[General anesthesia for magnetic resonance. Experience on 100 cases]. The diffusion of magnetic resonance imaging as a powerful non-invasive diagnostic procedure has led to an increasing request for general anaesthesia in patients who cannot lie still and/or who cannot guarantee adequate spontaneous breathing during the procedure. We report our own experience in 100 patients of this kind, in whom the need for general anaesthesia was due to neurological problems and/or tender age. Anaesthesia and monitoring devices were either devoted of ferromagnetic properties (allowing their location near the patient; as the ARM-S88 portable ventilator, which we used for adult patients) or connected to the patient with long connectors (allowing their location outside the resonance magnetic field; as the Draeger-Babylog pressometric ventilator, which we used in pediatric patients). On these bases administration of intravenous (86 patients) and inhalation (14 patients) anaesthesia during magnetic resonance proved safe in our experience.


[SCS (spinal cord stimulation) in severe ischemia of the legs]. Spinal cord stimulation (SCS) of the low thoracic spinal epidural space was carried out in 11 patients with pain from peripheral arterial disease of the lower limbs. Conservative treatment or vasoactive drugs also failed. Results are reported relating to pain, exercise endurance on the bicycle ergometer, trophic lesion changes and TCpO2. After a mean postimulation follow-up period of 15 months, substantial pain relief was preoperative non healing skin ulcerations, but gangrenous conditions were not benefited. Exercise tolerance as measured on a bicycle ergometer increased by 40%. It is concluded that SCS is vary promising in severe limb ischemia where reconstruction surgery is not possible or has been unsuccessful.


[Anesthesia with high dosage fentanyl in coronary patients: effects of pretreatment with droperidol and diazepam]. The Authors have considered the effects of droperidol or diazepam treatments in patients undergoing high-dose fentanyl anesthesia in cardiac surgery. Twenty patients have been examined and divided in two groups: group A received droperidol (0.2 mg.kg-1) and group B diazepam (0.1 mg.kg-1) five minutes after fentanyl anesthesia induction (500 micrograms.min-1) to reach the "sleep dose". The diazepam pretreatment, as regards droperidol, reduces a dose of fentanyl necessary to obtain the conscience loss (21.5 +/- 2.5 micrograms.kg-1 vs 28 +/- 2.9 micrograms.kg-1). Hemodynamically the droperidol group is very stable, whereas the diazepam group shows certain myocardial depression and less protection at the OTI time.


[Peridural anesthesia with 0.5% bupivacaine-fentanyl. Evaluation of the pre-heating effect]. The effect of preheated (37 degrees C) mixture of 0.5% bupivacaine and fentanyl on peridural anaesthesia have been studied in a double blind randomized clinical trial. Fifty patients of both sexes, ASA I-II, undergoing elective surgery for inguinal hernia repair or radical saphenectomy have been randomly assigned either to the control group (n = 25) receiving 0.5% bupivacaine-fentanyl at room temperature (20 degrees C), or to the group receiving the same anaesthetic mixture preheated for 12 hours up to 37 degrees C (n = 25). The latency period, extension, duration and quality of anaesthetic block were evaluated. A significative difference in the extension of anaesthetic block was detected at 6' (p less than 0.05 for extension up to T10 and T11, p less than 0.025 up to T12), and at 8' (less than 0.05 for extension up to T10). However no difference was observed between the two groups at 10' and later. The use of 0.5% bupivacaine-fentanyl mixture resulted in a short latency period, as previously observed, and its preheating does not seem to affect substantially the parameters evaluated in this study.


[Sub-arachnoid anesthesia with Sprotte and Whitacre types atraumatic needles in cesarean section]. Fifty patients undergoing cesarean section with spinal anaesthesia received hyperbaric 1% bupivacaine at the L1-L2-, L2-L3 or L3-L4 interspace. Intrathecal injection was performed with a 24 gauge Sprotte needle in 35 patients and a 25 gauge Whitacre needle in 15. Successful anaesthesia was obtained in 49 patients (98%). Fluid loading with 1 litre of crystalloid before spinal block was used for prophylaxis of hypotension. 36 patients (72%) received ephedrine iv after spinal injection. All newborns were in good condition (Apgar score greater than or equal to 9). No post-spinal headache was reported. Our experience confirms the smaller incidence of headache with the pencil point needles compared with conventional needles, the effectiveness of the method and the pleasurableness of the procedure for the mothers.


[Sodium naproxen in postoperative pain in orthopedics. Comparison of 2 different doses]. In order to use etiopathogenetic criteria for the treatment of postsurgical pain, non-steroid anti-inflammatory drugs (NSAIDs) can be used rather than narcotic analgesics. These agents are often classified as peripherally acting analgesic drugs; nevertheless in the last years many pages have who showed a central supraspinal analgesic effect. Sodium naproxen is commonly used in the treatment of postoperative orthopedic pain because of its pharmacokinetic properties. The aim of this study was to evaluate the suitable dosage of sodium naproxen for post-surgical pain relief. Forty patients submitted to foot surgery were randomized into two groups of 20 patients each. At the end of surgery one group of patients (group I) received sodium naproxen 275 mg i.m.; the same dose was administered after 12 hours. A second group (group II) received sodium naproxen 550 mg i.m. at the same time intervals. Based on a Descriptive scale for algometric measurements, the results showed significant differences in analgesic activity for the two treatments. The best results (70% of patients with no pain or slight pain vs 20% of patients) were obtained in the group that received sodium naproxen at the higher dosage (p less than 0.001). No differences were observed in the incidence of side-effects in the two groups. These results are discussed.


[Determination of drug costs in general anesthesia]. Drug costs of various general anaesthesia techniques have been assessed. These costs are used as a basis to point out the economies that could be made in the conduct of general anaesthesia.


[Epidemiology of malignant hyperthermia in Piedmont and Valle d'Acosta. A study conducted with 2 different methods]. The Authors report on the results of two researchers about malignant hyperthermia (MH) carried out in Piemont and Valle D'Aosta using two different methods. The former, based on a form sent to 492 anaesthesists got 22.7 per cent answers. They indicated 4 cases of MH during the years between 1982 and 1986, out of 213,444 narcoses with an average rate of 1:71,000. The latter was canned and by questioning directly the head physicians of anaesthesia and reanimation wards about the occurrence of MH in Piemont and Valle D'Aosta in the years between 1984 and 1988. According to this research, there were 5 cases out of 891,729 narcoses (that is 1:178,346).


[Synchronous and metachronous carcinomas of the large intestine]. The authors present their experience relative to 5 patients with multiple carcinomas (synchronous and metachronous) of the large bowel. They underline that full examination of the colon before operation in all patients with primary colorectal cancer is necessary, and they propose a lifelong follow-up program after resection for early detection of multiple carcinomas.


[Tumors of the small intestine. Case reports and comments]. Tumours of the small intestine are extremely rare and have a particularly severe prognosis. The impossibility of making an early diagnosis due to the scarcity of precise symptoms during the early stages of the disease and the lack of safe instrumental tests limits the results of treatment which is essentially surgical. In order to contribute to the study of the disease and improve its prognosis, the authors report the cases which they have observed and review the literature.


[Gastric leiomyoma. Our cases].

[Gastric leiomyoma. Our cases]. The authors describe 3 cases of gastric leiomyoma which they observed in the ten-year period 1980-1990. The most important aspects of this pathology are illustrated, emphasizing on one hand the slight incidence, also due to their underestimation, the seat represented by the body and gastric antrum, the asymptomatic submucosal growth or with atypical symptomatology; on the other hand, the low malignant potential linked above all to the voluminous bulk of the neoplasm.


[A case of double valve substitution in a female patient carrier of a factor X deficiency]. We present the clinical case of a patient affected by mitral and aortic valvular disease submitted to double valvular replacement. This patient was also affected by congenital deficiency of factor X. We describe the normal problems encountered in cardiac surgery and the specific implications of this clinical case.


[Anaplastic carcinoma of the thyroid. Our experience]. Nineteen patients, 12 females and 7 males, with mean age of 66 years, with anaplastic carcinoma of the thyroid, were treated between 1976 and 1990. At diagnosis, in 4 patients disease presented as intraglandular mass, in 11 as infiltration of the adjacent structures and as distant metastases in 4 cases. A preceding history of goiter was found in 7 patients. Total thyroidectomy was performed in 9 patients, subtotal thyroidectomy in 1 and a diagnostic biopsy only in 4 cases. All patients received external radiotherapy (4000-6000 rads). Median global survival was 6 months with no difference between patients receiving thyroidectomy plus RT or biopsy plus RT. All patients died of tumor except 1 who is alive and free of disease at 120 months. Combination modality treatment of anaplastic carcinoma of the thyroid represent, at times, a rational palliative therapeutic approach, even if, in selected patients with early intraglandular disease, total surgery may represent a curative therapy.


[Postoperative infections. A prospective analysis of 1396 cases]. Postoperative infections are the most frequent complications in surgery and are the commonest cause of the lengthening of hospital stay. The purpose of this study is to prospectively evaluate the incidence and predisposing factors of postoperative infections in 1396 surgical patients admitted to our Institute from 1984 to 1988. Patients undergoing minor surgical procedures (wound less than 2 cm) were excluded from the study. Patients were evaluated daily during hospital stay for onset of infections and results recorded on data sheet. Hemocultures in septic patients and samples of exudate at site of infection were taken whenever possible for aerobic and anaerobic cultures. 368 patients (26.36%) had at least one postoperative septic complication; (79 of them [5.65%] had two or more infections). The following infections were recorded: wound infections: 148 (10.60%); respiratory tract infections: 144 (10.31%); urinary tract infections 125 (8.95%); miscellaneous infections 11 (0.78%); thrombophlebitis 23 (1.64%); FUO 10 (0.71%). The most important predisposing factor for wound infection was endogenous contamination (wound infections: 18/499 [3.60%] in clean, 42/594 [7.67%] in potentially contaminated, 57/217 [26.26%] in contaminated and 31/86 [36.04%] in dirty operations). The duration of the anaesthesia was found to correlate with an increased incidence of respiratory tract infections (4.49% anaesthesia less than 60 min; 7.21% anaesthesia greater than 60 less than 120 min; 15.31% greater than 120 min anaesthesia). Urinary infections were more frequent when the patients where catheterized at least once in the postoperative period (24.86% vs 3.2%).


[Rhabdomyolysis in meningoencephalitis caused by echovirus]. We report one case of atraumatic rhabdomyolysis associated with Echo group viral encephalitis, not complicated by acute renal failure. Clinical and bio-humoral outlines are described, characterized by favourable evolution despite high muscular enzymatic peaks. We emphasize that the positive course is probably due to the early institution of prophylactic measures, and that, anyway, the subject still remains exposed to major rhabdomyolysis risk in the presence of stress factors, including general anesthesia.


[Bilateral pneumonia caused by Chlamydia psittaci. Description of a clinical case]. A mortal case of atypical pneumonia due to Chlamydia psittaci with acute respiratory distress, septic shock and multiple organ failure is described. Infection has been caused by an ill parrot imported clandestinely. Antibody titration with the immunofluorescence technique allowed diagnosis.


[Multiorgan failure syndrome in multiple pregnancy gestosis]. The Authors report a clinical case of Multi Organ Failure in a young woman who had given birth to triplets. After a short recall of Multi Organ Failure Syndrome, the Authors describe the clinical course and the therapy used in this case.


[The surgical treatment of biliary lithiasis in the patient of an advanced age]. The paper reports the authors' experience in the treatment of biliary lithiasis in elderly patients. The indications for surgery are examined taking into account the possibilities offered by the introduction of new technologies, and in particular preoperative EPST.


[Neuroleptic malignant syndrome. Problems of differential diagnosis. Description of a clinical case]. Neuroleptic malignant syndrome (NMS) in its most severe form ranging from disorders of consciousness to coma is now reported relatively frequently in intensive care journals. Having observed such a case in the intensive care ward of their hospital, the Authors investigate the possibility of differential diagnosis between this syndrome and other prevalently psychiatric and non-psychiatric types. It is underlined that the diagnosis of NMS is not straightforward taking into account both the type of patients who are mainly affected, that is to say psychopathic subjects undergoing prolonged therapy with heavy tranquillisers, in poor general condition, sometimes abandoned and then found in coma, and the fact that some psychiatric syndromes or drug overdoses may led to similar symptoms but require completely different treatment.


[The late complications and nutritional follow-up in 96 patients who underwent a total gastrectomy]. Clinical and nutritional follow-up was performed in 96 patients who had undergone total gastrectomy. We studied the incidence of clinical complications and alterations of nutritional parameters in those patients who had undergone curative resection and were alive and free of neoplastic disease 1 year (36 patients) and 2 years (26 patients) after operation. We observed a very low incidence of late complications, and nutritional parameters, 1 year and 2 years after operation, were normal in almost all the patients. We obtained these results because we performed a Roux en Y esophagojejunostomy using an at least 60 cm-loop; we also adopted a strict and rigorous follow-up, able to guarantee an adequate daily calorie intake. In fact, a close relationship between calorie intake and the variations of nutritional parameters was observed.


[Anesthesia of the brain stem after a retrobulbar block. Description of 2 cases]. The Authors report two cases of central nervous system complications after retrobulbar block. These complications have a 0.044% incidence in 4500 subsequent cases of retrobulbar blockade studied from 1981 to 1990. The Authors attribute the respiratory arrest and coma to direct access of the anesthetic to the central nervous system along the subdural space in the optic nerve sheath.


[Massive metachronous inguinal metastases of carcinoma of the anal margin. A clinical case report]. The authors report a case of epidermoid carcinoma of the anal margin with repeated metachronous metastases in the inguinal lymph nodes. The treatment of synchronous ad metachronous metastases is briefly discussed through a literature review.


[A case of primary carcinoma of the duodenum with subampullar localization]. The authors illustrate a case of previous duodenal adenocarcinoma with subvaterian localization and, after revising the literature and some general remarks, they explain their practice. They come to the conclusion that in some well selected cases, duodenal segmental resection can be correctly applied. They remember that the most important factor of the improvement of the prognosis is early diagnosis: it is indispensable for radical exerectical therapy.


[Warthin's tumor of the parotid. The signs of a case]. The authors report a case of Warthin's tumor associated with cat scratch disease placed in 2 nodes. Both arose at the same time and evolved rapidly. Diagnosis was made by histology after their removal. We underline the rarity of the pathology, the frequent diagnosis made after operation and recommend enuclouresection of neoplasm as the first choice, considering the benignity of the lesion and the modest aggression allowed.


[Usefulness and limits of a fetal biophysical profile in the management of pregnancy at risk]. Usefulness and limits of fetal biophysical profile (BPP) were determined in 132 high-risk pregnancies, evaluating the relationship between the last biophysical profile result and perinatal outcome. The presence of a low incidence of perinatal complications when BPP is normal permits the conservative management of these pregnancies. When the score is abnormal instead, there is also high false positive rate that may determine an unnecessary intervention with associated perinatal morbidity. On the other hand, BPP seems to become abnormal relatively late in the chronic asphyxial process, when it may be impossible to prevent mortality or a serious perinatal morbidity: its association with other tests is therefore necessary for a better evaluation of fetal risk.


[Proposal for the treatment of cervix dysplasia with immunomodulators]. The study included 60 patients: 43 suffered from slight portio dysplasia (12 had HPV infection also), while 17 had moderate dysplasia (7 had HPV infections also). The treatment was carried out by self-administration in 3 stages: attack (50 mg of thymopentin by s.c. injection every day for two weeks); maintenance (50 mg of thymopentin by s.c. injection every other day for ten weeks); recall 6 months after (50 mg of thymopentin every day for 4 weeks). The drug was well tolerated by all of the patients and the recovery rate in a 9-months follow-up period was significantly higher versus an historical control group.


[Effectiveness of transdermal administration of 17-beta-estradiol in the management of menopause]. Seventeen-beta-estradiol administered via a transdermic route was used to treat menopausal symptoms. The results obtained demonstrate the drug's good level of tolerability and considerable efficacy.


[Conservative treatment of tubal pregnancy with parenteral administration of methotrexate. Case contribution]. Three subjects with tubal ectopic pregnancy were treated with intravenous administration of methotrexate followed by oral administration of folinic acid. The treatment was effective in obtaining the resolution of ectopic pregnancies in all cases. Tubal patency was also preserved.


[Use of nabumetone in the treatment of primary dysmenorrhea. Report of 100 cases]. The aim of the study was to assess the efficacy and tolerability of nabumetone, a new nonsteroid anti-inflammatory agent with analgesic and antipyretic functions, in the treatment of primary dysmenorrhea in 100 patients. Treatment was administered at a dose of 1 g per day for slight and moderate cases and 2 g per day for severe forms, starting from the onset of painful symptoms and lasting while they persisted. Side effects were observed in 7% of cases but were limited to the gastroenteric tract. The analysis of results confirms that with regard to the remission of symptoms, treatment was efficacious from the second month and that a further improvement was obtained with continued treatment. However, the Authors observed that, although the remission of symptoms was partial in the majority of cases, there was a greater response in cases of moderate or severe dysmenorrhea and their duration was shorter in comparison to those months in which patients had not received nabumetone treatment.


[Calcium folate in pregnancy. Therapeutic efficacy]. An open, randomised multicentre study was carried out to compare pregnant women, treated with calcium folinate (Citofolin Bracco S.p.A.) 15 mg/day per os starting from the 12th or 20th week of gestation, with an untreated group. The results obtained confirm the efficacy of calcium folinate treatment on the trends of parameters analysed (serum and endoerythrocytic folatemia, hemoglobin and sideremia) which remained within the normal range. Moreover, no adverse effects of any type were reported during the study.


[A case of surgical ligature of the sacro-iliac joint from Renaissance Central Italy]. The paper reports a case of interbone ligature between the sacrum and right ileum using copper wire in an adult woman whose skeleton, dating from approximately 1600-1700 A.D., was exhumed from the Church of Sant'Egidio in Borrello (Chieti). Having described the ligature and the techniques used, the Authors discuss the reasons for the operation. In conclusion, it is suggested that the most plausible hypothesis is that it represent an interbone ligature during the course of autopsy to allow the recomposition of a corpse with a sacro-ileal dislocation. The absence of signs of sacro-ileal dislocation caused by mechanical levers during the course of autopsy leads the Authors to suppose the sacro-ileal rupture occurred while the subject was still alive. The Authors therefore hypothesise that the woman died while giving birth following the laceration of the pubic symphysis and rupture of the right sacro-ileal joint. The hypothesis of a corpse restoration is also suggested.


[Fetal bradycardia during the second stage of labor. Study of 72 cases]. The Authors analyse cardiotocographic patterns characterized by a constant frequency level below 120 beats/minute during the second stage of labour. Some aspects of "terminal bradycardia" (length, amplitude of oscillations, fetal heart rate in the 30 minutes preceding the onset of bradycardia) are related with the condition of the newborn (1st and 5th minute Apgar-score). Terminal bradycardia (Fischer 3, Melchior 2, 3 and 4, 2nd and 4th of Thiery) seems to have an unfavourable prognostic value especially when prolonged (more than 20 minutes), associated with low base-line variability and when cardiotocographic pattern previous to the fall of frequency is characterized by variable and late decelerations.


Effect of different agonistic experiences on behavioural seizures in fully amygdala kindled rats. Fully amygdala kindled rats were exposed to two different inter-male agonistic experiences in order to study the interaction between epilepsy and acute social stress. Victory experience did not influence the severity of seizure behaviour, whereas a single acute defeat modified both ictal and postictal seizure manifestations. Defeat resulted in less severe and shorter lasting motor seizures, and the accompanied postictal inhibition or behavioural depression was of shorter duration in comparison with pre-stress values. The ability of acute defeat to trigger anticonvulsant activity as implied by the weakened convulsive response is discussed.


[Pseudomyxoma of the peritoneum caused by rupture of a mucinous cystoma of the ovary. Description of a case]. A case of pseudomyxoma peritonei originating from spontaneous rupture of an ovaric mucinous cystoma is described: in this pathology we observe the spreading throughout the peritoneal cavity of free or encapsulated gelatinous masses arising from primitive lesion. The examined case presented a spreading of mucinous masses on contralateral ovary and omentum and a total laparo-hysterectomy, bilateral annessiectomy and omentectomy has been carried out. A year after surgery, on the base of a three months follow-up, no clinical or ultrasonic signs of local recurrence has been noticed. The pathogenesis of this pathology is discussed: the flogistic hypothesis considering such a spreading as a "foreign body" peritonitis and the neoplastic one, pointing out a metastatic process of mucus-secretive epithelia implantation as the etiopathogenetic moment of the injury, are actually the most accredited hypothesis by literature.


[Bilateral ovariectomy in gonadal dysgenesis with a Y chromosome]. The Authors report 4 cases of gonadal dysgenesis with a Y chromosome. Every patient underwent bilateral oophorectomy. Two cases of streak gonads, 1 case of streak gonad and gonadoblastoma and 1 case of non metastasizing bilateral gonadoblastoma with foci of dysgerminoma have been found. The Authors emphasize the importance of early bilateral gonadectomy in all cases of gonadal dysgenesis with a Y chromosome.


Hippocampal kindling leads to different changes in paired-pulse depression of local evoked field potentials in CA1 area and in fascia dentata. Monosynaptic evoked field potentials (EPs) in response to paired-pulse stimulation (20 ms interval) were recorded in area CA1 and fascia dentata of the same animal in the course of development of a kindled focus in the CA1 region. A significant reduction of paired pulse depression in response to medium and high stimulation intensity was found in CA1. A similar change was found in the fascia dentata in response to medium intensity stimulation of the angular bundle. In contrast, at high intensity, paired pulse depression was enhanced in the fascia dentata in the course of kindling. These results indicate that kindling epileptogenesis is accompanied by regionally different changes in recurrent inhibition: a reduction in CA1 and intensity dependent changes in fascia dentata.


[An unusual case of regular menstrual cycles and endocrine pattern typical for the reproductive age in a patient of advanced age]. The Authors report the persistence of regular menses in a very old woman. Although in the absence of a pulsatile gonadotropin pattern the patient showed estradiol levels typical of the reproductive age.


[Effects of estradiol on in vitro cultures of human fibroblasts]. This paper assesses the effect of estradiol on the in vitro growth of fibroblast taken from human breast skin. It was observed that estrogens stimulate the proliferation of phenotypically adult fibroblasts; that there is a threshold increase of hormonal concentration which can trigger off this process; and that the size of the single dose is more important than the number of doses of hormone received.


Different functional pools of acetylcholinesterase induce changes in rat locus coeruleus noradrenaline metabolism. The effects of acetylcholinesterase (AChE) inhibition in the locus coeruleus (LC) were studied in rats utilizing fasciculin (FAS) and BW248c51 (BW). Both inhibitors were stereotaxically injected into the right LC and the animals were sacrificed 24 h later. Similar groups received atropine (30 mg/kg i.p.) every 5 h during 24 h. Another group of FAS-treated rats received naloxone twice (5 mg/kg i.p.) in 24 h. Other groups of FAS-treated rats were sacrificed 3 and 7 days after injection. An inhibition of 70% of LC AChE activity was observed 24 h after FAS or BW injection. Either FAS or BW induced a significant increase in NA levels in the injected LC compared to control values. Atropine treatment failed to block the FAS effect but it was able to counteract the BW-induced NA increase. NA levels were still increased 3 days after FAS treatment and returned to control values at day 7.


Evidence for genetic determination in human twins of olfactory thresholds for a standard odorant. Olfactory thresholds for four odorants were determined in groups of monozygotic and dizygotic human twins. Odorants were presented in an ascending dilution series in odorless solvent, using a three-way forced choice method. For two of the tested odorants, 5 alpha-androst-16-en-3-one and isoamyl acetate, the thresholds showed a strong genetic component. This was demonstrated by respective values of 0.78 and 0.73 for the intraclass correlation difference, and of z = 3.69 and z = 2.71 in a within-pair difference analysis. The results for isoamyl acetate are novel, and suggest that genetic polymorphism in the affinity of odorant receptor proteins contributes to the (nearly normal) threshold distribution for this odorant.


Photo-ablation of single neurons in the fly visual system reveals neural circuit for the detection of small moving objects. Many animals use relative motion to segregate objects from their background. Nerve cells tuned to this visual cue have been found in various animal groups, such as insects, amphibians, birds and mammals. Well examined examples are the figure detection (FD) cells in the visual system of the blowfly. The mechanism that tunes a particular FD-cell, the FD1-cell, to small-field motion is analyzed by injecting individual visual interneurons with a fluorescent dye and ablating them by illumination with a laser beam. In this way, it is shown that the FD1-cell acquires its specific spatial tuning by inhibitory input from an identified GABAergic cell, the ventral centrifugal horizontal (VCH)-cell which is most sensitive to coherent large-field motion in front of both eyes. For the first time, the detection of small objects by evaluation of their motion parallax, thus, can be attributed to synaptic interactions between identified neurons.


Effects of locus ceruleus lesions on the pericapillary nerve terminals in the feline brain. The effects of bilateral locus ceruleus (LC) lesions on the pericapillary nerve terminals were investigated in the feline brain parenchyma using electron microscopy. LC lesions were induced stereotaxically and the animals were sacrificed after intravenous administration of 5-hydroxydopamine (5-OHDA). The diameter and number of dense-cored vesicles (DCVs) and clear vesicles (CVs) in the pericapillary nerve terminals were measured. The number of DCVs in the nerve terminal was significantly decreased by bilateral LC lesions. The diameters of the DCVs and CVs decreased significantly as compared with those in the non-operated control group. These data suggest that the LC is closely related to the pericapillary nerve terminals in the brain parenchyma and that not only nerve terminals with DCVs but also those with CVs are affected by LC lesions.


Preservation of Gi-protein inhibited adenylyl cyclase activity in the brains of patients with Alzheimer's disease. The coupling of inhibitory guanine nucleotide binding (Gi) proteins to the adenylyl cyclase signal transduction complex was compared in 4 brain regions from a series of Alzheimer's disease and matched control subjects by measuring the inhibition of membrane enzyme activities in response to guanosine 5'-[beta gamma-imido]diphosphate (Gpp[NH]p) and aluminium fluoride (AlF4-). Basal adenylyl cyclase activities were significantly lower in preparations of angular gyrus and frontal and temporal cortices, but not cerebellum, from the Alzheimer's disease cases compared to controls. Gpp[NH]p and AlF4- gave significant inhibitions of adenylyl cyclase activity in all brain regions. The magnitude of these inhibitions, when corrected for altered basal activities, were similar for the Alzheimer's disease and control cases. These results indicate that there is no impairment of Gi-protein mediated inhibition of adenylyl cyclase activity in Alzheimer's disease brain.


Concurrent wet dog shaking and inhibition of male rat copulation after ventromedial brainstem injection of the 5-HT2 agonist DOI. Systemic administration of drugs that augment 5-HT2 activity generally induces 'wet dog' shaking (WDS) in rats. This suggests that the naturally occurring form of WDS seen in untreated rats may also serve as a behavioral index of 5-HT2 receptor activation, during the performance of other behaviors. Indeed, spontaneously occurring WDS has previously been reported to be inversely related to male rat copulatory proficiency. In order to examine a potential central nervous system mechanism subsuming these behaviors, male rats were tested for WDS and sexual behavior after brainstem administration of the 5-HT2 agonist DOI. Male Long-Evans rats were implanted with cannulae terminating in the region of the nucleus raphe obscurus/inferior olive, through which they received injections of DOI (0.1-10 micrograms). DOI produced a dose-dependent decrease in sexual behavior and concurrent increase in WDS. Pretreatment with the 5-HT2 antagonist ritanserin effectively blocked the effects of DOI. The results suggest that WDS and copulatory behaviors are modulated by a shared brainstem substrate. It is possible that the results may be the behavioral concomitant of recently described brainstem cells, with bifurcating axons, that project to both the medial preoptic area and the cervical spinal cord.


Serotonin is found in myelinated axons of the dorsolateral funiculus in monkeys. Physiological measurements suggest that the inhibition of primate spinothalamic tract cells by serotonin is mediated by myelinated axons. Previous morphologic studies emphasize that most serotonin-containing axons in the spinal cord are unmyelinated. Accordingly, the possibility that some serotonin-containing axons in the primate dorsolateral funiculus of the spinal cord are myelinated was investigated. Macaque monkeys were given L-tryptophan and the monoamine oxidase inhibitor, nialamide, intraperitoneally 1 h prior to sacrifice to increase axonal stores of serotonin. The animals were perfused (0.05 or 0.5% glutaraldehyde, 4% paraformaldehyde), and transverse sections of the thoracic cord were reacted with antibody against serotonin and then prepared for electron microscopy. Many of the immunostained axons in the dorsolateral funiculus included fine, myelinated fibers with diameters of 0.7-2.2 microns. Unmyelinated serotonin-containing axons were also observed. The observation of myelinated serotonin-containing axons in the white matter of the monkey dorsolateral funiculus contradicts the view that the descending serotoninergic projection consists entirely of unmyelinated fibers, particularly since the conduction velocity of the fine fibers would be too slow to account for the earliest latency of descending inhibition following stimulation in the brainstem. The presence of myelinated serotoninergic axons presumably accounts for the latencies reported for the inhibition of primate spinothalamic cells following stimulation of the periaqueductal gray, an inhibition that can be blocked with serotonin antagonists and that is associated with the release of serotonin in the dorsal horn.


Passive electrophysiological properties of aged and axotomized cat spinal cord motoneurons: the effect of cell size and electrode shunt. Intracellular recordings were obtained from intact and axotomized lumbar motoneurons of aged cats. The sub-threshold electrical properties of these cells were measured, including input resistance, resting membrane potential, and the first two equalizing time constants as well as their associated amplitude constants. These data were used in a semi-infinite cable model of the motoneuron to estimate the size of the shunt resistance (Rshunt) which is created when the electrode penetrates the cell membrane. The average Rshunt for intact aged cells was 5.35 +/- 1.01 M omega, while that for the axotomized aged cells was 8.93 +/- 1.20 M omega. The statistically significant difference in mean shunt magnitude did not affect the measurements of membrane time constant because this constant is independent of the shunt in this model of the motoneuron. However, the determination of cell input resistance, which is not independent of the shunt, was shown to underestimate the real cell input resistance by 23-29%. We therefore conclude that the shunt resistance is an important factor which should be taken into account when measuring input resistance.


Near-infrared FT-Raman spectra of the rat brain tissues. Near-infrared Fourier transform (FT) Raman spectroscopy was applied to brain tissues in situ. The spectra were obtained from the cerebral cortex, white matter of the cerebrum, caudate-putamen, thalamus, synaptosomal fraction, and myelin fraction. High-quality Raman spectra in the 400 to 2940 cm-1 range were measured without interference of autofluorescence. Common spectral bands were assigned. The ratios of the intensity at 1664 (amide I), 1442 (CH2 deformation), 2885 (CH2 asymmetric stretching), 2938 cm-1 (CH3 symmetric stretching) could be used for differentiation between the gray and white matters.


A selective reduction of excitatory amino acids in cerebrospinal fluid of patients with Alzheimer type dementia compared with vascular dementia of the Binswanger type. We determined the concentrations of the putative transmitter amino acids in the cerebrospinal fluid of patients with Alzheimer type dementia (ATD) and vascular dementia of the Binswanger type (VDBT). In ATD, aspartate and glutamate concentrations were significantly and selectively reduced, while in VDBT, concentrations of aspartate, glutamate, gamma-aminobutyric acid (GABA) and many other amino acids were decreased non-selectively. In both ATD and VDBT, we found a tendency for all amino acids to increase with progression of the disease, and this reached statistical significance for some amino acids.


Calcium dependent release of gamma-aminobutyric acid (GABA) from human cerebral cortex. The release of the amino acids GABA, taurine, glycine, glutamine and leucine from human neocortex was investigated in vitro by utilizing brain tissue removed during 8 standard temporal lobectomies for epilepsy or tumor. Slices (0.5 mm thick) were cut from each biopsy and randomly placed in three different chambers. After 90 min preincubation, the three sets of slices were incubated for 60 s in wells containing, respectively, (A) regular ACSF (control), (B) ACSF with 50 mM K+ (to depolarize the cell membrane) and (C) ACSF with 50 mM K+, 0 mM Ca2+ and 4 mM Mg2+ (depolarization during blocked synaptic transmission). The content of amino acids in the wells was determined by high-performance liquid chromatography after pre-column derivatization of the amino acids with o-phthalaldehyde. Membrane depolarization (well B) increased the GABA release to 650% (620 pmol/mg) of control (well A, 95 pmol/mg). Blocking synaptic transmission (well C) reduced the evoked release by 50% (360 pmol/mg). The release of glycine, taurine, glutamine and leucine during membrane depolarization was not significantly different from the control values. The data provide evidence for a Ca(2+)-dependent release of GABA, supporting a possible role of this amino acid as a neurotransmitter in human neocortex.


Delta-6 desaturation of alpha-linolenic acid in brain and liver during development and aging in the mouse. During pre- and postnatal brain development, delta-6 desaturase decreased dramatically (approx. 4-fold) up to weaning, slowly (2-fold) up to 3 months, and remained nearly constant and extremely low thereafter. In contrast, in liver, the activity increased approximately 7-fold between day 3 before birth and day 11 after birth, then decreased slightly up to weaning, and was constant up to 9 months. Subsequently, the activity decreased during aging (4-fold between 9 and 26 months). During aging, the reduced activity in liver and the very low activity in brain raise the question of the origin of polyunsaturated fatty acids participating in the physiological turnover of brain membranes.


Improved direct sequencing of Alzheimer's amyloid precursor protein (APP) exons 16 and 17. Direct sequencing of exon 17 of the amyloid precursor protein (APP) gene led to the identification of 3 different types of APP717 pathogenic mutations associated with familial Alzheimer's disease (FAD). The low frequency of these mutations results in having to screen many samples in order to identify new families affected by them, which is laborious and time consuming. Thus, in order to help the identification of these mutations in additional countries and to search for new mutations in APP, perhaps in other exons also causing FAD, we have optimized the procedure and reduced the time necessary for sample preparation from 11 h to 3 1/2 h.


5-Hydroxytryptophan (5-HTP) augments spontaneous and evoked phrenic motoneuron discharge in spinalized rats. Experiments on anesthetized, spinalized rats were conducted to determine the effects of systemic 5-hydroxytryptophan (5-HTP) administration on: (1) spontaneous phrenic nerve activity and (2) evoked phrenic responses to short latency, non-serotonergic synaptic inputs elicited by electrical stimulation of lateral funiculus. 5-HTP augmented spontaneous phrenic activity and allowed expression of a second, longer latency evoked response. Both effects were antagonized by methysergide. Our results suggest that spinal serotonin increases the efficacy of synaptic inputs to phrenic motoneurons.


Endogenous opioid regulation of norepinephrine release in guinea pig hippocampus. Release of endogenous norepinephrine was detected in guinea pig hippocampal slices using a radioligand displacement assay. Focal electrical stimulation released endogenous norepinephrine and caused a calcium-dependent reduction in specific [3H]propranolol binding at beta-adrenergic receptors in the brain slice. The mu-opioid agonist PL017 decreased norepinephrine release, and the inhibition by PL017 could be blocked by the opioid antagonist naloxone. Endogenous opioid peptides concomitantly released by tissue stimulation also decreased norepinephrine release in a naloxone-sensitive manner. These results support the hypothesis that endogenous opioids can regulate excitability in the hippocampus by presynaptic modulation of norepinephrine release.


Concentrations of serotonin and its related substances in the cerebrospinal fluid in patients with Alzheimer type dementia. We studied concentrations of free and total serotonin (5-hydroxytryptamine, 5-HT) and its related substances in the cerebrospinal fluid from patients with Alzheimer type dementia (ATD) compared with controls. In ATD patients, concentrations of total 5-HT, tryptophan, 5-hydroxytryptophan (5-HTP), melatonin, kynurenine, and 3-hydroxykynurenine decreased significantly. The rate of concentration of tryptophan metabolites to that of tryptophan was significantly reduced for total 5-HT and 3-hydroxykynurenine only. The 5-hydroxyindoleacetic acid (5-HIAA)/5-HT ratio was significantly larger in ATD patients than in controls. The greater reduction in the 3-hydroxykynurenine concentration (81% vs. controls) than in the total 5-HT concentration (51% vs. controls) suggests that the metabolism of tryptophan to 5-HT and 3-hydroxykynurenine is in favor of 5-HT.


Theta rhythms in the rat medial entorhinal cortex in vitro: evidence for involvement of muscarinic receptors. Slice preparation obtained from the rat were used to study cholinergically induced field potentials in the medial entorhinal cortex. Perfusion of slices containing medial entorhinal cortex with acetylcholine, muscarine and eserine induced theta-like activity in a frequency range of 3-10 Hz and an amplitude of 200-300 microV. Nicotine, in contrast, did not produce any rhythmical slow waveforms. The cholinergically induced theta-like oscillations were abolished by perfusion of the muscarinic antagonists atropine sulphate and scopolamine but were unaffected by the nicotine blockers hexamethonium and mecamylamine.


Comparison of screening approaches.

Comparison of screening approaches. Neurobehavioral techniques have been used extensively in animal toxicology studies because, in many cases, such procedures are designed to evaluate neurobiological functions thought to be affected in chemical-exposed humans, e.g., changes in sensorimotor function. Procedures used to identify or screen for the presence of neurotoxicity are usually designed to test large numbers of animals and are not considered to be as sensitive to subtle effects as more specialized tests for neurobiological dysfunction. For purposes of screening, the use of a functional observational battery (FOB) is now generally accepted. In general, FOB evaluations in animals are similar to clinical neurological examinations in humans in that they rate the presence and, in some cases, the severity of behavioral and neurological signs. A number of batteries containing different observations and measurements have been developed in several laboratories for rodents, dogs, and non-human primates. Frequently, the FOB is used in conjunction with other measures of neurotoxicity, i.e., neuropathology or sensory evoked potentials. FOB used in screening typically assess several neurobiological domains including neuromuscular (i.e., weakness, incoordination, abnormal movements, gait, motor seizures, myoclonia, rigidity and tremor), sensory (i.e., auditory, visual and somatosensory) and autonomic (i.e., pupil response, salivation) functions. Most FOB used for screening do not assess cognitive function (i.e., learning and memory). FOB evaluations can yield important information concerning dose-response characteristics and data on the onset, duration and persistence of an effect. FOB should be able to differentiate neurotoxicants from non-neurotoxicants and neurotoxicants having different mechanism(s) or site(s) of action.


Neuroplasticity, the aging brain, and Alzheimer's disease. A variety of neurological disorders are associated with the loss of specific populations of neurons. Alzheimer's, Parkinson's, and Huntington's diseases present unique constellations of behavioral and neurological abnormalities which result from the degeneration of neurons in specific regions of the brain. Approaches to the treatment of these neurodegenerative disorders have met with either limited or no success. New treatment strategies based upon a better understanding of the inherent mechanisms of neuroplasticity might provide more rational approaches to prevent, limit, or treat these and other neurodegenerative disorders. The development and standardization of appropriate animal models of neurodegenerative disorders will be essential to realize this possibility. Using the cholinergic neurotoxin AF64A we have developed a rodent model of cholinergic hypofunction that exhibits behavioral, anatomical, and neurochemical deficits very analogous to those observed in Alzheimer's disease. Furthermore, we have found that administration of neurotrophic factors, such as ganglioside AGF2, and the transplantation of fetal cholinergic neurons into the hippocampus can attenuate both the behavioral and neurobiological alterations induced by AF64A. These efforts should lead to the development of innovative clinical strategies and they should also help to elucidate the neurobiology of brain injury and recovery of function.


Enhanced expression of glial fibrillary acidic protein and the cupric silver degeneration reaction can be used as sensitive and early indicators of neurotoxicity. The mammalian central nervous system is composed of a large and diverse array of its two principle cell types, neurons and glia. Given this extreme cellular heterogeneity, it is not surprising that targets of neurotoxic insult often are diverse and unpredictable. In devising strategies to assess neurotoxicity, one must overcome the obstacle posed by not knowing where to look for damage. Our approach to the detection and localization of sites of toxicant-induced damage has been to take advantage of two general responses to nervous system insult, astrogliosis and argyrophilia. Assays for GFAP, the principle intermediate filament protein of astrocytes, have been devised to quantify astrogliosis and a modified cupric silver degeneration stain has been employed to examine patterns of argyrophilia. Using these methods, we found that increases in GFAP and the occurrence of argyrophilia are consistent responses to neurotoxic insults. Moreover, increments in these two indicators reveal dose-, time- and region-dependent patterns of neurotoxicity at toxicant dosages below those that cause light microscopic evidence of cell loss or damage. The rapid onset of astrogliosis and argyrophilia following specific toxicant exposures suggests that the signals underlying these events are among the earliest that can be linked to the neurotoxic state.


Perturbation of axonal elemental composition and water content: implication for neurotoxic mechanisms. The concentration and distribution of labile elements in nerve cells is tightly regulated by multiple membrane transport processes and by binding to lipids and proteins. The multifaceted nature of elemental regulation provides numerous sites at which toxicants or disease processes might act to disrupt this regulation. Such disruption can affect cytoskeletal integrity, macromolecular synthesis, energy production, osmoregulation and other cellular processes. The possible role of perturbed elemental homeostasis in the mechanism of nerve injury caused by certain chemicals (e.g., acrylamide, 2,5-hexanedione) and neuropathic diseases (e.g., diabetes) has not been determined. To investigate this possibility, we have used electron probe x-ray micro-analysis (EPMA) to measure the distribution of elements and water in cellular compartments of myelinated axons (axoplasm, mitochondria) and glial cells (cytoplasm, myelin) in normal rat central and peripheral nervous systems. Results indicate that each compartment exhibits a characteristic composition of elements and water which might reflect function of that anatomical region or organelle. Injury-induced changes in elemental content of PNS axons and Schwann cells have been identified using several neurotoxic models (i.e., acrylamide, axotomy, diabetic neuropathy). Each type of injury initiated early alterations in element and water composition of both axons and glial cells. Compositional changes were specific and developed sequentially instead of simultaneously. Results of these studies suggest that, rather than being an epiphenomenon, altered elemental regulation might represent a primary component of many neurotoxic mechanisms.


Ca(2+)-dependent processes as mediators of neurotoxicity. The Ca2+ ion exerts a profound influence on cellular processes and an understanding of control mechanisms of intracellular Ca2 homeostasis while complex is mandatory in this discussion. The identification and recognition of prolonged sustained increase in [Ca2+]i as a manifestation of neurotoxin-induced destabilization of [Ca2+]i homeostasis will be related to a variety of neurotoxicant-induced cell injuries. The sites of toxicant interaction with ATP-regulated Ca2+ pumps located in the neuronal/glial membrane and/or calciosomes; availability of Ca2+ proteins; disruption in mitochondrial mechanisms for Ca2+ storage; triggers of voltage-dependent Ca2+ channels and modulation of the Na+/Ca2+ exchanger will be identified and related to presumptive toxin action. Failure of one or more of these systems will result in continuous elevation of ionized [Ca2+]i--a reflection of Ca2+ destabilization. The targets resulting from Ca2+ destabilization will be identified, to include phospholipase C activation, PLA2 activation, protein kinase C (PKC) translocation, and activation of Ca(2+)-dependent calpain 1. The use of specific inhibitors of neurotoxicity, e.g., natural sphingolipids, sphingosine, down regulation of PKC, inhibitors and activators of adenylate cyclase, and antiprotease agents will allow for investigation of the role of these final common pathways in the evolution of neurotoxicity.


Cross species extrapolation in neurotoxicology: neurophysiological and neurobehavioral aspects. The theory of phylogenetic continuity of animal species is the basis of any comparative or extrapolative endeavour (Calabrese, 1983). Cross species extrapolation is also a prerequisite for hazard identification in general and developmental neurotoxicology. Two steps must be distinguished: The first step is endpoint-based or qualitative, whereas the second is dose-based or quantitative. Comparison of different species, typically rodents, nonhuman primates and humans, in terms of endpoints is preferentially done within a framework of broad functional categories, such as sensory, motivational, cognitive, motor, and social variables. Within each category specific neurobehavioral as well as electrophysiological measures need to be considered; typically the degree of comparability is higher for electrophysiological than for most behavioral measures. For some frequently used behavioral endpoints in human neurotoxicology, such as psychometric IQ, there is no direct animal counterpart. Once the neural substrate of a particular neurotoxic effect has been identified, as is true for several chemicals such as the pyrethroid insecticides, the organophosphates, most nerve gases or MPTP, or if interspecies comparability in terms of endpoints has proven satisfactory, an effort towards quantitative, dose-based extrapolation is needed. Here species-specific differences in toxicokinetics and metabolism must be taken into consideration in order to arrive at valid translations of dose-response contingencies. If at all possible internal rather than external doses should serve as the frame of reference here. Neurotoxic chemicals of environmental concern for which an adequate data base is available for comparative purposes include alcohol, carbon monoxide, lead, methylmercury and polychlorinated biphenyls (PCB). Principles of cross species extrapolation in neurotoxicology will be illustrated by means of representative neurobehavioral and electrophysiological findings.


2,5-Hexanedione is a potent gliatoxin in in-vitro cell cultures of the nervous system. Of the metabolites of hexane, 2,5-hexanedione (2,5 HD) has the strongest neurotoxic effect. There is a wealth of experimental studies in animals showing an axonotoxic mechanism consisting of an accumulation of 10 nm neurofilaments. Only few studies deal with a possible action of 2,5-HD on Schwann cells, glia cells or both. Pure neurons, pure glia and mixed cultures prepared from dorsal root ganglia (DRG) of chick embryos were studied in this model. DRG were chosen because they constitute a linkage between the peripheral and central nervous system and provide the additional advantage of containing only few defined glial and neuronal cell types. Additionally, pure neuronal cultures of sympathetic ganglia and mixed cultures of spinal cord and brain were prepared. In cultures of the different parts of the nervous system investigated, we observed at a concentration of 0.25% 2,5-HD massive toxic alterations of glial cells, whereas neurons and neurites were virtually unaffected.


Specific neurotoxic effects of different organic solvents on dissociated cultures of the nervous system. Pure neurons were prepared from dorsal root ganglia (DRG) of 8 day old chick embryos (E8). The substances tested in this model were pure n-hexane, 2.5-hexanedione (2.5 HD) and methyl-ethyl-ketone (MEK). Differentiated cultures were exposed to these neurotoxins after two days in culture and then examined over a period of up to one week. For all three substances a specific neurotoxic effect could be demonstrated: (i) n-Hexane mainly altered the neurites, leading to focal swellings and in a second step to degenerative changes in glial cells; (ii) 2.5 HD had a minor effect on neurons and proved to be mainly gliatoxic; (iii) MEK primarily affected the neurons by swelling and disintegration of the cell body.


Irradiation neurotoxicity assessed in organotypic cultures of rat hippocampus. The neurotoxic effects of irradiation on the developing nervous system were studied in organotypic cultures of hippocampus prepared from newborn Sprague-Dawley rats. Hippocampus slices of 7-day-old rats were irradiated at the day of explantation at doses of 1, 2 and 4 Gy, and cultured in a roller drum for a fortnight. Light and electron microscopy showed remarkable damage to neuronal cells following irradiation, oligodendrocytes and myelogenesis being also affected. In contrast to alterations in neuronal perikarya, no morphological changes in synapses were obvious, though their number seemed to be reduced after irradiation with 4 Gy. These results confirm that low dose radiation produces damage to the central nervous system not only pre-natally, but even in post-natal periods of differentiation and development.


In vitro screening batteries for neurotoxicants. The need to develop, validate and utilize in vitro models to test chemicals for neurotoxic potential is widely appreciated. This lecture discusses the major advantages of using cell and tissue culture, the various in vitro models amenable for neurotoxicity studies, and the distinction between mechanistic and screening models. Considerations for designing screening batteries to evaluate neurotoxicants are discussed. Topics such as choice of appropriate cell models and endpoints (i.e., cytotoxic and neurotoxic), and technical considerations in the design of the battery are also presented.


The effects of 2,5-hexanedione on rods and cones of the retina of albino rats. Light microscopic morphometry has shown that albino rats exposed to 2,5-hexanedione (2,5-HD) or 2,5-hexanediol (2,5-HDol) develop degeneration of rods and cones in a 12 hr light/12 hr darkness environment. To determine whether there is selective damage to rods or cones, 7-week old, male Sprague-Dawley rats were exposed to 2,5-HD (1%) in their drinking water during equal periods of light and darkness for 5 weeks. At the end of this time the rats were paralyzed in the hind limbs. Half were then sacrificed and studied while the remaining rats were allowed to recover for 13 weeks. A control group of rats were studied in parallel under identical conditions. The outer nuclear layer in the exposed and control rats was assessed immediately following treatment. The rods were found to be strongly selectively reduced (p less than 0.01) but the cones (2% of all photoreceptor cells) were not significantly affected. Rats permitted to recover for 13 weeks and then sacrificed had lost almost all their rods (p less than 0.001) while the cones were reduced by about 50% (p less than 0.01). Most of the rats had a moderate residue of rods and cones at the ora serrata, an area protected from light energy. These findings suggest that rods are more sensitive than cones to the toxic effects of 2,5-HD in combination with light energy.


Evoked potentials are modified by long term exposure to trichloroethylene. Two groups of New Zealand albino rabbits were respectively exposed to 350 and 700 ppm of trichloroethylene (TRI) 4 hrs/day, 4 days/week for 12 weeks. Weekly, visual evoked potentials (VEP) recordings were obtained under mesopic condition. Blood samples were also collected weekly to determine the concentration of TRI and its metabolites. Recordings from the 350 ppm group showed a significant (p less than 0.001) decrease in the amplitude of VEPs, while a significant (p less than 0.001) increase was observed in the 700 ppm group. Both effects were reversed to baseline values within six weeks after the last exposure. The observed modifications in VEP amplitudes were related to blood level of trichloroethanol. These results thus confirm the neuro-ophthalmotoxicity of TRI and support the hypothesis that trichloroethanol is a reliable marker of the effective neurotoxic dose of this organic solvent.


Auditory brainstem evoked potentials (BAEPs) in lead-exposed workers. Brainstem Evoked Potentials (BAEPs) were recorded in 49 lead exposed workers, and in a control group of 49 age- and sex-matched subjects, never exposed to neurotoxic substances. The mean duration of lead exposure was 7.4 (SD 5.6) yr. Blood lead concentration was analyzed in the morning of the experimental day (PbBc); an averaged PbB level was based on the levels of the 3 previous years (PbBm). Interpeak latency differences (IPLD) I-V, I-III and III-V were considered. The mean PbBc level was 54.6 (SD 16.1) micrograms/dl while the mean PbBm level was 53.5 (SD 15.9) micrograms/dl. Lead exposed workers showed a significant prolongation of IPLDs. IPLD I-V was longer in the subgroup with PbBm greater than 50 micrograms/dl (4.06 vs 3.98, c.l. 95% 0.00-0.16). These results are consistent with literature data and show that BAEPs may be a sensitive detector of subclinical lead effects on brainstem auditory pathways.


Olfactory threshold shift following controlled 7-hour exposure to toluene and/or xylene. The present study was undertaken to examine olfactory perception threshold (OPT) shift following exposure of healthy subjects to toluene and/or xylene in an inhalation chamber. Five volunteers were exposed to 50 ppm toluene, 40 ppm xylene or an additive mixture of the two, for a period of 7 consecutive hr in an inhalation chamber. A Latin square design was used and subjects were exposed over 3 consecutive days/week, with an 11-day interval between each 3-day session. Olfactory perception thresholds, measured in decismels (ds), were ascertained for both toluene and PM-carbinol, contained in 100 ml bottles with serially increasing concentrations (Olfacto-Lab Kits # 191 & 11). Test administration was based on the forced choice method. Analysis of variance of pre-exposure OPTs indicated that for both toluene and PM-carbinol, significant differences were observed between individuals (p less than 0.05), but not between days or weeks. Measurements, made immediately following exposures revealed a significant six-fold increase in OPT for toluene (median: 15 ds), while PM-carbinol OPT remained stable. Individual differences were observed, but there was no effect of type of exposure, day, week, or interactions. OPT for toluene, determined at intervals following cessation of exposure, indicated a return to pre-exposure values at a mean rate of 6.8 ds/hr. The findings of this study suggest that there is a substantial olfactory threshold shift during a 7-hr period, specific to a particular solvent or family of solvents. Receptor-specific saturation is proposed as the underlying mechanism.


Comparative studies on the neuro- and reproductive toxicity of acrylamide and its epoxide metabolite glycidamide in the rat. The neurotoxicity of acrylamide (AA) has been the subject of extensive studies at the morphological and functional levels in both animals and man. The concern for human exposure to monomeric AA derives partly from its extensive use in molecular biology laboratories where, in the United States alone, 100,000-200,000 persons are potentially exposed. Initial work in this laboratory aiming at the development of techniques for using hemoglobin adducts as biomarkers for human exposure to AA, revealed the formation of glycidamide as a reactive epoxide metabolite of acrylamide in the rat (Chem. Res. Toxicol. 3, 406, 1990). In rats treated with 0-100 mg/kg of AA significant dose-rate effects were observed on adduct formation by both AA and glycidamide. The high rate of formation of the metabolite, especially at low doses where approximately 60% of AA was converted to glycidamide in vivo, prompted us to investigate its potential role in the induction of neurotoxic and reproductive effects attributed to AA exposure. In initial neurotoxicological experiments, the effects of the parent compound (8-14 days, 25 and 50 mg/kg/day) and the metabolite (8-14 days, 50 and 100 mg/kg/day) were compared. While at the higher dose both compounds affected the rats' performance on the rotarod, only acrylamide had a significant effect in the hindlimb splay test, which is considered a more sensitive indicator of peripheral neuropathy. On the other hand, a stronger effect was seen for glycidamide than for AA on the male reproductive system, especially on sperm cell viability.(ABSTRACT TRUNCATED AT 250 WORDS)


Interactive effects of toluene and hexane on behavior and neurophysiologic responses in Fischer-344 rats. Solvent mixtures are ubiquitous in industrialized environments and are used frequently for recreational purposes. Toluene and hexane are common components of many solvent mixtures and have characteristic, but different, neurotoxic consequences. Interestingly, Takeuchi et al., (1981) reported that toluene attenuated the peripheral neuropathy caused by n-hexane, possibly by blocking its metabolism to 2,5-hexanedione (Perbellini, et al., 1982). To confirm such effects at higher concentrations and to examine effects on the central nervous system (CNS), four groups of 12 rats each were exposed to air, toluene (1200 ppm), hexane (4000 ppm), or a mixture of toluene (1200 ppm) and hexane (4,000 ppm) 14 hr/day for 9 weeks. A battery of behavioral and electrophysiologic tests was used to assess the functional consequences of their exposures. The battery consisted of measures of grip strength, locomotor gait and landing splay, sensory sensitivities during conditioned avoidance performance, the action potential of the ventral caudal nerve, and the brainstem auditory evoked response. Measures of peripheral nervous system functions (e.g., grip strength and conduction velocity) showed interactive effects like those reported by Takeuchi et al. Toluene greatly reduced the neuropathy caused by hexane. Hexane-induced abnormalities in central components of the brainstem response were much less reduced in the presence of toluene. There was no reciprocal action of hexane on the motor syndrome and hearing loss caused by toluene.


Neurobehavioral and neuroendocrine effects of occupational exposure to perchloroethylene. The hypothesis that long-term low-level exposure to perchloroethylene (PERC) may impair the dopaminergic control of prolactin (PRL) secretion and negatively affect neurobehavioral performance, was tested in a cross-sectional survey of dry-cleaners. Sixty female workers exposed to PERC in dry-cleaning shops and thirty controls recruited in a cleaning plant not using solvents were examined. PERC air concentration during four-hour random periods varied from 1 to 67 ppm (median 15 ppm). PERC blood levels ranged 12-864 mg/l (median 145 mg/l). A set of tests from a computer-based performance evaluation system was administered, including Finger Tapping with both dominant and non-dominant hands, Simple Reaction Times, Digit Symbol, and Shape Comparison in two different versions constructed to test Vigilance and the response to moderate stress, respectively. During the proliferative phase of the menstrual cycle, PERC-exposed workers showed increased serum PRL (12.1 +/- 6.7 ng/ml) as compared to their matched controls (7.4 +/- 3.1 ng/ml, p less than 0.001). Prolonged reaction times were also observed in all tests. However, neither the duration of exposure nor air and blood PERC concentrations were significantly correlated with performance. Nor were exposure variables associated with the increased PRL levels.


Joint effect of gestational age and maternal lead exposure on psychomotor development of the child at six years. A prospective study has been carried out to assess the psychomotor deficit resulting from a moderate decrease in gestational age and pre-natal lead exposure. The general cognitive index of the McCarthy psychometric scale (adjusted for confounders) in six-year-old children was related to gestational age. Most of the psychomotor scores showed smoothing variations with gestational age ranging from 37 to 39 weeks, whereas sharp changes occurred between 39 to 40 weeks, with plateau values above such a cut-off for all spheres of development examined. Maternal hair lead content, used as an indicator of lead exposure during pregnancy, was found to be negatively related to general cognitive, verbal, quantitative, and memory subscales (p less than 0.01), whereas its relationship with perceptual and motor subscales was close to 0.05 significance level. Control for gestational age did not change the significance level of the associations. When controlling for maternal hair lead levels, the significance of the association between gestational age and the McCarthy subscales also remained stable, only the general cognitive index and verbal subscale reaching the conventional significance level.


Calcium-entry blockers-induced parkinsonism: possible role of inherited susceptibility. The risk of developing drug-induced parkinsonism (DIP) has been related to a number of factors but it remains up to now poorly defined. The aim of this survey has been to evaluate retrospectively the possible role of inherited components in 25 patients with parkinsonism induced by chronic exposure to the calcium-entry blockers cinnarizine and flunarizine. The finding of higher occurrence of a positive family history for Parkinson's disease (PD) and/or essential tremor (ET) and of higher frequency of secondary cases with PD and/or ET among close relatives of the patients as compared to age-matched controls, suggests the involvement of genetic susceptibility in developing this drug-induced disorder. DIP could be regarded as a multifactorial disease process resulting from potential neurotoxicity of drugs on a background of inherited predisposition.


Correlations between subjective disturbances due to acute exposure to organic solvents and internal dose. A general tendency to minor subjective disturbances ("susceptibility") were measured by questionnaire scores of psycho-/neurovegetative lability in 32 subjects independent of any experience with solvents. In series of experiments interrelations between subjective and biological variables during experimental exposures for 4 or 8 hr to acetone (1000 ppm), ethyl acetate (400 ppm), acetone/ethyl acetate mixture (500/200 ppm), or filtered air were investigated. Every two hr ratings of "tension", "tiredness", "complaints" and "annoyance" were reported and samples of urine were collected in order to analyse the internal dose of the substances. In exposures to ethyl acetate and to the mixture, the mean levels of urinary excretions of the substances show significant cross-correlations to rated complaints and annoyance, but not to rated tension and tiredness. Those subjects who showed higher susceptibility reported higher ratings of complaints and annoyance in those exposure conditions containing ethyl acetate. In exposures to acetone these relations were not found. Both, the quality of the substances and the individual tendency to report slight health impairments influence the variability of subjective reactions on exposure to solvents.


Neurotoxicology of PCBs and related compounds. Polychlorinated biphenyls (PCBs) are a family of 209 chemicals with two linked phenyl rings and variable chlorination. They are clear oils at room temperature. They were produced from the 1930s until banned in the 1970s because of toxicity and evidence of widespread environmental contamination. They were used mostly as insulators in electrical equipment; their widespread occurrence in the environment is more a consequence of uncontrolled disposal than of deliberate dissemination. In Asia, there have been two outbreaks of poisoning due to cooking oil contaminated by thermally degraded PCBs. Studies in workers exposed chronically to "clean" PCBs, workers exposed acutely to thermally degraded PCBs in clean-up of fires, and adult patients in Asia who ingested contaminated rice oil consistently show slowed nerve conduction and sometimes show headache, lassitude, and other CNS symptoms. In children exposed to background levels in the US, those with the highest transplacental exposure show hypotonia and hyporeflexia at birth and slowed motor development through age two, a defect in visual memory processing at 7 mon, and defects in short term memory at 4 years. Despite the presence of PCBs in breast milk, no association between breast milk exposure and any measured outcome has been seen other than lower activity levels at 4 years among long term breast fed children at the highest PCB levels. In Asia, children who were in utero at or after the 1968 exposure in Japan or the 1979 exposure in Taiwan showed clinically evident developmental delay. In Taiwan, the children were shown to have a variety of ectodermal defects, but the association between these defects and developmental delay was weak.(ABSTRACT TRUNCATED AT 250 WORDS)


Preclinical neurophysiological signs of parkinsonism in occupational manganese exposure. To study the effects from low level exposure to manganese, 30 men at steel smelting works and 60 nonexposed reference subjects, were neurophysiologically examined using: (i) Electroencephalogram (EEG), Event related auditory evoked potential (AEP/P300), Brain stem auditory evoked potential (BAEP) and diadochokinesometry. No group differences concerning EEG or BAEP were found. Diadochokinesis was slower and there was a tendency towards prolonged P300 latency in the exposed group as compared to the referents. These effects may be interpreted as early (subclinical) signs of disturbances of the same type as parkinsonism.


Accumulation of inorganic mercury in lower motoneurons of mice. The distribution of mercury within the lower brain stem and spinal cord of mice was investigated at various intervals after a single intramuscular injection of mercuric chloride. The autometallographic technique was used to demonstrate the presence of mercury deposits in tissue sections. Accumulation of mercury was observed in motoneurons of the anterior horns and in motor nuclei of the brainstem. In addition, mercury was present in the neuropil of the area postrema and within renal tubular cells. At the ultrastructural level, mercury was localized to neuronal lysosomes. The preferential accumulation of mercury in motoneurons within the spinal cord and brain stem is most probably due to an uptake of mercury in motor nerve terminals followed by retrograde axonal transport to the cell bodies.


Effects of diisopropyl fluorophosphate on muscarinic-M1-receptors and on receptor-mediated responsiveness of the phosphatidyl-inositol system in the cerebral cortex of rats. The effects of acute and repeated treatments with an anticholinesterase (anti-ChE) compound, diisopropylfluorophosphate (DFP) on M1-acetylcholine receptor (M1-AChRs) density and on M1-mediated breakdown of inositol phospholipids were studied in the cerebral cortex of rats. The DFP doses induced an about 75% inhibition of cortical ChE 48 hr after the last treatment. The acute treatment did not change Bmax of M1-AChRs (measured as 3H-pirenzepine binding), while 1-week and 2-weeks treatments induced their significant down-regulation, by 14 and 29%, respectively. The responsiveness of M1-AChRs was measured in cortical prisms as accumulation of inositol phosphate (IP) following stimulation with a cholinergic agonist, carbachol (from 10 to 1000 microM). The IP accumulation (expressed as ratio stimulated/basal IP content) was lower in acute DFP rats than in controls at few carbachol concentrations, and after 2 weeks at most carbachol concentrations. This resulted in a significant increase of EC50. The data indicate the involvement of cortical phosphatidyl inositol system during intoxication by anti-ChE agents, namely a decreased efficiency of post-receptor mechanisms.


Effects of malaoxon on phosphatidylinositol signaling in convulsing and non-convulsing non-pregnant and pregnant female rats and their offspring. Phosphatidylinositol (PI) signaling during organophosphate (OP) induced convulsions and tissue Ca2+ changes in 10 weeks old male, and 14 weeks old non-pregnant and pregnant female rats, and the offspring of the latter were explored. Brain inositol and inositol-1-phosphate (Ins1P) served as indices of alterations in brain PI signaling, and brain tissue Ca2+ as an index of early neuronal injury. A dose of malaoxon OP, which produced convulsions in about 60% of the exposed rats in different rat groups, was 39.2 for male, and 8.2 mg/kg for pregnant female rats, respectively. Malaoxon (8.2 mg/kg) did not produce convulsions in non-pregnant female rats. All the rats were followed for 1 or 4 hr subsequent to malaoxon. Malaoxon decreased cerebral inositol in both male and female rats, and the decrease was similar in spite of the dose difference. The decrease was larger in the convulsing than in the non-convulsing rats. A tendency towards a decrease of brain inositol also occurred in the offspring. Ins1P levels were markedly increased in male, and also in non-pregnant female rats, but not in the brains of pregnant female rats. Ins1P was not markedly changed in the brains of the offspring. Malaoxon elevated brain tissue Ca2+ in male but not in female rats or their offspring. Cholinergic systems and PI signaling in the brain seem to be associated with OP-induced convulsions both in male and female rats; females seem to be more sensitive than males. Malaoxon may also have slightly modified PI signaling in the offspring brain. Hormonal factors are likely to modify OP CNS toxicity and cholinergic stimulation of brain PI signaling.


Models for the in vitro assessment of neurotoxicity in the nervous system in relation to xenobiotic and neurotrophic factor-mediated events. We have been investigating the use of three culture types for both screening and mechanistic neurotoxicology in vitro. These are the neuroblastoma cell lines (IMR32 - human; C-1300 - mouse), primary mixed monolayer cultures of the rat and chick embryonic midbrain ('micromass' systems) and organotypic whole rat brain reaggregate cultures. The performance of these models for neurotoxicity resting has been investigated with ethylcholine mustard aziridinium (ECMA), vincristine, aluminium, glutamate receptor antagonists, MPTP, and 'hypothyroidism'. From a 'screening' viewpoint, in vitro exposure through a tiered testing system (ranging from simple cytotoxicological parameters in the neural cell lines to neurotransmitter measurements in the organotypic cultures) may permit detection of CNS neurotoxicity and delineation of possible mechanisms. The type of developmental neurotoxicological information gained is highlighted in the cases of aluminum and the glutamate receptor antagonists. High concentrations of aluminum caused significant neural cell death in differentiated neuroblastoma cell lines after approximately two weeks exposure in vitro. In contrast, cell death was detected in the developing midbrain cultures as early as 24 - 48 hr. Studies in whole brain reaggregates suggest that cholinotoxicity may occur in a similar time-frame and is consistent with some of aluminium's effects in vivo. Preliminary experiments have shown that exposure of immature developing midbrain rat primary cultured neurones to the glutamate receptor antagonists, AP3 and MK-801 induces neural cell death which may relate to control of NGF by glutamate cells. Developing neural culture systems may prove useful for testing agents which cause neurotoxicity through disturbances of neurotrophic function.


Regulatory developmental neurotoxicity and human risk assessment. A number of efforts, in the last 15 years, have been directed at developing protocols to assess the potential developmental neurotoxicity (DN) of test agents. Japan and the United Kingdom have general protocols that describe the behavioral parameters that should be evaluated as part of other types of testing protocols, such as standard developmental and/or reproductive toxicity studies. In 1986, EPA published a proposed separate guideline for the testing of glycol ethers. Since then, this protocol has undergone extensive review and comment by an agency-wide workgroup, participants of a workshop sponsored by EPA and NIDA, EPA's Scientific Advisory Panel, and the public. Comments were taken into consideration and the final DN testing protocol has been published recently by EPA's Office of Pesticide Programs. This protocol provides specific guidance on issues of study design, aspects of CNS function to be evaluated and criteria for selection of testing procedures. It is designed to be a "generic" protocol could be applied to testing of pesticides and other chemicals and that could be modified on a case-by-case basis depending on the data available on a specific agent of concern. With the development of testing protocols for assessing DN, there comes a need for the development of guidance as to how the data should be interpreted and applied toward conducting a risk assessment for extrapolation to humans. Some guidance was developed at the EPA-NIDA Workshop. EPA has published specific risk assessment guidelines in the area of developmental toxicity that include a section on interpretation of data on functional deficits, including DN.(ABSTRACT TRUNCATED AT 250 WORDS)


Reactive oxygen species: relation to aging and neurotoxic damage. The inherent biochemical, anatomical and physiological characteristics of the brain make it especially vulnerable to oxidative insult. Some of the features which account for a susceptibility to free radical induced insult, include a high lipid content, a major requirement for oxidative energy metabolism, and a paucity of enzymes dissipating reactive oxygen species. Recently it has become increasingly apparent that many drug and chemical-induced toxicities may be evoked by way of oxidative stress. Major points addressed in this presentation relate to xenobiotic-induced disruption of cerebral redox status, specific examples of neurotoxic agent-induced alterations in free radical production, as measured by the fluorescent probe dichlorofluorescein, and the regulation of neural free-radical generation by antioxidants and protective enzymes. Recent attempts to unify the diffuse discipline of neurotoxicology, have led to the concept of "final common pathways" that characterize frequently occurring cellular responses to disruption of homeostasis resulting from exposure to xenobiotic agents. The present work considers the thesis that oxygen radicals may be mediators of such a "final common pathway". Free radical mechanisms may thus contribute significantly to the expression of the harmful properties of diverse, unrelated neurotoxic agents. Studies with aged animals suggest that, while excess levels of oxidative species are not apparent in the aged central nervous system, prolonged exposure to such species may adversely modify proteins, and this may be a contributing factor to senescence. The extent to which normal physiologic aging and neurotoxic events interact, remains to be determined.


Supplementation of domestic sugar (sucrose) with fluoride. Effects on experimental dental caries, plaque pH, and fluoride levels in plaque and enamel. The minimum amount of fluoride which, when added to sucrose, will reduce caries in an intra-oral test was determined. Removable lower-arch appliances were worn by three adult subjects for 1 week, during which time plaque-covered enamel on one side was immersed in a 10 percent sucrose solution containing fluoride for 10 minutes four times per day. The effect of sucrose alone (control) was similarly determined on the other side of the appliance. Concentrations of 2 and 5 ppm F in sucrose solutions (20 and 50 ppm F dry weight) produced highly significant reductions in experimental caries of 43 and 44 percent respectively. A reduction in enamel dissolution due to re-precipitation of fluoride-rich apatite is probably largely responsible for the anti-caries effect. However, decreased plaque acid production may also play a role since the addition of 1 ppm F to 5 percent sugar reduced the plaque pH drop in artificial mouth experiments. Our results substantiate previous reports that fluoridation of sucrose to a level of 20 to 50 ppm F dry weight has potential benefits in caries prevention and may be useful when the F intake is otherwise low.


Current issues in gerodontology.

Current issues in gerodontology. Gerodontology involves much more than the treatment of dental disease in people aged over 65 years. Using the definition of Ettinger, a relatively distinct group of individuals are defined. However, a slightly broader definition is perhaps more appropriate, to include those who are in any way handicapped in the receipt of dental treatment due to their age. This group of patients may become victims of ageist behaviour by dentists. This may influence their treatment options, and become a barrier to older patients receiving the full range of treatment they may require. However, the elderly generally consider oral health to be of low priority, and many, including those with identifiable problems, do not have a perceived need for care. The main barrier to their seeking treatment is their own attitude to their problems, and only a few experience barriers that otherwise prevent their utilisation of dental treatment. The dental needs of the elderly can be anticipated to rise as more retain their teeth, many of which will be heavily restored. The cost of this treatment must be met by someone; if the patient cannot afford it, the State may be asked to provide the funds. On present form, the response to this suggestion is likely to be unfavourable, but a cheap alternative to specialist care is not desirable, as it will only be able to partially perform the task. There is a need for research in a variety of aspects of gerodontology.(ABSTRACT TRUNCATED AT 250 WORDS)


Oxygen saturation during intravenous sedation using midazolam. Intravenous sedation with midazolam was given to young, fit, adult patients undergoing third molar surgery; oxygen saturation (SpO2) was continuously measured during the surgery and for 30 minutes after the surgery. There were some instances of a brief fall in the oxygen saturation, during the surgery and in the immediate period following surgery. It is suggested that it may be necessary to observe and selectively monitor some patients in the immediate post-surgical period as well as during the period of operation. Although not addressed by this investigation, this would be particularly true of medically compromised patients and the elderly.


Has the process causing noninsulin dependent diabetes start at birth? Evidence in neonates from a population with a high prevalence of diabetes. to investigate whether differences in the glucose-insulin axis are present at birth in neonates from ethnic groups at high risk of diabetes. fructosamine samples were taken from Maori, European and Pacific Island expectant mothers at their 28 week appointment at the public outpatients clinic at National Women's Hospital, Auckland. Umbilical cord samples for insulin, C-peptide and fructosamine assay were taken at delivery and babies had their subscapular skinfold fat thickness measured by callipers. the mean maternal 28 week fructosamine was similar in the three populations in spite of a higher prevalence of gestational diabetes among Pacific Islanders. Of the 1066 deliveries, cord samples were available for 207 Europeans, 81 Maoris and 113 Pacific Islanders. Both Pacific Island and Maori babies had higher cord fructosamine concentrations than European babies. However, Pacific Island babies were also heavier, and had higher cord insulin concentrations and subscapular skinfold thickness than European babies. the elevated cord fructosamine concentrations suggest that Maori and Pacific Island babies, who share a high risk of noninsulin dependent diabetes mellitus later in life, are hyperglycaemic at birth. The paradoxical insulin results and the cause for the relative neonatal hyperglycemia warrant further investigation.


Death certification in Auckland.

Death certification in Auckland. to investigate the reasons behind general practitioner referral of cases of natural death to the coroner, and also the understanding of general practitioners of the relevant legislation. as cases of natural death were referred to the coroner over a seven month period, the deceased's general practitioner was contacted by telephone and questioned regarding his/her knowledge of the death and willingness to sign a cause of death certificate. Based upon this interview, cases were divided according to whether their general practitioner could have signed the death certificate or not. there were 314 cases where there was a contactable general practitioner. In 257 instances, the general practitioner would not have signed the death certificate: 183 found the death unexpected, and 74 had not seen the patient recently enough. In 57 instances the general practitioner would have signed the death certificate, but did not because: 23 were unaware of the death, 13 could not be contacted, 14 did sign a death certificate but this was rejected by the medical referee, and seven would have signed but did not for miscellaneous reasons. a disturbing finding was the general lack of understanding of certification legislation in particular the concept that the patient must have been seen in their last illness to be able to sign the death certificate. When signing death certificates, doctors should be thinking in terms of last illness rather than a vague period of time between two weeks and three months.


Chorionic villus sampling in Auckland 1989-90. to perform an audit of all 197 chorionic villus sampling procedures performed in Auckland in 1989-90. an attempt to trace the outcome in all 197 cases and this was possible in 188 cases. 89% of chorionic villus samples were performed transvaginally and 11% transabdominally. The total fetal loss rate was 9.6% (18) with six spontaneous miscarriages before 20 weeks gestation (3.2%), one intermediate fetal death and one neonatal death. There were 10 elective terminations of pregnancy following abnormal results so the spontaneous loss rate was 4.3%. the loss rate was lower than that reported in the European and Canadian multicentre trials. The sampling success rate, however, was poor with 13.7% failed procedures. This improved in the second year of the service to 10%. There were no failure cultures or examples of mosaicism.


Forensic psychiatry and prison liaison services in Auckland: the first twelve months. to assess referrals to a prison liaison service of regional forensic services in Auckland. data on forensic psychiatric referrals from Auckland prisons 1 October 1989 to 30 September 1990 were collected. This was the first year of the service. there were 127 forensic psychiatric referrals in the period. The characteristic profile of such a case was that of a 28.5 year old male, unemployed remanded of Maori ethnic background. The commonest charge was nonsexual assault together with a prominent history of polysubstance misuse. Schizophrenia was the most frequent diagnosis. these findings have implications for regional forensic psychiatry services and other mental health providers, and the community in general.


Hepatitis B vaccination in children: five year booster study. to demonstrate that appropriate doses of hepatitis B vaccines would be protective for at least five years in children. This would be shown by administering booster doses and measuring the response. 2 micrograms intramuscular (IM) doses of Merck Sharp and Dohme (MSD) recombinant DNA vaccine (rDNAV) were given to 318 children who had received age appropriate doses of MSD plasma derived vaccine (PDV) five years earlier. Sera were tested for hepatitis B virus (HBV) seromarkers pre- and postbooster. all children who had responsed to primary immunisation demonstrated an anamnestic response. The geometric mean titre (GMT) of antibody to hepatitis B surface antigen (antiHBs) rose from 89 to 4777 IU/L. AntiHBs was detected in 94% of vaccinees just prior to the five year booster, and 96.5% a mean of 10 days later. when initial vaccine seroconversion is satisfactory, protection of responders persists for at least five years, assuming that the response to vaccine boosters mimics the response to wild virus. Therefore, for population control of hepatitis B in children in endemic areas, booster doses are not required for at least five years.


Antral vascular ectasia: the watermelon stomach. Antral vascular ectasia (watermelon stomach) is an uncommon localised vascular abnormality which may cause occult gastrointestinal blood loss and iron deficiency anaemia. The endoscopic appearances are characteristic with well demarcated, often raised or nodular bright red streaks radiating from the pylorus back along the antrum. Endoscopic biopsies can be taken without risk of haemorrhage and may help distinguish this condition from gastritis. The aetiology remains obscure, but there is an association with achlorhydria, hypergastrinaemia, and cirrhosis of the liver. Four patients are described; two had antrectomy with long term control of their anaemia, and two were treated conservatively. The lesion may be diagnosed more frequently with more widespread recognition of the condition.


Peripheral trigeminal nerve injuries.

Peripheral trigeminal nerve injuries. Certain dental procedures being performed routinely can result in nerve damage. The following is a review of some of these surgical procedures coupled with a discussion of ways to avoid, diagnose and manage the nerve injuries associated with them.


Rhabdomyosarcoma of the infratemporal fossa. The outlook for children suffering from this most common soft tissue sarcoma is vastly better today than it was 15 years ago, when fewer than 20 percent of its victims survived. Continuing advances in treatment should increase survival rates even more in the future.


Sjogren's syndrome. Dental role in providing relief. This oftentimes underappreciated disease carries with it severe dental implications, all of which can affect the patient's quality of life. While there is no cure, it is possible to manage disease symptoms and to prevent irreversible dental damage.


Simplified aponeurotic ptosis surgery.

Simplified aponeurotic ptosis surgery. I present a simplified aponeurotic ptosis repair that minimizes surgical dissection and enhances the predictability of postoperative eyelid positions. Indications for the procedure are unilateral ptosis, bilateral ptosis where preaponeurotic fat excision is not indicated, mild congenital ptosis, and reoperations from standard levator surgery. The procedure is best suited for surgeons who have a thorough knowledge of the levator aponeurosis anatomy.


Orbital decompression for Graves' disease: exposure through a modified blepharoplasty incision. A "transorbital" three-wall decompression through a modified blepharoplasty incision was used to treat 19 orbits for either cosmetic disfigurement or optic neuropathy. In the 14 orbits with disfigurement, surgical retroplacement averaged 5.2 mm; vision improved to 20/40 or better in four of five eyes with optic neuropathy. Complications attributed to the surgery included: acquired strabismus (two transient, one permanent) and infraorbital hypesthesia (one transient, one permanent). This technique's advantages are: 1) a single incision with wide exposure, 2) a low incidence of permanent strabismus, 3) a lateral orbital rim and canthal tendon preservation, and 4) a large reduction in proptosis.


Effects of flurbiprofen and suprofen on the miotic activity of 1% acetylcholine and 0.01% carbachol. The nonsteroidal antiinflammatory agents (NSAIAs) flurbiprofen and suprofen applied topically to reduce miosis may counteract the desired effects of miotics used during ocular surgery. In a pigmented rabbit model, 1% acetylcholine was shown to cause a greater, significant initial (for the first 30 minutes) constriction (P less than .05) than 0.01% carbachol in eyes pretreated with flurbiprofen and suprofen. From 2 to 8 hours, NSAIA pretreatment had a greater miotic effect with carbachol than with acetylcholine. There were no significant differences between flurbiprofen and suprofen on the miotic effect of carbachol or acetylcholine.


Corneal edema following argon laser iridotomy. Laser iridotomy is generally a safe and effective procedure for narrow-angle glaucoma. However, since surgical success with the argon laser depends on a focal thermal effect, a corneal burn is a possible complication. I describe five patients with occludable anterior chamber angles and bilateral corneal guttata who developed uniocular progressive corneal edema with visual loss following argon laser iridotomy. These five patients underwent iridotomy with a total laser energy of 63, 48.5, 7, 25, and 25 J, respectively, and began to lose vision due to corneal edema immediately, and 5, 2, 4, and 2 years later, respectively. Following penetrating keratoplasty with cataract surgery, histopathology of the corneal buttons showed generalized endothelial cell loss in all five. Microstructural findings of guttata and thickened Descemet's membrane implied that prior endothelial dystrophy had predisposed these patients to laser-induced damage. Risk factors for immediate or delayed-onset bullous keratopathy after argon laser iridotomy include prior angle closure, preexisting endothelial guttata, and high laser energy with multiple applications. Recognizing the potential of this complication offers opportunities for preventive strategies.


Nonabsorbable suture material in cataract surgery: a comparison of Novafil and nylon. We compared the performance of 10-0 Novafil (polybutester, Davis & Geck, American Cyanamid Company, New South Wales, Australia.) with that of 10-0 nylon (Alcon) in 60 patients undergoing extracapsular cataract extraction and implantation of a posterior chamber intraocular lens. A standard technique was used, and the incision was closed with interrupted sutures of either 10-0 Novafil or 10-0 nylon. Length of follow up ranged from 6 to 26 months (average, 15 months). We assessed the intraoperative handling qualities of the suture materials, as well as their effect on wound healing and inflammation. We also compared the surgically-induced astigmatism in the two suture groups over the first 3 postoperative months and then in long-term follow up (average, 15 months). Sutures removed at long-term follow up were examined by scanning electron microscopy (SEM). Both suture materials handled easily at operation and were well tolerated by all patients. There was no significantly different surgically-induced astigmatism in the two suture groups after 12 weeks (P = .962) or during longer follow up (P = .401). SEM confirmed more advanced biodegradation of nylon as compared with Novafil sutures after they had been in place an average of 18 months.