Giant axonal neuropathy: a childhood disorder of microfilaments.

A sural nerve biopsy was performed on an 8-year-old boy with a chronic, slowly progressive polyneuropathy. Light and electron microscopy as well as teased nerve-fiber preparations demonstrated numerous giant axons filled with closely packed neurofilaments. Both myelinated and unmyelinated fibers were involved. Segmental demyelination, remyelination, and onion-bulb formation by multiple Schwann cell processes were observed, suggesting recurrent Schwann cell dysfunction. Abundant aggregates of cytoplasmic microfilaments occurred in Schwann cells, endothelial cells, perineurial cells, endoneurial fibroblasts, and endomysial fibroblasts. These findings support the proposal that giant axonal neuropathy is a generalized disorder of cytoplasmic microfilaments and that segmental demyelination occurs concomitantly with axonal and Schwann cell disease. The pathogenesis of this rare disorder is discussed with reference to experimental toxic neuropathies.     

Measurement of duodenogastric reflux with99mTc-HIDA in duodenal ulcer patients

There are contradictory reports as to whether the pylorus plays an important role in preventing duodenogastric reflux. In the present study we measured bile reflux under fasting conditions, employing a new radionuclide method which was modified for easy and standardized use. Intravenously administered^99mTc-HIDA (0.1 mCi) is detected in gastric juice aspirated during routine gastric secretion analysis. In order to prove that the radioactivity in the aspirate comes from reflux, in preliminary intraoperative experiments we clamped the antrum and measured the intraluminal activity. Only a very low amount of free activity was found. We found the same result in 3 Heidenhain pouch dogs. We then studied the bile regurgitation in 60 patients with duodenal ulcer disease and in 30 patients operated on for duodenal ulcers (selective proximal vagotomy with pyloroplasty). Preoperatively, we found bile reflux in 66% of the patients. There was a distinct difference between active and chronic ulcers. In the florid state, 76% of our patients had bile reflux as compared to 58% in the chronic state. After pyloric surgery, with a pyloroplasty appropriate to form and function, bile reflux was not increased. Our conclusion is that the pylorus seems to have no important reflux-preventing properties.

---

Résumé Le rÔle du pylore dans la prévention du reflux de la bile du duodénum dans l'estomac reste discuté. Dans cette études nous avons mesuré le reflux biliaire dans l'estomac chez le sujet à jeun en ayant recours à un radio isotope marqué modifié de faÇon à l'employer facilement et selon une technique standard. Le Tc 99 m HIDA (0, 1mCi) injecté par voie intra-veineuse a été dosé au niveau du liquide d'aspiration gastrique. Pour prouver que la radioactivité au niveau du liquide gastrique est le résultat du reflux nous l'avons dosé l'antre étant clampé: nous avons constaté alors que l'activité était faible; puis après levée du clamp.L'étude a été menée chez 3 chiens qui présentaient une poche de Heidenhain, 60 sujets qui étaient atteints d'un ulcère et 30 patients qui avaient été opérés pour un ulcère duodénal par vagotomie proximale et pyloroplastie.En pré-opératoire nous avons constaté l'existence d'un reflux biliaire chez 66 pour cent des porteurs d'un ulcère avec une différence significative suivant que l'ulcére était quiescent ou en poussée le taux du reflux étant de 58 pour cent dans le premier cas et de 76 pour cent dans la seconde éventualité.Chez le sujet opéré correctement, porteur d'une bonne pyloroplastie, le taux du reflux n'etait pas augmenté.De ces faits nous pouvons conclure que le pylore ne joue pas un rÔle important dans la prévention du reflux biliaire.

     

Metabolism of pholcodine in man

This paper describes studies on the metabolism of the antitussive 3-O-(-2'-morpholinoethyl)-morphine (pholcodine, Tussokon) in man. The metabolites were identified after cleavage of conjugates, extraction and derivatization by acetylation in human urine using gas chromatography-mass spectrometry. The following seven metabolites could be identified besides the unchanged pholcodine (P): Nor-P, desmorpholino-hydroxy-P, nor-desmorpholino-hydroxy-P, hydroxy-P, oxo-P, nor-oxo-P and morphine in traces. Therefore, the following four partly overlapping phase I metabolic pathways can be postulated: N-demethylation, N-desalkylation at the morpholino ring followed by reduction of the resulting aldehyde to the desmorpholino-hydroxy metabolite, oxidation of the morpholino ring to the hydroxy and oxo metabolite, and O-desalkylation to morphine. With the exception of morphine, pholcodine and its phase I metabolites were not converted to enzyme-hydrolysable conjugates. Pholcodine itself could be detected in urine 5-7 weeks after ingestion, the desmorpholino-hydroxy metabolite 1-2 weeks and the other metabolites only in the first few hours. It can be concluded that the low metabolism of the rather lipophilic pholcodine is the reason for the very slow elimination.     

Contribution of O6-alkylguanine and N-alkylpurines to the formation of sister chromatid exchanges,chromosomal aberrations,and gene mutations: New insights gained from studies of genetically engineered mammalian cell lines

O⁶-methyl- and O⁶-ethylguanine are the major premutagenic and precarcinogenic lesions induced in DNA by monofunctional alkyiating agents, albeit formed in minor amounts. The involvement of these lesions in SCE and aberration formation is less clear. We have analyzed the contribution of O⁶-alkylguanine to SCE and aberration formation, as well as its toxic and point mutation inducing effect in transgenic Chinese hamster ovary (CHO) cell lines that express variable amounts of human O⁶-methylguanine-DNA methyltransferase (MGMT). Cells that overexpress MGMT (or the bacterial Ada protein) gained resistance to the formation of alkylation-induced SCEs and aberrations, as compared to MGMT deficient cells. A correlation was apparent between the level of protection for SCEs and cell killing, indicating that both phenomena are interrelated. The protective effects were dependent on the level of MGMT expression, the agent used for alkylation, and cell cycle progression. Our data suggest that at least 2 kinds of lesions are responsible for SCE and aberration formation, namely, O⁶-alkylguanine and one or various N-alkylation products. The probability that O⁶-methylguanine is converted into cytogenetic effects has been estimated to be about 1:30 for SCEs, and 1:147,000 and 1:22,000 for chromosomal aberrations in the first and second post-treatment mitosis, respectively. The induction of SCEs and likely also of aberrations by O⁶-methylguanine requires two replication cycles and is supposed to involve the formation of secondary DNA lesions. Increased repair of 3-methyladenine and 7-methylguanine in CHO cells that overexpress the N-methylpurine-DNA glycosylase (MPG) after transfection with the human MPG-cDNA did not give rise to protection against methylation-induced SCEs and aberrations, probably because of incomplete excision repair. MPG overexpressing cells reacted even more sensitively to methylating agents, suggesting apurinic sites formed as a result of MPG action to be SCE and aberration-inducing lesions. © 1993 Wiley-Liss, Inc.     

Asymmetry of silent period evoked by transcranial magnetic stimulation in stroke patients

Introduction — A transcranial magnetic stimulus delivered during voluntary activity produces a prolonged postexcitatory inhibition (silent period) of this activity. Besides more conventional measurements of central motor conduction time and amplitude of evoked potentials, we investigated silent period changes in patients with ischaemic brain lesions. We aimed at finding a more reliable method of data processing to differentiate healthy subjects from patients with motor disturbances due to stroke. Methods — Standardized transcranial magnetic stimulation during sustained muscle contraction was performed on the vertex. Electromyographic activity was recorded via surface electrodes placed over the mm. abductor digiti minimi on both sides. 25 patients with different degrees of impairment due to stroke as well as 75 healthy control subjects were examined. Results — In the control group there was no statistically relevant interside difference with respect to silent period duration, whereas a marked interindividual variation was found. In the group of patients, we found mostly a significant prolongation and sometimes a shortening of the postexcitatory inhibition recorded from the affected side compared with the healthy side. This interside difference of silent periods is significantly greater than in the control group. Even greater group differences were found if ratios of silent periods (longer/shorter) were calculated. Conventional parameters were clearly less sensitive. Conclusion — Our findings show that the measurement of the silent period elicited by transcranial magnetic stimulation is a very sensitive neurophysiologic parameter for the assessment of central motor system disturbances, even more so if ratios are considered.     

Aza-, Di- und Triazaxanthone aus Azachromonen

Aza-, Di- and Triazaxanthones from Azachromones The acyl(methylthio)azachromones 7a and 7b , which are obtained from the pyridyl-substituted 1,3-dicarbonyl compounds 5a and 5b , react with amines, hydrazine compounds, amidine or CH-acidic compounds to yield the azaxanthones 8a, 8b, 9a and 9b, 11a and 11b , or 13 and 14 .     

Successful resuscitation in accidental hypothermia following drowning

After breaking through thin ice, a 4-year-old boy drowned in a lake. A quickly alerted rescue helicopter found and recovered the child, drifting underneath the clear, thin ice. Primary resuscitation by the helicopter crew was unsuccessful. Upon arrival in the hospital the child had fixed, dilated pupils and asystole. Core temperature was 19.8 degrees C. Rewarming was conducted slowly while cardiopulmonary resuscitation was continued. Twenty minutes after arrival at the hospital, ventricular complexes appeared in the ECG (temperature 22.1 degrees C); after another 10 min this converted to sinus rhythm. At short intervals, blood gas analyses and electrolyte determinations were carried out and corrected adequately. For cerebral protection methohexital was given and the child was hyperventilated. Seventy minutes after arrival at the hospital the child was brought to the pediatric ICU with stable circulation. There, further rewarming (centrally/peripherally combined) was carried out, aiming at 1 degree C rewarming per hour until a normal temperature was reached. The patient had to be kept on the ventilator for 10 days and after another 2 weeks was discharged home. He had recovered completely without any cerebral damage. One of the reasons why 88 min of cardiac arrest were tolerated by this patient without sequelae may have been rapid and deep hypothermia.     

Hypomagnesemic coma during therapy of septicaemia in a patient with acute lymphoblastic leukemia. (author's transl)

During induction therapy of acute lymphoblastic leukemia a 10 year old boy developed a hyperuremic nephropathy and subsequently a staphylococcal septicemia at the beginning of the 3. week. Specific treatment was started leading to severe hypomagnesemia and generalized seizures with coma for 30 hours, which finally responded to magnesium replacement. The possible additive effect of nephropathy, gentamicin, and furosemide due to urinary loss of magnesium is discussed and should encourage further observations.