Kleine-Levin syndrome: A neuropsychiatric disorder.

Kleine-Levin syndrome (KLS) is a rare, relapsing-remitting disease that affects mostly adolescents. It is characterized by episodes lasting from 1 to several weeks, and comprises neurological (hypersomnia, confusion, slowness, amnesia) and neuropsychiatric symptoms (derealization and apathy). Some psychiatric symptoms (megaphagia, hypersexuality, anxiety, depressed mood, hallucinations, delusions) arise during episodes, albeit less frequently, while patients are normal between episodes. However, sudden severe (>18h/day of sleep) and recurrent hypersomnia helps to differentiate KLS from other psychiatric mimics. Derealization, the striking feeling of unreality or of being in a dream-like environment, is strongly associated with hypoperfusion of the associative temporoparietal junction cortex, whereas apathy is almost complete loss of autoactivation: teenagers stop using their cell phones and their only spontaneous initiative is to sleep. The cause of KLS is not known, but evidence suggests it could be a recurrent inflammatory encephalitis. Up to 5% of cases are familial, although no abnormal gene has yet been found. Hypersomnia episodes tend to become less frequent and to disappear with advancing age. However, 28% of patients have long-lasting episodes (>30 days), and around 15% have no signs of recovery after >20 years of living with the disorder. Patients' cognitive and psychiatric status should be regularly checked during asymptomatic periods, as 20-40% develop long-term mild cognitive impairment or mood disorders. Lithium therapy is beneficial for reducing episode frequency, and intravenous steroids can reduce the duration of long episodes.

The association between developmental handicaps and traumatic brain injury during pregnancy: an issue that deserves more systematic evaluation.

AIMS: Trauma during pregnancy is commonly viewed as benign for the foetus when the delivery occurs normally. This study revisits that point of view. METHOD: We included eighteen patients having a neurological handicap with an anamnesis of an accident during pregnancy and a follow-up sufficient to determine a definite outcome. RESULTS: Pregnancy outcome and observed management. Foetal abnormalities were detected in six cases between the first and the thirteenth day after the trauma. Emergency delivery or rapid birth after signs of foetal distress occurred in five cases. One baby died soon after birth. One-third of cases were not submitted to any investigation. VARIOUS NEUROLOGICAL HANDICAPS WERE RECORDED: Congenital microcephaly (three patients), congenital hydrocephalus (three), Infantile cerebral hemiplegy (six), quadriplegy with severe encephalopathy (four), diplegy (one), clumsiness with cerebellar atrophy (one), Moebius syndrome (one), mental retardation with autistic features (two), learning disability (one) auditory agnosia (one). Cerebral imaging showed macroscopic abnormalities in fourteen patients, evoking various pathogenetic hypotheses. CONCLUSION: The association between maternal trauma and foetal brain lesions lacks sufficient investigation in many cases. Prospective studies are needed to clarify both medical and legal issues. Guidelines are proposed for obstetrical and paediatric management after significant maternal trauma.

Altered extent of cross-linking of beta1,6-glucosylated mannoproteins to chitin in Saccharomyces cerevisiae mutants with reduced cell wall beta1,3-glucan content.

The yeast cell wall contains beta1,3-glucanase-extractable and beta1,3-glucanase-resistant mannoproteins. The beta1,3-glucanase-extractable proteins are retained in the cell wall by attachment to a beta1,6-glucan moiety, which in its turn is linked to beta1,3-glucan (J. C. Kapteyn, R. C. Montijn, E. Vink, J. De La Cruz, A. Llobell, J. E. Douwes, H. Shimoi, P. N. Lipke, and F. M. Klis, Glycobiology 6:337-345, 1996). The beta1,3-glucanase-resistant protein fraction could be largely released by exochitinase treatment and contained the same set of beta1,6-glucosylated proteins, including Cwp1p, as the B1,3-glucanase-extractable fraction. Chitin was linked to the proteins in the beta1,3-glucanase-resistant fraction through a beta1,6-glucan moiety. In wild-type cell walls, the beta1,3-glucanase-resistant protein fraction represented only 1 to 2% of the covalently linked cell wall proteins, whereas in cell walls of fks1 and gas1 deletion strains, which contain much less beta1,3-glucan but more chitin, beta1,3-glucanase-resistant proteins represented about 40% of the total. We propose that the increased cross-linking of cell wall proteins via beta1,6-glucan to chitin represents a cell wall repair mechanism in yeast, which is activated in response to cell wall weakening.

Eyelid involvement in acanthosis nigricans.

We treated a 56-year-old man who had acanthosis nigricans associated with gastric adenocarcinoma and involving the axillae, hands, feet, anus, soft palate, and eyes. The patient developed epiphora from occlusion of the canaliculi with papillomatous lesions. Recognition of the ocular signs of this paraneoplastic syndrome may indicate to the ophthalmologist that the patient should have a thorough oncologic examination.

Intravesical chemotherapy. Studies on the relationship between pH and cytotoxicity.

The influence of pH on the antitumor activity of drugs used for intravesical chemotherapy was studied. A human continuous cell line derived from a transitional cell carcinoma of the bladder was exposed to 6 drugs (Adriamycin [doxorubicin], cisplatin, epirubicin, epodyl, mitomycin C, and thiotepa) for 1 hour at 11 pH values ranging from 5.2 to 9.7, and cytotoxicity was measured by inhibition of colony formation. pH had a marked influence on drug activity: cisplatin, mitomycin C, and thiotepa were most cytotoxic in acid media, Adriamycin, and epirubicin in alkaline media, while epodyl was the only drug whose cytotoxicity was unaffected by pH. In addition to these in vitro studies, comparisons were made of the pH of urine samples obtained from patients immediately before and at the completion of intravesical chemotherapy. Changes in pH up to a maximum of +/- 1.6 units were observed, although in most cases, values were similar before and after therapy. All the drugs used were acidic in solution, with the exception of thiotepa. It is concluded that by adjusting solvent and urine pH to the optimum value for each drug, the effectiveness of intravesical chemotherapy might be enhanced.

Intravesical chemotherapy: studies on the relationship between osmolality and cytotoxicity.

The effectiveness of intravesical chemotherapy for the treatment of superficial bladder cancer may be influenced by the conditions of administration, such as the osmotic strength of the instillate. Urine from patients with bladder cancer before treatment had osmolalities in the range 187 to 852 mOsm./kg. and these had decreased by an average of 135 mOsm./kg. at the completion of intravesical chemotherapy. Clinical preparations of drugs used for intravesical chemotherapy had osmotic strengths ranging from 65 to 1,038 mOsm./kg. The antitumor activities of the drugs most frequently used intravesically (doxorubicin, epodyl, mitomycin C and thiotepa), and of cisplatin and epirubicin in media of 6 different osmolalities were measured with a human bladder cancer cell line by inhibition of colony-forming ability. Reducing osmotic strength from 590 to 125 mOsm./kg. significantly increased the in vitro cytotoxicities of thiotepa, mitomycin C, cisplatin and epirubicin but not those of doxorubicin and epodyl. We conclude that the use of an instillate at the lowest achievable osmotic strength probably will be optimal for the intravesical administration of chemotherapeutic drugs.

Lateral hypothalamic lesions and fenfluramine increase thermogenesis in brown adipose tissue.

The effects of treatment with fenfluramine or electrolytic lesions in the lateral hypothalamus (LH) on binding of guanosine 5-diphosphate (GDP) by mitochondria from brown adipose tissue have been compared in 4 experiments. In 2 experiments the lesions were lateral to the anterior hypothalamic nucleus and in the other two they were lateral to the ventromedial hypothalamic nucleus. Binding of GDP to mitochondria was significantly increased 18 hours after an electrolytic lesion in either LH site. d,1-Fenfluramine, 20 mg/kg, also increased GDP binding in both acute experiments. In the other 2 experiments GDP binding was measured 11 days after the LH lesion or after 11 daily injections of fenfluramine. When the chronic lesions were lateral to the VMN, there was a transient drop in food intake and body weight. With more anterior lesions, body weight remained significantly lower than in sham-operated rats although food intake returned slowly to control levels. Fenfluramine-treated rats had lower body weights in both chronic experiments even after food intake returned to normal. GDP-binding to mitochondria from interscapular brown adipose tissue was elevated in both of the chronically-treated fenfluramine groups but was only increased in the LH-lesioned rats whose body weight remained below normal.

[Therapeutic and ethical problems of nephrostomy in tumor-related hydronephrosis]. / Die therapeutischen und ethischen Probleme der Nephrostomie bei tumorbedingten Harnstauungsnieren.

A total of 101 patients with hydronephrosis due to tumor obstruction underwent palliative nephrostomies. The average survival was 8.6 months; after 3 months, 32% of the patients were dead. The survival for patients with T3 tumors was 9.3 and for patients with T4 tumors, 6.0 months. The general postoperative health status did not improve in any of the cases. Retrospectively, 42% of the patients did not feel that the nephrostomy had done any good. In 17% of the cases, progressive development of tumor growth was predictable at the time of nephrostomy.

Ovarian development in 46,XY gonadal dysgenesis.

In humans the XY ovary is degenerative, there being scant evidence of persistence of that organ beyond the perinatal period. Here we describe indications of functional ovarian tissue in a 17-year-old female with male karyotype, H-Y+ cellular phenotype, and some signs of the Turner syndrome. Her gonads were removed after the onset of secondary amenorrhea. Histological examination revealed a degenerative right ovary devoid of germ cells and follicles, and a left streak gonad. There was no trace of testicular development in either side.