Negative symptoms in schizophrenia: considerations for clinical trials

There is little agreement about the methodology of clinical trials of antipsychotic drugs in patients with negative symptoms. A literature review revealed wide variation in experimental design, rating scales and study duration. This reflects differing views as to the definition and response to treatment of negative symptoms. Some degree of standardization would improve comparability of studies and aid the development of new compounds. Patients included in such studies should have displayed negative symptoms for at least 6 months. Depressive symptoms, positive schizophrenic symptoms and extrapyramidal signs may all influence or be confused with negative symptoms and may respond to treatment; they should be at a low level at baseline and should be measured during the study period. Studies should last at least 8 weeks. Several scales are available for measuring negative symptoms and are reviewed; a global impression score should be used additionally.     

Heart rate response to breathing: dependency upon breathing pattern

Summary. Heart rate responses to stepwise and periodic changes in lung volume were studied in seven young healthy males. Stepwise inspiration and expiration both resulted in an increase in heart rate followed by a rapid decrease in heart rate. The fastest heart rate was reached in 1·6 ± 0·5 s and in 3·6 ± 1·4 s in response to inspiration and expiration, respectively (P < 0·01). The slowest heart rate was reached in 4·8± 1·0 s and in 7·6± 1·9 s in response to inspiration and expiration, respectively (P < 0·01). Following this biphasic change the heart rate returned to a steady level. The difference between the fastest and the slowest heart rates was significantly larger in response to inspiration (21·7 ± 7·3 beats per minute) than in response to expiration (12·0±7·3 beats per minute; P < 0·01). Periodic changes in lung volume were performed with frequencies from 3·0 to 12·0 respirations per minute (r.p.m.). The changes in heart rate showed a constant amplitude in the frequency range below 5·5 r.p.m. Maximal heart rate changes were found at frequencies of 5·5 to 7·0 r.p.m. Changes in heart rate decreased in a linear manner on a log-log scale in the frequency range above 7·0 r.p.m. The relation between frequency and changes in heart rate is explained by interference between the transient changes in heart rate induced both by inspiration and by expiration. It is concluded that if heart rate changes in response to periodic changes in lung volume are to be used as a measure of vagal function a number of factors have to be taken into consideration and to simplify the analysis of heart rate responses to breathing we recommend, instead, the use of the transient changes in heart rate induced by stepwise changes in lung volume.     

Narrowband UVB therapy for vitiligo: does the repigmentation last?

BACKGROUND: Since 1997, a number of trials have shown promising results in treating generalized vitiligo with narrowband ultraviolet B (UVB) both in adults and children. However, there is little knowledge concerning the duration and permanency of the treatment-induced repigmentation. OBJECTIVE: Our main objective was to perform a follow-up trial of successfully treated patients receiving narrowband UVB for generalized vitiligo. METHODS: We have investigated to what degree the treatment-induced repigmentation remains stable for up to 2 years post-treatment. We performed an initial open trial including 31 patients with generalized vitiligo. They received narrowband UVB thrice weekly for up to 12 months. Patients experiencing > 75% repigmentation were defined responders and were included in the follow-up trial. Responders were followed every 6 months for up to 2 years after cessation of treatment. We observed the pigmentation status and registered any changes indicating loss of pigmentation and relapse. RESULTS: Eleven of the 31 treated patients were included in the follow-up trial. Six patients had relapse and five patients had stable response 24 months after cessation of treatment. Four out of six relapses were within 6 months post-treatment. CONCLUSION: In our study population of 31 patients with generalized vitiligo, five patients (16%) experienced > 75% stable repigmentation 2 years after cessation of a treatment programme of up to 1 years narrowband UVB therapy.     

Maternal glycated haemoglobin, pre-gestational weight, pregnancy weight gain and risk of large-for-gestational-age babies: a Danish cohort study of 209 singleton Type 1 diabetic pregnancies.

AIMS: To examine the association between maternal glycated haemoglobin in the second half of diabetic pregnancies and the relative risk of delivering large-for-gestational-age (LGA) babies, controlling for maternal body mass index (BMI) before pregnancy, weight gain, age, White class and smoking habits. METHODS: We identified all pregnant diabetic women in North Jutland County, Denmark from 1985 to 2003. Data on HbA(1c) values from the 20th gestational week to term were collected from medical records and the babies were classified as large, normal or small for gestational age. The association between glycated haemoglobin (HbA(1c)) and relative risk of delivering an LGA baby was quantified based on logistic regression models and stratified analysis controlling for the five covariates. RESULTS: We included 209 singleton pregnancies with assessable HbA(1c) values of which 59%[95% confidence interval (CI) 52-65%] terminated with an LGA baby. Increasing levels of HbA(1c), BMI and weight gain were all associated with increasing risk of delivering an LGA baby. Analyses stratified according to maternal BMI showed that the association between HbA(1c) and risk of delivering an LGA baby was restricted to pregnancies with pre-pregnancy BMI > 23 kg/m(2). We found no association between HbA(1c) and risk of delivering an LGA baby in pregnancies with lower BMI. CONCLUSION: The positive association between glycated haemoglobin and birth of an LGA baby seems to be restricted to women with BMI > 23 kg/m(2).     

Ongoing pregnancies after intracytoplasmic injection using cryopreserved testicular spermatozoa

We report two clinical pregnancies occurring after intracytoplasmic sperm injection (ICSI) using cryopreserved spermatozoa obtained from testicular biopsy, made in two different infertility situations in our clinic. The first patient showed a secretory azoospermia associated with elevated serum follicular stimulating hormone (FSH) level and spermiogenesis maturation arrest. The second patient was affected by azoospermia resulting from bilateral epididymal obstruction. Spermatozoa present in the wet preparation of testicular biopsy made on the day of scrotal exploration were cryopreserved within the testicular tissue for both men. Intracytoplasmic injections were performed at a later date, using spermatozoa prepared from frozen-thawed tissues. In each case, three embryos were obtained and transferred in utero. The transfers resulted in a twin pregnancy for the first case, and in a singleton pregnancy for the second. Living foetuses were seen in the ultrasound scan at the 7th week and both pregnancies are proceeding to date beyond 30 weeks without complications.      

Treatment of age-related macular degeneration by laser photocoagulation. Visual results 2-8 weeks and 2-4 years after initial laser treatment

Laser treatment with blue-green argon, green argon and/or krypton red was performed on 578 eyes in 443 patients with neovascular age-related macular degeneration (AMD). The visual acuity was examined in all eyes 2 to 8 weeks after initial treatment and in 204 eyes in 167 patients 2 to 4 years after initial treatment. The short term results were as follow: 91/578 eyes (16%) had improved (greater than or equal to 2 lines on Snellen's charge or equivalent steps), 445/578 eyes (77%) remained unchanged and 42/578 eyes (7%) had deteriorated visual acuity (greater than or equal to 2 lines on Snellen's chart or equivalent steps). The reduction in visual acuity, may in about half of the 42 eyes be caused by too intensive laser application in the beginning of this study in 1983 and 1984 where treatment was applied with blue-green argon, which has now been abandoned. In the group with an observation time of 2 to 4 years, 42/204 eyes (21%) had improved, 119/204 eyes (58%) remained unchanged and 43/204 eyes (21%) had a deteriorated visual acuity. In the 204 eyes the subretinal neovascular lesion(s) were located extrafoveally in 52 eyes, juxtafoveally in 114 eyes and subfoveally in 38 eyes. It is to be pointed out, that even patients with a pre-laser visual acuity of 6/60 or worse obtained an improvement of visual acuity in 12/27 eyes. About 40% of the eyes needed re-treatment from 1 to 8 times. It is unknown whether the obtained results are to be considered marginal or more substantial.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anal sphincter size measured by endosonography in healthy volunteers. Effect of age, sex, and parity.

The anal sphincter muscles consist of the circular internal and external sphincters together with the sling-shaped associated puborectalis muscle. Ten men, 10 women with no vaginal deliveries, and 10 women with one or more vaginal deliveries were studied with anal endosonography using a 7 MHz multiplanar endoprobe. The thickness of the internal sphincter and the thickness, length, and cross-sectional area of the external sphincter were measured and related to age, sex, and parity. Reproducibility was assessed by similar measurements on different days in 10 volunteers. Anal sphincter size was the same in men and women and was not affected by the number of child births. Internal sphincter muscle thickness increased with age. Anal manometry and electromyography with an anal sponge were performed in all volunteers but the results did not correlate to any of the anal sphincter dimensions. Our conclusion is that although there are some limitations, endosonography can be used to determine the size of the anal sphincter muscles.     

Congenital malformations among children of women working with video display terminals

In a case-base study among 214,108 commercial and clerical employees in Denmark the potential effect of the use of video display terminals on the risk of congenital malformations in pregnancy was investigated. The study base was identified by means of register linkage of the Medical Birth Register and the National Register of In-Patients. In the source population 24,352 pregnancy outcomes were registered, 661 of which with congenital malformations entered the case group, and a base sample of 2252 pregnancies was drawn. Data concerning the use of video display terminals, job stress, ergonomic factors, exposure to organic solvents, and life-style factors were obtained from postal questionnaires. The results of this study did not support the hypothesis that the use of video display terminals during pregnancy is associated with an increased risk of congenital malformations.     

Angiotensin-II contracts isolated human posterior ciliary arteries

The effect of angiotensin-II (A-II) was studied on ring segments of the terminal extraocular branches of the posterior ciliary artery isolated from human enucleated eyes. It induced a potent concentration-dependent contraction on top of the spontaneous myogenic tone of all arteries studied from five patients with the concentration required to give half-maximal response equal to 51 nM. The spontaneous tone and maximal increase in vessel wall tension induced by A-II was equal to 51% of Emax. The relative response and sensitivity to A-II was unchanged in three endothelial denuded vessels, but the spontaneous tone increased. The arteries became completely insensitive to A-II after one exposure. These results show an immediate direct contractile effect of A-II on human posterior ciliary arteries, but the development of pronounced tachyphylaxis indicates that A-II is probably not an important factor in reducing blood flow to the optic nerve head.