Auditory brain-stem responses in guinea pigs following middle ear implantation of Ceravital

Summary The effects on auditory function caused by implantation of the bioactive glass ceramic Ceravital in the middle ear of guinea pigs was investigated. Auditory brain-stem responses (ABR) were used to measure hearing function. A threshold shift due to a conductive hearing loss was observed immediately post-operatively. This threshold shift increased towards the 20th post-operative day and improved thereafter. Surgical manipulation of the middle ear and biochemical reactions between the Ceravital granules and the middle ear wall may have contributed respectively to the immediate and late temporary ABR threshold shift recorded. However, cochlear function was not affected by middle ear implantation of Ceravital. These results correlate well with morphological studies of Ceravital implanted in the middle ear and give further support to the safe use of Ceravital as an implantation material in middle ear reconstructive surgery. Offprint requests to: D. Zikk, Department of Otorhinolaryngology, Tel Aviv Sourasky Medical Center, Ichilov Hospital, 6 Weizman St., Tel Aviv 64239, Israel     

An ultrasonographic study of Peyronie's disease

A study was undertaken to determine the usefulness of ultrasonography as an investigative tool, and its role in deciding the management of Peyronie's disease. Fifteen patients with Peyronie's disease were studied by ultrasonography. The plaque could be demonstrated in all patients. The dimensions of the plaque varied from less than 1 cm to more than 7cm in length and 2-4mm in thickness. The disease was active in 26% of the patients, as indicated by the presence of hypoechoic areas around a central region of hyperechoism. Ultrasonogram was more accurate than clinical assessment in delineating the extent of lesions. In one-third of the patients, sonography demonstrated the plaques to be more extensive than had been detected by clinical examination. Calcification and activity of disease (which are clearly defined by ultrasonogram) are determining factors in the management of Peyronie's disease. This information allows the surgeon to select the modality of treatment, the timing of surgery and extent of excision. Thus, ultrasonography plays a vital role in the preliminary investigation and management of Peyronie's disease.     

Clearance of bilirubin from rat brain after reversible osmotic opening of the blood-brain barrier

Utilizing multicomponent spectrophotometry, we assayed the bilirubin content of rat cerebral hemispheres. With this assay, we determined the clearance of bilirubin from the rat brain following reversible, osmotic opening of the blood-brain barrier. Clearance was rapid, with a half-time of 1.7 h. This half-time was the same as that for clearance of bilirubin from the serum, suggesting that brain bilirubin was removed by transport or diffusion back into the general circulation. Osmotic opening does not damage brain tissue. Thus, in the undamaged rat brain, bilirubin is rapidly cleared, in contrast to its persistence in autopsy-proven human kernicterus. The potential for clearance of bilirubin from human neonatal brain should be considered, especially in the absence of underlying tissue damage.     

Ultrasonic measurement of rate and depth of human fetal breathing: effect of glucose

A recently developed ultrasonic tracking device was used to determine the effect of maternal intravenous glucose infusion on amplitude and frequency of breathing movements in six healthy human fetuses at 38 to 40 weeks' gestation. Following a 2-hour observation period, an intravenous injection of either 25 gm of a 50% glucose solution or an equal volume of saline was given to the mother. Observations were continued for a further 4 hours. Fetal rib cage and abdominal diameters were measured continuously with the ultrasonic tracking device and the information was recorded on a strip chart recorder for later analysis. Breath interval and incidence measurements were highly correlated with data obtained by an independent technique (r greater than or equal to 0.90). During the first 80 minutes after glucose injection, total fetal trunk movement recorded during breathing movements increased from 1.5 +/- 0.2 to 2.9 +/- 0.4 mm (P less than 0.05). There was no significant change in the frequency or variability of fetal breathing movements after glucose infusion.     

Parental feeding style and the inter-generational transmission of obesity risk

OBJECTIVE: This study was designed to determine whether a community sample of obese mothers with young children used different feeding styles compared with a matched sample of normal-weight mothers. Four aspects of feeding style were assessed: emotional feeding, instrumental feeding (using food as a reward), prompting/encouragement to eat, and control over eating. RESEARCH METHODS AND PROCEDURES: Participants were from 214 families with same-sex twins; 100 families in which both parents were overweight or obese and 114 in which both parents were normal weight or lean. RESULTS: We found that obese mothers were no more likely than normal-weight mothers to offer food to deal with emotional distress, use food as a form of reward, or encourage the child to eat more than was wanted. The obese and normal-weight mothers did differ on "control"; obese mothers reported significantly less control over their children's intake, and this was seen for both first-born and second-born twins. Twin analyses showed that these differences were not in response to children's genetic propensities, because monozygotic correlations were no greater than dizygotic correlations for maternal feeding style. DISCUSSION: These results suggest that the stereotype of the obese mother, who uses food in nonnutritive ways so that her child also becomes obese, is more likely to be myth than fact. However, the results raise the possibility that lack of control of food intake might contribute to the emergence of differences in weight.     

Progressive loss of cerebellar volume in childhood-onset schizophrenia

OBJECTIVE: Childhood-onset schizophrenia is a severe and unremitting form of the disorder. Prospective brain magnetic resonance imaging (MRI) studies have found progressive loss of total cerebral volume during adolescence, primarily attributable to accelerated loss of cortical gray matter. Because there is evidence of cerebellar involvement in schizophrenia, the authors examined cerebellar volume and its relation to cortical gray matter development during adolescence in patients with childhood-onset schizophrenia and healthy comparison subjects. METHOD: Total cerebellar volume was algorithmically calculated for 108 anatomical brain MRI scans from 50 patients (20 of whom were female) and 101 scans from 50 age- and gender-matched healthy volunteers (20 of whom were female). The age range of the patients and comparison subjects was 8 to 24. Midsagittal vermal area and posterior-inferior vermal lobe volume were measured by hand. Prospective rescans were obtained at approximately 2-year intervals. Cross-sectional and longitudinal data were combined in mixed model regressions to compare developmental changes for the groups. RESULTS: In contrast to healthy volunteers, patients with schizophrenia showed a progressive loss of cerebellar volume during adolescence. Cerebellar and cerebral volume decreases were significantly correlated in childhood-onset schizophrenia. CONCLUSIONS: Childhood-onset schizophrenia is associated with significant progressive loss of cerebellar volume during adolescence, consistent with previously reported decreases in total cerebral and cortical gray matter. At least in these patients with severe early-onset schizophrenia, the loss appears secondary to a generalized process.     

Clozapine-induced akathisia in children with schizophrenia

Akathisia is a relatively rare side effect with the newer atypical antipsychotic agents, particularly clozapine, and is easily misdiagnosed in children. As children are often unable to describe their symptoms verbally, their akathisia can be misdiagnosed as worsening of their psychosis, prompting an unnecessary increase in their neuroleptic dose. Two cases of childhood-onset schizophrenia associated with clozapine-induced akathisia responsive to beta-blocker treatment are described. Akathisia should be considered in all cases of apparent nonresponse to atypical antipsychotics.     

Progression of corpus callosum atrophy in Alzheimer disease

BACKGROUND: Atrophy of the corpus callosum in the absence of primary white matter degeneration reflects loss of intracortical projecting neocortical pyramidal neurons in Alzheimer disease (AD). OBJECTIVES: To determine individual rates of atrophy progression of the corpus callosum in patients with AD and to correlate rates of atrophy progression with clinical disease severity and subcortical disease. METHODS: Magnetic resonance imaging-derived measurements of corpus callosum size were studied longitudinally in 21 patients clinically diagnosed as having AD (mean observation time, 17.0 +/- 8.5 months) and 10 age- and sex-matched healthy controls (mean observation time, 24.1 +/- 6.8 months). RESULTS: Corpus callosum size was significantly reduced in AD patients at baseline. Annual rates of atrophy of total corpus callosum, splenium, and rostrum were significantly larger in AD patients (-7.7%, -12.1%, and -7.3%, respectively) than in controls (-0.9%, -1.5%, and 0.6%, respectively). Rates of atrophy of the corpus callosum splenium were correlated with progression of dementia severity in AD patients (rho = 0.52, P<.02). The load of subcortical lesions at baseline (P<.05) predicted rate of anterior corpus callosum atrophy in healthy controls. Rates of atrophy of corpus callosum areas were independent of white matter hyperintensity load in patients with AD. CONCLUSIONS: Measurement of corpus callosum size allows in vivo mapping of neocortical neurodegeneration in AD over a wide range of clinical dementia severities and may be used as a surrogate marker for evaluation of drug efficacy.     

Clinical evaluation of biomarkers in Gaucher disease

Novel or candidate biomarkers require thorough evaluation to establish their utility in a clinical setting. This paper describes an evaluation of several established enzyme markers of Gaucher disease and a newly-described chemokine, pulmonary and activation-regulated chemokine (PARC). The ability of the biomarkers to rank patients with Gaucher disease in order of disease severity and organ bulk, and to reflect changes in key clinical parameters in response to enzyme replacement therapy were evaluated. PARC concentrations were found to be reliably correlated with visceral disease and with key clinical responses to enzyme replacement in an unbiased manner. Unlike chitotriosidase and serum angiotensin-converting enzyme activity, genetic variation in serum PARC did not appear to influence its utility as a biomarker.
Conclusion: For each new candidate biomarker of lysosomal storage diseases, a similar clinical evaluation will be required, though the approach will need to be modified according to the clinical features and natural history of each disorder.