction may identify those with more severe LV diastolic dysfunction and increased LV filling pressure.


Angiographic findings in the coronary arteries after thrombolysis in acute myocardial infarction.

The angiographic appearance of the coronary arteries was examined in 308 patients with acute myocardial infarction (AMI) who received high-dose intravenous thrombolytic therapy. Coronary angiography was performed on day 7 after admission to the hospital. Patients had an average of 2.4 discrete arterial narrowings or obstructions. The narrowings were proximal and related to bifurcations. Four fifths of the culprit arteries were patient; 104 (34%) had a ruptured plaque, 22 (7%) had an ulcerated plaque, and in 190 (62%) the lesions were eccentric. Patients differed from a comparable, previously studied, control series of 302 patients with chronic stable angina pectoris who had more extensive disease. They had 5.7 narrowings/patient, also located proximally and at bifurcations, but more widely distributed in the coronary tree. Patients with AMI who are suitable for thrombolysis have a unique coronary angiographic picture. The data confirm that AMI is caused by sudden rupture of a localized atheromatous plaque that initiates an obstructive thrombotic cascade.


Analysis of the signal-averaged P-wave duration in patients with percutaneous coronary angioplasty-induced myocardial ischemia.

To assess the impact of angioplasty-induced myocardial ischemia on the duration of the surface P wave, patients undergoing elective angioplasty of isolated lesion in the left anterior descending, circumflex or right coronary arteries were monitored with a 3-channel electrocardiographic Holter system. The leads used were modified bipolar chest leads V5, aVF and V2 (CM-V5, CS-aVF and CM-V2). After echocardiographic signal-averaging, the earliest onset and the latest offset of the P wave were identified in all of the above time-aligned signal-averaged leads, and the composite maximal P duration was measured under 10 x magnification. The maximal ST-segment shift during balloon inflation was also measured in all of the above leads at 60 ms after the J point. In the study group comprising 47 patients, the mean signal-averaged P-wave duration was 125.0 +/- 16 ms at baseline versus 130.0 +/- 15 ms during balloon inflation, p less than 0.005. In the left anterior descending coronary artery group (n = 23), the mean signal-averaged P-wave duration was 122.4 +/- 17 ms and 131.3 +/- 16 ms during balloon inflation, p less than 0.005). In the group with a right coronary artery lesion (n = 18), the values were 127.3 +/- 14 ms and 128.4 +/- 13 ms respectively (p = not significant). Significant increases in the P-wave duration were found to occur in groups both with (n = 34) and without (n = 13) ST-segment shift greater than or equal to 1 mm (both p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)