The impact of etiology in lesion-symptom mapping - A direct comparison between tumor and stroke.

INTRODUCTION: Lesion-symptom mapping is a key tool in understanding the relationship between brain structures and behavior. However, the behavioral consequences of lesions from different etiologies may vary because of how they affect brain tissue and how they are distributed. The inclusion of different etiologies would increase the statistical power but has been critically debated. Meanwhile, findings from lesion studies are a valuable resource for clinicians and used across different etiologies. Therefore, the main objective of the present study was to directly compare lesion-symptom maps for memory and language functions from two populations, a tumor versus a stroke population. METHODS: Data from two different studies were combined. Both the brain tumor (N = 196) and stroke (N = 147) patient populations underwent neuropsychological testing and an MRI, pre-operatively for the tumor population and within three months after stroke. For this study, we selected two internationally widely used standardized cognitive tasks, the Rey Auditory Verbal Learning Test and the Verbal Fluency Test. We used a state-of-the-art machine learning-based, multivariate voxel-wise approach to produce lesion-symptom maps for these cognitive tasks for both populations separately and combined. RESULTS: Our lesion-symptom mapping results for the separate patient populations largely followed the expected neuroanatomical pattern based on previous literature. Substantial differences in lesion distribution hindered direct comparison. Still, in brain areas with adequate coverage in both groups, considerable LSM differences between the two populations were present for both memory and fluency tasks. Post-hoc analyses of these locations confirmed that the cognitive consequences of focal brain damage varied between etiologies. CONCLUSION: The differences in the lesion-symptom maps between the stroke and tumor population could partly be explained by differences in lesion volume and topography. Despite these methodological limitations, both the lesion-symptom mapping results and the post-hoc analyses confirmed that etiology matters when investigating the cognitive consequences of lesions with lesion-symptom mapping. Therefore, caution is advised with generalizing lesion-symptom results across etiologies.

Disruptive mood dysregulation disorder at the age of 6 years and clinical and functional outcomes 3 years later.

BACKGROUND: Little is known about the predictive validity of disruptive mood dysregulation disorder (DMDD). This longitudinal, community-based study examined associations of DMDD at the age of 6 years with psychiatric disorders, functional impairment, peer functioning and service use at the age of 9 years. METHOD: A total of 473 children were assessed at the ages of 6 and 9 years. Child psychopathology and functional impairment were assessed at the age of 6 years with the Preschool Age Psychiatric Assessment with parents and at the age of 9 years with the Kiddie-Schedule of Affective Disorders and Schizophrenia (K-SADS) with parents and children. At the age of 9 years, mothers, fathers and youth completed the Child Depression Inventory (CDI) and the Screen for Child Anxiety Related Disorders, and teachers and K-SADS interviewers completed measures of peer functioning. Significant demographic covariates were included in all models. RESULTS: DMDD at the age of 6 years predicted a current diagnosis of DMDD at the age of 9 years. DMDD at the age of 6 years also predicted current and lifetime depressive disorder and attention-deficit/hyperactivity disorder (ADHD) at the age of 9 years, after controlling for all age 6 years psychiatric disorders. In addition, DMDD predicted depressive, ADHD and disruptive behavior disorder symptoms on the K-SADS, and maternal and paternal reports of depressive symptoms on the CDI, after controlling for the corresponding symptom scale at the age of 6 years. Last, DMDD at the age of 6 years predicted greater functional impairment, peer problems and educational support service use at the age of 9 years, after controlling for all psychiatric disorders at the age of 6 years. CONCLUSIONS: Children with DMDD are at high risk for impaired functioning across childhood, and this risk is not accounted for by co-morbid conditions.

Tocolytic effectiveness of nifedipine versus ritodrine and follow-up of newborns: a randomised controlled trial.

BACKGROUND: Several studies have demonstrated the superior tocolytic effectiveness of nifedipine over ritodrine. Only 1 trial conducted a long-term follow-up of newborns and found no difference in psychosocial and motor functioning. In a randomised, multicentre trial, we compared the tocolytic effectiveness of nifedipine and ritodrine and included a long-term follow-up of the newborns after 2 years of age. METHODS: Patients with imminent preterm labour were randomised and received either nifedipine or ritodrine. Side-effects, tocolytic effectiveness and neonatal outcome were studied. Development of the children was studied after the age of 2 years by a parental questionnaire. RESULTS: Ninety-three patients were included. Birth was postponed for an average of 4.3 weeks in the ritodrine group and 5.0 weeks in the nifedipine group (p=0.4). Patients who received ritodrine experienced significantly more side-effects compared to patients who received nifedipine (29 versus 4%, p<0.05). No significant differences were found in either group for average birth weight, Apgar scores after 1 min, neonatal intensive care unit (NICU) admission and neonatal complications. Parental questionnaires after 2 years had a response rate of 70%. Two-thirds of the children had developed normally in both groups. In both groups, only a few children were severely retarded (n=4). No significant differences in development were found between the 2 groups. CONCLUSIONS: Both nifedipine and ritodrine proved effective tocolytic drugs, however ritodrine caused significantly more maternal side-effects. Neonatal outcome and long-term development after 2 years of age were not significantly different. We favour nifedipine over ritodrine as a tocolytic drug.

Quinacrine sterilization: a retrospective.

OBJECTIVE: To trace development of quinacrine sterilization (QS). METHODS: Review of published reports. RESULTS: The high prevalence of septic abortion among high parity women in Santiago, Chile, motivated Zipper to find a safe, inexpensive method of non-surgical female sterilization. Various cytotoxic drugs were tried in rats. Because quinacrine was already accepted for intrapleural injection it was chosen for the first clinical trial. A slurry consisting of quinacrine and xylocaine was instilled into the uterine cavity with a transcervical syringe. Reasonable efficacy was noted and a limited scar of the intramural tube demonstrated. However, a side effect of cortical excitation and reports of 3 deaths ended this approach. Zipper and Wheeler hypothesized that the difficulty was due to rapid absorption of quinacrine under pressure and designed a pellet form that dissolves slowly and could be delivered transcervically using a modified IUD inserter. A standard protocol of 252 mg in seven 36 mg pellets placed at the uterine fundus on two occasions a month apart has now been widely used with considerable evidence for safety and efficacy. Indeed, protection is greater than 98% at 2 years of use. CONCLUSION: QS is ready for widespread use, especially where surgical sterilization is not safely available or when women are poor candidates for surgery or have such a fear of surgery that they will not seek surgical sterilization.

Quinacrine sterilization: a retrospective.

OBJECTIVE: To trace development of quinacrine sterilization (QS). METHODS: Review of published reports. RESULTS: The high prevalence of septic abortion among high parity women in Santiago, Chile, motivated Zipper to find a safe, inexpensive method of non-surgical female sterilization. Various cytotoxic drugs were tried in rats. Because quinacrine was already accepted for intrapleural injection it was chosen for the first clinical trial. A slurry consisting of quinacrine and xylocaine was instilled into the uterine cavity with a transcervical syringe. Reasonable efficacy was noted and a limited scar of the intramural tube demonstrated. However, a side effect of cortical excitation and reports of 3 deaths ended this approach. Zipper and Wheeler hypothesized that the difficulty was due to rapid absorption of quinacrine under pressure and designed a pellet form that dissolves slowly and could be delivered transcervically using a modified IUD inserter. A standard protocol of 252 mg in seven 36 mg pellets placed at the uterine fundus on two occasions a month apart has now been widely used with considerable evidence for safety and efficacy. Indeed, protection is greater than 98% at 2 years of use. CONCLUSION: QS is ready for widespread use, especially where surgical sterilization is not safely available or when women are poor candidates for surgery or have such a fear of surgery that they will not seek surgical sterilization.

Characterisation of aerobic gram-negative bacteria from subgingival sites of dogs--potential bite wound pathogens.

Ninety-eight aerobic, gram-negative bacterial isolates from subgingival samples from family-owned dogs with naturally occurring periodontitis were characterised phenotypically by conventional biochemical testing, by cellular fatty acid profiling and by the use of commercial identification systems. The majority (48, 81%) of the fermentative isolates but only 18% of the non-fermenters were identified by conventional biochemical testing alone. With additional cellular fatty acid profiling, another 7 (12%) fermentative and 23 (59%) non-fermentative isolates were identified to genus or group level. Cellular fatty acid analysis was essential for the identification of most non-fermenters, many of which are difficult to identify due to a paucity of positive reactions in routine biochemical tests. Commercial identification systems were less useful and did not contribute to further identification of these problematic isolates. This study underlines the difficulties encountered in the identification of canine oral bacteria--a group of potential bite wound pathogens--and presents schemes for microbiology laboratories to characterise such isolates.

A randomized controlled study comparing the endocrine effects of pulsatile intravenous gonadotropin-releasing hormone after gonadotropin-releasing hormone agonist pretreatment versus clomiphene citrate in patients with polycystic ovary syndrome.

OBJECTIVE: To compare the endocrine changes in the follicular phase in infertile patients with polycystic ovary syndrome (PCOS) treated with either pulsatile IV GnRH after GnRH-agonist (GnRH-a) down-regulation or clomiphene citrate (CC). DESIGN: Subgroup analysis within a randomized, controlled, multicenter study. SETTING: Women referred to the Infertility Clinic, Catharina Hospital Eindhoven, The Netherlands. PATIENT(S): Twenty-eight infertile patients with PCOS. INTERVENTIONs): Patients were randomly assigned to pulsatile IV GnRH (10-20 microgram/90 min) after GnRH-a down-regulation or CC (50-150 mg; cycle days 3-7). Patients were monitored on alternate days with ovarian sonography and serum concentrations of E(2), LH, and FSH. Serum P and sonography confirmed ovulation. MAIN OUTCOME MEASURE(S): Serum concentrations of E(2), LH, and FSH were assessed before treatment was started and after each ovarian sonography. RESULT(S): In ovulatory cycles, no statistically significant differences were observed during the follicular phase comparing serum concentrations of E(2), LH, and FSH between the treatments. However, a significant increase in LH occurred in the GnRH group. CONCLUSION(S): No significant endocrine differences were observed between GnRH and CC treatment. However, there was a significant increase in the serum LH concentration during the follicular phase in the GnRH group. Increments of LH in the GnRH group may be due to recovery of endogenous LH secretion.

Quinacrine sterilization: an assessment of risks for ectopic pregnancy, birth defects and cancer.

Quinacrine sterilization (QS) involves transcervical insertion of quinacrine pellets using a modified Copper TIUD inserter. Pellets are placed at the fundus in the proliferative phase of the menstrual cycle. Efficacy is presently estimated at 1 pregnancy failure per 100 women at 2 years. Early complications are lower for QS than surgical sterilization and this is also true for risk of ectopic pregnancy with newer insertion protocols. The risk of birth defects is very low, when estimated from a model with reasonable assumptions for probability of insertion in a pregnant uterus or within 30 days of conception, probability of such exposed pregnancy being carried to term, and probability of quinacrine exposure to the fetus causing a birth defect. Although quinacrine is a mutagen it is unlikely to be a carcinogen. Concentrations of quinacrine in the uterus after transcervical insertion are higher than for oral administration for only a matter of a few hours, although this brief exposure is adequate to cause injury to the tubal epithelium, leading to inflammation and an occluding scar. Oral administration of quinacrine is accepted as non-carcinogenic. Each site of use of QS must make its own risk/benefit assessment. The benefits of any contraceptive that can raise contraceptive prevalence is greatest for developing countries.

Ischemic colitis and acquired resistance to activated protein C in a woman using oral contraceptives.

We present the case history of a 22-yr-old woman diagnosed with ischemic colitis associated with the use of oral contraceptives (OC). At the time of her presenting symptoms activated protein C (APC) resistance, a risk factor for thrombosis, was demonstrated. There was no laboratory evidence of inherited thrombophilia; that is, antithrombin III, protein C and protein S levels were normal and the factor V Leiden mutation was not present. The OC were discontinued and the patient's symptoms improved. Subsequent evaluation revealed that the activated protein C resistance had resolved. This case illustrates APC resistance as a potential link between OC use and its known association with ischemic colitis.

Characterization of anaerobic, gram-negative, nonpigmented, saccharolytic rods from subgingival sites in dogs.

We characterized 52 anaerobic, gram-negative, nonpigmented, saccharolytic rods that were isolated from healthy and diseased subgingival sites of 16 family-owned dogs with spontaneous, clinically diagnosed periodontitis. Phenotypic features were determined with use of standard biochemical methods, by enzymatic profiling with the API ZYM system, and by cellular fatty acid profiling. Genotypic characterization was performed by DNA-DNA hybridization. Four phenotypic groups, defined as the Bacteroides fragilis group, the Prevotella buccae-like rods, the Prevotella heparinolytica/Prevotella zoogleoformans-like rods, and the slimy bile-tolerant rods, designated the Bacteroides pyogenes/Bacteroides tectum group, were detected. P. buccae and the B. pyogenes/B. tectum group organisms were isolated significantly more often (P values, < .05 and < .005) from the diseased than the healthy subgingival sites. The phenotypically similar group of bile-tolerant organisms, including B. pyogenes and B. tectum, most likely constitutes a major component of the anaerobic, gram-negative, saccharolytic microflora in periodontal lesions in dogs, a flora different from that in humans.

[The Outpatient Pediatric Neurology Service of Moscow today]. / Ambulatornaia detskaia nevrologicheskaia sluzhba Moskvy na sovremennom étape.

The organisation of children's neurological service was considered in terms of 25 years of medical-diagnostic work of children's consultative neurological out-patient clinic (CCNC) attached to one of Moscow children's clinical hospital (Morozov hospital). The work of appropriate departments of CCNC was presented together with the consideration of the main problems of child's neurology as well as of the peculiarities of nervous system's pathology in terms of age. The close connection was emphasized between CCNC and child's neurologists of general out-patient clinics as well as the role of CCNC both in coordination of their work and in the rise of their qualification.

Concentrations of tinidazole in gingival crevicular fluid and plasma in dogs after multiple dose administration.

Tinidazole 15 mg/kg was administered to eight Beagle dogs with gingivitis or periodontitis twice daily for 3 days. Tinidazole concentrations in blood and gingival crevicular fluid (GCF) were measured 1, 3, 6 and 9 h after the morning dose each day. The concentration of tinidazole was determined by high performance liquid chromatography (HPLC). The mean concentration of tinidazole in GCF for each dog ranged from 6.05 to 9.32 micrograms/mL at different time points after the first dose, and on the first day the highest concentration was observed 6 h after the drug administration. Tinidazole concentrations were 34 +/- 4%-72 +/- 9% (mean +/- SEM) of simultaneous plasma concentration. At steady-state, on the third treatment day, the mean tinidazole concentrations in GCF ranged from 6.68 to 13.1 micrograms/mL, i.e. 44 +/- 6%-75 +/- 25% of the corresponding concentrations in plasma. Tinidazole concentration in GCF exceeded the MIC values for putative path-ogenic periodontal bacteria and it is concluded that, when indicated, tinidazole could be used for chemotherapy of periodontitis in dogs.

100,000 quinacrine sterilizations.

100000 quinacrine nonsurgical female sterilizations have been completed over the past decade involving transcervical insertion of quinacrine (252 mg) as pellets by one, two or three monthly insertions. No deaths have been reported and serious complications are far fewer than for surgical sterilization. Side-effects are mild and transient. Efficacy has improved from 3 pregnancy failures per 100 women at one year to approximately 1 by improved insertion technique and use of adjuvants. Long-term follow-up of early cases in Chile shows no increased risk of cancer for this method. The main advantage of quinacrine sterilization is its ability to raise contraceptive prevalence and thereby reduce maternal mortality and morbidity, especially in rural and urban slum areas of developing countries. It should be made available as an option to well informed women everywhere as an economical and safe permanent family planning method.

Asia-Pacific AIDS incidence on the rise.

PIP: Thailand's first case of AIDS was reported in 1984. A steep trajectory to 6340 cases did not occur, however, until 1993, and then increased to 11,113 cases in 1994. The first leveling of the steep trajectory is anticipated in 1995. 77.9% of cases in Thailand between 1984 and 1995 are associated with sexual contact, mainly heterosexual with prostitutes. 7.1% of cases are due to IV drug use, 6.6% to maternal-fetal transmission, 0.2% to blood transfusion, and 8.2% to unknown causes. 870,000 AIDS cases and 1,826,000 cases of HIV infection are projected for Thailand by 2005. A high proportion of HIV infected and AIDS cases in Thailand are men, but equal proportions of men and women are projected to be afflicted. With India's larger population base, the numbers of HIV infected and people with AIDS will be markedly higher. India may already have 100,000 HIV-infected citizens and it may surpass sub-Saharan Africa early in the next century as the main focus of the HIV epidemic. The author notes that Japan is the only advanced developed country which has not experienced a steep AIDS case rate; condom use is greater there than in any other country.^ieng