Chloramphenicol toxicity associated with severe cardiac dysfunction

Summary A 9-month-old infant experienced severe chloramphenicol toxicity associated with high serum levels (313 g/ml). Cardiovascular collapse with cardiomyopathic changes and impaired left ventricular function was documented by echocardiography. Serial echocardiographic evaluation showed resolution of the cardiomyopathic findings as the chloramphenicol levels were spontaneously cleared. Clinical course was complicated by the development of liver disease and coagulopathy compatible with disseminated intravascular consumption. Patient's recovery was complete and uneventful, nevertheless, chloramphenicol toxicity in childhood is associated with a significant mortality rate of 40%. The related impaired cardiac function, although reversible, appears to play a major role in the pathogenesis and eventual outcome in this syndrome.     

Hereditary neuropathy with liability to pressure palsies

Summary Clinical, neurophysiological and pathological investigations were carried out in 11 affected members of 2 families with hereditary neuropathy with liability to pressure palsies (HNPP). The observations were related to findings in 261 cases of 47 families published in the literature. It was concluded that HNPP is a nosological entity characterized by the following diagnostic criteria: (1) an autosomal dominant inheritance; (2) the clinical presentation of a recurrent mononeuropathy simplex or multiplex, frequently related to an inadequate trauma to peripheral nerves; (3) a significant slowing of motor and sensory conduction velocity in clinically affected, but also in clinically unaffected nerves; (4) characteristic morphological findings in sural nerve biopsy featuring tomaculous swellings of myelin sheaths, transnodal myelination and segmental demyelination. The pathogenesis of HNPP is not clear. Hypothetical explanations of the pathogenesis of HNPP are discussed.In memory of Albert Bischoff (1921–1981), Professor of Neurology, University of Berne     

Effects of small dose of brotizolam on P300

Nine healthy men (mean age, 22.2 years) participated in two experimental sessions cross-overed randomly in a double blind manner; one with a placebo and the other with 0.125 mg of brotizolam (BTZ) administered in the morning. Resting electroencephalogram and event-related potential under oddball paradigm was recorded before and 1, 2, 4, 6 and 8 h after the administration. Mean 30-msec bin amplitude from 240 msec to 450 msec after the stimulus was compared between placebo and drug sessions in order to observe P300. Brotizolam reduced the amplitude of P300 at 6 h after administration. It was noted that the effects of BTZ were most marked at Fz.     

嗅觉诱发电位的实验研究

目的：观察电刺激家兔嗅区黏膜记录的诱发电位的波形及其稳定性，探讨一种可以客观评价嗅觉功能的方法。方法：将双极刺激电极经家兔前鼻孔置于嗅区黏膜，给予电刺激，在颅顶记录嗅觉诱发电位(OEPs)；改变刺激参数和部位，观察对电位潜伏期、阈值和波形的影响。结果：在颅顶前方近嗅球处记录到一组波形稳定的N1-P1-N23相复合波。潜伏期为：N1波20．6ms，P1波33．5ms，N2波58．3ms；改变刺激强度对各波无明显影响；改变刺激频率对各波影响较大，频率过高．波形分化较差。结论：正常OEPs是一组波形稳定的负-正-负3相复合波，波形稳定、重复性好，各参量可作为评价嗅觉功能变化的有用指标。     

Age-related changes in dividing cells of the olfactory epithelium of the maturing guinea pig

Changes in dividing cells of the olfactory epithelium from guinea pigs of different ages were examined by immunohistochemical staining using anti-proliferating cell nuclear antigen antibody. Numerous dividing cells were scattered diffusely in the basal layer of the olfactory epithelium at 1 and 2 months following birth and then gradually decreased with maturation until 4 months. Findings then remained constant between 4 and 24 months. Subsequently, cell numbers were found to decrease as animals became older. The number of olfactory receptor cells did not vary significantly between 1 and 30 months. Although no correlation could be found between the numbers of dividing cells and olfactory receptor cells, it is still possible that the longevity of the olfactory receptor cells changes to maintain the overall size of the neuronal population. Received: 18 February 1998 / Accepted: 9 April 1998     

Clinical validation of a new olfactory test

A new approach to clinical olfactometry is presented using nasal sprays. A special dosage valve was used to standardize an aerosol size to 40 μm. For evaluation a 6 × 6 matrix (substance/olfactory quality) with verbal associative clues was used according to test psychological findings. Validation took place in three steps after determining smell-associated thresholds in preliminary examinations. Recognition of different aromas administered either by spraying into the open mouth from a distance of 5 cm using nasal sprays or sniffing opened bottles was compared in 50 subjectively normosmic subjects. Findings showed that the correspondence between the two procedures was relatively high, with global identification of odorous substances as high as 98.4% in the spray test. The number of substances used was next reduced to those six substances providing the most reproducible results in an investigation with 56 normosmic and 55 hyposmic subjects. Verbal associative clues were also tested. In a last step 50 patients with hyposmia of various origin and 110 normosmic subjects were tested, allowing previous results to be reproduced regardless of the cause of hyposmia. The spray test was shown to be easily performed and was suitable as a screening test, with a sensitivity of 88% and a specificity of 100%. Received: 29 September 1997 / Accepted: 11 February 1998     

Regional differences in brain monoamine oxidase subtypes in an animal model of geriatric depression: effects of olfactory bulbectomy in young versus aged rats

Geriatric depression is often associated dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis, and with poor responsiveness to antidepressants that work through inhibition of monoamine reuptake; accordingly, it has been suggested that MAO inhibitors may represent a therapeutic alternative in this group. In the current study, we evaluated expression of MAO subtypes in brain regions of young and aged rats subjected to olfactory bulbectomy (OBX), a procedure that reproduces many of the biochemical and functional changes associated with human depression. Activities of both MAO A and B were elevated in aged rats as compared to young rats in most regions, but not in the midbrain, and the OBX lesion failed to produce any change in this pattern. These results stand in contrast to the differential effects of glucocorticoids, which reduce brain MAO in young animals but induce activity in aged rats. Our results support the view that the aged brain possesses biochemical characteristics that distinguish its monoamine biochemistry from that of young brain, and that these distinctions may work in conjunction with HPA axis dysregulation to influence the etiology and therapy of geriatric depression. The use of appropriate animal models for depression and for disruption of HPA axis function can allow for the testing of potential human biomarkers (such as platelet MAO) that may serve to predict treatment outcome.     

Paradoxical embolization via a patent foramen ovale following acute pulmonary embolism

The foramen ovale is usually obliterated following establishment of the adult circulation but remains patent in 25% of individuals. This potential communication between the venous and arterial circulations can allow thromboembolic material to bypass the lungs and enter the systemic circulation. We report two cases of paradoxical embolization through a patent foramen ovale following acute large pulmonary embolism (PE) and discuss the factors that predispose to paradoxical embolization following PE.     

A Severe Case of Reye's Syndrome with Multiorgan Dysfunction after Epstein-Barr Virus Infection

A 20-month-old male infant with multiorgan dysfunction after Epstein-Barr virus (EBV) infection developed Reye's syndrome. He also suffered from acute liver failure, life-threatening cerebral edema, severe disseminated intravascular coagulation (DIC), and myocardial involvement. EBV infection aggravated the progress of Reye's syndrome, leading to death despite full supportive and symptomatic therapy. This critical case suggested that pediatricians should pay attention to multiorgan involvement of severe EBV infection.     

Thyroid dysfunction during PD-1 inhibitor treatment in patients with cancer: Incidence and association with progression-free survival

The use of programmed cell death-1 (PD-1) inhibitors has recently been approved in China. As a consequence, the identification of relevant prognostic markers that can assess the efficacy of these compounds is required. Therefore, the present study aimed to explore the incidence of thyroid dysfunction and its ability to predict progression-free survival (PFS) in Chinese patients with cancer who received PD-1 inhibitor treatment. Data from 72 patients with cancer who received treatment with PD-1 inhibitors alone or in combination with chemotherapy or targeted drugs were analyzed. Moreover, the expression levels of free triiodothyronine, thyroxine, and thyrotropin during treatment were assessed to evaluate thyroid dysfunction. A total of 26 (36.1%) patients who had received PD-1 inhibitors developed thyroid dysfunction. Specifically, the incidence of thyroid dysfunction was 35.6% in patients with lung cancer, 25.0% in patients with malignant melanoma, and 46.7% in patients with other types of cancer. In addition, the median PFS was 7.0 (95% confidence interval, 4.9-9.1) months, whereas the 1- and 2-year PFS rates were 35.1 and 26.2%, respectively. Generally, patients with thyroid dysfunction exhibited longer PFS compared with those without thyroid dysfunction (P=0.001). Subgroup analyses were subsequently performed, which demonstrated that thyroid dysfunction was associated with longer PFS in patients with malignant melanoma (P=0.039) and other types of cancer (P=0.002), but not in those with lung cancer (P=0.083). These findings were noted in patients who received PD-1 inhibitor monotherapy (P=0.003), but not PD-1 inhibitor plus chemotherapy (P=0.172) or PD-1 inhibitor plus targeted therapy (P=0.582). Finally, thyroid dysfunction [P=0.001; hazard ratio (HR)=0.260] and PD-1 inhibitor monotherapy (P=0.015; HR=2.231) were identified as independent factors that could predict PFS. In conclusion, the present study demonstrated that thyroid dysfunction during PD-1 inhibitor treatment could be used as a potential marker for the prognosis of favorable PFS in patients with cancer.