McArdle's disease with myoadenylate deaminase deficiency: observations in a combined enzyme deficiency

Exercise and work potential of a patient with coexistent myophosphorylase and myoadenylate deaminase (AMPDA) deficiency was compared with that of three patients with myophosphorylase deficiency alone. The patient with the combined defect failed to produce an abnormal rise in serum ammonia or hypoxanthine as seen in the other patients after forearm exercise. Maximum oxygen consumption and work rates during cycle ergometer testing were similar in all patients, but well below controls. The occurrence of two defects involving short-term energy metabolism in muscle presents an opportunity to define further the metabolic role of AMPDA.     

Human exposure to 3-carene by inhalation: toxicokinetics, effects on pulmonary function and occurrence of irritative and CNS symptoms

Terpenes, especially 3-carene, may irritate the skin and mucous membranes and prolonged exposure may result in allergic contact dermatitis or chronic lung function impairment. The toxicokinetics of 3-carene were studied in human volunteers exposed by inhalation (2 hr 50 W) in an exposure chamber on three occasions. The exposure concentrations were approximately 10, 225, and 450 mg/m3 3-carene. The relative pulmonary uptake was high, approximately 70% for the higher exposure levels. Total uptake increased linearly with increasing exposure. The blood clearance of 3-carene observed in this study, 0.9 liter.kg-1.hr-1, indicates that 3-carene is fairly readily metabolized. About 3% of the total uptake was eliminated unchanged via the lungs while less than 0.001% was eliminated in the urine after the end of exposure. A long half time in blood was observed in the terminal phase which indicates a high affinity to adipose tissues. A statistically significant divergence between ratings of irritation during the high exposure level and during the medium and control levels was observed. The difference in airway resistance after exposure to a high concentration of 3-carene compared to control level was not significant (P = 0.02).     

A Chinese adolescent girl with Fechtner-like syndrome

We describe a 15-y-old girl with Fechtner-like syndrome, who is the first Chinese reported to have this rare syndrome. She presented with left homonymous hemianopia and neuroimaging revealed haemorrhage in both parietal and occipital lobes. Peripheral blood smear showed macrothrombocytopenia and intracytoplasmic inclusion bodies inside leucocytes. Thrombocytopenia and proteinuria responded to intravenous immunoglobulin and pulsed methylprednisolone. This case illustrates that life-threatening haemorrhage can occur in patients with Fechtner syndrome. Although there was no effective treatment reported in the literature, high dose steroid and immunoglobulin seemed to be useful in our patient. Our patient also had nephritic-nephrotic syndrome with renal insufficiency, which is unusual in adolescent female patients.     

Occurrence of the t(2;5)(p23;q35) in non-Hodgkin's lymphoma

Primary CD30(Ki-1)-positive anaplastic large-cell lymphoma (ALCL) is considered by some to be a distinct clinicopathologic entity associated with the t(2;5) (p23;q35). However, the specificity of t(2;5) for ALCL has not been carefully studied. Therefore, we performed a detailed analysis of all cases of ALCL with abnormal cytogenetics results in the Nebraska Lymphoma Study Group registry, as well as all other cases of non-Hodgkin's lymphoma with t(2;5) in the registry. We found the t(2;5) in only five of 10 cases of ALCL, four of whom were young patients. However, we also found the t(2;5) in 11 other cases of nonanaplastic lymphoma, including eight children with typical peripheral T-cell lymphomas of various types. The t(2;5) was also found in three older adults with B-cell lymphomas of various types. Thus, the t(2;5) was not specific for CD30+ ALCL. However, t(2;5) may define a clinicopathologic entity in children and young adults characterized by variable morphologies with a T-cell or indeterminate phenotype, CD30-positivity, nodal disease with frequent extranodal involvement, advanced stage, and an excellent response to therapy, including bone marrow transplantation for relapsed disease. The clinical relevance of the t(2;5) in older patients requires further study.     

Development of brain damage after neonatal hypoxia-ischemia: Excitatory amino acids and cysteine

The aim of this study was to investigate the possible role of excitatory amino acids (EAAs) and cysteine in the development of brain damage after hypoxia-ischemia (HI) in neonates. In a rat model of neonatal HI, changes in extracellular (ec) amino acids in cerebral cortex were measured with microdialysis and correlated with the extent of brain damage at the site of probe placement. Extracellular concentrations of glutamate, aspartate and cysteine increased during HI and remained elevated during reperfusion. During HI the pattern of EAA changes was the same in the infarcted, undamaged and border zone regions. During reperfusion, however, the ec concentrations of glutamate, aspartate and cysteine were higher in infarcted and border zone areas compared to undamaged tissue. HI also produced a slight increase of tissue concentration of cysteine and decrease of tissue concentration of glutamate in parietal cortex of the HI hemisphere. The effect of cysteine on brain damage induced by HI and glutamate was also investigated. A subtoxic dose of cysteine potentiated glutamate toxicity in the arcuate nucleus and enhanced brain infarction after HI in neonatal rats. The results show that in neonatal HI the extracellular levels of EAAs during HI are not directly related to brain injury but the EAA levels during reflow predict the extent of infarction. Cysteine increases HI-induced brain injury and potentiates glutamate toxicity in neonatal rats. Speculatively, elevated level of cysteine during reperfusion may participate in the excitotoxic cascade leading to brain injury.     

Morphological study of neocortical areas in Rett syndrome

Various neocortical areas from four females aged 16–24 years with Rett syndrome (RS) were investigated and compared with brains of therapy-resistant partial epilepsy (TRPE) patients (18–25 years), infantile autism (IA), and control brains (24 and 58 years). The cytoarchitecture of area 10 (frontal), area 21 (temporal), area 4 (primary motor cortex), and area 17 (primary visual cortex) was studied by the combined Klüver-Barrera (luxol fast blue and cresyl violet) standard procedure. Autofluorescence of lipofuscin, immunofluorescence of synaptic vesicle proteins [synaptophysin (p38)] and lectin-stained (Wisteria floribunda agglutinin) perineuronal nets (PNs) were studied in the cortices using dual-channel confocal laser scanning microscopy. The brains of RS females show various types of morphological/cytoarchitectonical abnormalities of single pyramidal neurons in layers II–III, and V–VII of different cortical areas. The abnormalities include mild losses of pyramidal neurons, more pronounced in layers II and III than in layers V and VII, and more evident in frontal and temporal areas than in the visual cortex. Microdysgenesis, including abnormalities due to neuronal migration disorders, was not found in RS, in contrast to the observations in TRPE patients, strongly indicating that RS is not a neuronal migration disorder. Lipofuscin distribution was normal but amounts were lower in RS cases than in control and TRPE brains. PNs were less expressed in cortices of the IA case, but were clearly overexpressed in the motor cortex of RS. Quantitative analysis of p38 showed a decrease in the area occupied by p38 immunoreactivity by 20–40% in RS compared with controls. It is concluded that RS could best be explained by a postnatal synaptogenic developmental deficiency; the basic defect, however, is still completely unknown. Received: 26 February 1996 / Revised, accepted: 11 July 1996     

Effect of propentofylline (HWA 285) on extracellular purines and excitatory amino acids in CA1 of rat hippocampus during transient ischaemia.

1. The adenosine uptake blocker propentofylline (HWA 285) has previously been shown to protect hippocampal CA1 pyramidal cells from ischaemia-induced delayed neuronal death. The influence of propentofylline, on the extracellular concentrations of purines, aspartate and glutamate in the CA1 of the rat hippocampus during transient forebrain ischaemia was investigated. 2. Twenty min of ischaemia was induced by four-vessel occlusion in Wistar rats, extracellular compounds were sampled by use of microdialysis and EEG was recorded by a tungsten electrode attached to the dialysis probe. 3. Propentofylline (10 mg kg-1 i.p.) did not influence the basal levels of any of the compounds in the hippocampal dialysates. 4. The EEG became isoelectric within 20 s after induction of ischaemia. 5. Extracellular adenosine, inosine, hypoxanthine, aspartate and glutamate increased several fold during ischaemia and remained elevated during early reflow. Within 2 h of reperfusion the concentration of all compounds was normalized. Xanthine increased upon reperfusion and remained elevated after 2 h. 6. Propentofylline (10 mg kg-1 i.p.) administered 15 min before ischaemia significantly enhanced the ischaemia-evoked increase of adenosine but attenuated the increases of the other purine catabolites and of glutamate. 7. In separate in vitro experiments, propentofylline did not inhibit adenosine deaminase activity. 8. The present data show that propentofylline enhances extracellular adenosine and lowers extracellular glutamate in vivo during ischaemia. These findings may be important in relation to the neuroprotective properties of propentofylline.     

INVOLVEMENT OF NON-NMDA AND NMDA RECEPTORS IN GLUTAMATE-INDUCED PRESSOR OR DEPRESSOR RESPONSES OF THE PONS AND MEDULLA

1. Fifty-five intact and six baroreceptor denervated and vagotomized cats of either sex were anaesthetized intraperito-neally with urethane (400 mg/kg) and a-chloralose (40 mg/kg). Responses of the systemic arterial pressure (SAP), mean SAP (MSAP) and sympathetic vertebral nerve (VNA) and renal nerve activities (RNA) were recorded. 2. In intact animals, monosodium L-glutamate (Glu, 0.1 mol/L, 50 nL) was microinjected into pressor areas of the locus coeruleus (LC), gigantocellular tegmental field (GTF), rostral ventrolateral medulla (RVLM) and dorsomedial medulla (DM), and the depressor areas of caudal ventrolateral medulla (CVLM). The induced actions were compared before and after microinjection of either glutamate antagonists, glutamate diethylester (GDEE, 0.5 mol/L, 50–100nL), a competitive AMPA receptor blocker, or 2-amino-5-phosphonovaleric acid (D-AP5, 0.025 mol/L, 50–100 nL), a competitive N-methyl-D-aspartate (NMDA) receptor blocker. GDEE completely blocked the increases of SAP and VNA elicited from all pressor areas. D-AP5 only partially blocked the pressor but slightly blocked VNA and RNA responses from LC, GTF and DM, particularly those from RVLM. Neither GDEE nor D-AP5 blocked the depressor responses of SAP and two nerve activities elicited from CVLM. 3. In baroreceptor denervated animals, NMDA (2 mmol/L, 50–100 nL) and AMPA (0.2 mmol/L, 50–100 nL) were micro-injected into the same pressor areas of GTF, RVLM and DM and the depressor area of CVLM responsive to Glu activation (0.1 mol/L, 30 nL). In RVLM, DM and CVLM, the results of either NMDA or AMPA were similar to those induced by Glu. However, in GTF, microinjection of either NMDA or AMPA did not induce similar responses to Glu. This suggests that the nature of GTF may differ from RVLM and DM. 4. The above results suggest that the Glu-induced pressor responses from LC, GTF, DM and especially RVLM, are primarily mediated through AMPA receptors. The Glu-induced depressor responses from CVLM may not be predominantly mediated by either AMPA or NMDA receptors. 5. In both baroreceptor-intact and -denervated cats stimulation of the pressor areas often produced an increase of VNA and a decrease of RNA, while in the depressor CVLM decreased both VNA and RNA. The VNA, but not RNA were positively correlated with the pressor responses, while both VNA and RNA were positively correlated with the depressor responses. This may suggest that neurons of the sympathetic vertebral and renal nerves are topographically organized in the brain.     

Impact of occupations and job tasks on the prevalence of carpal tunnel syndrome.

In this investigation reported epidemiologic studies on carpal tunnel syndrome (CTS) (15 cross-sectional studies involving 32 occupational or exposure groups and six case-referent studies) were reviewed. The prevalence of CTS in the different occupational groups varied between 0.6 and 61%. The highest prevalence was noted for grinders, butchers, grocery store workers, frozen food factory workers, platers, and workers with high-force, high-repetitive manual movements. Odds ratios greater than 10 were reported for exposed groups in three studies. On the basis of epidemiologic and other evidence, it was concluded that exposure to physical work load factors, such as repetitive and forceful gripping, is probably a major risk factor for CTS in several types of worker populations. At least 50%, and as much as 90%, of all of the CTS cases in these exposed populations appeared to be attributable to physical work load.